Testosterone, thyroid, cortisol, growth hormone. From benefits, risks, side effects, blood tests, signs, symptoms, products.
Testosterone, thyroid, cortisol, growth hormone. From benefits, risks, side effects, blood tests, signs, symptoms, products.
Improving your hormones for performance, wellbeing and longevity.

How To Fix Your Hormones: The Ultimate Guide

About the author: I am a final year medical student. At the age of 23 I started to replace all of my major hormones. I wrote a number of articles to counter the vast amount of misinformation I have come across. The information outlined below took years of research, experimentation, engineering and modifying. Had I known then what I know now, it would have saved me lots of money, time and effort. Also, it would have protected me from a lot of suffering. Here I share with you some of the things I have learned along the way.

The comprehensive guide I wish I had

Note: This article is long. There is a short tl;tr version at the top.

This guide discusses safe, effective, physiological hormone replacement. It covers a wide array of topics including benefits, risks, side effects, ethical issues, blood tests, symptoms, products, therapy of choice, dosages, doctors, costs, and sources. It is suitable for males and females alike.

I have been using natural, bioidentical hormones (testosterone, thyroid, cortisol, growth hormone) to bioengineer my health, body and mind for several years. Hormone replacement therapy gave me my life back. It can do the same for you.

Hormones have a considerable impact on our energy, mood and health. Thus, in a way, hormones determine the quality of our lives. If they deteriorate so does our wellbeing. Sadly, many of us have hormonal imbalances.

It is therefore unfortunate that few comprehensive information sources about hormones are available, however, there is lots of misinformation.

Worse still, good hormone specialists are incredibly rare and very hard to find. Subspecializations in medicine have produced doctors who are often unable to detect even blatant signs of hormone deficiencies, thus causing great suffering. They claim nothing is wrong with us. They give us stimulants, antidepressants, or send us somewhere else. They belittle us when we look for alternative treatments or try to fix hormonal issues on our own.

That is why I wrote this guide.

While there are some performance-enhancing aspects to even physiological hormone replacement, please note that my primary focus is not on performance enhancement (e.g. bodybuilding, doping, etc.), but rather on safe, effective, physiological and sustainable hormone replacement that can be applied throughout our lifetime and is focused on health, disease prevention, longevity and self-optimization.

My goal is to help you achieve optimal energy levels, mood and health. At baseline. This does not mean taking stimulants, being productive for a few hours, then crashing. We are in for the long game, a marathon, not a sprint.

Our goal is to arrive at a state with great energy, mood, health. At baseline. This is not like taking stimulants, being productive for a few hours, then crashing. We are in for the long game, a marathon, not the sprint.

Many of the facts, tips, tricks, insights I found out throughout my journey cannot be found anywhere else on the Internet. Having learned a lot along the way, I want to share the most important findings with you.

Disclaimer: I am not a doctor. None of what is presented in this article is medical advice. Everything is for informational and entertainment purposes only. If you have any queries related to health, diagnosis or treatment, always consult with a medical professional.

Article structure explained.

This article is divided into two parts. In Part I you will learn how hormones first destroyed and then saved my life and how they could do the same for you. I also briefly address whether hormone replacement is healthy, natural or if it is cheating. I conclude with a cost-benefit analysis explaining under which circumstances someone should or should not consider hormone replacement.

Part II is mostly practical. I present my replacement protocol and describe some of the changes I have noticed over the years. Then I discuss purely practical issues (if you are interested only in the practical aspects, feel free to go straight to this section).

PART I (general part):

1. Vitality. The importance of a good hormonal profile.

2. Health and ethical aspects.

3. Should we replace our hormones?

PART II (practical part):

4. My hormone replacement protocol. Changes I have noticed over the years.

5. Improving hormones naturally?

6. General and practical stuff about hormone replacement

7. Guides on how to replace individual hormones. (Brief overview of the benefits of hormone therapy, Cortisol, Thyroid, Male Sex Hormones, Female Sex Hormones, Growth Hormone)

8. Risks and side effects.

9. Sources and costs.

10. Conclusion

Tl; tr.

This article is really long. However, because I realize that many of you do not have enough time to read the full-length version, here is a summary.

Part I. (general part)

  • Hormones are underrated. Our hormonal profile is one of the most important things influencing our life. By affecting our wellbeing, thinking patterns and behavior, the effect of hormones ripples into every corner of our lives (e.g. career, relationships, income, lifestyle, happiness, etc.). Unfortunately, it is something few of us know much about.
  • Hormonal imbalances are very common. There are millions of people worldwide who have hormonal deficiencies, which are often unrecognized and untreated. A hormonal imbalance can destroy our lives. Common issues such as anxiety, depression or fatigue often have hormonal imbalances at their root cause. Unfortunately, neither patients nor doctors ever look at hormones more closely.
  • You cannot ‘out-drug’, ‘out-biohack’ or ‘out-lifestyle’ a bad hormonal profile. When it comes to health-improvement, the focus is usually on drugs, diet, sleep, exercise, gut health and supplements. Each of them being billion-dollar industries. While all these are important, few measures have as profound of an impact on human health as restoring optimal hormone levels. Besides, a good hormonal profile makes all the other lifestyle choices much easier.
  • Vitality matters. Life can be so much easier and so much more enjoyable if we are full of energy, in a great mood and have good health all the time. Whatever we want in life, whether that is creating, contributing, achieving a specific individual goal or simply enjoying the only life we can be sure of having, great vitality is the most important requirement to get us there. As it turns out, our vitality is closely dependent on our hormonal balance.
  • Compound interest is the most powerful force in the universe. If we improve our energy, mood and health, we will get value out of it every day, which we can then reinvest, day after day. Imagine if you had your best, most vital hour of the day extended to the entire day. 7 days a week. 365 days a year. Imagine how much more productive you could be. Imagine where your life could be in 10 years from now (psychologically, physiologically, financially, socially, intellectually). Also, how much more could you enjoy your time? How much more could you contribute to the well-being of others? Compound interest…the earlier we start, the more compound return we get.
  • We are not aware of our “baseline”. The way we feel from one moment to another strongly depends on our hormone levels at that given moment in time. Most of us have no idea what it “feels” like if one of our hormones changes and how much better we could feel and function.
  • Hormones are powerful. Each hormone affects our whole body. In fact, every single cell in our body has a receptor for all four hypothalamic hormones (sex hormones, thyroid hormones, growth hormone, cortisol). Each of them unlocks a specific portion of the genetic code, acting at the most downstream level possible. If we alter our hormones, we send whole-body messages to all our cells and alter their expression of our genetic code. Thus, hormones are much more powerful than drugs or lifestyle interventions, whose effects pale in comparison.
  • All hormones drop with age. There is a reason most of us have their peak energy/mood/health/looks from age 18 to 25. During this time, our hormonal profiles are at their best. Evolutionarily, Homo sapiens´ reproductive success was primarily determined before the age of 30. Thus, there were never the necessary evolutionary pressures to keep us healthy and functioning well beyond this age. As we get older, all of our hormones decline naturally across the board. Naturally. And our vitality does as well.
  • Why are hormonal therapies underused? The medical system is a huge industry and as is the case with other industries, it depends on revenue generation. Most revenue is made from patents. But hormones are natural molecules, which nobody is allowed to patent. Thus, since not much money can be made from hormones, they are not studied as extensively as pharmaceutical drugs (which often just treat symptoms but not the root causes). As a result, large, well-designed RCTs are often lacking.
  • Is replacing our hormones healthy? Many of us have the “there-is-no-free-lunch”-mindset, assuming that taking any drug (or hormone) is “bad” and that we will surely pay the price down the line. However, this is not how the world works. When hormones are replaced correctly, it is healthier compared to living with one or more deficient hormones.
  • Is replacing our hormones (un)natural? Our genetic, biochemical, physiological machinery evolved for different times and has not (yet) adapted to the modern environment we currently live in (e.g. constant distress, artificial lightning, pollutants, highly processed foods, fast-spiking carbohydrates, sedentary lifestyles, living beyond the age of 40, etc.). Thus, our mental and physical operating system is outdated. Updating or upgrading it is just as natural as living in our unnatural world in the first place is.
  • Is replacing our hormones cheating? Hormone replacement certainly does give you and me an advantage, but since energy, mood and health are certainly not equally distributed, there was never a level playing field to begin with. Furthermore, humanity is more about cooperation than competition. Thus, even though hormone replacement can be seen as cheating, overall, the effects on others and humanity might be good, because if we become more healthy and productive members of society, society as a whole might benefit (besides the fact that our life would be easier and more enjoyable -the primary reason most self-optimize).
  • The danger of being left behind. Great vitality (energy, mood, health) is on average the most important factor that determines the trajectory and success of most people’s lives (e.g. status, wealth, relationships, happiness). Now, for the first time in human history, we can think about stretching and even transcending these biological constraints. I predict that (multiple) hormone replacement will be mainstream in the coming years. In fact, many people do this already. Unfortunately, these are mostly people who are already high up on the socioeconomic ladder. Multiple hormone replacement is widespread among the rich and powerful who have access to expensive longevity doctors. Consequently, economic inequality furthers biological inequality, which then increases economic inequality even more. Over time, this leads to widening wealth disparity. To sum up, the future is already here. It is just unevenly distributed.
  • The risk of inaction. When it comes to hormone therapy, many people are scared and worry about the side effects, nuisances, risks, costs, etc., but most of us only look at this side of the equation. What are the risks of not replacing deficient or suboptimal hormones? What are the opportunity costs of inaction? In the end, it is a complex calculation of tradeoffs, but there are risks from doing nothing as well. The last point is often dismissed.¹ To read how hormones destroyed and saved my life, click here.

Part II (practical part).

Note: Each single one of these points is explained in much more detail in the respective section.

  • Before starting hormone replacement, get your diet and sleep in order. A “bad” diet (esp. insufficient caloric intake) or bad sleep can have a severe impact on our hormonal balance. Once these issues are corrected, hormones often recover naturally. Insufficient caloric intake (e.g. due to obsession with “fitness”) is one of the most common causes of hormone deficiencies. Read more about this important point in Section 5.
  • Improving hormones naturally. There are many things we can do/try to improve our hormones naturally (see Section 5). These often fix the issue. But they often also do not. Some people just have a great hormonal profile naturally, often despite an unhealthy lifestyle. Others can lead the most healthy lifestyle possible, and yet their hormone levels remain low, simply because suboptimal hormones is their natural state. We all have specific, more or less fixed “setpoints” for each of our hormones. If the setpoints for one of these hormones is naturally low, no supplement, diet or life-style intervention will help.
  • Why do doctors often not recognize hormone deficiencies? Firstly, the (sub)specializations in medicine (and undertraining in endocrinology) have left us with doctors who are often unable to detect even blatant signs of hormone deficiencies. Second, results of laboratory tests often show our hormone levels are “normal”. In fact, many people who seek out doctors for problems with hormone deficiencies at their root cause, do often not fall below the medical reference range, thus flying under the radar of the modern healthcare system in which doctors just look at values that are flagged. Their values come back “normal”, but they are only normal for someone 30 years their senior.
  • Before spending thousands of dollars on a doctor, the first step we can do is to get a blood test. A good hormonal panel is useful and a great starting point. (See the respective section below for more details on what I would test). All of the major hormone deficiencies (thyroid, sex hormones, cortisol, growth hormone) have (partially) overlapping signs and symptoms (e.g. energy levels, libido, sleep, emotionality, body composition, etc.). Thus, by considering only physical signs and symptoms it is often almost impossible to determine whether a hormone is deficient and certainly not which one. Blood tests are particularly helpful here.
  • When it comes to hormones, signs and symptoms matter just as much as numbers on a paper. While blood tests are useful, they have a major downside: They measure what is currently in the blood. However, hormone levels in the blood do not tell us much about cellular action, which is the only thing that matters. Because of this, there is no definite indicator (e.g. cut-off number on a blood test, a specific sign or symptom) that can tell us in a clear-cut way, whether we are deficient in a specific hormone or not. To determine a deficiency, we need to look at physical signs, symptoms and blood values together. We need all three.
  • Reference ranges. Reference ranges are statistical ranges that cover 95% of the natural variation found in a population. Simply falling somewhere within the laboratory reference range is not “optimal”, because certainly more than 5% of the population have hormones bad enough to warrant intervention.
  • We are all a little different. There is no “one-size-fits-all”. All of us have differences in our absorption, binding proteins, metabolism, cellular sensitivity, function and quantity of receptors and nuclear cofactors, degree of gene methylation, etc. Thus, hormone replacement needs to be tailored to each patient individually. The optimal dosages (and even plasma levels) often differ between individuals.
  • Hormones need to be balanced. If one member of the orchestra is off, the orchestra as a whole does not sound good. Hormones too need to be balanced. However, this process can become tricky very fast. Turn one gear and many others are set in motion as well. Thus, replacing hormones is as much an art as it is science. There will be some (educated) guesses and trial & error involved. An experienced doctor is a great help (if we are lucky enough to find one).
  • Using multiple hormones is safer than (ab)using a single hormone in high dosages. In general, most people start with the replacement of just a single hormone. Often, results do not manifest as they expected or wished. Many then try to compensate for multiple hormone deficiencies (that they are not aware of) by raising the dosage of whatever hormone they are replacing. This over-replacement and abuse of a single hormone is quite common. Instead of going above the physiological range, it is much healthier (and also more “natural”/physiological) to add one or more other hormones in small, physiologic dosages. To maintain good energy, mood, health, libido, sleep and emotional wellbeing we need to have adequate levels of all the major hormones.
  • The U-shaped curve. When it comes to hormones more does not mean better. For most hormones, optimum resembles a U-shaped curve. Small, physiological doses of hormones are both safe and healthy which is why they have been extensively used by anti-aging specialists for decades. While everyone is different, on average, titrating levels to around the 75th percentile gives the best tradeoff between health, longevity and wellbeing. In most cases, it can be considered safe and the benefits generally outweigh the risks.
  • How to start therapy: Start low & go slow. Hormones act directly on gene expression, which changes the internal machinery of our cells. Tissue structure and function will change as a consequence. By starting with low dosages, cells and tissues will not be thrown off balance as much. Starting with a dosage too high (or increasing the dosage too fast) comes with increased side effects, most of which could be avoided or at least drastically reduced by following the low&slow-approach.
  • How long until benefits will be evident? While some benefits will be immediate, most changes take some time to materialize, because our cells and tissues need to adapt both structurally and functionally to the altered levels of hormones. Because of this, for most benefits to be fully evident, a wait of around 3–4 months is required after starting therapy.
  • Will I develop a “tolerance”? The use of exogenous hormones is always accompanied by some endogenous suppression. However, endogenous suppression is not the same as tolerance. Because hormones act on nuclear receptors (and not on transmembrane receptors like most pharmaceutical drugs do), they directly alter the gene expression of our cells. Thus, hormones act at the most downstream level possible. To these effects, there is little to no tolerance. However, there will be some tolerance to some effects on neurotransmitter systems (e.g. increased levels of dopamine). If you truly want to understand what hormones are and why they are so powerful, read my unconventional introduction to endocrinology.
  • Overreplacement. The overreplacement of any hormone (although tempting) carries more risks than benefits. A minor overreplacement might ”feel good” but at the risk of trading off performance for health and longevity down the line. In case of a severe overreplacement, whether intentional or not, the list of possible adverse effects is long. Some adverse effects can be severe and very dangerous in both the short and long term.
  • Should you go to a doctor? When it comes to replacing or balancing hormones, the quality of doctor advice can make or break your life. Unfortunately, when it comes to hormones, good doctors are incredibly rare and very hard to find. In general, most are 20 years behind science. Even the ones who do know the science were first and foremost trained to not harm (as this could lead to losing our license). Even if we would replace hormones differently in ourselves and our families, for treating patients, we would rather stick to the guidelines optimized for safety.
  • Energy levels. For good energy levels, we need all hormones at adequate levels. If one of the hormones is off, this will be our limiting factor. Furthermore, each hormone deficiency is associated with a specific kind of fatigue. To learn more, click here. Energy levels are mostly determined by our levels of thyroid hormones and cortisol. The thyroid sets the idle for your system, cortisol is your gas pedal. Getting these two right/wrong will have life-changing consequences (+/-).
  • Personality changes. Whenever we make sustained alterations to our (neuro)biochemistry, over time, our core personality (slightly) changes. See Section 5, where I explain the personality changes I have noticed in myself over the years.
  • Will I have to continue hormone replacement for life? In most cases, one of three scenarios apply. Firstly, no cause can be found (or a cause can be found but can not be removed) and the risk or downside of living with baseline hormones are larger than the risk or downsides of therapy. Secondly, there is always a (small) risk of permanent endocrine suppression. Thirdly, after having seen life on the other side, many people do not want to go back. For around half of people who start hormone therapy, one of these applies, making hormone replacement a life-long therapy.
  • Hormones need to be weaned off slowly. Stopping the use of hormone therapy suddenly can have dangerous consequences. If one wants to stop (for whatever reason), a gradual, progressive reduction in dosage is required (tapering). This will allow sufficient time for the hypothalamic hormone generators to pick up again, and for the endogenous gland to hypertrophy again, which will take weeks to months. Temporarily, one might need to accept to live in a state of partial hormone deficiency.
  • The risk of (permanent) endogenous suppression. In general, endocrine suppression is just partial (e.g. 50%) and temporary (i.e. it persists only as long as exogenous hormones are present). Given physiological dosages are used (and tapering off is done correctly), most people will gradually return to baseline within a few weeks to months after stopping treatment (or to even higher levels, if the cause for their hormone deficiency was found and removed). However, it is possible that some do not. The higher the dosage used, the greater the risk of this happening. In this case, hormone replacement needs to be continued for life. For a scientific explanation, see the respective section.
  • Altering/tweaking/optimizing hormones is a long journey. It takes quite some time, effort, money and experimentation to optimize and balance hormones, but it is worth it.
  • It is easy to get used to the benefits. If we have been living with one or more deficient hormones for a long time and then start to replace what was missing, in the first few months we are often incredibly grateful to have been given “our life back”. We regard the costs, side effects or downsides of therapy as a tiny price to pay. But after we have been in that “new” state for some time, we tend to get used to it. We often start to take our new/restored energy, mood, sleep, motivation and emotional wellbeing for granted, completely forgetting how we felt before. This can go so far, that now, suddenly, the nuisances associated with therapy seem to outweigh the benefits, simply because we forgot how life used to be before.
  • Guides on how to replace individual hormones. (Brief overview of the benefits of hormone therapy, Cortisol, Thyroid, Male Sex Hormones, Female Sex Hormones, Growth Hormone/IGF1)

I´ll talk about all these points in much more detail below.

Part I

1. The importance of a great hormonal profile.

Vitality.

Note: Google defines “vitality” as “the state of being strong and active”. For the sake of this article we will define vitality as a catch-all-term encompassing 1) energy levels, 2) mood, 3) health. All of these are of course intricately linked.

In my early twenties, my life went down the gutter. I felt awful (understatement) all the time. I attributed it to weakness and bad lifestyle choices. For a long time, I was unaware of the invisible forces I was up against.

I did not know that my bad lifestyle choices were a consequence (of trying to make up for my low energy levels), not a cause.

Despite having been a social, well-rounded guy before, between 20 and 23 I was like a hermit. Withdrawn, judgemental, obsessive. A major cause of this change was my hormones spiraling to the ground. The gradual drop in my hormones eroded many things I held dear. My wellbeing, my personality, my relationships, my career, my life.

Hormonal deficiencies left untreated for too long destroy lives.

I started to replace what was missing. Whereas the start was rocky, within a few years of trial & error I got my life back. It realized how much easier and enjoyable life gets if we have great energy levels, mood and health all the time. The upwards spiral started again. An upwards spiral that otherwise would never have happened.

I was not always lethargic anymore. I had more drive to do things and motivation to study. I had more energy after waking up and felt more optimistic about starting a new day. I needed around an hour less of sleep, a quarter of which I was able to use for morning meditation, for which I did not have time and energy before.

I had more self-confidence to approach people. I was not as tired anymore and more “present”. I finally had the necessary energy to apply some of the self-help stuff I read, whereas before I was a rigid, irritable asshole on autopilot.

I was more eager to move and exercise. With a greater amount of energy, drive and motivation my willpower increased. I made better food choices, exercised more and slept better.

Next to hormones direct effects on muscle, fat, skin, hair, etc. I began to look better. The gains in looks, self-confidence, energy, mood and zest for life, improved my social life. Now I wanted to go out and be around others whereas before I was a socially anhedonic hermit. And because energy and mood are contagious, others enjoyed my company as well.²

Among other things, the improvement enabled me to go out of my comfort zone and to talk to Paula, a girl I was blown away by from the first second after I met her. A month later she was my girlfriend.

Over time I became different. No further knowledge or “insight” is required, no painstaking habit formation, which leads to slow and unreliable progress at best.

As my hormones improved, many other facets of my life automatically started to improve as well. (But I also had experienced the reverse). Of course, all this did not happen overnight, but rather over long periods of time (months to years) due to a lot of complex and cross-interacting feed-back and feed-forward loops spanning all domains of my life.

Slowly but surely, my new-found, above-average vitality gave me value on a daily basis and I automatically reinvested it, both consciously and unconsciously. Each day anew, 7 days a week, 365 days a year. Compound interest is the most powerful force in the universe.

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Credit: Samuel Tillian

What about my happiness? Well, I did not just feel better from a biochemical perspective but many “objective” facets of my life improved as well (e.g. status, looks, career, social life, love life). I felt better about myself and life in general, independent of any neurobiochemical effects.

What is more, ‘my life is just as good as my mind is’ (Buddhism). However, as it turns out, the mind is what the brain does and hormones have a major say in that.

With better energy and mood, (all else being equal) I feel better at every given moment. Given that my life is simply a string of single moments, my area-under-the-curve happiness increases.

To sum up all of the above: As I improved my hormonal balance, my outer life (objective life situation) and my inner life (subjective wellbeing) have improved. The way I feel moment-to-moment has improved. Everything was an automatic byproduct of improving my hormonal profile and being patient.

The downstream effects of all of these things will, likely and hopefully, enable me to be a better contributor to humanity as well. Thus, if I become a healthier, happier and more productive individual, it is not only my outer and inner life that is better off for it, but likely and hopefully also the lives of the people I have directly and indirectly touched along my journey through everything I do.

So, what is the most important lesson I have learned? Vitality (energy, mood, health) is perhaps the most important condition that determines how our life turns out (compound interest).

To read a more in-depth version of how hormones destroyed and saved my life, read here.

Poker. Get your ace.

Many people with great conventional life success (wealth, status, relationships) such as politicians, actors, CEOs, athletes, etc. often credit their accomplishments and high-tier place in society to their intelligence, effort, perseverance, talent or grit.

For them it feels natural to believe they deserve it, looking down upon “the lazy masses” binging Netflix, eating a crappy diet, consuming without creating, never opting for the hard things but rather being complacent in their comfortable rut of the status quo “living a life of quiet desperation” as Walden put it.

But what were the conditions and enabling factors that led to their intelligence, effort, perseverance, talent, grit in the first place?

They are often unaware of the luck they had. There is an innumerable number of conditions completely outside their and our influence. From genetics to being born in a prosperous country, schooling, race, looks, caring parents who were cherishing and motivating along the way and many more.

Conditions that enabled them (or us) to work hard in the first place.

Great vitality (energy, mood, health) is on average the most important factor that determines the trajectory and success of most people’s lives (e.g. status, wealth, relationships, happiness).

Hormones are one of the two most important factors determining our vitality, the other being genetics, which though as of yet we cannot negotiate.

Life is like poker — we can get a good hand, play it perfectly, but still end up with a bad outcome. Great vitality (energy, mood, health) is our ace in the game of life. Even with an immaculate vitality, we can screw up the game, but chances are we do so much less likely.

If we feel tired, unmotivated, moody all the time, making the best out of the only life we have got is just not on the cards. “Living each day fully” much less.

Energy levels, health, mood, motivation, looks, concentration, memory, cognition, recovery, etc. all impact us every day. Compound interest. The earlier we start, the exponentially more return we get.

Among other things, all these depend on mental states, which strongly depend on hormones, much more than most of us are aware. If our hormones aren’t balanced, success in other parts of our life will be elusive.

Those lucky enough to have been bestowed upon with a great vitality (e.g. genetics, hormones) by the age of 20 are on average a lot further ahead compared to most of us who are not significantly regressing from the mean.

Whatever we want in life, whether that is creating, contributing, achieving a specific individual goal or simply enjoying the only life we can be sure of having, great vitality is the most important requirement to get us there. As it turns out, our vitality is closely dependent on our hormonal balance.

We all know people who seem to have boundless energy and just seem to be able to live life to the fullest (full of energy, experiencing intense emotions, cognition, health, drive and motivation). In order to live life to the “fullest” a great hormonal profile is a prerequisite.

Are you aware of your baseline?

Most people’s hormones are certainly not “pathological”. Everyone is falling somewhere along a huge spectrum of countless different possible permutations.

Most of us cluster somewhere around the middle of the bell curve distribution, but some are at the very tail end on either side. This has huge implications for individuals’ lives.

We are biological creatures. Most of us are simply not aware of how these invisible biochemical gods are pulling our strings in the background. How they affect the way we are feeling in each moment, the way we are feeling now. Unaware of how these changes ripple every facet of our life.

Vitality is first and foremost determined by two things. Genetics and hormones. Both of these are far more powerful than any lifestyle factors. While genetics are more or less static and we cannot do much about it, hormones are not.

The way we feel from one moment to another strongly depends on our hormone levels at that given moment in time. Most of us have no idea what it “feels” like if one of our hormones changes.

There is a reason people, in general, have their prime vitality from 18 to 30. Their hormonal profiles are at their best, thus they experience their biological heyday. They have lots of energy, brain performance is at its peak, they look their best and are their healthiest. They can eat whatever they want while still staying “lean and mean”. Starting in their thirties, many people lose the zest for life and their performance begins to suffer. Their body visibly ages and they become less fit.

While there are many other factors involved, hormones are perhaps the most important. Achieving and maintaining a great vitality for decades after our physiological peak is just impossible without the use of hormone replacement, at least for most of us.

If you are 40 or older, I would wish for you to be able to relive a single day when you were 20. The difference in how everything feels (mood, energy, motivation, etc.) would be like night and day. For many, the difference would be akin to cleaning dusty glasses for the first time in years. And the main reason for this difference was a gradual decline in hormones. Too gradual for you to notice.

Other than the temporary boost of stimulants, most have no idea how better we could feel and function. Most people are not aware and, in fact, are completely blinded, as to how their “baseline”-vitality compares to that of others.

Imagine if you had your best, most vital hour of the day extended to the entire day. 7 days a week. 365 days a year. Imagine how much more productive you could be. Imagine where your life could be in 10 years from now.

If one could perform a multivariate regression analysis to determine the factors that correlate the most with a “great” life (from a “conventional” perspective), we would undoubtedly find that there is a strong correlation with above-average vitality.

And those of us with subpar vitalities progressively occupy more and more space in society towards the bottom of conventional life success.

Most of us though are by definition “average”. But why would we want to settle for that? If we go by statistical “normality”, this eventually evolves into overweight, unhealthy, unhappy, perhaps even anxious or depressed. Not necessarily what I would want for myself in the only life I have got.

Let’s say in a new high-tech virtual-reality console with a perfect computer-brain-interface-integration, we could try out how it would feel if we tweaked our hormones.

It would strike us how different we possibly could feel in this very moment. especially if we have been lowish in any of the major hormones.

If our new hormonal profile was “much better”, over the course of a few days, we would realize that many of the problems we struggle with on a daily basis would be gone. From not being able to fall asleep, feeling tired, procrastinating or unmotivated, having brain fog, struggling to lose weight, having little confidence in interactions, etc. Quite likely, we would not want to go back.

However, if the engineered hormonal profile was drastically worse, we would conclude that although health might not be everything, without it, everything is nothing. Perhaps our judgment for certain fringes of society would turn into compassion.

Well, I had done this VR-CBI-thought experiment in real life. I have been both low and high in every major hormone, in many different constellations.

Tweaking my hormones on a monthly and sometimes even weekly basis, I experienced first-hand just how much our “baseline” energy and “baseline” mood and how I felt on a daily basis, can be changed. It can be improved.

And of course, I did not want to go back.

You cannot ‘out-drug’, ‘out-biohack’ or ‘out-lifestyle’ a bad hormonal profile

Life consists of cells. Cells are biological machines emerging from the laws of chemistry and physics and just do what they are programmed to. The blueprint for this program is written in form of the genetic code. Hormones, by acting at the level of this code directly, are one of the main factors that determine which programs are running in any given cell at any given point in time.

Hormones talk directly to cells. They affect gene expression. Every single cell in our body has receptors for all four types of these hypothalamic hormones. Each of them unlocks a specific portion of the genetic code, depending on what part of the code is accessible (which differs between tissues).

By adding or tweaking hormones, we intervene at the most downstream level possible. We are directly telling our cells how to behave because we interfere with the genetic code they express.

Furthermore, next to each of the major hormones affecting every single cell in the body directly, each hormone also affects every single cell in many ways indirectly (e.g. by affecting other hormones and mediators, by affecting metabolism and nutrients, by affecting the lifestyle choices we make).

Thus, if we change our hormones, we are sending whole-body messages to all of our cells. Thus, by tinkering with hormones we are tinkering with every single cell in our body. It is now us who is telling all of our cells how they should behave. This is far more powerful than taking a certain drug just affecting a single target (usually a certain protein).

Thus, every hormone has system-wide effects: genome → cell → tissue → organ → organ system → physiology → behavior → life. This is what makes them uniquely powerful. It applies whether we correct them or not. (If you truly want to understand what hormones are and why they are so powerful, read my unconventional introduction to endocrinology.).

If things go wrong with our hormones or are suboptimal, our bodies will follow. And so will our life. Certainly in my life, the malfunction of this tiny part in my brain wreaked a ton of havoc on many levels. I am certain the same holds for many of you as well even though most of you will never be aware.

From what I have seen, I guess around 1 in 5 of you have a hormonal imbalance severe enough to warrant intervention. It causes life to be much harder, less enjoyable, less healthy compared to how it could be.

There are millions of people worldwide who have been living in states of pitiful energy, mood and health for years. Chronically lethargic, unmotivated, depressed, sick. For many of them, hormonal problems are the root cause.

All the focus is on drugs, diet, sleep, exercise, gut health, supplements. All of them billion-dollar industries. While all these are important, we simply cannot “out-drug” or “out-lifestyle” a bad hormonal profile. Too bad most people do not know much about hormones.

Note: Everyone focuses on nutrition, exercise, sleep, supplements. However, if for some reason our hormones are not adequate (and if lifestyle changes are not able to correct for that because perhaps our setpoint for one ore more hormones is low/suboptimal), we will always be living, functioning, experiencing life massively below our potential. In fact, we can have the most perfect lifestyle we want but this this hormonal “suboptimality” will be our limiting factor.

Diets, exercise, sleep, stress reduction, connection with others, are all important for living a long and healthy life. However, few things have as profound of an impact as restoring hormones to optimal levels. Besides, a good hormonal profile makes all the other lifestyle choices much easier.

Restoring or creating a good hormonal profile, whether naturally or not, is by far the most important and potent health and life-improvement there is. It affects everything else.

Note: My guess is that around two thirds of our vitality directly comes from our hormones, regardless of whether good/bad levels are caused by genetics, being young and resilient, lifestyle-induced (both ways), or replacement therapy.

2. Health and ethical aspects.

Is replacing all of my hormones healthy?

Many of us have the “there-is-no-free-lunch”-mindset, assuming that taking any drug is “bad” and that the artificiality of intervention per se has to be somehow associated with adverse effects .¹⁰

In my case, thus, it might seem that replacing all of my hormones has to be somehow bad. Or, that I am at least setting myself up for problems later in life.

I thought so too for a long time.

We have data from thousands of people whose pituitary glands were destroyed or removed (e.g. cancer, injury, radiation damage, etc.). It is called “panhypopituitarism”.

Within only a few days, their endogenous hormone production drops to zero, forcing them to replace all their hypothalamic hormones for life (growth hormone, thyroid, sex hormones, adrenal hormones). From that point on, all of their hormones are completely introduced externally.

Sometimes it happens in their teens or early twenties and these people live well into their 70s and 80s.

Note: Some early studies have shown mortality for these people to be elevated, mainly due to cardiovascular diseases. Later it was found that this was mostly due to excessive doses of glucocorticoids, supplied due to concerns that patients would suffer from a life-threatening adrenal crisis. A contributing factor was that growth hormone was often not replaced at all. Given hormones are replaced well, this difference in mortality withers away. What is more, these people live longer and healthier lives than their peers, whose hormones decline naturally across the board with aging.

Furthermore, optimizing hormones gives us higher energy, mood, health, all of which also allow for a healthier lifestyle. Given that around 80% of deaths in Western countries are due to CVD, cancer and neurodegeneration, all of which are lifestyle diseases, replacing our hormones has indirect beneficial effects on our health as well.

Replacing hormones is an inconvenience and nuisance. But that is all. It is just an inconvenience and nuisance. It does not cause any subjective suffering like depression does or any debilitating symptoms such as physical pain. In fact, if treated well, one can live a long and (very) healthy life. If hormones are optimized, I argue a better life overall.

Hormonal optimization is not reserved for just the elderly and sick. In fact, going to any renowned anti-aging or longevity physician (e.g. Peter Attia, Thierry Herthogue, etc.) they sometimes choose to completely replace all of the major hormones.

Multiple hormone replacement therapy is one of the most fundamental pillars of anti-aging medicine. Usually reserved for the rich and powerful, who then become even richer and mightier.

The price to pay is taking pills and doing injections. Once you are used to it and have finetuned your replacement protocol to your needs and liking, it takes less than 5 minutes per day.

And just as there are risks and side effects associated with hormone replacement, there are also risks and side effects if we choose to not replace a (deficient) hormone. Most people forget about this.

Note: Why hormones are neglected by mainstream medicine the way they are, is beyond me. Hormones affect everything. By acting at every single cell in our body, they have potent effects on systemic health directly. Also, by affecting many different organs, tissues and countless other signaling molecules (all of which have their own ramifications on our health), they have a powerful influence on systemic health indirectly. Furthermore, by having a major impact on our energy levels, mood and wellbeing they have a mighty say in the lifestyle we lead, which has a major effect on our health all by itself (e.g. most of our modern, chronic diseases are to a large extent lifestyle-induced). Given this, from a financial perspective, paying for hormonal therapies would be a great economical decision for the government because many individuals would most likely need way fewer health-care resources down the line. This does not even include the astronomical financial gain from having a more healthy, more functional, more productive workforce.

But hormone replacement is “unnatural”!

1) Our mental and physical operating system is outdated.

You are sitting here reading this on a computer or mobile device while data is being streamed to you with the speed of light via a fiber optic cable connected to a source of electromagnetic radiation. In this respect, what does “natural” even mean?

Our bodies and minds have evolved for different times and have not (yet) adapted to the modern environment we currently live in (e.g. artificial lightning, pollutants, highly processed food, fast-spiking carbohydrates, sedentary lifestyles, living beyond the age of 40, constant low-level stress, intense schedules, loneliness, large social networks, a requirement for everpresent 24/7 mental alertness, altered circadian rhythm, etc.).

Thus, our bodies and minds abound with “evolutionary mismatches” because evolution adapted our genetic, biochemical, physiological machinery as well as our mental faculties (e.g. cognitive biases) to be suited for a completely different world. In fact, our mental and physical operating system is outdated. “Counter regulating” in an artificial way is just as natural as is living in our unnatural world in the first place.

Hormone replacement is not natural. But our modern world is not “natural” either. Our endocrine system (the coordination of the whole cell colony via messengers) evolved for a completely different environment to which it is meant to be adapted to. Consequently, this same system now responds to these modern, unnatural conditions in often maladaptive ways (e.g. circadian rhythm, thyroid and diet, cortisol upon perceived stress). By using targeted interventions, all we would do is to update our endocrine system to be more suited to these new, unnatural conditions. In fact, this is what updates are for. If some upgrading happened along the way, I personally do not mind.

2) Our bodies were never intended to live beyond the age of 40, a time when multiple hormone deficiencies sets in.

I hear it all the time: “Hormone replacement is unnatural”. We live in a society where we value living beyond our reproductive years. Then why are we not entertaining things that are “unnatural”? It is an asinine argument to me.

Homo sapiens´ reproductive success was mostly determined before the age of 30, 40 maximum. Before this age, our bodies were made to be full of energy and health. Living beyond this age is unnatural.

Thus, as we surpass the lifespan we evolved for, among many other degenerative processes, our hormone levels decline naturally across the board. However, our bodies and minds were never made for being this old and neither were they made for being in this state of multiple hormone deficiencies.

Thus, living with low hormone levels is not just unhealthy, it is also unnatural because our bodies were not made for being healthy and well-functioning beyond this age. After all, there were never the evolutionary pressures necessary for it. Replacing what is now missing, is just as unnatural as it is living beyond the age of 40 in the first place.

Biology is perhaps the main common denominator of how the life of a human being turns out -within cultural and socioeconomic limits of course. For more about this, read here.

For the first time in history, we can think about transcending our individual biological limits which have always been strong determinants of happiness and life success.

We as a species got this far because we were never accepting of the conditions thrown at us. Ever since we have been engineering ourselves out of conditions or problems we wanted to change. Otherwise, we would still be in the caves, if not even in the trees.

However, I can also see the other side and I do respect it.

Is hormone replacement therapy cheating?

Cheating as per definition means “to act unfairly to gain an advantage”. Well, hormone replacement certainly does give you and me an advantage, but since energy, mood and health are certainly not equally distributed, there was never a level playing field to begin with. People with naturally great vitality are disproportionately overrepresented in the ranks of CEOs, politicians, sportsmen, doctors, etc. Natural selection surely applies in terms of these positions.

What is more, not everyone in these positions is (or remains) “natural”. You and I do not know what pills others are taking every morning. For example, the use of smart drugs is rampant in every professional domain. I bet many of the people we consider “rich and powerful”, people in the top tiers of society, are on extensive hormone replacement, from CEOs to politicians to actors. While some people are open about it, people admitting to using hormones are very few. They like to be seen as “genetically gifted”.

Even if you do not believe in “enhancing” yourself because it is “cheating”, many others simply do not share your beliefs. People you compete against might not shy away from cheating because of ethics.

So yes, one could argue that hormone replacement is giving you or me an unfair advantage. Hormonal changes are much more potent than any other created by lifestyle interventions (sleep, diet, exercise, meditation, etc.), whose gains pale compared to gains resulting from correcting a hormone (even in terms of longevity and health promotion).

I have a great hormonal profile nowadays, certainly “better” than what nature intended for me. I keep most of my major hormones in the upper third of the youthful reference range, bestowing myself with the kind of vitality some of us naturally experience after sexual maturity, but which I was deprived of.

If we stay within the upper third of the reference range, generally there is little risk. Most risk comes from deficiency (no replacement) or excess (overreplacement).

Optimized both for longevity and performance, I can and do keep the different hormones where I feel and function best.

Keeping all my hormones where I want them to gives me a significant advantage in life across many areas. The value I get out of it is reinvested every single day and there will be many dividends over the years.

Thus, even though hormone replacement can be seen as cheating, overall, the effects on others and humanity might be good, because if we become more healthy and productive members of society, society as a whole might benefit (moral bioenhancement).

I will impact many other human beings on my way, either because I directly interact with them or because I intangibly “touch” them in myriad ways through my actions and inactions. This is besides the fact that my life is easier and more enjoyable -the primary reason I self-optimize.

If I decided to do nothing, it is not just me that is hurt but also my loved ones. Also, society would be indirectly hurt in countless and often quite obscure ways. I would not be contributing what I otherwise could, instead, I might have become an involuntary parasite living off society’s resources.

If my energy, mood and health are better, I can be a better contributor to others (regardless of the fact that my life is easier and more enjoyable). Humanity is more about cooperation than competition.

Joe Rogan could not do what he does without testosterone replacement or growth hormone (he openly admits to both). As a result, he and the world are better off for it.

Hormones and economic inequality.

My dad is a self-employed lawyer. Starting in his mid-40s to early 50s his energy and motivation began to wane. In the first year after putting my dad on testosterone replacement restoring his sex hormones to youthful levels, he made about 50% more money.

Also, ever since humans accumulated wealth, biological inequality was a major contributing factor to economic inequality. Energy mood, health, motivation and focus all depend on our hormones.

From brain wiring to performance in school, to motivation for studying, the ability for sustained attention, confidence, mood, energy and charisma in social relationships.

Enhanced productivity, energy, motivation, mood, performance, looks, relationships and confidence down the road affect our professional and socioeconomic standing in major ways.⁷

If we improve these biologically determined traits at any point in life, we will get value out of it every day. We can then reinvest this value day after day.

Down the road, we will be wealthier (physiologically, financially, socially, psychologically, intellectually.) Again: Compound interest. The earlier we start the more compound return we get.

The danger of being left behind.

Individual biological limits have always been strong determinants of life success.

Now, for the first time in human history, we can think about stretching and even transcending these biological constraints. In fact, many people do this already. Unfortunately, these are mostly people who are already high up on the socioeconomic ladder.

The powerful and wealthy have access to “high-tier”-health care and personalized medicine focused on “enhancing” rather than “repairing”.

As Tim Ferris points out, new breakthroughs in performance enhancement generally career like this: elite athletes and bodybuilders and scientists → rich people → the rest of us. The last jump from the rich to the general public can take 10–20 years if it happens at all. It often does not.

The future is already here. It is just unevenly distributed.

Consequently, economic inequality furthers biological inequality, which then increases economic inequality even more. Over time, this leads to widening wealth disparity.

Given the capacities of modern medicine for bioenhancement, I seriously wonder and worry about the emergence of two biological classes a few decades down the line.

But will I still be “myself”?

Does such radical intervention into my own cell colony´s signaling make me “fake”? Am I still myself?

Many people have an inner resistance against intervening in a way that they feel “alters” themselves. They feel that they´d take things like antidepressants or hormones they would just not be themselves anymore. They would feel “fake”.

But the line is arbitrary. Most are fine with having caffeine constantly in their system, which certainly does affect neurobiochemistry.

And regarding hormones, 20 years down the line, your hormones will be radically different across the board compared to how they are now. Are you then not “yourself” anymore?

Am I becoming a “robot”?

Many people I talked to raised the concern that because I can and do keep my hormones the way I want them to, I am moving in the direction of becoming a “robot”. A robot whose biochemistry “I” can control, thus also affecting my emotionality and personality traits.

Even though there certainly is a performance increase from optimizing my hormones, “enhancing” myself does not make me a robot just more effective at solving tasks. We, humans, are way more than that and no intervention will change that. We are not just about solving tasks, rather about setting them. We humans want the real, the raw. Rather than achievement, we are seeking love and beauty.

My overall emotionality is greater compared to what it was before. The mind is what the brain does and every mind state emerges from a brain state. And on my hormone replacement protocol, my brain can now generate emotional intensities I never experienced before.⁹

The highs are much higher and the lows much lower. For example, when my girlfriend broke up with me recently, it almost killed me, but I didn´t care.

Despite biohacking sounding “roboty”, given you do it correctly, it makes you less of a robot. Before I was a robot to my biological chains, a puppet of my neurobiochemistry. In my opinion, transcending my biological limitations is a very, very human thing to do. Now I can act and make choices that are truly my own.

3. Should we replace our hormones? Or should we not?

Let’s make an analogy. Let’s say we are a chronic insomniac. We tried out countless different remedies, lifehacks and “natural” supplements but other than transient short-term improvement nothing really seems to have a lasting impact.

The lack of sleep makes us fatigued during the day, we cannot focus, our willpower is low and thus our propensity to make bad food choices and to forgo any exercise is high. Our metacognition is awful and our attention span non-existent. We are much less efficient and effective at work. We are more withdrawn but also markedly more irritable in social interaction. Our life enjoyment is much lower compared to what it could be.

Let alone all the negative effects from the increased sympathetic drive and chronic hypercortisolemia wreaking havoc on our metabolic health, which along with our suboptimal diet and exercise regime led to us bordering on metabolic syndrome. We have read how “bad” all this is and that it is supposed to drastically increase our risk for neurodegeneration, cardiovascular disease and cancer, the three of which cause around 80% of deaths in Western civilization.

We thought about taking sleeping pills, but after doing some research online, we decided against it. They just seem to have many nasty side effects, cause tolerance build-up, interfere with memory consolidation and people cannot get off them. They are just simply “very bad” for us.

True, all of these are legitimate concerns and relying on sleeping pills is “bad”. However, bad compared to what? The question should not be, whether something is “good” or “bad”, but what is worse? For our health, our wellbeing, our life? Sleeping badly for years on end (including all the ripple effects this entails) or taking sleeping pills?

It is always a complex calculation of tradeoffs, but many of us usually just consider the risks associated with doing something. Well, there are risks from doing nothing as well. The last point is often dismissed.

Our hormonal profile is one of the most important things in our life. Unfortunately, something few of us ever look into.

If one of our hormones is low it will hold us back in life.

Even if there are side effects with hormone therapy, they need to be weighed against the side effects of no treatment, because not intervening has some side effects as well. We need to look at both sides of the equation

It is always a complex calculation of tradeoffs and many aspects have to be considered:

  • Side effects, costs, downsides of therapy
  • Long-term effects on our health (a) direct effects as every hormone directly interacts with every cell, tissue or organ; b) indirect effects via energy, mood or health affecting our lifestyle choices, which then affect our health)
  • Long-term effects on our mental health (for more about the risks of not replacing hormones, click here). Needless to say, the mind is all we have.
  • Moment-to-moment wellbeing and quality of life (How we feel right now. Great energy and mood simply feel good.)
  • How the decision to (not) intervene will (likely) affect our “objective” life situation down the line (e.g. income, looks, partner, wealth, relationships) Also, considering that many of these effects are permanent. For example, a partner we are able to find or get. A breakup. A promotion.)
  • The effects we have (or do not have) on others
  • Healthspan (how long we can live more or less free from pain/suffering/disease) and lifespan
  • Lifespan (for example, both T3 and GH reduce maximum theoretically possible lifespan but via their countless ripple effects both on our biochemical health (e.g. weight, atherosclerosis, brain health, IS, metabolic health) but also on our vitality and wellbeing (-> lifestyle choices) likely increase lifespan overall (…and no question about healthspan and QoL)

So in our risk-benefit analysis, all of these factors need to be addressed. How each of these points is (likely) going to be with vs. without intervention.

The risk of inaction.

Analogy to vaccination: It is true that if we did not vaccinate there would not be any (rare) complications nor other risks and downsides. But instead, we would now have a world full of infectious diseases!

Would we rather have “no side effects, risks, cost or inconvenience + no benefits” OR ”side effects, risks, cost and inconvenience + benefits”? Also, what are the risks, side effects, costs of not intervening?

In the case of vaccines, when comparing the upsides and downsides of both sides of the equation, the decision becomes a no-brainer.

The same holds for hormone replacement. Many people are scared and worry about the side effects, nuisances, risks, costs, etc., but the problem is they look at just this side of the equation. What are the risks and drawbacks of not replacing a deficient or suboptimal hormone? What are the opportunity costs of inaction?

The positive effects of smart intervention (e.g. replacing a deficient or suboptimal hormone correctly) often outweigh the downsides (e.g. risks, nuisances, costs, drawbacks). Given it is done correctly, for most there is likely a large net benefit (health, quality of life, life enjoyment, productivity, contribution to others).

For example, having youthful levels of GH/IGF1, thyroid hormones, sex hormones, all independently improve metabolic health (e.g. reduction in CVD, cancer, neurodegeneration), improve mental health (e.g. cognition, mood, reduction in depression and anxiety), improve looks (which help us in all of our interaction with other humans), improve wellbeing (which then makes leading a healthy lifestyle with good exercise. sleep and nutrition much easier also improving our metabolic health, mental health, looks, wellbeing, etc. secondarily).

Let’s say you cloned yourself two times. Clone I chooses not to intervene. Clone II chooses to do so and continues the intervention for life. You observe how the lives of both of your clones progress and at the end of their lives, you are allowed to choose which life you would rather have.

I performed this thought experiment on myself and made the educated guess that the life of Clone II is better. This is how I chose to do what I do, guessing and hoping that overall I and others will be better off for it.

Most people intuitively assume that artificial intervention is “bad” per se: “For sure we/he will eventually pay a price because there is no free lunch.” Unfortunately (or fortunately), this is just not how the world works.

Of course, there might be side effects and downsides, but in many instances, they are smaller than the risk of inaction. And if we have the means to do so, inaction is also action.

Part II.

4. How I replace my hormones and some changes I have noticed over the years.

Links to practical guides (article continues below):

How To Fix Your Hormones: The Ultimate Guide (main article)
Brief Overview Of Different Hormone Therapies
How To Replace Thyroid Hormones
How To Replace Cortisol&Adrenals
How To Replace Male Sex Hormones
How To Replace Female Sex Hormones
How To Replace Growth Hormone
Different Types Of Fatigue For Different Hormone Deficiencies
A Diet That Works For Everyone

Note: What works for me, might not work for others. This is not medical advice. Below I simply outline what I personally do and how I would go about it if I had to do it all over again. I personally need or choose to optimize all hormones, but often, it is only one hormone that is imbalanced or deficient and replacing that is sufficient. Most people certainly don’t have to be that “radical” to get similar effects.

My goal with hormone replacement is to maximize the intersection of three things that usually require tradeoffs:

  1. Short-and long-term health
  2. Short- and long-term performance/productivity
  3. Short- and long-term wellbeing and life-enjoyment

So, here is what I found works well for me. Engineering this protocol laid out below, took years of finetuning and tinkering. A huge amount of research, experimentation, blood tests, monitoring, suffering, etc. went into the following few lines talking about 30s reading time

  • Sex hormones: Testosterone cypionate (50mg subQ 2x/week), HCG (250iu subQ 2x/week), FSH (50iu subQ 2x/week) (For how to replace male sex hormones, click here for more info.)
  • Adrenals: 20mg hydrocortisone-equivalent (split into multiple daily doses), fludrocortisone 0.1 mg/d morning (glucocorticoid sparing), 25mg DHEA, 25mg pregnenolone. (Click here for more info.)
  • Thyroid: 1.5 grains NDT (I used to experiment with different ratios of T4/T3 but NDT is best and also convenient) (Click here for more info.)
  • GH/IGF1: 1 IU Genotropin pre-bed (aiming for IGF1 of 250 -hoping to marry performance with longevity.) (Click here for more info.)

Note: I also take 0.25mg melatonin before bedtime and 20.000iu vitamin D per week. These two are hormones as well, but since most people do rather consider them to be “supplements” (which our body frankly does not give a shit about), I describe their effects in more details here: Supplements everyone should take.

Within a year or so, this protocol completely remodeled my body, mind, health, life.

For an overview of the effects that each of these hormones had on me individually, read here.

Many of you might think “this guy is crazy”. Anyhow, most of you just cannot imagine the dreadful state I was in, with energy levels that left me feeling like life was not worth living anymore. Once you have been in such a state for a long enough and have seen how many aspects of your outer and inner life are taken from you, you are desperate to try anything.

Even if my lifespan were reduced (which I doubt -If you are one of the people that just skipped forward to the practical part, you might go back up and read the section “Is hormone replacement healthy?”), I would rather opt for a below-average-length life of feeling great and enjoying the time I am given instead of living for much longer but feeling awful all the time. In fact, if I had to, I would even sign a contract to live just 10 more years in the state I am in now and then die, rather than living for over one hundred more years in the vegetating state I was in previously.⁸ Life is about filling time and not merely passing it.

I have been high and low in every major hormone in many different combinations. When it comes to determining our energy, our mood, our overall health, hormones are underestimated. In fact, I would go as far as to say they account for about two-thirds of the way we feel daily.

From the outside, all this does seem to be a lot of effort, but it truly is not. The hard part is just figuring out what to take and how much, but once a stable protocol is established, administering all these hormones takes less than a minute per day and with prepared pillboxes (morning and evening), no more thought or organization is involved whatsoever. A tiny price to pay for the reward I get.

The target range I aim for is the upper tertile of the youthful reference range. Remember, though that when it comes to endocrinology, physical signs and symptoms matter just as much.

In my opinion, with this protocol, for the average healthy male, all hormones will be around the 75–85th percentile of the youthful reference range. With choices and dosages presented above, hormone levels will be well in balance with each other.

I believe, this hormone replacement protocol marries performance with longevity and strikes a reasonable tradeoff between these two.

For rationale and explanation about why I replace my hormones the way I do, read the respective sections for the individual hormonal axes.

For different people, individual hormones might/should/need to be (slightly) adjusted based on wants, needs, conditions or preferences.

Note: I am supervised by doctors, but if I took what they prescribed lots of potential well-being, performance and health benefits would be left behind. They would treat my thyroid with just T4. They would use 30mg HC for adrenals (way too high and only proposed out of fear of a potential adrenal crisis). Testogel for sex hormones (dermal T is awful for DHT) because “it is more convenient than injections”. No growth hormone because “I do not need it”.⁹ So, in summary, they would be replacing every single hypothalamic axis suboptimally. In my opinion not just “suboptimally”, but in many respects their approach is complete bovine excrement.

Due to my unique story, extensive knowledge and personal experience, there are few people out there that know as much about hormones and all their interactions, details and technicalities. When it comes to hormones, the right or wrong choice can make or break your life. To ask questions about your own hormones, contact me via email (hormetheus@gmail.com). I’m able to offer you insights about your individual situation almost nobody else can.

Other stuff I do

Some of the other stuff I do to improve my vitality: low carb diet (For more: A Diet That Works For Everyone), exercise every day (either zone 2 cardio, HIIT, gym), sleep around 6.5h (wake up refreshed without an alarm whereas before I needed 8+ hours), weekly rapamycin, 3 days of 100mg dasatinib 3x/year during a fasting-mimicking diet, a bunch of supplements (See here.), meditate daily, no caffeine.

I do take some other metabolic drugs (e.g. low dose rosuvastatin, allopurinol, acarbose) for which I believe (based on an educated guess) the risk of taking them is lower compared to the risk of not taking them. If you are interested to know which ones you can email me. In general, I choose drugs instead of supplements. Why? Read here.

I am aware that all this is rather uncharted territory. I am well aware of the risks. But to me, the cost-benefit analysis makes it a straightforward decision. What did I have to lose?

Whether I can keep this up for decades, I do not know. However, I can not see a reason why I should not be able to. Also, I simply do not know how long the world will still exist. Climate change, (an engineered) superbug, supervolcano, singularity. While the chances that we become something far greater in the 21st century are high, the chances we screw up are high as well. In the case the world falls apart in the next 20 years or so, I have certainly made a good deal.

This project has been my main focus for about 3 years. Optimizing my biology was my main driving force, my purpose. Everything else was secondary and collateral.⁶ From a biological perspective, for me, there is not (that) much left to optimize. My reversely engineered vitality will help me with whatever else I want to do in life.

And I know what I want to do. I want to help others with improving their vitality the same way I bio-engineered mine. Helping others to enjoy their life more fully. Helping others to work on whatever is their purpose, hopefully advancing humanity and increasing the wellbeing of other fellow humans.

Changes I have noticed over the years.

Some of the benefits I have noticed while on HRT. For more details about the specific effects of each hormone, click here.

Energy levels:

The most “life-changing” benefit I have got from hormone replacement is the vast improvement in energy levels. Thyroid and adrenal treatment brought me back to life (continue further to the respective sections for more info).

Before hormone replacement, it took me forever to wake up, I was lethargic most of the day, everything seemed hard to do and required tons of willpower and “pushing”.

I always got sleepy half an hour after sitting down and starting any cognitive task. Conversations were drudgery. Socializing was dreadful. I had to rely on stimulants to function. Without caffeine, modafinil or ephedrine I could not have done anything, neither school nor the little socializing I still did.

With low hormones, I wanted to lead a quiet and secluded life and only engage in low-effort activities that do not require a lot of movement. Upon starting treatment I regained the energy and motivation I remember from my adolescence: I suddenly wanted stress and challenges. Now want to go out and do something physical. I wanted to meet friends again. I wanted to enjoy life.

Whereas before I was below the 5th percentile in energy levels, now I feel I am close to the top. Nowadays, I could be productive during most of my waking hours if I wanted to. This does give me a significant advantage in life.

From personal experience, I would guess about 70% of my/our energy levels come directly from hormones. 30% is everything else (which often mediates parts of its impact on our energy via the endocrine system as well).

From all this I learned 2 things about hormones and fatigue:

  1. Each hormone deficiency can cause chronic fatigue (even if all other hormones are at optimal levels).
  2. Each hormone deficiency is associated with a distinct kind of fatigue.

To learn more about how the fatigues associated with different hormones can be differentiated, click here.

Sleep:

My sleep is good. I wake up refreshed without an alarm after +/- 6.5 hours, whereas before it took me 8–9h (but I still did not wake up refreshed at all). Because I replace all my hormones, a lack of sleep does not interfere with my energy levels much. For example, when I only sleep for 3–4h for whatever reason, my energy levels are still the same. But I feel somewhat “drunk” and can´t think well and straight, all my executive functions are diminished. Improving sleep improves everything else.

Cognition:

Before hormone replacement, I tried out many different stimulants and nootropics to make up for my lack of energy levels (like many of us do but are not open about it).⁴ Cognition is tightly linked with energy levels. My cognition is almost always sharp, no brain fog anymore, most of the time I am very alert (which I think is a pleasurable state to be in). The combination of good sleep + cardio + low carb + good hormones is healthier and more sustainable than any stimulants or nootropics.

Motivation:

Most of the time my motivation is high with little to no procrastination. For me, motivation/willpower/self-discipline mostly correlates with energy levels. In fact, to me, it seems that procrastination and “half-assing” always happen in times of low energy (e.g. fasting, sickness, low blood pressure, sleep deprivation ). If I increase my energy levels (whether via sleep, exercise, cold shower, hormones, stimulants, coffee, etc. doesn’t matter) I automatically stop procrastination and half-assing around. No further willpower required.

I bet many “chronic procrastinators” (or people with ADHD) are in fact procrastinators (or have been diagnosed ADHD) because their energy levels are quite low most of the time. And when our energy is low, everything requires lots of effort. We always have to “push” to do something. Many of us try to rectify it with coffee or other stimulants, which is both unhealthy and unsustainable.

Mood:

My mood is good and stable, including normal highs and lows which are not biochemically mediated. Mood, motivation, energy levels are all intricately linked and we can´t look at them separately.

If I want to change my thoughts, I should focus on my body. At least for me, my biochemistry to some extent determines my thoughts and outlooks (e.g. if I am lethargic or low energy -which is mostly biochemical-, it is just a matter of time until my biochemical state is reflected in my mental state (i.e. thoughts, outlooks, thinking patterns). For example, a good night's sleep, good food, or “you are only one workout away from a good mood”, is often the only therapy I need and many “existential questions” will take care of themselves. And then my mental state does not just affect my “inner” life but also affects my behavior, which ultimately affects my “outer” life.

For example, one time in the past, I quit T3-administration cold-turkey. This caused all my thoughts and outlooks to be completely different and led to me having a panic attack. If you want to read more about some of the lessons I learned from this brief encounter with “almost-suicide”, read here: Why depression is a chemical imbalance, but not the way you think. Lessons from MDMA, bipolar disorder, self-experiments.

Libido:

Read the respective subsection in Section 4 in “How to replace male hormones.”

Calmness/relaxation:

Before HRT my mind was always racing, I could never “turn it off”. I was incredibly restless, yet my energy levels were low and I felt awful. I could not just “enjoy” the moment or “be present”. This has changed. Now, I can just be there. This is worth a lot to me.

Life enjoyment:

Up until my early twenties, I was very social, able to enjoy life fully. As my hormone levels declined between 20 and 23, I was plagued by anhedonia. I could not derive joy from anything.

After just a year of hormone replacement, every form of anhedonia is gone. I am able to enjoy myself simply because I now can do so again.

How can I enjoy nature, a beautiful view, a good conversation, a movie, etc., with a racing mind, low energy levels and a bad mood?

Many people who seem to be able to “live life to the fullest” -which most of us admire but could not do, have high hormones. Living life to the fullest (full of energy, experiencing intense emotions, cognition, health, drive and motivation) is just not possible without an adequate hormonal profile.

My shift from obsessivity, rigidity and productivity to more life enjoyment does have some downsides as well. I am no longer in this chronic state of a racing mind and mental unease so I stopped asking the “why” questions many would not bother asking in the first place. Before I really wanted to understand things (e.g. physics, medicine and any other science). My inability to “turn it off” was the foundation of many of my personal accomplishments. For example, I would not have delved into endocrinology allowing me to have written this guide.

Personality changes

Note: Whenever we tinker with neurobiochemisty (e.g. hormones, drugs, coffee, etc.), over time our personality changes.

The direct effects of hormones as well as their indirect effects on certain neurotransmitter systems (esp. monoamines) alters short-term, moment-to-moment brain function (e.g. mood, wellbeing, cognition) and over long periods of time induce structural and functional neuroplastic changes. Personality is structural (synapses) and functional (strength of these synapses) brain wiring.

Thus, whenever neurobiochemistry is influenced in a sustained way for longer periods of time (e.g. hormones, antidepressants, coffee every day etc.) this will alter our thinking-patterns (e.g. coping mechanisms, outlooks on life), which will eventually manifest in behavioral changes.

Obsessivity: Before HRT my mind was always racing. I just couldn´t “turn it off”. I was living in my head. I was in a chronic state of “mental unease”. I was rigidly self-disciplined bordering on obsessivity (which can be both good and bad). I measured everything based on how productive something was, how much “utility” it had for me (+/-). While rigid self-discipline is good for productivity and advancing our objective life situation (e.g. career, knowledge, fitness, money, etc.), it is not an enjoyable way to live nor a conducive way to interact with others.

Empathy: Before hormone replacement, I was judgemental towards others. What is more, most of the time I was quite parasitically looking for my own advantage. Now though, I am much more empathetic, much less of an asshole. Now I truly care about others and genuinely want the best for them. Among other things, this certainly has a lot to do with my individual serotonergic tone as well as oxytocin signaling (both of which change with our hormones).

Sociality: Previously, social interaction gave me no pleasure whatsoever. I just needed and wanted to be by myself. This has changed. Now I thoroughly enjoy meaningful social interaction and long for emotional closeness. On the other hand, while social anhedonia is not a desirable state to be in, it can be a very productive one (e.g. during med school).

Emotionality:: With all hormones being low, I was void of intense emotions, because my brain simply could not generate them ( →The mind is what the brain does). I was more of a “robot”, quite technocratic and data-driven in my approach to life. Nothing could get to me. Some friends called me an “imperturbable rock”. Now though, I am more emotional in general. A minor downside of this is that the intensity of my negative emotions has increased as well. For example, when my girlfriend recently broke up with me, I experienced emotional intensities never known before. What is more, decreased emotionality can have upsides in terms of productivity.

Note: Deliberate intervention into one´s neurobiochemistry is certainly not necessary for personality to occur. In fact, perhaps the strongest reason so many of us undergo subtle changes in personality over the years, is simply due to all of our hormones gradually dropping across the board as we get older (e.g. males get less aggressive, more calm, etc.).

So, even if I did not intervene, some aspects of my personality would have changed “naturally” anyway, just not as strongly and fast.

Of course, these changes were not just due to hormone replacement alone. However, an adequate hormonal profile was undoubtedly a primary catalyst. As you might have noticed, each of these changes also carries some downsides (e.g. less objective, less productive, increased negative emotions, etc.). In my opinion, the minor downsides are a small price to pay, but whether the second-and-third order consequences for me or others will be good, remains to be seen.

Note: Regarding these changes in personality, the biggest differences were caused by estradiol and cortisol. If any of these is truly low, obsessivity, rigidity, emotional coldness, social anhedonia are almost certainly a given. For more about which hormones were responsible for which changes (as far as one can segregate their effects), read further down below in the respective sections for each hormone.

For an overview of the effects each of the hormones had on me, read here.

Looks:

Maintaining low body fat year-round without any effort. To see how I look after four years of hormone replacement therapy, Click Here.

Lifestyle:

The best way to change your life is to change what your life is made up of — your rituals, your habits. Changes that seem small and unimportant at first will compound into remarkable results if you’re willing to stick with them for years. In fact, big achievements are about the tiny, non-sexy things, done day in and day out, for very long periods of time. But guess what? With low energy and mood, changing your habits (let alone sticking to them) is just impossible. For me, bad habits are mostly a function of my energy levels and mood at any given point. If I feel lethargic and unmotivated all the time, eating well, sleeping well, exercising well is just impossible.

Effects on others:

I am less aggressive, less judgemental, less of an asshole. My emotionality is higher, my capacity for empathy greater. Before I was just parasitizing and consuming, now I have the necessary energy, mood and desire to give back.

Note: If we become a healthier, happier and more functional and productive individuals, not only us but also others are better off for it. Not only it is beneficial to the people we directly interact with (e.g. family, friends, contacts) but also to society as a whole (e.g. whatever we contribute, whatever we do that touches the lives of others) (Moral bioenhancement).⁵

General health:

VO2 max is great. I have not been sick in years (1–2x runny nose per year at most).

Some select health markers (average numbers collected over years):

  • BMD (My bone mineral density increased from a Z-score -2.2 (almost osteoporosis) to -0.7 within 1 year (!) of treatment.)
  • Spermiogram: Astheno-teratozoospermia → normal spermiogram
  • Pancytopenia → normal blood count
  • Body fat: around 10% (hasn´t changed much)
  • RR: 105/60 → 125/60
  • RHR: around 50 (hasn´t changed much)
  • Average HR: 55/min
  • Core body temperature: 36.5 am → 37.0 afternoon (before, morning and afternoon body temperature were about 0.4 C lower)
  • Ketones: average around 1 mmol/l
  • Blood glucose: between 80–90mg/dl with little SD
  • HBA1C: 4.8% (hasn´t changed much)
  • HDL always above 120 and LDL below 50 ( I did not confuse these two) (Note: HDL is likely a worthless proxy. And LDL is not meaningful either, it is all about particle number. My ApoB is around 50 mg/dl.)
  • Liver enzymes: could be better (GOT/GTP between 30–40 U/L)
  • CRP: in the last 10 or so blood tests it was measurable only once
  • Sleep: most of the time 1h REM (could be better) and 1.75h SWS (Oura ring)

Note: Are hormones more important than lifestyle? Can an artificially optimized hormonal profile protect us against a bad lifestyle? Are an optimized hormonal profile combined with a healthy lifestyle additive, synergistic or are there diminishing returns? My dream experiment would be to clone someone a few times. Then compare the effects on health & longevity in terms of:

a) a great lifestyle vs.
b) optimized hormones + a bad lifestyle vs.
c) optimized hormones + a great lifesyle

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5. Improving hormones “naturally”

When I tell others about what I do, one of the most common arguments I hear is: “Well, have you found the cause? I bet if you make the appropriate lifestyle changes your hormones will be back to normal”.

But what if being at the very left tail end of a Bell curve distribution is my “normal”? By definition, 5% of people naturally fall below the 5th percentile. When it comes to hormones, they simply haven´t been dealt a good hand.

After hundreds of hours of agonizing back and forth, I decided that I do not want to accept my “normal”.

One of the most common misconceptions about hormones is that they will regulate themselves if we just live a healthy lifestyle.

The internet is full of guides and advice on how to improve hormones “naturally”. And in fact, some of the many points mentioned are indeed valid.

There are some things we can do to improve hormonal health in general:

Note: The following list is not like the many bullshit-lists circulating everywhere around the Internet intended for nudging you towards buying someone´s shitty product. Each single point on this list works. However, keep in mind that while many points on this list are incredibly simple, they are easier said than done.

  • Make sure our caloric intake and insulin levels are not too low — perhaps the most important point on this list which has its own subsection below.
  • Make sure our caloric intake and insulin levels are not too low.
  • Make sure we get enough sleep. Sleep deprivation disrupts hypothalamic signaling to peripheral glands.
  • Eliminate any chronic stressor as much as possible (e.g. caloric restriction, infection). In the most extreme case, prolonged chronic stress can lead to burnout syndrome. For more info on burnout syndrome, what it is, what causes it and how to reverse it, see here.
  • We should make sure our general levels of stress are not too extreme for too long. (Although as vertebrates who evolved to live in the wild, we should naturally be quite resilient and able to tolerate a fair amount of stress.).
  • Make sure we do not exercise excessively.
  • Make sure we have no vitamin or mineral deficiency. (e.g. vitamin B12, vitamin D, iron, zink, magnesium)
  • Forget about all the lists of “super-foods” and “super-supplements” to improve estrogen “naturally.” Most of them are a scam. Others, at most, will give a gain in the single-digit % range. (But there is a list of supplements I do recommend. See here.)
  • Make sure we are not taking any molecules that interfere with hormone signaling or production. (e.g. opioids, weed, alcohol, some prescription drugs).
  • Make sure we are not taking too much melatonin, which in high dosages inhibits thyroid, sex hormones, cortisol. Although interindividual sensitivity varies. For a more detailed discussion about melatonin and how to best supplement with it, see the respective entry here.
  • Two supplements that might help slightly are Ashwagandha and Rhodiola. Both seem to have serotonergic properties and the 5HT2A-receptor stimulates hormone production throughout the hypothalamus. What is more, anything serotonergic decreases (perceived) stress, therefore they facilitate recovery from stress-induced hormonal decline. (In general, though, I recommend avoiding most “unnatural” supplements, read my article about why you should choose drugs instead of supplements.)
  • Avoiding excessive amounts of xenoestrogens (esp. soy products). They mimic estrogen, which leads to negative feedback on the gonadotropic axis.
  • Sometimes, supplementing with pregnenolone, which is a precursor hormone to all steroid hormones, can in select cases lead to an increase in the levels of the final target hormones (cortisol, testosterone, estradiol, progesterone, aldosterone). For a more detailed discussion on pregnenolone and how to best supplement with it, see “How To Replace Non-Major Hormones: An Ultimate Guide”.
  • Make sure that we did not have any major (or minor) head trauma. Head trauma (e.g. football, military, boxing, etc.) is a common, but neglected cause for hormonal problems. During a major (or minor) blow to the head, the axons making up the pituitary stalk often break, sometimes causing permanent hormonal deficiencies (or a slight reduction in one or more hormones, which often remains subclinical for the rest of the individual’s life without anyone ever getting to know.) If this is the case, there is not much “natural” stuff we can do other than going down the replacement route.

Indeed, sometimes prolonged sleep deprivation, bad diet, no exercise, and extreme stress take a toll on our hormonal health. However, often our lifestyle has not much to do with why one or more of our hormones is low.

While some people will be able to improve their hormone levels naturally via lifestyle changes and patience, many others will not (or at least not satisfactorily). Many of them will do everything by the book and lead an “improve-your-hormones-naturally-lifestyle”, often sacrificing lots of time, effort, happiness, life enjoyment in the process. Sometimes hormone levels do not budge at all. Sometimes the improvement is a mere 10–20%, which does not move the needle much in real life. Whether that is worth it to you or not is up to you.

When it comes to natural hormone levels, we all have a certain set point for each of these hormones. Some people just have a great hormonal profile naturally, sometimes even despite an unhealthy lifestyle doing everything almost diametrically opposed to the list above (e.g. bad diet, little sleep, lots of partying, no exercise). However, some people’s setpoints are naturally low, even when all external conditions are optimal.

If the setpoints for one of these hormones is naturally low, no supplement, diet or life-style intervention will help. In fact, these differences in endocrine setpoints account for many of our natural differences in temperament, energy and personality.

For example, let’s say our testosterone or thyroid hormones are rather at the low end. We try to eliminate potential causes (e.g. stress, sleep, diet, chemicals, etc.). Regardless of what we do or do not do, hormones often do not budge.

If one of our hormones is naturally lowish, there is nothing we can do about it. Blaming your parents and early life development is futile.

It is up to us to decide whether we want to intervene or not.

Many shy away from hormone replacement because they worry about the side effects, nuisance, risks, costs, etc., but the problem is this…in general, we humans only look at the risks associated with action. But we should look at the other side of the equation as well. What are the risks and drawbacks of not replacing a deficient/suboptimal hormone? In the end, it is always a complex calculation of tradeoffs. But don´t forget that there are risks (and opportunity costs) from doing nothing as well. This last point is often dismissed.

In my case, even though hormone issues may not be my fault but it is my life and thus resolving them is my responsibility. I decided to take matters into my own hand. It surely does help to arrive at a point where you do not have much to lose anymore. (For more, read how hormones destroyed and saved my life.)

Insufficient caloric intake: A very common and overlooked cause of hormone deficiencies

Given our nutrient intake is somewhat adequate (which is usually the case), the most important factor in our diet is simply the number of calories we eat. Unfortunately, this point is widely and heavily neglected and all the focus is just on nutrient and vitamin and “superfood” intake. We are heterotrophic creatures. Energy intake is one of the most important things animals do. To ensure adequate functionality and health (esp. hormonal health), a sufficient caloric intake is required.

Obsession with fitness has become pervasive, in fact, ubiquitous. Both males and females try hard not to gain any fat (or losing fat), often restricting calories for long periods of time.

It sure doesn't help that people use online calculators to determine their TDEEs. Most of these algorithms severely underestimate the calories a human body needs to function properly.

In fact, many guys I know try to survive on 2200 kcals per day. That would work well for a girl in her teenage years, but not for a grown male with a crazy work and workout schedule. What is more, many often do crazy (intermittent) fasting/keto protocols and drink lots of coffee in addition to that. They love “how energetic” they feel. Well, that is your cortisol through the roof because you are starving. However, down the line, many severely crash because their hormones do so. In many cases, they never recover. I have seen it many times.

Maintaining too low of a body fat percentage, prolonged caloric restriction, intermittent fasting, a ketogenic diet, excessive exercise can all lead to hormonal imbalances and deficiencies. All via the same mechanism.

This chronic restrictive eating often drives leptin to very low levels (esp. if body fat is already low). Leptin is a hormone secreted by adipose cells (fat tissue), depending on how “full” they are. It can be considered the body’s “fat report”. Among other things, high levels of leptin (= lots of body fat) signal to the hypothalamus “Go ahead with being energetic and breeding, you have plenty of fuel reserves” and low leptin signals “We have a fuel crisis. Conserve resources. Stop breeding.”

Evolutionarily, low leptin was a signal for starvation. Leptin is a master control hormone and whenever it falls to low levels, this completely turns your endocrine system upside down.

Dieting/fasting causes an unusually large drop in leptin (much greater decline than just linearly with body fat), and the hypothalamus responds by shutting down the thyroid and reproductive hormones while ramping up stress hormones. GnRH drops → Females often lose their periods (which is an all-or-nothing thing) and male sex hormones take a major hit as well.

Note: A diet low in insulin (e.g. very low carb diet, intermittent fasting) causes an even more messed up hormonal profile. Firstly, insulin directly stimulates sex hormones and thyroid hormones at the level of the hypothalamus. Secondly, insulin is a potent stimulator of leptin secretion (regardless of caloric intake). In fact, many people who contacted me, did so because of their history of fasting, dieting or restricting from which they did not seem to recover and which had caused multiple hormonal imbalances.

There are thousands to millions of people out there in this chronic state of “fitness anxiety”, bordering on orthorexia and anorexia. By restricting calories for long periods of time, thyroid hormones drop, sex hormones drop and over time their adrenal axis burns out leading to low levels of cortisol. What is more, many often drink lots of coffee, putting additional pressures on the adrenals.

For more about (intermittent) fasting, ketogenic diets and caloric restriction and how these diets can mess with mental health, personality, hormonal health, read Note 3-Note 6, here.

This causes your energy levels, mood, immune system to tank and leads to neurotic and obsessive mental states ( → Minnesota starvation experiment). There is no value in looking good but feeling like crap all the time.

Sometimes all that is needed to restore hormonal health is to eat a sufficient amount to raise insulin levels and to gain a little bit of body fat (to raise leptin levels, whose secretion is also stimulated by insulin).

Does eating enough again restore hormonal balance for everyone? No. Eating disorders (or long periods of insufficient caloric intake) can “imprint” on your endocrine system by affecting gene methylation as well as hormonal generators within your hypothalamus.

Note: Most participants of “The Biggest Loser” never recovered their baseline leptin levels resulting in permanent hormonal imbalances. In the months after the show, most of them returned to their unhealthy baseline bodyweight, but were now burning around 500kcal less than before despite having the same body weight as before. Their period of extreme stress and starvation likely did cause permanent changes in gene methylation patterns in various parts of the brain.

There are lots of people out there that destroyed their hormonal balance permanently by severe or prolonged dieting during adolescence and early adulthood. Most of them without being aware of it. The road to recovery is long and painful in such cases. Sometimes gaining a little fat and eating enough or more will somewhat elevate your hormones, though unfortunately, many do never recover their baseline hormonal profile. In this case, hormone replacement is (often) the only thing that helps.

Note: There is one way to kickstart metabolic processes again and to break this vicious cycle of permanent “starvation mode” turned on. However, if approached incorrectly, it can be dangerous. This is why I do not lay out the protocol to do so here in the open. If you are interested you can contact me via email provided below.

6. Practical stuff: General things about hormone replacement.

So, how to start? Blood tests.

Before spending thousands of dollars on a doctor, the first step we can take is to get a blood test. Without it starting any hormone treatment is akin to throwing darts into the darkness.

A good hormonal panel though is incredibly useful and perhaps the best starting point.

These are the serum values I consider indispensable.

  1. basic: differential blood count, vitamin D, B12, ApoB, ALT, AST, CRP, uric acid, homocysteine, ferritin (results are only valid if CRP is 0)
  2. hormones: TSH, fT4, fT3, LH, FSH, testosterone, bioavailable/free T, SHBG, E2, IGF1, DHEA-S, progesterone (and perhaps ACTH and 24h-urinary free cortisol)

Note: Blood tests measure what is in the blood. They do not measure cellular action, which is what it is all about.

Thus, when it comes to endocrinology, blood values matter just as much as physical signs and symptoms. Blood tests MUST NOT be interpreted in isolation. It is quite common that someone with adequate blood values is hormone deficient (and that someone with deficient blood values is not deficient at a cellular level).

Practical takeaway: We should get a complete hormonal panel at least once in our life. While the cost is comparably small, the opportunity cost of not doing this is extremely high. Not just financially.

What about saliva and urine?

In my opinion, urine and saliva tests are of little value in this matter. Their only advantage is convenience. There are simply too many variables (e.g. hydration status) that can influence results between one day and the next in the same patient, let alone from patient to patient.

Thus, in case someone wants to rely on urine or saliva testing two things need to be kept in mind:

  1. Tests need to be repeated multiple times on multiple days to reduce intra-personal variability.
  2. Individual test results must not be compared to other people because there are just too many factors regarding inter-personal variability.

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Reference ranges

Reference ranges are statistical ranges that cover 95% of the natural variation found in a population. Certainly more than 5% of the population have hormones bad enough to warrant intervention.

Merely falling somewhere within the laboratory reference range is not “optimal”. In fact, many people by whom this statistical range is established, live lives of quiet desperation (which perhaps you don´t want in the only life you have got!). You want to fall into the upper half and even better at around the 75th percentile. However, with all hormones, there is a U-shaped curve (although skewed to the right).

A quick note about binding proteins: Ideally, binding proteins should be around the middle, but if the free target hormone (T, E2, fT3, fT4, IGF1, C) is where it should be, it does not matter that much. Beware though, T3 and E2 elevates all binding proteins (SHBG, CBG, TBG, IGFBP-3, albumin), while androgens, IGF1 and cortisol reduce all binding proteins.

Results

When a doctor looks at our blood work, they usually treat it as an “all-or-nothing”. If we fall anywhere within the “normal” range, our doctor will tell us everything is alright. If we are just slightly above or below an arbitrary number, they will tell us something is wrong.

In general, I aim for the upper third of the youthful reference range for most hormones. Not above and not below, ideally around the 75th percentile.

If you are below the age of 30 and you are in the lower third (and certainly if you are in the lower quarter), chances are the opportunity cost of inaction is high.

When it comes to hormones more is not better! With all hormones, there is a U-shaped curve (although skewed to the right). For example, going too high in thyroid hormones can make us hungry all day, which is super distracting to whatever else we doing. For many, going too high in testosterone will increase their libido to a point, where they waste a lot of time only thinking about sex. Going too high in cortisol will impact our slow-wave-sleep (and much, much more).

Thus in my personal opinion, the lower end of the upper third of the youthful reference range delivers the best tradeoff between wellbeing and longevity.

Follow-up.

Whenever any changes are made (e.g. dosages, products), we should get a blood test. Not just for a single hormone, but ideally the full hormone panel (if money is not an issue). The reason why is that often following the alteration of a single hormone, multiple hormones slightly change due to the hormonal impact on binding proteins such as SHBG/CBG/TBG, aromatase, 5a-reductase, metabolizing enzymes, hypothalamic feedback machinery, cellular uptake, deiodinases, etc. However, many of these changes are due to changes in gene expression, which usually take around 2–4 weeks to settle and stabilize. Thus, after making changes give it about four weeks before retesting because results from earlier testing might still be subject to some change. How much individual hormones change, depends on genetic, endocrinological, metabolic and lifestyle factors.

The most important changes that are of great clinical significance (there are many more):

  • adding/increasing thyroid: estrogen will increase (aromatase stimulated), SHBG will increase, DHEA-S and adrenal steroids will increase
  • adding/increasing GH: fT3 will change (deiodinase stimulated), AUC-cortisol will fall (HSD-II stimulated)
  • for more, see the respective hormone sections further down.

Should you see a doctor?

I choose to do it all myself because most doctors are first and foremost trained to not harm. They are 20 years behind the science and optimize for safety.

For example, let’s say we have 100 hypothyroid patients. In modern endocrinology, all of them are given T4-only therapy. But most of them would benefit if some of the T4 is substituted with T3. However, 8% of these 1000 would have some side effects and for 2% the side effects could be severe (esp. older people with weak hearts and bones). For mainstream medicine, this is not acceptable.

In fact, even if a single person suffers from a severe adverse event, the doctor could lose his license if he treats against the recommendations laid out in guidelines. These guidelines in general make blanket statements and do not stratify which patients are likely to benefit or are harmed.

Due to this overfocus on “primum non nocere”, massive potential well-being is left behind, causing millions of people worldwide to not be or live the best way they could.

Good doctors are out there, but they are quite scarce.

When it comes to finding and choosing a doctor, there is some luck involved. Given the importance of hormones, if we happen to have the bad luck to find and trust the wrong one, this can have devastating consequences on our lives and others as well. At the same time, finding and trusting the right doctor can have life-changing consequences.

If someone goes to ten different endocrinologists, longevity doctors, or functional medicine practitioners, chances are high that all of them will treat differently (yes/no, therapy of choice, dosage, multiple hormones), based on their opinion and experience.

So, should we choose to see a doctor? I cannot give you the “right” answer. I would say if multiple hormones are deficient, you would be better off after seeking at least one or more second opinions.

Having an experienced doctor greatly helps (e.g. endocrinologist, functional medicine doctor, anti-aging doctor). In fact, for most, an experienced doctor is a must if there are multiple hormone deficiencies, because multiple hormones need to be balanced (more on that later).

Even if our doctor costs over 10k a year, if we are self-employed we make this money more than back, given the downstream effects of daily increased energy, mood, health.

There is nothing better than to invest our money into our own health or vitality, perhaps even finances. Nonetheless, a highly functional body is worth more than all the money in the world.

The same way a hormonal imbalance left untreated for too long can destroy a life, the therapeutic use of hormones is the most efficient and effective way to improve every facet of our life. In fact, I have repeatedly seen it in myself and others. If someone is put on one or more hormones (esp. if they have been deficient), over time their whole life changes. Not only the outer life but the inner life as well. Therefore, when it comes to hormones, you (or your doctor) make the right choices because bad initial decisions can be extremely costly down the line.

Three important points to keep in mind.

1) Blood tests are not enough

While blood tests are useful, they have a major downside: They measure what is currently in the blood. However, hormone levels in the blood do not tell us much about cellular action, which is the only thing that matters.

When it comes to endocrinology, the symptoms and physical signs matter just as much, perhaps even a little more, than blood tests. Although as mentioned above, a good hormonal panel though is useful and, in my opinion, the best starting point.

To determine a deficiency, we need to look at physical signs, symptoms and blood values together. We need all three. Read this last sentence again, it is one of the most important points in this article.

  1. Blood values
  2. Physical signs (=what a doctor can see without us telling him) (e.g. dark circles, hair or skin problems, etc.)
  3. Symptoms/complaints (=what a doctor cannot see unless we tell him) (e.g. type of fatigue, brain fog, urinary incontinence, etc.)

Note: Hypothyroidism/cortisolism/gonadism and GH deficiency all have (partially) overlapping symptoms. For example, a deficiency in just one of these hormones will cause some fatigue, lower mood, reduction in libido, worse sleep, or a suboptimal immune system. Thus, without physical signs and blood tests it is often almost impossible to determine a hormone deficiency based on symptoms alone. In general, the symptoms of thyroid deficiency overlap with signs and symptoms of cortisol deficiency (e.g. lethargy, fatigue at night and in the morning, taking forever to wake up). On the other hand, the signs and symptoms of sex hormone deficiency overlap with the signs and symptoms of GH deficiency (e.g. less vigor, less zest for life, anxiety/less calmness/reduced wellbeing)

2) We are all (a little) different.

Hormone replacement needs to be tailored to each person individually. Attention has to be paid not only to where a number falls on a range but also to physical signs and symptoms.

The optimal dosages and even plasma levels of certain hormones often slightly differ between individuals. All of us have differences in binding proteins, metabolism, cellular sensitivity (e.g. function and quantity of receptors and nuclear cofactors, degree of gene methylation, etc.)

For example, my testosterone at 800ng/dl is not your testosterone at 800ng/dl.

Unfortunately, there is no definite indicator (e.g. cut-off number on a blood test, a specific sign or symptom) that can tell us in black and white whether a hormone “needs” to be replaced or not. Signs and symptoms matter just as much as clear-cut numbers. Thus, hormone replacement is as much an art as it is science.

3) With hormones it is all about balance.

If one member of the orchestra is off, the orchestra as a whole does not sound good. It is similar to the endocrine system. Hormones need to be balanced: for adequate energy/mood/health we need all 4 hormonal axes performing quite well.

If even one of these hypothalamic hormones is off or deficient or suboptimal the effects of all the other hormone therapies will be as well! And so will our energy, mood, physiology and health. This will then be our limiting factor.

In general, most people start with the replacement of just a single hormone. Often, results do not manifest as they expected or wished. Many then try to compensate for multiple hormone deficiencies (that they are not aware of) by raising the dosage of whatever hormone they are replacing. This over-replacement and abuse of a single hormone is quite common.

Instead of going above the physiological range, it is much healthier to add one or more other hormones in small, physiologic dosages. To maintain good energy, mood, health, libido, sleep and emotional wellbeing we need to have adequate levels of all the major hormones.

It does improve some symptoms (esp. energy levels) and because of this people assume they simply haven´t increased the dosage high enough! In general, our hormone levels determine our energy levels. Cortisol, thyroid, testosterone, growth hormone: each single one of these hormones can be (ab)used as a stimulant if dosages are high enough!

Instead of going far above the physiological range, it is a whole lot healthier to add one or more other hormones in small, physiologic dosages.

For example, many males overly fixate on their testosterone level. They try TRT and feel better. However, if their energy does not improve as they wished, they raise their doses of testosterone repeatedly.

Some symptoms improve (e.g. energy, mood) and thus it seems obvious they were still deficient, despite TRT. In reality, though, it would be safer, more natural, healthier, more effective if they kept their dosages of testosterone physiological, but rather focused on thyroid and adrenals.

Note: For some effects (e.g. libido, energy levels, hair growth) adequate levels of not just one but multiple hormones are needed. The receptors for androgens (AR), estrogens (ER), cortisol (GR), thyroid hormones (TR) are all transcription factors. This means that they bind to the promoter regions of hunderts of genes throughout the genome and increase (or rarely decrease) the rate of their trascription. Part of the reason why for some effects adequate levels of multiple hormones are needed is that for the expression of certain genes a combinatorial binding of multiple transcription factors (TFs) on the same promoter region is required. In terms of how much a certain gene is expressed, this binding can be additive, less than additive or synergistic. Furthermore, for some other genes it is more like an all-or-nothing response, which means that if not a full specific set of transcription factors is present, the gene will not be transcribed at all -at least not in a meaningful way. For example, hair growth requires both testosterone as well as cortisol. Adequate libido requires both the presence of androgens and estrogens. If either of these is lacking, libido will be as well, even if levels of the other hormone are very high.

Most of us have the mentality “one intervention is safer or healthier than two.” Well, when it comes to hormones, this mentality leads us astray. It is also the reason for lots of side effects (and thus “hormone scare”) associated with hormone therapies.

Note: When it comes to determining the proper dosage as well as hormone balancing (multiple hormones), some trial&error is often needed.

When it comes to hormones, the right or wrong choice can make or break your life. To ask questions about your own hormones, contact: hormotheus@gmail.com

Make sure you thoroughly understand ALL THREE of these points.

7. How to replace individual hormones. A quick step-by-step guide.

Note: Before you read further, I advise reading Part III, “Your hormones might be screwed.” In fact, both of these once were once a single article, but I split them because it got too long.

Before doing anything else: we should get our sleep and diet in order.

If we do this, hormones often improve naturally. Then we should check the blood again in a few months. Sometimes the deficiency corrects itself.

Given diet affects our hormone levels and also their cellular action, a few points about an optimal diet (from my perspective) can be found here: A diet you can´t go wrong with.

Summary (tl;tr): Most people do well with a diet quite low in carbs (titrated to leanness and activity), while the main energy source should be good fats. Cycling occasionally into ketosis keeps you metabolically flexible. Eat meat. Avoid dairy, sugar, and excessive quantities of omega-6 fatty acids. Eat adequate amounts of salt. Increase Omega-3 and get both soluble and insoluble fiber. Your staples should be veggies, meats, fish, eggs, nuts, some fruits, good fats (butter, olive oil, dark chocolate, etc.). Once you find what works, not much variety is needed from a health perspective. Following these few points gives you 80% of the benefit for 20% effort. Do not miss the forest for the trees. Overly focusing on tiny details has a terrible cost-benefit ratio delivering massively diminishing returns.

Also, see the subsection “Insufficient caloric intake” in Section 5.

Step 1. Learn about hormones. Test your blood.:

  • Blood tests (see above).
  • Educate yourself. Learn about physiology. Learn about endocrinology. Las well as signs and symptoms of hormone deficiencies.
  • Look out for signs and symptoms of hormone deficiencies. Also measure RR, pulse, temperature and track them for a few weeks.

Beware: Many want results now. This approach is wrong. Take your time. Err on the side of caution. With all hormones, start low and go slow.

Step 2. Decide which hormones to replace or supplement:

  • Vitality: For adequate health, performance, wellbeing, all of the hormones must be at adequate levels. There is almost always room for optimization.
  • Which axis to skip: If a target hormone is well in range (above the 50th percentile of the “normal” reference range on a blood test) it is unlikely (but not impossible) that this is causing our signs and symptoms → Occam's razor: Skip these for now.
  • Is a single hormone enough? Many are fine with replacing only a single hormone. However, many others are not. For approaching the “optimum” -whatever that means to you- a single hormone is often not enough and multiple hormone replacement is often needed (esp. if someone is over 40). This is just the way it is. Many do make the mistake of thinking that “one” is healthier than “two”, thus over-replacing a single hormone to compensate for a deficiency in others. This is more unhealthy than to replace multiple hormones in small physiological doses.
  • Thyroid and sex hormones can often be replaced in isolation. Thyroid and sex hormones are the most common axes, whose deficiency occurs in isolation, which can also be replaced in isolation. In fact, both thyroid and sex hormones will (slightly) improve all other hormones.
  • Energy levels: Perhaps the most common symptoms of hormone deficiency pertain to fatigue and low energy levels. For good energy, every single hormonal axis needs to be good or at least adequate. Furthermore, all of the following need to be “alright” as well: sleep, diet, exercise, gut health, no major inflammatory process.

Note: How much “energy” a person has, is to a large extent determined by thyroid and adrenals hormones. The symptoms of cortisol and thyroid hormone deficiency overlap, but the fatigue feels very different. With low cortisol, people feel “like crap” in the morning, whereas with low levels of thyroid hormones, people simply feel groggy and sleepy but not “like crap”. With low thyroid hormones, people get lethargic and sleepy at rest, whereas with low levels of cortisol people feel best when resting. While thyroid sets the “idle” for the system, cortisol is the “gas pedal”. In fact, thyroid and/or adrenal treatment are often enough to “give people their life back”. Each hormone deficiency is associated with a specific kind of fatigue. To learn more, click here.

Beware: Our energy levels by themselves have quite a lot to do with who we are. Thus, if we change our energy levels, we should be aware that we change our personality. (Holds for mood as well).

  • Throughout the journey: lots and lots of research → educated guesses → trial and error → symptoms, signs, blood panels→ repeat.
  • Continuous follow-up: “Listen” to your body (i.e., learn about and monitor signs and symptoms). Get a blood test at least twice per year (and having bloods redrawn around 1 month after whenever any changes are made).

Beware: Do NOT just rely on blood tests. Neither to determine deficiency nor to determine efficacy of treatment! This is worth repeating again and again. Also, before starting any hormone therapy, make sure you understand all the points outlined in Section 7, general risks and side effects associated with hormone therapy, see Section 9.

How to start therapy. Start low & go slow.

With hormones, it is always wise to follow the principle of “start low and slow”. As hormones act directly on gene expression the internal machinery of our cells will change. Tissue structure and function will change as a consequence. By starting with low dosages (e.g. one-fourth of the final/target dose), cells and tissues will not be thrown off balance as much, because they aren’t forced to adapt and change as quickly to the new balance of hormones they are exposed to and to the altered levels of different proteins they now express. Starting with a dosage too high (or increasing the dosage too fast) comes with increased side effects, most of which could be avoided or at least drastically reduced by following the low&slow-approach.

A good, generic way that works for many is to start with 25% of the final/target dose and then gradually increase the dosage over a 2 month period.

How long until benefits will be evident?

While some benefits will be immediate, most changes take some time to materialize, because our cells and tissues need to adapt both structurally and functionally to the altered levels of hormones. Because of this, for most benefits to be fully evident, a wait of around 3–4 months is required after starting therapy.

Note: Onset of changes with hormone replacement: Cortisol (hours to days) >>> thyroid hormones (days to weeks) > sex hormones (weeks) > growth hormone (months).

Will I develop a tolerance?

The use of exogenous hormones is always accompanied by some endogenous suppression (more about this in Section 9). However, endogenous suppression is not the same as tolerance.

Because hormones act on nuclear receptors (and not on transmembrane receptors like most pharmaceutical drugs do), they directly alter the gene expression of our cells. Thus, hormones act at the most downstream level possible. To these effects, there is little to no tolerance. However, there will be some tolerance to some effects on neurotransmitter systems (e.g. increased levels of dopamine). For more about the science of hormones, read here.

Everyone is a little different. There is no “one-size-fits-all”.

This point is so important that it deserves repetition.

All of us have differences in our absorption, binding proteins, metabolism, cellular sensitivity, function and quantity of receptors and nuclear cofactors, degree of gene methylation, etc. Thus, hormone replacement needs to be tailored to each patient individually. The optimal dosages (and even plasma levels) often differ between individuals.

What is more, hormones need to be balanced with each other. When it comes to balancing hormones, it becomes tricky very fast. Turn one gear and many others turn as well. Replacing hormones is as much art as it is science. There will be some (educated) guesses and trial & error involved. An experienced doctor greatly helps (if we are lucky enough to find one).

To ask questions about your own hormones, contact: hormetheus@gmail.com

For a summary and brief overview of the most prominent mental, behavioral, physical, physiological changes to be expected with the replacement of the different hormones, click here.

3) How to replace thyroid hormones. Click Here.

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Summary: Our thyroid is our largest endocrine gland. Thyroid hormone controls the speed of metabolism in every cell in our body. Thus, it also regulates whole-body blood flow. Downstream this affects everything and has numerous effects on every facet of our body and mind. A well-functioning thyroid is a game-changer for life. Analogously but opposite in valence, this holds for a badly functioning thyroid as well. Replacing a deficient thyroid increases health and quality of life in pretty much every domain. Adequate levels of thyroid hormones are crucial for mood, energy levels, cognition, circulation, metabolic health. As always, the greater the deficiency, the more prominent these changes will be!

3a) How to replace male sex hormones (TRT). Click Here.

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Summary: Sex steroids prime the body and brain for mating and reproduction. Testosterone is what makes males. It improves “manliness” in looks, physiology, behavior. Its effects are mediated in a combination of estradiol and DHT. The greater the deficiency, the more prominent these changes will be!

3b) How to replace female sex hormones (HRT). Click Here.

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Summary: Estradiol is what makes females female. It improves “feminity” in looks, physiology, behavior. Its effects are partially mediated in combination with testosterone and progesterone, all of which are needed for optimal health and wellbeing of a female human body. Too bad that post-menopause all three of these sex hormones to fall to zero, causing women to live in a severe hormonal deficit for about half of their life. For most females, HRT has fewer risks and side effects compared to living with low sex hormones (and yes, this does include mortality rates due to the powerful protective effects of the sex hormone against cardiovascular disease and neurodegeneration).

4) How to replace growth hormone/IGF1. Click Here.

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Summary: Growth hormone rejuvenates our whole body and mind. The decrease in growth hormone (and IGF1) occurs linearly with age and parallels the degeneration of our body in terms of strength, agility, looks, function, health. Growth hormone would be better named “cell repair, healing, and cell maintenance hormone” because it repairs just about everything in the body at the cellular level and taking growth hormone can be compared to taking our body to a repair-shop: A few months down the road, we will look younger (e.g. better skin, hair, less fat and more muscle) and feel more youthful (mood, energy levels, calmness, feel at ease). Our whole body recovers faster, we need less sleep, we are calmer, have better cognition and are more resilient, both physically and mentally. Generally, people do well on (low-dose) GH-therapy unless they have low cortisol levels. The lower IGF1 at baseline, the greater the improvement.

5) How to replace cortisol & adrenals. Click Here.

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Summary: Cortisol prepares the body and mind for action. It gives us energy and vitality. It gives us “punch”. Cortisol sharpens thoughts, clarifies our thinking, improves cognition and concentration, all of which give us a “clear” head. Furthermore, cortisol provides plasma nutrients and regulates our immune system. Since cortisol levels are higher in times of stress, all of this makes physiologic and evolutionary sense. It is the hormone that causes us to feel the most miserable if we are deficient in it. It is also the hormone that has the quickest the most drastic improvement following its replacement. The greater the deficiency, the more significant will be the change! Unfortunately, cortisol is the hardest to figure out whether or not we are deficient in it. It is also the hardest and the most dangerous hormone to replace.

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6) Other, “unconventional” hormones that can be replaced.

Note: This section is kept very short because these hormones aren´t part of the “major”, big-four hypothalamic axes. For a more detailed discussion on these hormones, their science, benefits, practical aspects, and when and how to best replace them see here: “How To Replace Non-Major Hormones: An Ultimate Guide

  • DHEA: DHEA is the most abundant hormone in our blood. It circulates in its sulfated form (DHEA-S) and has a long half-life. DHEA is a metabolic intermediate to sex hormones but can also exert some androgenic and estrogenic effects itself. Furthermore, it is also a neurosteroid and as such has effects independent of its androgenic and estrogenic effects. It decreases significantly with age.
  • Pregnenolone: Pregnenolone is a precursor to all other steroid hormones. Furthermore, it also fulfills a role as a neurosteroid and as such it might improve mood and cognition and memory.
  • Progesterone: Unlike DHEA and pregnenolone, progesterone is not just a hormone precursor and a neurosteroid but also a “real” hormone itself. By “real” hormone I mean that it has its own receptor. As a hormone, progesterone has a variety of important functions in the body, most of which are related to female reproduction. Furthermore, progesterone itself is a neurosteroid, as well as a precursor to other neurosteroids, in the brain. It is the major precursor of the potent neurosteroid allopregnanolone, which has powerful calming effects.
  • Melatonin: Melatonin entrains the circadian rhythm. Given in appropriate dosages (0.25–0.5mg) it improves every aspect of sleep (latency, depth, quality, SWS, REM, cortisol-awakening response, growth hormone release, etc.). However, at high doses (2mg or more) it inhibits all other hormonal axes (HPTA, HPA, HTA). On the other hand, both sex hormone and cortisol treatment will decrease melatonin secretion. (Melatonin is not a supplement, but a hormone. I have included it in the list of “supplements” I do recommend. For a much more detailed discussion of melatonin see here.)
  • Aldosterone: Aldosterone mediates salt and fluid retention, which increases blood pressure. This reduces drowsiness and dizziness and “brain fog” due to low blood pressure and orthostasic hypotension. Furthermore, by stimulating sodium and fluid retention it reduces the need to urinate frequently. Replacement of aldosterone (in the form of fludrocortisone) is useful in people with low blood pressure, orthostatic hypotension, excessive urination and for people on glucocorticoid treatment.
  • ADH: Vasopressin is a neuro-hormone. Its main function is to regulate plasma osmolarity (solute concentration) by increasing water reabsorption from the kidneys. Very low levels of vasopressin (diabetes insipidus) lead to excessive fluid loss and unquenchable thirst.
  • Oxytocin: Oxytocin is my favorite hormone. Oxytocin has been dubbed the “love hormone” because oxytocin levels surge when people fall in love. It acts both as a hormone (i.e. via the bloodstream) as well as a neurotransmitter. As a hormone oxytocin induces labor and stimulates milk let-down. As a neurotransmitter, oxytocin´s effects are highly complex and context-dependent. In general, it promotes pro-social behavior and bonding. In most mammals oxytocin is largely responsible for the mother-offspring bond, which in us humans also evolved to constitute the neurobiochemical program we call romantic love. However, oxytocin does not just strengthen parental and romantic but also social bonds. It increases trust and empathy and therefore mediates “bonding” between individuals. Furthermore, it increases the desire to be social, promotes prosocial behavior, and also enhances pleasure derived from social interaction. Among other things, it leads to this “warm fuzzy feeling” when we give gifts or makes people smile. Furthermore, oxytocin improves libido and enhances pleasure from sex. Oxytocin´s main regulator is the hormone estradiol. Among other things, this is one reason why females are more emotional than males.
  • Insulin: Insulin is the most anabolic hormone in human body. It increases growth of everything (muscle, fat, bones, organs, etc.). Out of all the hormones, insulin is -next to cortisol- by far the most dangerous hormone to replace (esp. in the long-term). The only difference is, that, unlike cortisol, exogenous replacement/supplementation does not carry the risk of permanent endogenous suppression. For a more nuanced discussion on insulin, read Note 2 in the Science section here, A diet that works for everyone. In this article, I talk quite a lot about the science of insulin and its massive influence on our physiology. For more about insulin, read Note 2 in the science section of A diet that works for everyone.
  • Vitamin D: Vitamin D is a steroid hormone. It is synthesized in a complex cascade involving the skin, liver, and kidneys. It speeds up every aspect of calcium metabolism. What is more, it seems to have direct effects on the immune system (“sharper” immunity), central nervous system (mood, cognition), musculoskeletal system (stronger bones and muscles). F(Vitamin D and melatonin are not “supplements”, but hormones. I have included it in the list of “supplements” I do recommend. See here.)

Route of administration

Every cell in our body has a receptor for the hormones above. The receptors are saturated depending on the local concentration of the hormone. This means that:

  • With oral administration, a larger dose will act in the duodenum and esp. liver. (e.g. HC, T3, ethinylestradiol, oral androgens will all disproportionately exert their effects in the liver.)
  • With injection (i.m. or s.c.) there will be a local effect as well. (e.g. insulin increasing adipose tissue at the site of injection, growth hormone leading to localized lipolysis (and possibly soft tissue or bone growth), testosterone leading to localized muscle growth as androgen receptors are more saturated at the injection site).
  • With transdermal administration, there will be a localized effect as well (e.g. transdermal estradiol stopping hair growth, transdermal testosterone stimulating hair growth, transdermal cortisol causing skin atrophy)

Should dosages be kept the same all the time?

Even though the body adjusts hormone levels depending on circumstances (e.g. increase in cortisol due to stress, seasonal adjustment of sex hormones, caloric restriction and the adaptation of thyroid hormones, etc.), in general, after a stable replacement protocol has been found, I recommend keeping dosages the same and constant. The reason for this is this: The endocrine system is incredibly multi-layered and complex. By varying dosages of a single hormone, we will throw off the balance of many other hormones as well, which in turn requires not just frequent blood tests but likely also some counter-balancing and tinkering with other hormones.

For example, an increase in thyroid hormones will cause an increase in cortisol needs and an increase in levels of estradiol. An increase in growth hormone will cause a greater cortisol breakdown and thus an increase in glucocorticoid doses but due to increased conversion of T4 →T3 a reduction in thyroid hormone dosage, which in turn will also affect our sex hormones. There are many, many, many more examples with highly complex second-and third-order consequences. Furthermore, if and how much other hormones change as a consequence of a change in a single hormone is highly individual.

Some exceptions where a temporary dosage adjustment can be helpful:

  • A slight decrease in thyroid hormones during the summer months
  • A slight increase in T3 during a period of active weight loss to make up for the central thyroid shutdown as well as the increased peripheral thyroid resistance
  • A slight increase in GH/IGH1 in times of injury to speed up healing
  • An increase in glucocorticoid dosage in times of sickness or extreme physical or mental stress

Note: Changing dosages of hormones depending on circumstances requires an integrated understanding of endocrinology. I strongly advise against doing this without the help of an experienced professional because turn one gear will set many others in motion as well.

8. Risks and side effects.

Note: The side effects upon starting therapy vary widely. Common is a tranisent increase in fluid retention (exception: thyroid hormone treatment). For more details on side effects, see the respective guides for the hormone in question.

Overreplacement:

Small, physiological doses of hormones are both safe and healthy and have been used extensively over decades by anti-aging specialists. If treatment is titrated in a way that levels of target hormones fall within the upper tertile of the normal, healthy reference range, in most cases treatment is safe and the benefits outweigh the risks.

But the overreplacement of any hormone (although tempting) carries risks. Often more risks than benefits. With slight overreplacement, it might ”feels good” ( →every hormone can be (ab)used as a stimulant), but that carries the risk of making performance vs. health or longevity- tradeoffs down the line.

With severe overreplacement (whether intentional or not), the list of possible adverse effects is long. Some adverse effects can be severe and very dangerous in both the short and long term if levels of hormones approach very high levels in the blood. This article is already very long. Google the signs and symptoms of hormone excess for the specific hormone in question.

Sudden withdrawal:

In the same way, that (partial) endocrine suppression happens over weeks, so does the (complete) resumption of the endocrine function. Thus, it is always a bad idea to stop a hormone cold turkey. This can lead to a host of adverse effects, depending on the hormone. For example, vital signs (blood pressure, pulse, body temperature) might be all over the place, water retention, insomnia, anorexia, nausea, wild mood swings (e.g. PMS-like symptoms), me having a panic attack when I stopped T3 cold turkey (read here), etc.

Note: Especially cortisol and thyroid treatment must NOT be stopped suddenly. In the worst-case scenario risks can be life-threatening (e.g. adrenal crisis).

(Permanent) endocrine suppression:

In general, if individuals’ hypothalamus and pituitary are healthy/plastic/resilient enough, then endocrine suppression is just partial (e.g. 40%) and temporary (i.e. persists as long as exogenous hormones are present). Given physiological dosages are used (and tapering off is done correctly), most people gradually return to baseline within a few weeks to months after stopping treatment (or even higher levels if the cause for hormone deficiency was found and removed).

However, if one´s hypothalamus is “weak” for whatever reason, complete endocrine suppression is a possibility even if small, physiological doses are used (e.g. LH/TSH/ACTH fall to low, unmeasurable levels in the blood, despite the target hormone being well in range and despite no signs and symptoms of over-replacement). Most people recover even from complete endocrine suppression (although recovery takes longer).

Stopping hormones requires tapering down slowly. With the use of any exogenous hormones, there is a negative feedback to the hypothalamus/pituitary, which reduces or even completely shuts down the signals sent to the peripheral endocrine gland. In the short term, the gland simply slows (or ceases) production, but over time some atrophy does happen (depending on the dosage). Thus, stopping the use of exogenous hormones (for whatever reason) needs to occur gradually to allow sufficient time for the hypothalamic hormone generators to pick up again as well as the endogenous gland to hypertrophy again. This will take weeks to months. Temporarily, one might need to accept to live in a state of partial hormone deficiency. Out of all the hormonal axes, this risk is greatest (and most severe) with the adrenal gland.

However, it is possible that someone does not bounce back to their baseline and the endocrine suppression remains permanent. The scientific mechanism behind this is twofold. Firstly, there are epigenetic adaptations at the level of the individual cells associated with hormone monitoring or secretion. Secondly, there are neuroplastic changes at the network level in the hypothalamus turning the hormonal pulse-generators and feedback machinery down or off. The higher the dosage, the greater is the risk of this happening.

If one does not bounce back to normal for whatever reason, the person will have to keep replacing the hormone(s) in question for life. In most cases this risk is low, given physiological dosages are used.

Note: Thyroid medication is the most prescribed medication on the planet. The anti-contraceptive is close behind. As long as normal doses are used, people almost always bounce back completely after a few months of stopping. Why should it be different with the other hormones?

Will I have to continue hormone treatment for life?

The risk is not so much about being unable to get back to baseline (which was likely suboptimal in the first place as otherwise, we would not have started hormone therapy), but rather with having seen the other side and not wanting to go back. This can be a real issue (e.g. if you are not able to afford or procure therapy anymore if any medical issues arise that make continuing therapy not an option, etc.).

In most cases, one of three scenarios apply. Firstly, no cause can be found (or a cause can be found but can not be removed) and the risk or downside of living with baseline hormones are larger than the risk or downsides of therapy. Secondly, there is always a (small) risk of permanent endocrine suppression. Thirdly, after having seen life on the other side, many people do not want to go back. For around half of people who start hormone therapy, one of these applies, making hormone replacement a life-long therapy.

9. Source and costs

Costs:

How much does all of this cost? All this costs me about 400 Euros per month. 300 for the growth hormone and 100 Euro for all the rest. Not that much, considering how much money some of us spend on supplements for perhaps a 5% return compared to hormones. Downstream the extra mood, energy, focus, health, willpower, social skills (esp. compounding over years) will pay me back massively. (Regardless of well-being and life-enjoyment -which are priceless.)

Note: I only get pharmaceutical grade. Never would I ever put anything potentially impure/mis-dosed/mis-labelled into my body.

Source:

I get most of it prescribed from doctors, however, I need to pay for it out of pocket (i.e. full pharmacy price).

Sourcing hormones without a proper prescription can be tricky. There are a lot of “fake” hormones (bad or inconsistent quality, impurities, being something completely different, differences in dosages between batches and even single pills from the same batch, etc.) on the black market. Never in my life would I risk that. Hormones are powerful molecules and getting them from a sketchy source is like playing roulette. The Russian version.

While I don´t sell anything, I can point you in the right direction. Contact me via email (at the bottom of this article).

10. Conclusion

Improving my hormones in a DIY-kind of way took months to years of studying, testing, experimenting, trial&error, repeat. Starting anything with the potential for compounding growth sucks, but the hardest part is just getting started. In 10 years you may wish you started now.

In my opinion, we are here to grow personally, contribute and to enjoy. Our capacity for these depends on our biology, which is greatly influenced by our hormonal profile. Improving our biology enables you to better tackle problems and goals in life with much more energy, mood, motivation, enthusiasm, clarity, cognition, persistence, resilience, health. What is more, we can now enjoy the whole journey more and better, which is the main aim of hormone replacement.

As you might have guessed by now, I believe hormones are very underused. In fact, I have no idea why something of such importance is mostly neglected by mainstream medicine.

Altering, tweaking or optimizing hormones is a long journey. It takes quite some time, effort, money and experimentation. However, at the end of the day, it is worthwhile.

Hormone replacement is all about prevention and longevity. The point is to prolong healthspan and not just lifespan.

Hormones are all about prevention and longevity. The point is to prolong healthspan, and not just lifespan.
Hormones are all about prevention and longevity. The point is to prolong healthspan, and not just lifespan.
It is about healthy, high-quality years lived, not just total lifespan.

Life is like poker. If our hormones are deficient, “living life to the fullest” is just not on the cards. Life is too precious to live with low energy, mood, health, etc. for a long time.

Life can be so much easier and so much more enjoyable if we are full of energy, in a great mood and have good health all the time. As I have experienced this like few others, in my early days of hormone replacement I felt like a cheater (for more, click here and read the last few sections).

In the past the fact that I replaced many of my hormones was a kink in my story, something I was not proud of and it even made me somewhat ashamed. I tried to hide from others.

After I have been doing this for a few years, I came to terms with being my own bio-engineer. I simply have no other choice. Without it, I don´t know where I would be right now.

Would I be seriously depressed? Would I have turned to drugs because at one point I just could not “push” anymore? I do not know the answer to these questions, but for sure I would not be here writing this.

Hormone replacement has given me my life back. And I am only given a single life in this universe. A life I can now fulfill and not waste.

In the first few months of having been brought back from the living dead, I was indescribably grateful (words are useless here), moved to tears multiple times every day.

Perhaps one needs to have seen the darkness to really appreciate the light.

When people try to beat cancer it is their only problem. They regret what they cared about when life was normal. They wish they just had all the petty problems others have.

Health might not be everything, but without it, everything is nothing.

After winning the war against cancer, what follows is a period of utter bliss. However, it does not last. It is easy to get used to any change that is permanent, so, quite soon they take their health for granted again.

Soon though the groundhog day sets in again and people fall back into the same old habits, with their brains in default-mode.

I went through a similar sequence. Within a year or so I got used to my new, reversely self-engineered vitality. Whenever I catch myself taking my new vitality for granted (and esp. whenever any of this biohacking feels like a nuisance), from time to time I leave out the cortisol for a day or so.

I guess most of you do not know what it feels like to live without any significant amount of cortisol in your system. The effects on how I feel are instant (unlike with any other hormone). So, these occasional days of severe adrenal insufficiency give me a glimpse of how I felt in the past. They then rekindle my gratitude, often for weeks. It reminds me of how small is the price I pay for the reward I get.

I experienced how a reduction in biological vitality can send you on a relentless downward spiral. The stronger the decrease in your vitality the steeper the slope.

In its wake over months to years my life, the only life I can be sure of having, went downhill. Many people are unsuspecting. Unaware of these invisible forces exerting their power relentlessly every single day.

Along the way, it is not just you that is hurt but also your loved ones. Also, indirectly society is hurt in countless and often quite obscure ways. You are not contributing what you otherwise could and instead, you become an involuntary parasite, living off society’s resources.

On the other hand, I experienced how an improvement in my biological vitality sent my life onto an upward spiral. In just a few years of optimizing my hormones my outer and inner life changed, thanks to the most powerful force in the universe.

I started to dream again, which used to be impossible with low energy, mood and health. I found my purpose. I found something I want to contribute. I also gained the energy, mood and health to keep working on my dreams, to enjoy working on my dreams.

If your hormones are out of balance (or have deteriorated for some reason) you just cannot function in such a state long term.⁵ Many fail not because their dreams don’t work out, but simply because they have no energy left, at least not long enough for their dreams to bear fruit.

How different would the world be if these young enthusiastic founders just had enough energy to keep burning? How many Bill Gates alternatives did not make it because their failing biology put a padlock in front of their dreams? How many Elon Musks did not begin to make the world a better place because they just did not have the necessary energy to even start their endeavor?

To even start to dream in the first place?

My purpose is to raise awareness. People need to know that there are biological shackles many of us carry.⁶ Shackles which make it much harder to live a life we like. Shackles that make it harder to find purpose in the first place and certainly much harder to have the necessary persistence, drive, energy and health to keep working towards it.

Finally, as a doctor, I want to improve the vitality of others. Help them to greater personal wellbeing and increase the impact they have on others. Make the world a better place and help others to do so as well. I make no small plans in the only life I have got. My goal, with all my writing, is to point people in the right direction towards removing biological shackles holding them back from becoming a better version of themselves, living life fully and being better contributors to humanity.

This short guide took years of studying, researching, blood tests, experimentation (timing, dosage, therapy of choice, changes in other hormones), legal hurdles, side effects and suffering.

I know there are many others out there. Had I known what I know now, it would have saved me lots of money, happiness, effort, researching, experimenting and suffering.

I hope sharing what I have learned can help some of you.

Due to my unique story, extensive knowledge and personal experience, there are few people out there that know as much about hormones and all their interactions, details and technicalities. When it comes to hormones, the right or wrong choice can make or break your life. To ask questions about your own hormones, contact me via email (hormetheus@gmail.com). I’m able to offer you insights about your individual situation almost nobody else can.

I also encourage you to join the subreddit r/HormoneEnhancement.

Footnotes:

  1. A small “tradeoff” with the future is not always necessarily bad. For example, what you create during these periods of intervention stays (e.g. get a promotion, meet a partner, build a company, write a book -vs. just being withdrawn and neither advancing nor enjoying life). Also, it should not be neglected that your life is even now and not just in the “future”.
  2. Social exchange theory: A relationship or friendship is always about a balance between giving and taking. The more you have to give (e.g. knowledge, looks, status, resources) the more you can demand or get.
  3. This article has got over 4000 views in the first month, but not a single person commented (perhaps because most people are logged in with their real name?). This shows that there is some stuff people would rather do without others knowing. We all want to be seen as genetically gifted, while nobody wants to be seen as a cheater.
  4. Even though the capacity to do damage might be multiplied as well, overall I believe most humans are intrinsically good at their core.
  5. Even though I did all of this pretty much myself, I am well aware that in many respects I had been quite lucky (e.g. What if I were born 20 years earlier? What if I did not make it to med school?).
  6. Making it my “meta”-purpose, if you will.
  7. For a recent guideline for panhypopituitarism, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722397/.
  8. If this were the case, everything we did in medicine would not make sense. We run RCT to assess whether overall people are better off taking a specific drug vs. not taking it. Often these are drugs intended to be taken for life.
  9. How a seemingly unified consciousness or mind can emerge from a brain made of countless different substructures with different responsibilities that operate partially independent from other structures is one of the greatest mysteries of science. One of the few things that is more baffling is why there is something rather than nothing.

About the author.

My goal with all my writing is to point people in the right direction towards removing biological shackles holding them back from becoming a better version of themselves, living life fully and being better contributors to humanity.

To get non-lame stuff about becoming the best version of yourself, sign up here.

I also encourage you to join the subreddit r/HormoneEnhancement.

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For self-optimization or solving health-related problems, contact: hormetheus@gmail.com

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