Contrarian Endocrinology Part II: Estrogen and Progesterone for Men

by Karlis Ullis, MD with Josh Shackman, MA

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When you saw the title of this article, your first reaction might have been "has Dr. Ullis lost his mind?" or "Why the hell would I want to put these hormones into my body that will make me fat and grow breasts?" But before you have me committed, remember from Part I of this series on Contrarian Endocrinology that there is no such thing as a "good" or "bad" hormone, nor is there such thing as a strictly "male" or "female" hormone. Just as testosterone plays an important role in the female body and has many positive health benefits for woman, estrogen and progesterone also have numerous health benefits for men if used properly. However, remember that the arena of sex hormone research is highly politically laden and is still in somewhat of a state of infancy regarding long term research. Just as there is precious little research on testosterone for women, there is also very little research on progesterone or estrogen for men. But given both the research data currently available as well as my own clinical experience, I am very excited about the potential of these two traditional "female" hormones for their use and role in men.

Estrogen for Men

Yeah, yeah, I know – most male readers of Mesomorphosis are far more concerned with keeping their estrogen levels down than raising them. No, I am not crazy in case you are wondering, and this is not an article aimed at transsexuals. To be sure, if my male patients have estrogen levels that are too high I may prescribe anti-estrogen therapies which may include such drugs as Arimidex (an aromatase inhibitor most commonly used in women with breast cancers and have estrogen sensitive tumors), Tamoxifen (an estrogen tissue receptor blocker) and natural methods of blocking the potent estrogen effects on tissues with phytoestrogens (soy, flax seeds and many other plants that contain the weak estrogen like compounds), or decreasing the negative effects of some of the "bad estrogen metabolites" (16 alpha hydoxyestrone, and 4 hydroxyestrone) with the use of the cruciferous vegetables or their extracts (i.e. indole -3 -carbinole or its related more potent cousin diindoylmethane) as part of an overall hormone replacement/anti-aging treatment program. Most men as they get older will have an increase in estrogen levels and decrease in testosterone as they get older. Overall, the ratio of testostesterone to estrogen declines with age and I believe the increased load of different estrogens and some of their toxic metabolites contributes to some of diseases associated with aging in men (prostate, cardiovascular, and immunological diseases, and even age associated gynecomastia).

With this above disclaimer, I would also like to add that estrogen also has many benefits and is far from being a "bad" hormone. Just as women are more sensitive to the effects of testosterone to women, some men are very sensitive to the effects of estrogen. Giving brief spikes of estrogen to a man may induce surges in energy and libido similar to what you would expect to see in a woman given a testosterone injection. A recent review article in the Journal of Clinical Endocrinology and Metabolism (June, 1999) by one of the world’s authorities on brain biochemistry and function, B.S. McEwen describes the many potent effects estrogen can have on the brain and the central nervous system and the two estrogen receptors. For example, estrogen has been shown to have wide ranging effects on the noradrenergic, dopaminergic, and cholinergic systems, all of which are profoundly important for mood and energy (8). The stimulatory effects of estrogen on our neurotransmitter systems and other aspects of the central nervous system may be a major reason why some men get a big boost of energy and libido when their estrogen levels rise.

So should I go steal some of my wife’s or mother's Premarin tablets and pop a few before my workouts? The answer is of course not! Just as I don’t recommend estrogen replacement therapy for all women and without a concurrent testosterone replacement program, I most certainly don’t recommend giving estrogen directly to men. Instead, I have chosen alternative treatments that give a produce a physiologic rise in both testosterone and estrogen for maximum libido and energy.

One drug that is extremely effective for enhancing libido is Human Chorionic Gonadotrophin (HCG, a form of lutenizing hormone or LH), which when injected even subcutaneously gives both a simultaneous boost in both testosterone and estrogen levels. From clinical experience, I have found it much more effective than plain testosterone for enhancing libido. However, I do not think it is the best drug for bodybuilders or athletes. HCG is popular drug for bodybuilders who use it to boost their natural testosterone production during or after an anabolic steroid cycle. However, some bodybuilders complain develop gynecomastia from HCG use, due to the surge in estrogen. In addition, HCG only stimulates natural testicular output briefly (a few days) but is counter-productive to use in the long run. Chronic use of HCG may shut down natural testosterone production by negative feedback signalling and thereby blocking the brain-pituitary gland production of LH.

A much simpler choice for athletes or bodybuilders seeking a natural concurrent boost of estrogen and testosterone is a much cheaper supplement that you have all heard of before – androstenedione! In spite of the "shocking" revelation that androstenedione causes increases in estrogen in the recent EAS sponsored study (6) in JAMA, my response to this study was "No @#$^ Sherlock!" Androstenedione is well established and well known to be a precursor to both testosterone and estrogen. I have found that many people notice more of an energizing effect from androstenedione than from any of the other testosterone prohormones. I believe this is largely due to the increase in estrogen levels.

It should be noted that finding the "optimal" or "normal" level of estrogen for men is extremely problematic. Estrogen levels can be difficult to measure accurately, as medical doctors in some countries even resort to using sex hormone binding globulin as a rough measure of estrogen levels. Since most men experience an increase instead of a decrease in estrogen as they get older, little attention is paid to the importance of estrogen deficiency in men. It has recently been shown that too little estrogen is linked to male osteoporosis. Studies of men who genetically lack the enzyme for the conversion of testosterone to estrogen, (aromatase deficiency), can be very osteoporotic. However, testosterone replacement therapy, if sufficient, is usually enough to restore both testosterone and estrogen levels high enough to prevent osteoporosis.

Progesterone for Men

Once again, I am not crazy. I know that most of you think of progesterone as an "evil" catabolic and fattening hormone. What many of you may not remember is that the extremely popular anabolic steroid nandrolone decanoate (aka Deca Durabolin or nortestosterone) is in fact classified as a progestin (hormone with progesterone-like activity)! In addition, many progestins given to women in birth control pills and other drugs such as norgestrel and norethidrone are classified as 19-nor-testosterone or 19 nor- progesterone derivatives. Eastern German female Olympic athletes were known to have taken large quantities of these nor-testosterone derivatives to build muscle with the notorious masculinizing side effects that was obvious to all Olympic observers. Modern Olympic testing can now distinguish the difference between nor-progesterone and nor-testosterone derivatives. Since birth control pills aren’t yet on the list of drugs banned from competition, these "women" were able to pass all drug testing without any worries. Of course, I don’t suggest you raid your girlfriends birth control pill case in order to make yourself "feel like Deca". Recent studies at UCLA (9) have shown that different types of birth control pills have different androgenic capacity and can change the Olympic doping standard of testosterone to epitestosterone ratio of six to one with an increase of that ratio.

Are you confused yet? How can one of the most manly of anabolic steroids such as Deca Durabolin be considered a female hormone? How can female birth control pills be used as anabolic steroids? The simple answer to this question is that progesterone is best not considered as a female hormone, but as a hormone with properties somewhere in the middle between testosterone and estrogen. You can tweak the progesterone molecule slightly one way and have a hormone that is androgenic, or tweak it another way and be less androgenic or become more neutral in effect like the natural progesterone in the human body. Progesterone has its reputation as a female hormone due to its role in promoting pregnancy. But natural progesterone is still present in the male and also plays an important role in male physiology, but it has not yet been clearly elucidated. It should be noted that the "masculine" hormone nor-testosterone, that is the basis for the anabolic steroid Deca Durabolin, is actually found in highest concentrations in pregnant women (10).

So how can progesterone like molecules make me big or improve my athletic performance? Are large doses of Deca what you are referring to when you talk about "progesterone for men"? The answer is that nortestosterone drugs and prohormones have disadvantages over testosterone for use in hormone replacement therapy and in athletics / bodybuilding. The main reason nortestosterone is so popular is because of its lower androgenicity. It competes with testosterone for the 5-alpha reductase enzyme that converts testosterone to DHT and instead converts to dihydronortestosterone which is much less androgenic. Therefore you are less likely to experience side effects often associated with testosterone such as acne, hair loss, etc.

However, some people don’t know about nor understand the drawback of nortestosterone. For one thing, it can drastically lower libido. This is not surprising since other progestin based drugs are given to sex offenders to purposely lower their libidos. For male hormone replacement therapy, this can make nortestosterone a big no-no. Most men considering hormone replacement therapy are already suffering from a loss of libido, and nortestosterone can be almost like a castration agent for them. In addition, nortestosterone has a lower aromatization rate than testosterone. Since estrogen can raise HDL levels while androgens tend to lower HDL, this lack of estrogen from nortestosterone can cause HDL levels to drop further than when on testosterone. While temporarily low HDL levels may not be a big concern for a healthy young athlete, this is obviously a bigger concern for older men or those with heart disease risk factors.

Instead of using nortestosterone for hormone replacement therapy, I recommend a combination of natural testosterone and pulses of natural progesterone when testosterone is used. Progesterone, like nortestosterone, competes with testosterone for the 5-alpha reductase enzyme. A combination of testosterone/progesterone could allow for the benefits of increased testosterone while keeping DHT levels balanced. The concept is to help maintain a natural and youthful testosterone/estrogen/progesterone ratios throughout your lifetime. I believe a proper balance is the key to a healthy libido, prostate, and cardiovascular system.

While synthetic progesterone derivatives have been used to lower libido in men (1, 5), I believe that natural progesterone may in fact have the opposite effects in some men. I have heard patient anecdotes and from other medical doctors saying that application of a natural progesterone cream to the scrotum can increase libido and enhance orgasmic pleasure in some men.. I believe that just as high doses of synthetic progesterone derivatives can lower libido, so can low levels of natural progesterone. Natural progesterone can have a calming effect on the nervous system and may help those men who are "rapid ejaculators" or have other anxiety related sexual problems. Restoring or pulsing progesterone may enhance libido, and sexual function. While large doses of synthetic progestins may cause you to get fatter or lose muscle, the role of progesterone in increasing body temperature has been well studied in women (3) and may help bring back resting metabolic rate to a more youthful levels in men as well. Progesterone has the benefit of boosting metabolism but too much can lead to high insulin levels which would likely cancel out any benefits of increased metabolism.

Conclusion: The Future of "Contrarian Endocrinology"

I believe that the effects of "female" hormones on men have been greatly over demonized and understudied and there are many benefits to be derived both for body compositioning and for anti-aging purposes. Just as testosterone use effects women more noticeably than men, other hormones found in smaller amounts in men such as estrogen and progesterone can effect men more profoundly than women. Too much estrogen and progesterone will of course lead to loss of muscle mass, gains in fat, and loss of libido. But proper levels and more importantly the ratios of these hormones could actually be beneficial for libido and body composition.

While much more research needs to be done, I believe the best protocol for hormone replacement therapy for men will be quite similar to the one I use for women. As you may recall from Part I of this series, my usual protocol for female hormone replacement therapy is to restore a balanced ratio of testosterone/estrogen/progesterone through use of natural testosterone and progesterone gels and small doses of natural estrogens if necessary. I believe a good protocol for men may soon be a similar protocol of maintaining a natural balance of testosterone/estrogen/progesterone. Once a proper baseline level of sex hormones is achieved through use of natural gels, both men and women may desire an additional spike in energy or libido from time to time. For this purpose, occasional use of the short acting forms of the prohormones such as androstenedione or 4-androstenediol can be extremely effective in causing temporary boosts of testosterone and estrogen without disrupting your hormonal balance.

As for body compositioning and athletics, young adult men (not teenagers) can probably benefit most from spiking estrogen levels occasionally since they may have the lowest estrogen levels to begin with. Young adult men may also wish to increase muscle mass through nortestosterone or nortestosterone prohormones, since these should have less androgenic side effects. Older men should probably avoid nortestosterone and should instead use natural testosterone with a small amount of natural progesterone pulsing to minimize androgenic side effects.

I am eagerly looking forward to the day when my ideas are no longer considered "contrarian". As advanced as medicine is in the United States, the American medical establishment and the media often act like emotional and irrational children when it comes to sex hormone research. Testosterone and other androgens have been highly politicized and demonized in the past to the point where no constructive research could be done. Only recently has the importance of estrogen and natural progesterone in men and testosterone in women is starting to be looked at seriously. As more and more research is done, I am highly confident that it will be shown that keeping all of these three main sex hormones balanced throughout your lifetime can both extend life as well as improve the quality of your life.

References

1. Berlin FS. "Chemical castration" for sex offenders. N Engl J Med. 1997 Apr 3;336(14):1030

2. Crenshaw, Theresa L. ,With Goldberg, James P. "Sexual Pharmacology; Drugs That Affect Sexual Functioning", W. W. Norton & Company, March 1994

3. Cagnacci A, et al " Regulation of the 24-hour Rhythm of Body Temperature in Menstrual Cycles with Spontaneous and Gonadotropin-induced Ovulation" Fertil Steril. 1997 Sep;68(3):421-5.

4. Gladkova AI. "The Regulation of Male Sexual Behavior by the Sex Hormones"

Usp Fiziol Nauk. 1999 Jan-Mar;30(1):97-105

5. Kiersch TA. "Treatment of Sex Offenders with Depo-Provera." Bull Am Acad Psychiatry Law. 1990;18(2):179-87

6. King, DS, et al, "Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men: a Randomized Controlled Trial". , JAMA. 1999 Jun 2;281(21):2020-8

7. Mauvais-Jarvis P, et al. "Inhibition of Testosterone Conversion to Dihydrotestosterone in Men Treated Percutaneously by Progesterone" J Clin Endocrinol Metab. 1974 Jan;38(1):142-7.

8. McEwen BS.," Clinical Review 108: The Molecular and Neuroanatomical Basis for Estrogen Effects in the Central Nervous System." J Clin Endocrinol Metab. 1999 Jun;84(6):1790-7

9. Personal communication to K. Ullis, M.D. from UCLA Sports Medicine researchers.

10. Reznik Y, et al. Rising plasma levels of 19-nortestosterone throughout pregnancy: determination by radioimmunoassay and validation by gas chromatography-mass spectrometry.

11. Thorneycroft IH. "Update on Androgenicity" Am J Obstet Gynecol. 1999 Feb;180(2 Pt 2):288-94