HPTA Supraphysiological Overcompensation: The Holy Grail Of Optimized Natural Human Performance

The first and most important How-to answer in the optimization of human performance begins with HPTA Supraphysiological Overcompensation. Learn more...

During the 70's and early 80's supplement makers had little to offer in the way of anything useful for athletes, okay, other than vitamins and poor quality protein powders that tasted like sweetened dog food. Well, actually it was mostly animal grade soy protein with sugar added so I guess it was.

In the 90's, a few viable performance-enhancing options such as creatine monohydrate and whey protein made their way into the market thus finally offering health and performance oriented alike something of statistical value.

What Happened?

In today's media-hysteria-managed environment, athletes, supplement companies and drug dealers alike are seen in the same shady light. Why? In the new millennium performance enhancement through supplementation became a science. (No joke, really!)

As the better companies employed more real scientists, they became more apt at researching and marketing substances that truly could be said to be "steroid-like" in effect. And of course, the pharmaceutical industry, sports organizations and government agencies took interest. The pharma industry because of money, sports organizations because players wanted more, and the government because of both reasons.

It has to be a sad state of affairs when a society has reached a point in its ineptitude that government intervention is deemed necessary as a means of controlling individual choice for performance enhancement, or not, from over the counter supplementation. Yet the only qualification required for purchase of enough alcohol to kill ones self is 21 years of age and the capacity to say "Bud".

After all, no one seems appalled by the unfair advantage performance enhancement drugs like Viagra© (sildenafil citrate) and Cialis© (tadalafil) allows cheaters. (Don't get me started on the unfair advantages women with large breast augmentations have over post-nursing mothers...Okay, like I care)

Are Viagra & Cialis Unfair Advantages Or Divine Blessings?

Unfair Advantages.
Divine Blessings.

We're Not In Kansas Anymore...

    As a result of today's media-hysteria-managed environment, everyone wants to write a tell-all book and government intervention, we have moved into an era of supplementation skepticism leaving only a few options left to truly innovative supplement makers. Well, at least those with an interest in the future of our industry and an authentic interest in the edge science can offer athletes (and every day normal people as well):

    1. Work to maximize human performance through health promoting physiological optimization (WADA, IOC and pro-sports friendly)

    2. Bring on greater government intervention and regulation for the entire sports and supplemental industry.

    3. Move to Mexico where no one cares what you do to yourself...and take lots of Viagra or Cialis.

Where To Start

The first and most important How-to answer in the optimization of human performance begins with HPTA Supraphysiological Overcompensation: The Holy Grail of optimized natural human performance enhancement.

Before I go on, realize that this is the catalyst for all of the good things you really want to happen if performance optimization is your goal...so take the time to read it!

The human body has the ability to naturally produce amazing amounts of anabolic goodies like testosterone, GH (growth hormone), IGF-1 (Insulin Growth Factor-1) and insulin. It also has the ability make more thyroid hormones and other fat burning substances than you could ever reasonably want (never met a reasonable bodybuilder but I did hear of one once)

In regard to everyone's favorite naturally occurring man-making androgen, testosterone is king of the muscle building anabolics...and your body can make WAY more than you need through HPTA Supraphysiological Overcompensation.

Warning: Science Geek Stuff (That Actually Matters)

    Both men and women produce testosterone naturally, but here lets primarily focus upon the men. (I will show you a diagram of how the ladies do it as well anyway for the curious)

    Endogenous (made inside the body) testosterone production is predominantly a result of, and governed by, the HPTA (Hypothalamus-Pituitary-Testes-Axis). It all begins with a gland located in your head called the hypothalamus when it releases a measured amount of GnRH (also known as LH-releasing hormone).

    What Is The Hypothalamus?
    An integral part of the limbic system, the hypothalamus is involved in regulation of the internal milieu of the body or, said another way, for homeostatic control.

    It does that by means of its neuroendocrine role in conjunction with the pituitary gland as well as by its influence on the the autonomic nervous system, which helps regulate body temperature, the cardiovascular system, and food and water intake.

    The small amount of GnRH then makes its way to the pituitary gland to tell it to kick out two other hormones called LH (Luteinizing Hormone) and FSH (Follicle-Stimulating Hormone). Nope, the job is not done yet.

    Okay, LH and FSH then take a trip via the vascular system to the testes (testicles, "The Boy's", testes... whatever) and make contact with the Leydig cells and Sertoli cells ...which results in testosterone synthesis and sperm production respectively.

HPTA Function Pathways

    The amount of GnRH, LH and FSH produced regulates the amount of testosterone, androstenediol and DHEA your body produces...or not. If the HPTA produces supraphysiological amounts of GnRH, LH and FSH, it actually also produces more performance enhancing goodies like testosterone, androstenediol and DHEA by way of overcompensation. Getting the idea here?

    THAT is HPTA Supraphysiological Overcompensation.

The Question You Really Want To Ask...
Why Don't "My Boy's" Do That Naturally?

Like all things we really like in life, there is a series of checks and balances that keep things in control and limit the amounts of good stuff we can have (like girlfriends). In the case of HPTA-function and optimized testosterone production, it is due to 2 primary negative feed-back loops. (Most know this first one, but let's recap to be sure).

Estrogen Negative Feed-Back Loop

    High estrogen levels are not the sole propriety of women with amazing sweater puppets and bizarre mood swings. Men produce it too, and in most cases, there is way too much in any man's system than nature meant there to be. This also helps to explain way males produce less testosterone and sperm today than they did only 2 generations ago.

    This is due significantly to un-natural (exogenous) exposure to the overabundance of plant-derived phytoestrogens (such as those found in soy products) and xenoestrogens in plastics and herbicides today.

    What Is Xenoestrogen?
    Literally, xenoestrogens are estrogens that are foreign: i.e. not produced in ones own body. (Xeno comes from the Greek, meaning strange or foreign.)

    Thus estrogen produced by a cow (which is present throughout the meat) is a xenoestrogen. As such if one eats beef, one is eating a xenoestrogen.

    Unless of course it is a bull and then one is eating xenotestosterone.

    Don't get me started on chemically raised meats and pesticides either.

    Natural (endogenous) estrogen is predominantly made in the male body from the aromatization of endogenous (made inside the body) androgens (such as testosterone) into estrogens. This is the responsibility of an enzyme called aromatase that is present pretty much everywhere in the body...even the brain around the hypothalamus (remember that).

    When too much estrogen interacts with the estrogen receptors of the hypothalamus, there is a negative feed-back loop that tells the gland that there must be too much testosterone as well. The result is a dramatic unhealthy reduction, or even shut-down, of the HPTA and girl status for the owner of the saggy-sack problem. But it gets worse...

Androgen Negative Feed-Back Loop

    The hypothalamus also has lots of androgen receptors for sensing the level of testosterone and other androgens circulating in the body. When too many androgen receptors of the hypothalamus become activated, there is a decrease or even total shut-down in GnRH release. This means that "The Boy's" pretty much have nothing to do because the lack of GnRH release also means no LH or FSH release.

    So the end result is your testes have no reason to produce testosterone or sperm...and no reason to optimize muscular activities, recovery or have sex. Hmmm, look bad, feel bad and not care. That is ugly.

Anabolic Steroid Users & Saggy-Sacks

The reason most AAS users employ the drugs is to un-naturally increase their testosterone levels to 2-5 times what is so-called natural or normal. Of course the results are obvious: Increased muscle mass, decreased fat mass, a marked increase in metabolic rate, better focus, and improved performance in every manly area. The bad results are all of the negative side-effects from excessive estrogen and lipid issues that synthetic androgens can cause.

Normal total testosterone production for a healthy male is about 500-600ng/dl (too many are in the 200-350ng/dl range due to environmental estrogens alone), but some AAS users push the levels into the 2000-3000ng/dl plus area. As a result of all of this excess testosterone floating aroundthe body, there is a lot of aromatization to estrogens and an overabundance of androgen receptors of the hypothalamus being over-stimulated. The outcome is obviously the loss of testicular function due to both negative feed-back loops occurring.

Many AAS users know that by decreasing the amount of circulatory estrogen, they are also able to somewhat decrease HPTA down-regulation. Post-cycle AAS therapy, in most cases, includes something to decrease estrogen levels and activity, and some other drug to replace LH. If done correctly the end result again is an increase in actual natural testosterone product 1-2 times above normal for a brief period.

Clomiphen, Anastrazole and HCG...Oh My
(The Most Common PCT)

PCT stands for Post-Cycle-Therapy and refers to HPTA regeneration or stimulation. Anabolic steroid users and those looking to increase endogenous androgen production alike, have used this so-called stack almost like a religious rite not realizing there was an error in its structure.

Clomiphen Citrate is the generic name for Clomid® which is a fertility drug used to stimulate ovulation in women and increase sperm production in men. Clomiphen citrate is actually a very weak estrogen in itself. It works by blocking more powerful and active estrogens from merging with the hypothalamic estrogen receptors. The end result is the hypothalamus "perceives" that there is less circulatory estrogen and responds by increasing GnRH release. In addition there is some degree of decrease in estrogen activity throughout the rest of the body as well for the same reason. As a rule 50mg daily for 2-3 weeks of clomiphen citrate has been noted as effective for this purpose.

Anastrolzole is a generic name for the drug Arimidex®. This is an aromatase enzyme inhibitor that decreases conversion of susceptible androgens into estrogens. This action results in a decrease in total circulatory estrogen. As little as 1mg 3 times weekly post-cycle for 30 days has been shown to decrease estrogen by 50% and have some benefits in regard to HPTA regeneration due to its mopping up effect.

But this combination only helps clean up the effects of the Estrogen Negative Feed-Back Loop leaving the Androgen Negative Feed-Back Loop unaffected.

HCG refers to Human Chorionic Gonadotropin. This is a hormone that is produced by pregnant women and used in fertility medicine. In males, HCG has been shown to mimic LH thus administration results in direct stimulation of the testes resulting in minimal increases in sperm production and significant increases in testicular testosterone production.

Human Chorionic Gonadotropin
Human Chorionic Gonadotropin, or hCG, production begins approximately 8-10 days after conception when the embryo starts to burrow itself into the lining of the uterus.

It is this hormone that is measured by early pregnancy tests and if present, will return a positive result.

An hCG beta blood test is much more sensitive than an HPT, and can detect pregnancy as early as 10 days after fertilization.

Interestingly enough, this pregnant woman's hormone is effective to a point that some studies have shown it to be able to prevent testicular dysfunction during anabolic steroid use. But again, that is a whole other article. Most have realized notable HPTA recovery and/or androgen production stimulation form administering 1000iu HCG 3 times weekly for 21 days post-cycle.

Hmmm, still nothing to "positively" affect the Androgen Negative Feed-Back Loop.

And Things That Go Hump More In the Night

The ideal situation would be the ability to decrease estrogen levels in the whole body while decreasing androgen activity of the hypothalamus specifically. Of course we would not want to decrease androgen receptor activity in other peripheral areas like muscle tissue, and we would want focused estrogen control around the hypothalamus to create the best performance enhancing synergy naturally. Can that be done? Of course it can, just as Nolvadex® is way more specific to breast tissue, some really cool compounds are WAY more specific to the hypothalamus.

The result would be long term HPTA Supraphysiological Overcompensation and viable naturally occurring testosterone production at a significant and highly effective level. This would (and has) obviously allow for optimization of human male performance. That is a perfect example of correct application of the body's natural health promoting Action/Reaction Factors.

If you have read this far, then you already realize that I have explained the physiological and environmental factors that foster an un-natural chain of events resulting in significant reduction and limitation for every male's performance...in every aspect of the word.

If you are interested in legal and natural ways to optimize male physical and mental performance (and improve the fun of what goes Hump in the night) then read on.

We Had To Start Somewhere...


    Sometime in the early 80's Dan Duchaine proposed that a plant aromatase called Chrysin (Flavone X) was comparable in effect to the well-known biosynthesis inhibitor/anti-aromatase Cytadren (Aminoglutethimide).

    Dan Duchaine, 1952-2000
    Known as the Steroid Guru, Dan Duchaine was the author of The Underground Steroid Handbook. He died from complications related to polycystic kidney disease on January 12, 2000.

    Fellow writer and friend Will Brink set up The Dan Duchaine Memorial Fund in his memory. Contributions can be made by sending donations to: The Dan Duchaine Memorial Fund, c/o CEO Steve Evangelista, National Kidney Foundation, 129 Morgan Drive, Norwood MA02062.

    This was due to the structural similarities the two compounds possessed. Dan was sharp (he kept us all thinking), but he missed on this one. In truth Chrysin totally bombed out in the real-world as it is actually just another phytoestrogen making male users fat and less masculine.


    Until recently the only well known and statistically effective OTC supplemental anti-aromatase for systemic (whole body) estrogen control was delta-4-10, 13-dimethyl-cyclopenta[a]phenantrene-3,6,17-trione (A.K.A. 4-androstene- 3,6,17-trione) or "AT" for short. (One trade name for it was Aromax© by Applied Lifescience Research Industries Inc.).

    One main concern with the "AT" structure is its potential conversion to the feminizing estrogens 6-keto-estrone and 6-keto-estradiol (Estradiol's of any kind are as much as 10 times more powerful than estrogen's).

    Naturally there is a dose dependant issue here which is a supplemental oxymoron: Low bioavailability means higher dosages needed, that in turn result in greater amounts of AT being converted to the feminizing estrogens 6-keto-estrone and 6-keto-estradiol. Read on, you will understand better...

    Depending upon bodyweight and level of estrogens in a man's body, at 600mg daily AT appears to be reasonably useful, and in truth it was the only viable option for sometime.

    The main limitation for this compound is that it has poor oral bioavailability (the reason for required dosages being above the half gram mark daily), and of course it only aids inhibition of the Estrogen-Negative-Feed-Back-Loop.

    This is not to say that it was not a useful compound. However, the Androgen-Negative-Feed-Back-Loop still remains the main limiting factor.

Key To An Optimization Matrix

There are some very effectual options currently coming to market that have viable research behind them that specifically address both the estrogen-negative-feed-back-loop and the androgen-negative-feed-back-loop on multiple levels.


    6,17-dioxo-etiocholene-3-ol (A.K.A. 3-OHAT) is a natural occurring metabolite of the popular anti-aromatase supplement 4-androstene- 3,6,17-trione (AT) mentioned prior. It possesses a much longer half-life (stays active in the body longer) thus allowing for improved efficiency from a single daily dosage. Additionally it is noted as a non-androgenic aromatase inhibitor. This means that 3-OHAT is an excellent fast-acting long-term destroyer of the testosterone limiting Estrogen-Negative-Feed-Back-Loop...and does not stimulate androgen receptors of the hypothalamus and the Androgen-Negative-Feed-Back-Loop. Studies have shown that even acting alone, 3-OHAT increases HPTA activity resulting in more testosterone production via natural pathways in humans and animals.

ATD & Focus

    3,17-dioxo-etiochol-1,4,6-triene (A.K.A. ATD) has a prolonged affinity for the estrogen mediating aromatase enzyme. In fact, it is actually about 2.8 times more powerful than AT for this reason. So great, it is more powerful than AT and even more powerful than 3-OHAT in a different way. Big deal?

    In vitro studies have shown ATD to be a powerful androgen receptor blocker of the hypothalamus...but not of peripheral androgen receptors. What's this mean in English? It means that ATD blocks the Androgen-Negative-Feed-Back-Loop and aids in decreasing estrogen production while increasing natural testosterone production. (If you are paying attention and focusing a little here, I am sure the real point of this article just hit you)


    There is a need for synergy in anything in life and physiological Action/Reaction Factors are no exception. As you know by stopping Both negative feed back loops, the hypothalamus will produce more GnRH which in turn means that the pituitary will produce more LH/FSH and "The Boy's" will kick out a whole lot of male optimizing testosterone. Sounds good in theory?

    Of course some studies have shown that the correct ratio of 3-OHAT and ATD administered to adult human males results in an average increase in bioavailable testosterone of up to 400% and a direct decrease in estrogens of an average 50%. (No joke!) Up to 4 times the man and half the girl is not a bad natural improvement for a lad.

Okay, But What About The Real World...

I personally do not believe anything I cannot prove myself in the lab. As such we used 8 healthy males as human guinea pigs to test what the research claims to be factual.

4 acted as a placebo base-line group receiving 6 capsules daily of cornstarch, and the other 4 got the real deal consisting of a proprietary 50mg blend of both 3-OHAT and ATD.

During the pre-administration period we tested for Total Testosterone, Free Testosterone and Estradiol, then tested again at 14 and 42 days.


Placebo Group

    No significant changes (Gee, are you surprised?) in total or free testosterone and estradiol.

Subject 1 (24 year old male)


    Total Testosterone: 350ng/dl
    Free Testosterone: 83.00pg/ml
    Estradiol: 39pg/ml

14 Days

    Total Testosterone: 1803ng/dl
    Free Testosterone: 522.20pg/ml
    Estradiol: 27pg/ml

42 Days

    Total Testosterone: 2895ng/dl
    Free Testosterone: 839.20pg/ml
    Estradiol: <20

Total Testosterone,
Free Testosterone & Estradiol

Click To Enlarge.

Subject 2 (33 year old male)


    Total Testosterone: 538ng/dl
    Free Testosterone: 129.0 pg/ml
    Estradiol: 30pg/ml

14 Days

    Total Testosterone: 988ng/dl
    Free Testosterone: 233.0pg/ml
    Estradiol: 22pg/ml

42 Days

    Total Testosterone: 1416ng/dl
    Free Testosterone: 421.3pg/ml
    Estradiol: <20

Total Testosterone,
Free Testosterone & Estradiol

Click To Enlarge.

Subject 3 (25 year old male)


    Total Testosterone: 555ng/dl
    Free Testosterone: 104.00pg/ml
    Estradiol: <20

14 Days

    Total Testosterone: 1624ng/dl
    Free Testosterone: 405.7pg/ml
    Estradiol: <20

42 Days

    Total Testosterone: 1837ng/dl
    Free Testosterone: 547.40pg/ml
    Estradiol: <20

Total Testosterone,
Free Testosterone & Estradiol

Click To Enlarge.

Subject 4 (51 year old male)


    Total Testosterone: 584ng/dl
    Free Testosterone: 13.40ng/dl
    Estradiol: 47pg/ml

14 Days

    Total Testosterone: 851ng/dl
    Free Testosterone: 26.10ng/dl
    Estradiol: <20

42 Days

    Total Testosterone: 875ng/dl
    Free Testosterone: 30.30ng/dl
    Estradiol: <20

Total Testosterone,
Free Testosterone & Estradiol

Click To Enlarge.

Interpreting The Data

    Test results showed a net increase in total and free testosterone ranging from 50-800% with a significant reduction in estradiol of about 50%. More importantly is that the elevation was maintained for a long enough period to allow notable benefits from a physiological stand-point (weeks, not just a few minutes). Huh, go figure, the studies are right.


Testosterone is the anabolic steroid that all other AAS (Anabolic-Androgenic-Steroid) are compared to...and your body can naturally and legally produce far more than you actually need. Most negative side effects come from the use of AAS, not from the excess of natural endogenous testosterone itself.

I would like to see the results from the same test subjects using the 50mg 3-OHAT/ATD proprietary blend with the addition of Agaricus bisporus extract (white button mushroom from a specific region) and 7b-hydroxy-DHEA. The Agaricus bisporus extract because the right method of extract provides some very effective site-specific aromatase enzyme inhibition, and the 7b-Hydroxy-DHEA because it is preferential physiological base compound for many good things. But we will save that for future articles.


  1. Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis. Kaplan ME, McGinnis MY. Department of Anatomy, Mount Sinai School of Medicine, CUNY, New York 10029.

  2. J Clin Endocrinol Metab. 1984 Dec;59(6):1088-96. Related Articles, Links Inhibition of aromatization stimulates luteinizing hormone and testosterone secretion in adult male rhesus monkeys. Ellinwood WE, Hess DL, Roselli CE, Spies HG, Resko JA.

  3. J Steroid Biochem. 1986 Oct;25(4):593-600. Effect of 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A) on the 5 alpha-reduction of androgens in the rat prostate. Motta M, Zoppi S, Brodie AM, Martini L.

  4. Horm Behav. 1989 Mar;23(1):10-26. Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis. Kaplan ME, McGinnis MY. Department of Anatomy, Mount Sinai School of Medicine, CUNY, New York 10029.

  5. Effect of steroid aromatase inhibitors on the catecholamine content of the hypothalamus of neonatally androgenized rats][Article in Russian] Nosenko ND, Reznikov AG.

  6. J Steroid Biochem Mol Biol. 1992 Oct;43(4):281-7.In vitro potency and selectivity of the non-steroidal androgen aromatase inhibitor CGS 16949A compared to steroidal inhibitors in the brain. Wozniak A, Holman SD, Hutchison JB. MRC Neuroendocrine Development and Behaviour Group, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, England.

  7. J Clin Endocrinol Metab. 1993 Dec;77(6):1529-34. Differential effects of aromatase inhibition on luteinizing hormone secretion in intact and castrated male cynomolgus macaques. Resko JA, Connolly PB, Roselli CE, Abdelgadir SE, Choate JV. Department of Physiology, Oregon Health Sciences University, Portland 97201-3098.

  8. J.Steroid Biochem. 1987 Sep;28(3):337-44 Studies on aromatase inhibition with 4-androstene-3.6.17-trione: Its 3-beta reduction and time dependant irreversible binding to aromatase with human placental microsomes. Numazawa M, Tsuji M, Mutsumi A. Tohoku College of Pharmacy, Sendai, Japan.

  9. Biol Reprod. 1994 Dec;51(6):1273-8. Prenatal inhibition of aromatase activity affects luteinizing hormone feedback mechanisms and reproductive behaviors of adult guinea pigs. Choate JV, Resko JA. Department of Physiology, Oregon Health Sciences University, Portland 97201.

  10. Biol Reprod. 2003 Feb;68(2):370-4. Estrogen synthesis in fetal sheep brain: effect of maternal treatment with an aromatase inhibitor. Roselli CE, Resko JA, Stormshak F. Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon 97201-3098, USA. rosellic@ohsu.edu