16 Ways to Fight Gynecomastia

Gynecomastia = Gyno

Most people think the only way to combat gyno is to use Nolvadex or Clomid. Considering the undesirable side-effects of these drugs, I generally don’t prefer these as the first line of defense. I have expressed my concerns about SERM’s in my article – Clomid & Nolvadex – The Dark Side.

In this article I summarize alternative methods for combating the occurrence of gyno. The advice given in this article is the result of over 10 years experience in counseling individuals with AAS induced gyno.

If you have gyno as a result of an endocrine disorder, I advise consulting your doctor before making changes to your prescribed medical regimen.

You Do Not Have Gyno!

During mammary tissue growth (the onset of gyno), you may notice the following symptoms –

  • Puffy or swollen nipples
  • Overly sensitive nipples
  • Itchiness around the nipples

Editorial note: I promise — that is the last time I will ever say nipples.

Now, just because you may have these symptoms does not mean you HAVE GYNO. It simply means that you HAVE GYNO SYMPTOMS. Remember, it is normal to have a small flat pea sized lump under the nipple. This is NOT gyno.

Now, if you allow these above symptoms to progress for several weeks then you may develop gyno. So if you are experiencing any of the above symptoms then you are smart to take action before it’s too late – But please stop emailing me saying you “have gyno” after 3 days on a cycle – this is physiologically impossible.

The good news is that even if you do have a slight case of gyno that you developed from a cycle, it’s probably 100% reversible. Read on…


Gyno Hysteria

No level of gyno is “permanent”. Any level of gyno can be reversed by dietary, supplemental and/or hormonal intervention. Mammary tissue (gyno) can be catabolized like any other tissue in the body. It’s just a matter of creating the right physiological environment within your body. Therefore, as far as I’m concerned, all gyno is temporary or semi-permanent at worse.

Here are the basic levels of gyno –

Level 1 – A dime sized glandular lump – which can emerge as soon as 2-3 weeks after “gyno symptoms” appear. This type of gyno can transform into a more serious level 2 gyno if left untreated for more than 4-6 weeks. In most cases, this initial level 1 gyno disappears once the hormonal environment improves, which is generally 2-3 weeks after the inflicting steroids clear the system.

Level 2 – A quarter sized glandular lump. This type of gyno does not completely disappear on its own, but may gradually shrink to “Level 1” size after discontinuing the inflicting steroids. Completely reversing level 2 gyno requires aggressive dietary and supplemental intervention in conjunction with prescription grade drugs.

Generally, the levels of gyno can be referred to in the following way –

level 1 = temporary

level 2 = semi-permanent

Be warned, if gyno is allowed to grow large enough, the cost of surgery may be more cost efficient than trying to battle the gyno through drug and lifestyle changes – which could otherwise take months or years of intervention.

Following the 16 points below will help you prevent and reverse level 1 & 2 gyno –

The 16 Points

Consider all the following points. Remember, there are many factors that can contribute to gyno and performing just a handful of the points below may be the key to avoiding gyno all together.

1. Your naturally occurring 5a-reduced metabolites are your friends in preventing and reversing gyno. 5a-reduced metabolites include androsterone, androstanedione, androstanediol and dihydrotestosterone (DHT) as the most powerful 5a-reduced hormone. These hormones help prevent gyno by lowering estrogen and blocking the effect of estrogen at the hormone receptor. (1-8) Unless you have serious androgen related hair loss you want to keep your 5a-reduced metabolites relatively high to avoid gyno.

Methods for increasing 5a-reduced metabolites (DHT) are listed in preferred order –

  • Use a DHT pro-hormone such as androsterone, found in AndroHard. This will raise DHT with zero risk of estrogen conversion.
  • Injectable testosterone along with an AI to prevent excessive estrogen conversion.
  • High dose oral 4-DHEA or DHEA along with an AI to prevent excessive estrogen conversion.

2. If you are concerned about gyno, avoid finesteride at all costs. It lowers all 5a-reduced metabolites to undesirable levels and has an extremely long half-life which continues to suppress DHT levels long after discontinuing the drug. (9) Progesterone would be a better anti-DHT alternative if you are concerned with hair loss. Plus, progesterone can clear the system within 24hrs making a mistake in dosing much less risky.

3. Almost all sources of gyno can be linked back to having insufficient levels of 5a-reduced metabolites in the body. In theory, any amount of estrogen/progesterone can be blocked by sufficient DHT. (10-14) Also, high DHT and enlargement of the prostate is a myth, however high estrogen and high DHT can lead to an inflamed prostate, so you want to at least make an effort to keep estrogen in a normal range. (14)

4. Trenbolone, TREN, Nandrolone can cause gyno because they lack a potent 5a-reduced metabolite (dihydronandrolone is weaker than dihydrotestosterone). (15) If you are worried about gyno from progestational steroids you should consider boosting your 5a-reduced metabolites during the cycle (mentioned above). This can avoid most if not all of the gyno problems associated with progestational hormones. I should mention here that aromatase inhibitors alone (AI’s) will not help prevent gyno from progestational compounds. It is the antagonistic action of 5a-reduced hormones that is required.

5. Nothing is going to antagonize estrogen at the estrogen receptor (ER) better than actual DHT. While DHT derivatives or analogs such as Anavar, Winstrol, Masteron, Epistane, Superdrone, ect may be 5a-reduced, they cannot convert to actual DHT and thus cannot directly inhibit gyno at the receptor level (since they lack the ultra-high binding affinity for the AR that true DHT possesses). (16)

6. Natural anti-estrogens (resveratrol, chrysin, I3C, DIM, ect) are great for PCT and can stimulate the HPTA and manage healthy estrogen metabolism, but they are not strong enough to prevent aromatization from high doses of aromatizing steroids. Don’t rely on these to prevent gyno during a cycle.

7. Reducing prolactin will reduce the overall stimulation on mammary growth. Suppressing prolactin is useful as a temporary method to help slow or stop gyno growth. However, continuing anti-prolactin treatment is not recommended to be continued beyond 8 weeks. Methods of suppressing prolactin include –

  • Vitex at 460mg/day
  • Vitamin B6 at 200-400mg/day
  • Mucuna Pruriens (15%-20% L-Dopa) 4-6g/day
  • Increasing DHT may also lower prolactin release (17)

8. Don’t fiddle with your nipples. This increases prolactin release which can make gyno worse.

9. IGF-1, GH, insulin and prolactin are all potent growth factors in gyno growth. Limiting these hormones will reduce the likelihood of experiencing gyno symptoms. “Bulking” (aka., eating-a-shitload-of-everything) will increase most of the growth factors listed above. Cutting calories (especially carbohydrates) will suppress insulin and IGF-1 therefore reducing the overall stimulatory effect on mammary growth. Ketogenic diet = less risk of gyno.

10. Body fat (adipose tissue) is the main site for androgens to convert to estrogens. Therefore, being overweight or having high body fat increases your gyno risk. This is another good reason to go on a cutting cycle if you are gyno prone. Reducing body fat will lower your rate of estrogen conversion from aromatizing steroids. (18)

11. Caffeine consumption can inhibit clearance of estrogen from the liver by competing for the P-450 oxidase system. Avoid caffeine if you are concerned about high estrogen levels.

12. Avoid supplements containing forskolin if concerned about gyno. Forskolin increases aromatase activity via cAMP modulation and can increase formation of estrogen. (23,24)

13. Increasing fiber intake (both soluble and insoluble) can enhance clearance of estrogens from the intestines. Research shows that increasing fiber intake in humans can reduce estrogen levels by up to 22%. (19)

14. Reducing estrogen below the normal range (such as over dosing arimidex, letrozol, aromasin or formestane) can eventually reduce SHBG levels, thus allowing more estrogen to freely circulate (by offsetting it from SHBG). Higher levels of freely circulating estrogen can amplify breast tissue growth (20). SHBG also appears to have anti-estrogenic effects at the cell receptor level. (21, 22) Avoiding over suppression of SHBG will reduce your gyno risk.

15. Don’t be afraid to lower the dose mid cycle. People have a tendency to panic at the first sign of gyno and drop everything. Generally, just lowering the dose of the afflicting steroid can offer gyno relief within 4-5 days.

16. Save SERM’s as your last resort against gyno. You do not need a SERM (tormifene, clomid or nolva) to avoid gyno from a properly planned cycle. If you are still having gyno problems after following the above points, consider the fact that you have a poorly planned cycle and you need to revaluate the compounds you have chosen.

discuss this article in the forum

References –

1. Dihydrotestosterone may inhibit hypothalamo-pituitary-adrenal activity by acting through estrogen receptor in the male mouse.
Lund TD, et al.
Neurosci Lett. 2004 Jul 15;365(1):43-7.

2. Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor.
Szelei J, et al.
Tufts University School of Medicine, Department of Anatomy and Cellular Biology, Boston, Massachusetts 02111, USA.

3. The non-aromatizable androgen, dihydrotestosterone, induces antiestrogenic responses in the rainbow trout.
Shilling AD, et al.
Agricultural and Life Sciences Building, room 1007, Oregon State University, Corvallis, OR 97331, USA.

4. The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus.
Lund TD, et al.
J Neurosci. 2006 Feb 1;26(5):1448-56.

5. Steroid modulation of aromatase activity in human cultured breast carcinoma cells.
Perel E, et al.
J Steroid Biochem. 1988 Apr;29(4):393-9.

6. Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation.
Killinger DW, et al.
Steroids. 1987 Oct-Dec;50(4-6):523-36. Review.

7. The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture.
Perel E, et al
J Clin Endocrinol Metab. 1984 Mar;58(3):467-72.

8. FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens.
Chan WK, et al
J Endocrinol. 1986 Mar;108(3):335-41.

9. The effect of 5 alpha-reductase inhibitors on erectile function.
Canguven O, Burnett AL.
J Androl. 2008 Sep-Oct;29(5):514-23.

10. Comparative Pharmacokinetics of Three Doses of Percutaneous Dihydrotestosterone Gel in Healthy Elderly Men – A Clinical Research Center Study*
C. Wang et al.
Journal of Clinical Endocrinology and Metabolism Vol. 83, No. 8 (1998)

11. Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature.
Benveniste O et al.
Clin Infect Dis. 2001 Sep 15;33(6):891-3.

12. Gynecomastia: effect of prolonged treatment with dihydrotestosterone by the percutaneous route.
Kuhn J et al.
Presse Med 12;21-25. (1983)

13. Percutaneous dihydrotestosterone (DHT) treatment. In: Nieschlag E, Behre HM, eds. Testosterone: action, deficiency substitution.
Schaison G, Nahoul K, Couzinet B.
Berlin: Springer Verlag; 155-164. (1990)

14. Transdermal dihydrotestosterone and treatment of ‘andropause’.
de Lignieres B.
Ann Med 1993;25: 235-41.

15. Metabolism and receptor binding of nandrolone and testosterone under invitro and invivo conditions.
Bergink et al.
Acta Endocrinol Suppl (Copenh). 271:31-7, 1985

16. Pharmacology of Reproduction
David E, et al.
Principles of Pharmacology (second edition) p. 510 (2008)

17. Antagonism of estrogen-induced prolactin release by dihydrotestosterone.
Brann DW, et al.
Biol Reprod. 1989 Jun;40(6):1201-7.

18. Aromatase – a brief overview
Simpson ER, et al
Annu Rev Physiol. 64:93-127, 2002

19. Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: the Multiethnic Cohort Study.
Monroe KR et al.
Nutr Cancer. 2007;58(2):127-35.

20. Williams Textbook of Endocrinology.
Wilson, et al.
9th ED. Philadelphia: Saunders, 1997

21. Sex steroid binding protein receptor (SBP-R) is related to a reduced proliferation rate in human breast cancer.
Catalano MG, et al.
Breast Cancer Res Treat. 42(3):227-34, 1997

22. Biological relevance of the interaction between sex steroid binding protein and its specific receptor of MCF-7 cells under SBP and estradiol treatment.
Fissore F, et al.
Steroids, 59(11):661-7, 1994

23. Progestin-dependent effect of forskolin on human endometrial aromatase activity.
Tseng L, Malbon CC, Lane B, Kaplan C, Mazella J, Dahler H, Tseng A.
Hum Reprod. 1987 Jul;2(5):371-7.

24. Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R.
Watanabe M, Nakajin S.
J Endocrinol. 2004 Jan;180(1):125-33.

Transdermal Steroids – Expanded

If there is one topic that is misunderstood in the steroid community, it’s Transdermal Steroids (TS’s). The value of TS’s are under-estimated, and the science has been over looked by the vast majority. In this article, I intend to shed some light on TS’s and introduce a few new transdermal options that can offer benefits to athletes, bodybuilders and HRT patients alike.

As a developer of several transdermal products, and a counselor to a number of TRT patients; I’ve learned that a majority of men consider Androgel™ and Testim™ the only real viable topical hormones. This makes sense, being they are the most popular FDA approved testosterone gels currently available. However, there are more options to be considered. Steroid hormones such as nandrolone and boldenone offer useful advantages when delivered topically. Legal prohormones such as DHEA and pregnenolone can also offer great benefits when used topically (Found in Dermacrine). One benefit with all TS’s is their quick clearance from the body (generally less than 72hrs for most hormones). This is advantageous for PCT, when the quick clearance of hormones is desired (often a problem with long-acting injectable steroids which may take months to clear the system.)

Before we review some of the alternatives to testosterone gel, let’s take a quick look at some basic rules so we can have a better understanding of how we can manipulate the hormonal effects for our best interest.

Application site –

The site of application is one way to maximize the effectiveness of our topical hormones, while also altering the action the hormone has on the body. For instance, the skin on the front of the neck is thin and very vascular, making it ideal for systemic transdermal delivery. The skin on the shoulders and upper back – areas where you may have had acne as a teenager — are highly concentrated with steroidogenic enzymes such as 3b HSD and 17a HSD. These are the enzymes required to make hormonal conversions, such as DHEA > androstenediol > testosterone. On the flip side, the stomach area tends to carry a higher amount of the aromatase enzyme, especially if you’re prone to holding fat in the abdominal region. This would be an area to avoid applying testosterone gel, since the increased aromatase activity could increase the conversion to estrogen.

One area which can be advantageous to use for topical application is the scrotal skin. This area is extremely thin and easily penetrated by topical ingredients for systemic delivery. In fact, its absorption rate is about 4-5x more than anywhere else on the body. (1,2) This makes it the perfect spot for the delivery of topical ingredients, giving you more bank for the buck.

One thing to be aware of with scrotal applications is the higher conversion rate to DHT when applying testosterone to this area. There is heavier conversion to DHT because the scrotal skin carries a high concentration of the 5a-reductase enzyme. When the testosterone travels through the scrotal skin it interacts with the 5a-reductase enzyme and converts to DHT. This gives you a significant spike in DHT when you apply testosterone cream to your scrotum, which may or may not be a good thing. (see below for alternatives to testosterone and how to avoid the DHT)

An enlarged or irritated prostate is generally a symptom associated with high DHT. However, the DHT may not be entirely to blame. In fact, research has shown that topical DHT treatment can actually keep the prostate healthy and even reduce its size, as long as estrogen levels are also kept in control. (3,4) Plus, DHT is an antagonist of estrogen, so it’s going to help reduce gyno (male breasts) and water retention, while it also increase libido and erectile function. It could even be argued that DHT is more critical to a man’s well-being than testosterone.

Unfortunately, DHT can increase hair loss if you’re genetically prone to it, although this could be prevented if DHT levels are kept in range, bringing us to the next topic – the progesterone/DHT relationship. That’s right, progesterone can be healthy for a male too.

The word progesterone may sound frightening to some since it’s primarily known as a female hormone. However, it also offers health benefits for the male if used in very low and controlled amounts. You see, progesterone can naturally inhibit the conversion of testosterone to DHT thus helping to keep DHT in a healthy range (similar to finasteride albeit to a lesser degree). So how does this apply to real life?

Well, pregnenolone cream is legal and readily available in most counties, and as it passes the skin, pregnenolone readily interacts with the skins enzymes (3b HSD) and makes partial conversion to progesterone. (The reason for applying pregnenolone rather than strait progesterone is the added cognitive enhancements of pregnenolone.) In most cases, a 10-20mg application of pregnenolone cream would convert to sufficient amounts of progesterone to control DHT conversion from testosterone supplementation. (given via IM or topically)

If for whatever reason you don’t want to deal with combating DHT, or are extremely sensitive to its hair loss effects, you may want to consider using nandrolone or boldenone for topical application as alternatives to testosterone. If you’re lucky enough to have access to nandrolone or boldenone base powder, they are easily compounded into a topical and are perfect for transdermal delivery. These hormones are gentler on the hairline because they don’t convert to DHT. More specifically, when they interact with the 5a-reductase enzyme, they are converted to a less powerful 5a-reduced steroid, thus being ‘gentler’ than testosterone. Note: Nandrolone (Deca) can be a double edged sword given that it lacks a powerful 5a-reduced metabolite. It’s beneficial for preventing hair loss, but notorious for erectile dysfunction causes known as “Deca Dick”.

If you’re interested in staying legal and you don’t have access to AAS’s such as testosterone, nandrolone or boldenone, then DHEA is an excellent legal alternative, especially when used as a transdermal. When taken as a transdermal, DHEA is absorbed about 10x better than when taken orally. (5) Plus there is the additional benefit of increased metabolic conversion of hormones when they are taken through the skin. (6) As mentioned earlier, the shoulder and upper back skin have the highest concentration of enzymes required to make hormonal conversions (3b HSD & 17b HSD). Since DHEA is an immediate precursor to several anabolic hormones, the topical application of DHEA can cause a sharp rise in androstenediol, androstenedione and testosterone within a few hours of application. (These are the primary hormones that make Dermacrine so effective)

Remember, no matter what hormones you choose, be aware of moderation and balance.



1. Hypogonadal impotence treated by transdermal testosterone.
McClure RD et al. Urology 1991;37:224-8.

2. Testoderm TTS, Testoderm, and Testoderm with
adhesive [package inserts]. Mountain View, Calif: Alza Pharmaceuticals, 1998.

3. Percutaneous dihydrotestosterone (DHT) treatment. In: Nieschlag E, Behre HM, eds. Testosterone: action, deficiency substitution.
Schaison G, et al Berlin: Springer Verlag; 155-164. (1990)

4. Transdermal dihydrotestosterone and treatment of “andropause”.
de Lignieres B. Ann Med 1993;25: 235-41.

5. High bioavailability of dehydroepiandrosterone administered percutaneously in the rat C Labrie, M Flamand, A Belanger, et al. Endocrinol., Sep 1996; 150: S107 – S118.

6. The in vitro metabolism of dehydroepiandrosterone in human skin.
I Faredin, et al. Med Acad Sci Hung, Jan 1967; 23(2): 169-79.

Clomid & Nolvadex – The Dark Side

Preface – Over the past 15 years, the use of Clomid and Nolvadex, as Selective Estrogen Receptor Modulators (SERMs) has become a staple in the Hormone Replacement Therapy (HRT) and bodybuilding communities.

The popularity of these drugs stems from the popular advice to use these drugs for everything from testosterone recovery, bloat reduction, to gyno prevention. In many communities SERMs have become akin to vitamins — vitamins that can do no wrong and provide seemingly endless benefits.

This article is not intended to examine the proper use or possible applications of Clomid or Nolvadex. Instead, we will be exploring the historical development of these drugs, the short-term side-effects and long-term consequences.

As I will illustrate, these drugs are truly dangerous to men’s health.

Synthetic estrogens, the beginning –

It was the 1930s and there was a new age of hormone-dependant pathologies on the rise. Scientists were eager to determine the structural requirements of estrogen for new drug design.Diphenylethane

In 1937 Sir Charles Dodd of the Middlesex Hospital of London found estrogenic activity in a molecule with two benzene rings linked together via a short carbon chain (e.g., diphenylethane). (1) Soon thereafter, a synthetic, non-steroidal estrogen known as diethylstilboestrol (DES) was created from this basic molecular backbone. (1) By 1941, DES was an FDA approved drug, and by the 1950s, DES gained widespread popularity as the drug of choice for menopausal symptoms, cancer treatment, and prevention of miscarriages. (2)Diethylstilboestrol

DES sparked the interest of ambitious drug manufactures who saw this synthetic molecule as a potential “molecular backbone” which could be tailored for estrogenic activity, and patented for maximum profit.

Within months, a research group from the University of Edinburgh found that the addition of a benzene ring to the original diphenylethane structure created somewhat of an anti-estrogen known as triphenylethylene. (1) Although it had very weak estrogenic activity, it was called an anti-estrogen because it competed with the body’s more powerful estradiol for the ER receptors.

Although the complex estrogenic action of triphenylethylene was not fully understood, it was considered the perfect molecular platform for future drug development because of its high oral bioavailability and extended half-Triphenylethylenelife due to its lipophilicity (fat solubility). As it was later discovered, the estrogenic action could be manipulated with structural modifications for more specific agonist/antagonist actions. (3) Despite the lack of understanding of its many physiological effects, triphenylethylene would become the molecular backbone for generations of SERMs to come.

By the early 1940s, the world’s largest chemical manufacturers, including Imperial Chemical Industries (ICI), got word of the triphenylethylene development, and seized the opportunity to expand this new class of compounds. By the 1950s, the synthesis of new triphenylethylene based molecules had begun picking up momentum, as the first FDA approved SERMs started appearing on the market.

One of the first was Triparanol, which was sold as a cholesterol lowering SERM, until it was eventually pulled from the market in the 1950s for causing cataracts in patients. (7) Later, Ethamoxytriphetol (MER-25) was discovered and found to be a reliable contraceptive and anti-cancer agent in rats, but failed in humans due to the drug’s severe toxicity and stimulation of “acute psychotic episodes”. (6)

Despite these early warning signs, development continued.

Among one of the newer SERMs to appear in the late 1950s, was a mixture of two stereoisomers — zuclomiphene and enclomiphene — both having unique estrogenic and anti-estrogen actions. This mixture was collectively called clomiphene, and later marketed as Clomid.


Then, in 1962, ICI synthesized ICI-46474, another mixture of a trans and cis isomers with mixed estrogenic and anti-estrogenic activity. (7) Ultimately, the trans isomer was found to be the predominate anti-estrogen, which was isolated and eventually named tamoxifen, and later marketed as Nolvadex.

Originally, ICI pushed these new SERMs to market as a “morning after” contraceptives, which were eventually approved by the FDA. (4) Yet again, the profit hungry and presumptuous drug manufacturer based its findings on rat studies, which would prove to be a mistake upon subsequent human research that showed the SERMs induced, rather than inhibited ovulation. (4) Needless to say, tamoxifen was withdrawn as a contraceptive.

And remember DES, the original synthetic estrogen developed back in the 1930s? As it turned out, DES was found to increase the risk of breast cancer by 50%. Further research linked DES to millions of vaginal and testicular cancers among the children of mothers who took DES during pregnancy. (2, 5)

The light on synthetic anti-estrogens was dim, and by the late 1960s, there was little enthusiasm to continue R&D with triphenylethylene based SERMs, especially considering their inherently toxic effects (7, 10)

It wasn’t until 1971, that tamoxifen would be dug up from the dead and considered as a candidate for cancer treatment.

Treating cancer with a carcinogen –

When research is done on anti-cancer drugs (such as SERMs), the aim is to find a drug that prolongs life, with the least amount of acute side-effects. In other words, the goal isn’t so much about finding a cure, as it is finding something that can alleviate the symptoms and/or prolong life. Tamoxifen

For an estrogen dependant cancer, the idea was simple – Block the proliferative action of estrogen with an anti-estrogen and slow the cancer growth. What could be more appropriate than an already available, orally active, patentable synthetic estrogen such as tamoxifen? It was a practical shoo-in.

Therefore, in 1971, when drug researchers decided to examine all of the historical anti-cancer SERM data, they found that all of the SERMs showed anti-proliferative activity on estrogen dependant cancer, and all of them demonstrated some extent of toxicity. (10, 37-39) However, the SERM that happened to show the least amount of toxicity was tamoxifen. (clomiphene missed the mark by showing a high rate of cataract formation)

At the time, Pierre Blais, a well known drug researcher, commented on the finding (5) –

“Tamoxifen is a garbage drug that made it to the top of the scrap heap. It is a DES in the making.”

In spite of the criticism from a number of researchers, the FDA approved tamoxifen as a cancer treatment in 1977, and in 1985 ICI was awarded a US patent for tamoxifen in the treatment of breast cancer. (5) Soon, tamoxifen would become the most popularly prescribed cancer drug.

“Its FDA approved for cancer treatment. It must be safe!”

It’s wrong to assume that an “FDA approved” drug has a proven safety profile. The FDA has continually issued stronger health warnings for tamoxifen over the years. For instance, in 1994 the FDA demanded that the tamoxifen manufacturer Zeneca (an ICI sub-division), issue warning letters to health care practitioners about the increased risk of endometrial and gastro-intestinal cancers with tamoxifen use. Zeneca also reported adverse effects similar to those seen with DES, such as reproductive abnormalities in the animals whose mothers received tamoxifen. (remember, DES was the original synthetic estrogen, and also an analog to tamoxifen)

A number of cancer researchers have pointed out the health risks too, such as Elwood et al (6) –

“[Tamoxifen], therefore, is not appropriate for use in the general population because of the known increased risk of endometrial cancer”

“So why is tamoxifen the most popularly prescribed cancer drug, if it’s so toxic?”

The answer is simple. Tamoxifen is the lesser of two evils.

Tamoxifen remains the most popularly prescribed drug because it is one of the few drugs that has shown a “statistically significant” improvement of the survival rate of breast cancer patients.* (Not to mention, tremendous financial motives for its patent holder, Zeneca)

Remember, the goal in cancer treatment is to prolong life — even if it means committing to therapy that is potentially cancerous or injurious to future health (as confirmed in long-term follow ups and close examinations of tamoxifen patients).

So, perhaps the risks are worthy for the cancer patient, but are they worthy for the health conscious male?

* Most research has shown tamoxifen to improve the survival rate by 4-14%. For instance, over a 5 year period, 74% of the women survived who used tamoxifen, compared to 70% of the women on placebo. Depending on the type of cancer, this may translate into an extra 2-3 years of life for a cancer patient. (9) Continuing tamoxifen therapy for more than 5 years, results in increased tumor recurrences and serious side effects. (8)

Translating the science, for men’s health –

Fast forward 30 years, through hundreds of human and animal trials, and we find that the research is quite extensive, and contradicting. (21)

The damaging evidence from many early rat studies showed severely toxic effects, including the development of cancer in the liver, uterus, or testes upon tamoxifen administration. (30-34,41) However, this evidence was largely disregarded by further test tube studies on human cell-lines which appeared to show a lack of toxic effects. (21)

This misleading test tube data gave the green flag to perform large scale human studies with tamoxifen in the 80s and 90s. Even more misleading, the majority of the human research described tamoxifen as having a “low incidence of troublesome side effects” and that the “side effects where usually trivial”. (22)

As science would uncover, the lack of human toxicity reported in original tamoxifen research was a result of insufficient study duration, inability to detect low level DNA damage with insensitive methodologies, and/or misdiagnosis of collateral cancers as metastases from the breast cancer itself. (15, 21, 28-34)

A word on clomiphene (Clomid) –

Clomiphene (Clomid) consists of two stereoisomers which possess radically different pharmacodynamics. Zuclomiphene has predominantly estrogenic effects and slow clearance while the enclomiphene isomer has predominately anti-estrogenic effects and quick clearance. (9) This creates a divergent effects between estrogen blockage and estrogen stimulation and an acute imbalance once Clomid administration is discontinued. Bodybuilders will often complain of “estrogenic rebound” after stopping Clomid, which could be attributed to the lingering estrogenic isomer zuclomiphene as the anti-estrogenic enclomiphene has long cleared the system. (Recently, enclomiphene has been isolated by the pharmaceutical company Repros, for use in Androxal™.)

For all intents and purposes, tamoxifen is a superior SERM, simply for the fact that tamoxifen provides a purely anti-estrogenic isomer, whereas Clomid provides a mix of anti and pro estrogenic effects.

In regards to the health consequences about to be listed, it can be safely assumed that Clomid will share similar detrimental effects as tamoxifen, since it shares the same triphenylethylene backbone and carcinogenic tendencies. (44,45,57,58)

Liver cancer –

Originally, tamoxifen was accepted as being non-toxic to the human liver upon finding that tamoxifen did not cause noticeable liver damage (DNA adducts) during short-term test tube studies with human liver cells. (35,36)

However, it became apparent that test tube research was largely flawed due to the low rate of metabolism in such a superficial environment. (21) It was soon discovered that the hepatotoxic effects from tamoxifen stem from the metabolism and buildup of the a-hydroxytamoxifen and N-desmethyltamoxifen metabolites, which would only appear in an in vivo environment. (15) Surely enough, the results from the original rat studies showing dramatic carcinogenic effects on the liver, (30-34, 41) soon correlated with human data when researchers found the same type of liver DNA adducts in tamoxifen patients. (15, 28-34)

More recent human research has reported tamoxifen treated women to have 3x the risk of developing fatty liver disease, which occurs as soon as 3 months into therapy at only 20mg/day. (24-26) In some cases, the disease lasts up to 3 years, despite cessation of tamoxifen therapy. Five and ten year follow-ups with patients on long term tamoxifen therapy show cases of deadly hepatocellular carcinoma. (27-29)

In 2002, a bizarre study examined the use of tamoxifen for hepatocellular carcinoma treatment in humans. It was assumed that since tamoxifen could inhibit proliferation of breast cancer, it could offer the same benefit for liver cancer. The devastating results could not have been more indicative of tamoxifen’s hepatotoxic nature, as the tamoxifen treatment significantly increased the rate of death, compared to the group not receiving tamoxifen. (14)

Finally, in a case study reviewing tamoxifen induced liver disease; D.F Moffat et al made a profound statement –

“Hepatocellular carcinoma in tamoxifen treated patients may be under-reported since there may be reluctance to biopsy liver tumours which are assumed to be secondary carcinoma of the breast.”

In other words, it appears that liver carcinomas from a large number of breast cancer patients on tamoxifen therapy have been misdiagnosed as an infection from the breast cancer itself. (28)

Although tamoxifen induced liver cancer may take years to manifest in a healthy male, its damaging effects could easily be exaggerated by other popular hepatotoxic drugs, such as 17aa oral steroids. (15)

Prostate cancer –

In 1996, the International Agency for Research on Cancer (IARC) concluded that tamoxifen clearly promotes uterine cancer in humans – at a standard 20mg/day dose. (16,23,42) This is due to tamoxifen acting as an estrogen agonist in the uterus, presumably from the 4-hydroxytamoxifen metabolite, which triggers abnormal growth of the uterus and the formation of cancer causing DNA adducts. (33, 40)

Contrary to popular thought, these implications are quite scary for a male when we realize the male equivalent to the uterus is the prostate – which differentiates from the same embryonic cell line, shares the same oncogene, Bcl-2, and high concentration of estrogen receptors. In fact, there is no reason to assume that tamoxifen would not initiate the same cancerous growth in the prostate. (60-62) It is no wonder that tamoxifen failed as a treatment for prostate carcinoma. (43)

Note: This same risk would be applicable to Clomid, which has also been linked to uterine cancer and ovarian hyper-stimulation. (18, 19, 57, 59)

Libido reduction & erectile dysfunction –

Erectile dysfunction, low libido, and general impotence are typical complaints from men recently discontinuing steroids or HRT therapy, which is often combated by Clomid or Nolvadex, paradoxically so.

Regardless of any positive effects on fertility or testosterone levels, Clomid and Nolvadex use is highly correlated with erectile dysfunction, libido suppression, and even emotional disorders. (10,47)

Research with male breast cancer patients has also reported decreased libido, and thrombosis associated with tamoxifen use. (47) The thrombotic effect (blood vessel clogging) could explain the mechanism by which SERMs may inhibit erectile function, by reducing circulation to erectile tissue. (47, 52)

Increased susceptibility to gyno –

Tamoxifen is often used to combat gyno during cycle when “flare ups” occur. While tamoxifen may provide immediate inhibition of proliferation, and serve as valuable tool, it can actually increase future susceptibility to gyno.

This is caused by tamoxifen’s ability to up-regulate the progesterone receptor. (54-56) This can dramatically increase the chances of developing gyno in future cycles when utilizing progestin based anabolics such as Nandrolone (Deca) or Trenbolone (or any pro-hormone acting upon the progesterone receptor).

It is interesting to speculate. Is tamoxifen use directly related to the increased gyno occurrences seen with modern day steroid users?

Ocular toxicity –

Another possible side effect associated with SERMs is visual cloudiness, loss of vision and even cataract formation. Although this tends to be a more common side effect from high dosed SERM therapy, standard 20mg/day tamoxifen regimes have been reported to cause these symptoms of ocular toxicity. (17, 46)

Newer SERMs –

As the medical community became more aware of the side-effects associated with tamoxifen treatment, newer and safer SERMs, such as toremifene and raloxifene hit the developmental fast track. Toremifene appears to be less liver toxic, but it is a closely related analog of tamoxifen, so it also carries many of the related genotoxic effects. (48,49) Raloxifene

Raloxifene is a newer SERM based on a benzothiophene structure, which appears to make it less toxic in the liver, uterus or prostate. (50-52) Unfortunately, Raloxifene has been associated with a higher incidence of thromboembolism (52), and also has very low oral absorption, making it an expensive alternative at a typical dose (120mg/day). (53) Still, Raloxifene could presumably be equally effective as Clomid or Nolvadex at restoring HPTA function, while imparting fewer side effects. (53)

Newer SERMs are already being evaluated such as bazedoxifene, arzoxifene, and lasofoxifene, in hopes of reducing risk even further. (This further underscores the evidence of toxicity with the tamoxifen generation of SERMs)

What to do now?

Firstly, it should become a priority to create awareness about the possible side effects of SERMs. Once educated, users will be able to start reducing their use of these drugs, and begin adopting healthier, more responsible alternatives.

Carefully planned cycles, and the proper use of aromatase inhibitors (AIs) should prevail over haphazard combinations of excessive doses of aromatizing AASs — which require high doses of SERMs to reduce possible side-effects. Whereas avoiding SERMs in HRT will involve the natural clearance and management of endogenous estrogens.

It is important to maintain testicular function during a cycle for a quick and efficient recovery of natural testosterone production for PCT – negating the need for high dose 2-3 month SERM based PCT’s. (For more information on the proper use of hCG during cycle, visit here)

Thus, abolishing the bad habit of SERMing calls for community wide enlightenment with careful, comprehensive sharing and planning of worthy alternatives.

discuss this article in the forum

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32. Antiestrogens and the formation of DNA damage in rats: a comparison.
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HCG – Unraveled

Post-Cycle-Therapy is a must upon cessation of steroid use. Many great Post Cycle Therapy protocols have been outlined over the years, and many individuals have had success with following such protocols. Nevertheless, what works can always work better, and I intend to show you the most effective way to recover from AAS. This is especially the case for those that have had a lack of success following popular advice. In this article I will address the misunderstanding and misuse of Human Chorionic Gonadotropin (hCG) and show you the most efficient way to use hCG for the fastest and most complete recovery.

HCG unraveled –

Human Chorionic Gonadotropin (hCG) is a peptide hormone that mimics the action of luteinizing hormone (LH). LH is the hormone that stimulates the testes to increase testosterone levels. (1) More specifically LH is the primary signal sent from the pituitary to the testes, which stimulates the leydig cells within the testes to produce testosterone.

When steroids are administered, LH levels rapidly decline. The absence of an LH signal from the pituitary causes the testes to stop producing testosterone, which causes rapid onset of testicular degeneration. The testicular degeneration begins with a reduction of leydig cell volume, and is then followed by rapid reductions in intra-testicular testosterone (ITT), peroxisomes, and Insulin-like factor 3 (INSL3) – All important bio-markers and factors for proper testicular function and testosterone production. (2-6,19) However, this degeneration can be prevented by a small maintenance dose of hCG ran throughout the cycle. Unfortunately, most steroid users have been engrained to believe that hCG should be used after a cycle, during Post-Cycle-Therapy. Upon reviewing the science and basic endocrinology you will see that a faster and more complete recovery is possible if hCG is ran during a cycle.

Firstly, we must understand the clinical history of hCG to understand its purpose and its most efficient application. Many popular “steroid profiles” advocate using hCG at a dose of 2500-5000iu once or twice a week. These were the kind of dosages used in the historical (1960’s) hCG studies for hypogonadal men who had reduced testicular sensitivity due to prolonged LH deficiency. (21,22) A prolonged LH deficiency causes the testes to desensitize, requiring a higher hCG dose for ample stimulation. In men with normal LH levels and normal testicular sensitivity, the maximum increase of testosterone is seen from a dose of only 250iu, with minimal increases obtained from 500iu or even 5000iu. (2,11) (It appears the testes maximum secretion of testosterone is about 140% above their normal capacity.) (12-18) If you have allowed your testes to desensitize over the length of a typical steroid cycle, (8-16 weeks) then you would require a higher dose to elicit a response in an attempt to restore normal testicular size and function – but there is cost to this, and a high probability that you won’t regain full testicular function.

One term that is critical to understand is testosterone secretion capacity which is synonymous to testicular sensitivity. This is the amount of testosterone your testes can produce from any given level of LH or hCG stimulation. Therefore, if you have reduced testosterone secretion capacity (reduced testicular sensitivity), it will take more LH or hCG stimulation to produce the same result as if you had normal testosterone secretion capacity. If you reduce your testosterone secretion capacity too much, then no amount of LH or hCG stimulation will trigger natural testosterone production – and this leads to permanently reduced testosterone production. (recovering full testosterone production is a topic for another article)

To get an idea of how quickly you can reduce your testosterone secretion capacity from your average steroid cycle, consider this: LH levels are rapidly decreased by the 2nd day of steroid administration. (2,9,10) By shutting down the LH signal and allowing the testis to be non-functional over a 12-16 week period, leydig cell volume decreases 90%, ITT decreases 94%, INSL3 decreases 95%, while the capacity to secrete testosterone decreases as much as 98%. (2-6)

Note: visually analyzing testes size is a poor method of judging your actual testicular function, since testicular size is not directly related to the ability to secrete testosterone. (4) This is because the leydig cells, which are the primary sites of testosterone secretion, only make up about 10% of the total testicular volume. Therefore, when the testes may only appear 5-10% smaller, the testes ability to secrete testosterone upon LH or hCG stimulation can actually be significantly reduced to 98% of their normal production. (3-5) So do not judge how “shutdown” you are by testicular size!

The decreased testosterone secretion capacity caused by steroid use was well demonstrated in a study on power athletes who used steroids for 16 weeks, and were then administered 4500iu hCG post cycle. It was found that the steroid users were about 20 times less responsive to hCG, when compared to normal men who did not use steroids. (8) In other words, their testosterone secretion capacity was dramatically reduced because they did not receive an LH signal for 16 weeks. The testes essentially became desensitized and crippled. Case studies with steroid using patients show that aggressive long-term treatment with hCG at dosages as high as 10,000iu E3D for 12 weeks were unable to return full testicular size. (7) Another study with men using low dose steroids for 6 weeks showed unsuccessful return of Insulin-like factor-3 (INSL3) concentration in the testes upon 5000iu/wk of HCG treatment for 12 weeks (6) (INSL3 is an important biomarker for testosterone production potential and sperm production) 20

In light of the above evidence, it becomes obvious that we must take preventative measures to avoid this testicular degeneration. We must protect our testicular sensitivity. Besides, with hCG being so readily available, and such a painless shot, it makes you wonder why anyone wouldn’t use it on cycle.

Based on studies with normal men using steroids, 100iu HCG administered everyday was enough to preserve full testicular function and ITT levels, without causing desensitization typically associated with higher doses of hCG. (2) It is important that low-dose hCG is started before testicular sensitivity is reduced, which appears to rapidly manifest within the first 2-3 weeks of steroid use. Also, it’s important to discontinue the hCG before you start Post-Cycle-Therapy so your leydig cells are given a chance to re-sensitize to your body’s own LH production. (To help further enhance testicular sensitivity, the dietary supplement Toco-8 may be used)

Based off the above information, an optimal dose of hCG during the cycle would be 250iu every 4 days, or as a less desirable alternative, once a week shot of 500iu. Keep in mind, that the half-life of hCG is 3-4 days, while the half-life of LH is only 1-2 hours. Considering this difference in excretion time, it is best to space each dose of hCG at least 4 days apart for the optimal “peak and valley” replication. However, going more than 7 days between each hCG shot may promote increase the rate of desensitization from lack of LH or hCG stimulation.

If you are starting hCG late in the cycle, one could calculate a rough estimate for their required hCG “kick starting” dosage by multiplying 40iu x days of LH absence. (ie. 40iu x 60 days = 2400iu HCG dose) Remember, since the testes will be desensitized later in a cycle, you will require a higher dose. Also, the maximum daily dose of hCG should not exceed 5000iu, and 4-7 days must be taken off between each shot. Generally, a higher dose will require a longer off period between each shot. (eg., 2500iu = 7 days between each shot)

Note: If following the on cycle hCG protocol, hCG should NOT be used for PCT.


For preservation of testicular sensitivity, use 250iu every 4 days starting 14 days after your first AAS dose. At the end of the cycle, drop the hCG two weeks before the AAS clear the system. For example, you would drop hCG about the same time as your last Testosterone Enanthate shot. Or, if you are ending the cycle with orals, you would drop the hCG about 10 days before your last oral dose. This will allow for a sudden and even clearance in hormone levels. This will initiate a strong LH and FSH surge from the pituitary, to begin stimulating your testes to produce testosterone. Remember, recovery doesn’t begin until you are off hCG since your body will not release its own LH until the hCG has cleared the system.

In conclusion, we have learned that utilizing hCG during a steroid cycle will significantly prevent testicular degeneration. This helps create a seamless transition from “on cycle” to “off cycle” thus avoiding the post cycle crash.

References –

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15. The aging Leydig cell III Gonadotropin stimulation in men.
Nankin HR, et al. 1981
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16. Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin.
Harman SM, et al. 1980
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17. Prolonged biphasic response of plasma testosterone to single intramuscular injections of human chorionic gonadotropin.
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Opioid Modulation for Preventing AAS Induced HPTA Suppression.

Suppression of the HPTA (Hypothalamus, Pituitary, Testicular Axis) is seemingly unavoidable during a steroid cycle. What I will be presenting in this article is a new idea to the world of AAS users. This exciting new concept addresses the possibility of limiting and possibly preventing suppression of the (HPTA) during cycle. More specifically, I will show you how to actively modulate the hypothalamus & pituitary pulse generator during cycle and how this can prime our endocrine system for a quicker, smarter, and healthier recovery from anabolic androgenic steroids (AAS).

For a moment, let’s forget the concept of “post cycle therapy”, and embrace the idea of “on cycle therapy” – active therapy throughout a steroid cycle. The HPTA involves a constant biological interplay of responses and feedback loops that can ultimately become shutdown and degraded during AAS administration. However, research suggests suppression of the hypothalamus and pituitary may be preventable during steroid use. Before we delve into the details, lets first take a quick recap on the HTPA and how it responses to AAS.

HPTA ñ The basics

When the hypothalamus senses low hormone levels, it secretes gonandotropin releasing hormone (GnRH). This GnRH then travels a short distance to the nearby pituitary gland to stimulate the release of the gonadotrophins — luteinizing hormone (LH) and follicle stimulating hormone (FSH). These gonadotrophins travel all the way down to the testes, to activate their respective leydig and seritoli cells. LH initiates testosterone production by stimulating the leydig cell receptor (steroidogenesis), while FSH initiates sperm production by stimulating the sertoli cell receptor (spermatogenesis).

AAS’s inhibit hormone production just as your body’s own hormones do. Testosterone interacts with the androgen receptor (AR) and estrogen interacts with the estrogen receptor (ER). When these hormones are in high concentration, they cause the hypothalamus to decrease its release of GnRH, which decreases LH and FSH production from the pituitary. (1) This cuts off the signal to the testis and halts all hormone production. This process is a daily event for the rhythmic endocrine system. Spikes in LH & FSH are followed by spikes in testosterone, and spikes in testosterone result in a reduction of LH & FSH release until testosterone levels decline and LH & FSH is released again. The caveat with most steroids, is that hormone levels remain chronically high (24/7) and do not allow release of LH or FSH, thus leaving the pituitary and testis in a dormant state for as long as the steroids are administered.

While low-dose on-cycle hCG is a good protocol to mimic LH and keep the testes from atrophy, (discussed here) it won’t help prevent pituitary atrophy. We forget that the pituitary is susceptible to the same degradation and atrophy as the testes. That is, when the GnRH secretion from the hypothalamus stops (during a steroid cycle), the pituitary reduces its number of GnRH receptors and becomes less and less responsive to GnRH stimulation as time goes on. (11) This is analogous to atrophy of the testis, during absence of an LH or FSH signal. On the other hand, both the pituitary and testis will decrease receptor concentration during over stimulation as well, as its been found from too much hCG use or too much GnRH stimulation.(12,13) The point here, is that only minor stimulus is required for the preservation of sensitivity in the endocrine organs. Perhaps a completely neglected and suppressed pituitary (or testes) may explain the lack of full and prompt recovery for many steroid users, despite adherence to a “tried and true” PCT regimen. So the question is ñ How can we prevent suppression of the testes, and better yet, how can we prevent suppression of the pituitary?

A closer look ñ

There are several ways that steroids can inhibit LH & FSH release from the pituitary based on the receptors they occupy, and this is important to understand if you plan on blocking AAS induced suppression. For instance, it appears that AAS which bind strictly to the AR only inhibit LH & FSH release by suppressing GnRH release from the hypothalamus (ie Primobolan, Proviron, Anavar or Masteron). (34,37,39) However, AAS which possess estrogenic (ER) or progestogenic (PR) activity inhibit LH & FSH by directly down-regulating the GnRH receptors on the pituitary, while also reducing GnRH release from the hypothalamus. (35,38) Therefore, progestin based AAS such as trenbolone and nandrolone are “double suppressive” because they are binding to the AR and PR and suppressing LH & FSH by two different mechanisms. (36) The same can be said for steroids that aromatize, such as testosterone or methandrostenolone since they can activate both AR and ER receptors.

Evidence suggests that estradiol is about 200x more suppressive than testosterone on a molar basis (37), and that administration of Arimidex can greatly reduce testosterone’s suppression of LH release. (42) However, since progesterone based AAS’s such as nandrolone and trenbolone are inherently progestogenic based on their hormone structure, there is no way to prevent them from activating the PR. Therefore, it’s virtually pointless to try to block the suppression from progestin based anabolics. However, we can block suppression from the ER by using either non-aromatizing AAS’s or aromatase inhibitors. So this now leaves us with suppression of LH & FSH via the AR, but this suppression can be blocked, and that’s exactly what I’m going to show you.

When it comes to suppression of the hypothalamus, there is more than a simple on/off switch for the hypothalamus control center. Evidence suggests that there isn’t even a direct AR or ER receptor on GnRH secreting neurons. (2-6) Meaning, steroid hormones do not directly influence GnRH release from the hypothalamus, but actually communicate through an intermediary. (7)

It was well summarized here by A. J Tilbrook et al,

“It follows, that the actions of testicular steroids on GnRH neurons must be mediated via neuronal systems that are responsive to steroids and influence the activity of GnRH neurons.”

And again here by FJ Hayes et al,

“It was thus postulated that estrogen-receptive neurons were acting as intermediaries in the non-genomic regulation of GnRH by estrogen”

There is a network of neurogenic intermediaries in the hypothalamus governing GnRH release from steroid hormone influence. More specifically, it is the combined efforts of neuro-active peptides and catecholamines which send the message of “suppression” to the GnRH neurons once activated by steroid hormones. (16) These primary messengers are known as a group of neuro-active peptides called endogenous opioid peptides (EOP’s). (7,16) The EOP’s consist of the three main peptides — b-endorphin, dynorphin, and enkephalins, which act upon their respective u-opioid, k-opioid, and s-opioid receptors. It appears that the most influential EOP in GnRH modulation is b-endorphin, acting upon the u-opioid receptor. (8-10) For this reason, b-endorphin will be the main focus of the article (although there are other minor intermediates involved.)

When steroid hormones reach the hypophysial portal, they activate the EOP’s, which suppress GnRH and consequently suppress LH & FSH. We know that steroid hormones must communicate with these opioid receptors in order for them to inhibit the release of GnRH from the GnRH neurons, since the GnRH neurons do not have their own AR or ER receptors. What’s most interesting here is that the suppression on GnRH neurons can actually be intercepted by a u-opioid receptor antagonist ñ such as naloxone, and the orally active congers naltrexone, and nalmefene.

This is accomplished by blocking the u-opioid receptor and preventing the inhibitory effects of b-endorphin upon the GnRH releasing neuron. It should be noted that this “antagonism” of suppression is not due to antagonism of the AR or ER itself, since u-opioid antagonists to not bind to hormone receptors. (15,32)

The effect of a u-opioid receptor antagonist on the HPTA is demonstrated here —

Essentially, a u-opioid antagonist such as naloxone takes the brakes off of GnRH release and allows pulses of GnRH to occur as if no steroid hormones are present. (17) Naloxone, and related u-opioid antagonists have consistently proven to block the suppressive effects of testosterone, DHT, and estrogen administration in both animals and humans. (18-25) It also appears that these drugs have the ability to increase pituitary sensitivity to GnRH. (26,27)

U-opioid antagonists have long been used for treatment of opioid dependence; not only to control cravings of narcotics, but to restore a suppressed endocrine system. (28,29) It’s well known that strong opioid based drugs such as methadone, cocaine, heroin and alcohol can suppress GnRH and therefore suppress LH & FSH. It seems that this decease of GnRH, LH & FSH is due to the same EOP mechanisms seen with AAS induced suppression. (33) In alcoholics, cocaine and heroin users, naltrexone and naloxone have been used to restore LH and testosterone levels. (28,29) Naltrexone has even been proposed as a treatment for male impotence and erectile dysfunction. (30,31)

Naloxone, naltrexone and nalmefene seem progressively more powerful in their potency to block b-endorphin, respectively. (14,18) Naloxone lacks oral bioavailability therefore injection is required. An injectable preparation could easily be made with BA water due to the water solubility of the compound. A 40mg subcutaneous injection would be a typical dose of naloxone. Naltrexone is orally active, with a safe and effective oral dose being about 100mg for a 220lb male. (18) While a lower dose of about 25-50mg of nalmefene would seemingly have the same benefit. (20,24) Increasing the dose of these drugs will surely increase the likelihood of side-effects without notably increasing the benefit. A twice a week dosing protocol would seem appropriate with these drugs, as only to increase GnRH and LH release enough to prevent pituitary and testicular shutdown ñ Just enough to keep them in the “ball game” so to speak. Also, a twice a week dosing protocol would most likely limit the increased opioid sensitivity induced by the long-term use of the drugs.

A word of caution: The opioid antagonists mentioned in this article are recognized as safe and non-toxic at the given dosages; however they can cause severe withdrawal symptoms in opiate users (methadone, morphine, cocaine, and heroin addicts.) Caution is also advised when using opioid antagonists prior to sedation or surgery as they can reduce effectiveness of anesthetics. Temporary nausea, headache or fatigue, are occasional side-effects associated with the use of these drugs. Naltrexone has been reported to heighten liver enzymes, while naloxone and nalmefene do not appear to have this issue. At any rate, a twice a week protocol for 4-16 weeks is unlikely to cause any liver issues that may be associated with naltrexone. Contrary to popular believe, opioid antagonists do NOT have any addictive properties.

A few points to consider –

For those who choose to embark on an opioid antagonist protocol several things should be considered.

  1. Remember, progestin based anabolics such as trenbolone and nandrolone are “double suppressive” because they desensitize the pituitary directly by PR activation. It also appears that no opioid receptor antagonist or aromatase inhibitor can prevent suppression via the PR. Therefore, trenbolone or nandrolone are going to cause unavoidable inhibition of HTPA function by causing suppression via the ER, AR and PR. (40,41) If one hopes for a prompt and full recovery post cycle, perhaps progestin based anabolics are better avoided, or at least limited in duration of use.
  2. As it was pointed out earlier in this article, estrogen has a markedly stronger effect on suppression of LH release compared to androgens since estrogen suppresses the hypothalamus and pituitary. Usage of an AI such as anastrozole, letrozole, or exemestane (Aromasin) can reduce estrogen and greatly reduce suppression on GnRH, LH and FSH release by preventing excessive ER activation in the hypothalamus and desensitization of the pituitary GnRH receptors. (35,37,38) Anastrozole has ~50% maximal total estrogen suppression at 1mg/day. Exemestane has ~50% maximal total estrogen suppression at 25mg/day. While letrozole has ~60% at 1mg/day. These are averages based on compiled data from several studies. Similar estrogen suppression can also been seen from only twice a week administration of these AI’s. (43-47)


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