by Author L. Rea

Publication Date: May 7, 2004

Nothing in this article is intended to take the place of advice from a licensed health professional. Consult a physician before taking any medication.

Q: I already read your awesome book Chemical Muscle Enhancement and ordered your new one Building The Perfect Beast today. Thanks for a no Bullshit source of in the trenches information!

My question is about anti-estrogens. I read where you said some of them can really shut down IGF-1 in the body. I am pre-contest and need to keep all the muscle I can while cutting the fat. What is the best anti-estrogen and what makes the others good or bad?

A: Thank you for reading CME and I hope that you enjoy Beast. It is always great to know people benefit from my efforts!

Most of the available studies on anti-estrogens (aromatase inhibitors and estrogen receptor antagonist) are performed upon breast cancer patients. As such, to some extent, the results may vary in regard to healthy male athletes. Personally I have always found this boarder-line idiocy due to the fact that there are millions of males with gynecomastia (bitch tits) and corresponding inhibition of HPTA function (the body’s androgen producing system) that would crawl over glass to participate in medical studies of this nature.

A Very Quick Physiology Lesson

The male body uses an enzyme called aromatase to convert a percentage of susceptible androgens into estrogens. Naturally this includes both those the body produces and those introduced from outside the body such as AAS (Anabolic Androgenic Steroids). In most cases the result is predominantly a very powerful estrogen called estradiol.

Aromatase is present in most body tissues and the circulatory system. Unfortunately fat cells produce a scary amount of this man-altering enzyme…which of course explains why fat guys get boobs. (Yikes!)

When we think of aromatase inhibitors we often assume that they are all the same with various levels of results…depending upon dosages. While the latter may be true, the prior statement certainly is not.

Aromatase Inhibitor "Types"?

Let’s do a quick review of the types of aromatase inhibitors that are available. These include type 1, or steroidal inactivators, and type 2, or nonsteroidal inhibitors. The type 1 aromatase inhibitors include exemestane and formestane and are actually androgen analogues (cool stuff if applied right!). The type 2 inhibitors include aminoglutethimide, anastrozole, letrozole, and vorozole.

There are both similarities and differences between the type 1 and 2 aromatase inhibitors. Their similarities include the fact that both inhibit aromatase in a very specific fashion and reduce endogenous or circulating estrogens. On the other hand, the steroidal inhibitors are rather better classified as inactivators, in that they bind to the aromatase molecule in an irreversible fashion (they hold on and do not let go). Because aromatase is rapidly replaced within the body, however, the significance of this property in terms of clinical benefit is unclear in some ways. In addition, the "inactivators" have a structure quite similar to that of androgens and may, in higher doses, have anabolic steroid or androgen-type properties.

Of the type 2 agents, letrozole tends to be more potent than anastrozole and both are more potent than aminoglutethimide in regard to estrogen production. Of the type 1 agents, exemestane is considerably more potent than formestane. But again in each case this may be dose dependant more so than a question of effectiveness of the drug itself. In vivo (tested in live subjects rather than a test tube), the aromatase inhibitors can be graded as shown in the basic table below.

So far it would appear that Letrozole is the leader, huh?

Anti-Estrogens And IGF-1 Production

GH (Growth Hormone) is like a master hormone for tissue growth and fat regulation due to its own intrinsic qualities and its propensity to be converted into or trigger the production and release of Growth Factors. Of these Growth Factors, one of the best known in regard to muscle growth is IGF-1 (Insulin-Like Growth Factor-1).

As most are aware by now, IGF-1 is a powerful anabolic and anti-catabolic hormone. Whether in pre-contest mode or packing on the mass, the amount of circulating and stored IGF-1 an athlete maintains plays a powerful role in the results achieved. Obviously as IGF-1 levels decrease so does the potential for packing on the beef, and the amount of lean tissue lost during calorie-restricted periods increases as well. (Not good)

Estrogen, and more so estradiol, can trigger GH release from the pituitary gland. Aromatase inhibitors decrease the amount of circulating estrogen/estradiol and estrogen receptor antagonist keep estrogen out of the specific pituitary receptors. So in many regards the use of anti-estrogens can effect IGF-1 production and in some cases affect the number of IGF-1 receptors our tissues posses.

Hmmm, so now we have some major points in favor of Cytadren, Aromasin and Formestane.

Other things to consider pre-contest or simply as a matter of achieving desired results at any point in the pursuit of freak status include…

When attempting to evaluate "the best" choice for any item, the question of specific-intent should come into play first. If you asked for solely my opinion, then I would choose the product that covered the greatest number of needs for specific-intent or goal(s). Personally I prefer Formestane (under whatever name the product is provided, in the purest most active form).

Why?

• Formestane increases IGF-1 secretion and activity.
• Formestane decreases the number of progesterone receptors (inhibits the trenbolone and "deca-dick" type side effects and increases fat loss)
• Formestane inhibits 91.9% of aromatase enzyme production
• Formestane increases HPTA activity similar to HCG and Clomid together
• Formestane is anabolic and androgenic (At 500mg weekly the product is similar in effects to 250mg of Primobolan Enanthate)
• Formestane is a "suicide inhibitor" of aromatase. Specifically this means that it will irreversibly bind to the aromatase enzyme and permanently deactivate it
• Formestane (The sterile injectable form) possesses a 4-day half-life
• Formestane decreases SHBG 34% thus increasing androgen activity.
• Formestane inhibits DHT (dehydrotestosterone) formation and activity.
• Formestane possesses 1% of the binding affinity of DHT to DHT receptors
• Formestane has been shown to decrease prostate concerns such as BPH.
• Formestane has been shown to continue to increase HPTA function above natural levels even after 22 weeks of continuous administration.

Oh, As To Water Retention…

Naturally the anti-estrogen value of any of the aromatase inhibitors does decrease the affects of the water retention hormone aldosterone. Those that are androgenic in structure seem to do so better. The point is that though some of the other products discussed do posses these qualities, none but formestane has them all. Fewer drugs or products are always a "better choice".

Cool, But Where Can Formestane Be Found?

When you read my newest book Building The Perfect Beast you will find that at the time of printing I was looking for a reputable manufacturer for Formestane to refer to. The medically prescribed product Formestane is administered as a deep intramuscular injection. It is commonly known as Lentaron I.M. Depot. Its active ingredient is 4-androstenoldione acetate in a pure isomer form. The product is normally administered for breast cancer patients at a dosage of 250mg every 2 weeks to 250mg weekly. Since androstenoldione acetate has a half-life of about 4 days when administered I.M. the dosing protocol has been less than perfect for those athletes whom have opted to utilize it.

Reports and anecdotal returns have shown that 200-250mg of Lentaron I.M. Depot every 3^rd day has resulted in excellent estrogen/progestin control during AAS protocols. I have personally seen the product at a few pharmacies in Mexico and have employed it while there (and just prior to leaving the country) with effective success. (Smuggling is a very bad idea!)

Available OTC?

I know, it sucks to find out there is something you really want but cannot get to. Hmmm? Several products that are used pharmacologically fall under the protection of the natural substance act (so far) and can be sold as nutritional supplements. In this case, 4-androstenoldione acetate (Formestane Acetate) is a metabolite of 4-androstenedione and therefore naturally occurring. This means that the product can be legally sold OTC (Over The Counter) in the US and some other countries as an oral only supplement.

There are a few companies doing so at this time including a rather respectable company called ProMatrix. ProMatrix has named their product Primobolan and can be found at many stores on-line or off. Their home site for tech info is www.promatrixtech.com.

Though the purer products do have some effectual value, there is the hassle of the required 4-8 times daily oral dosing required due to the half-life of oral administration being only about 3-5 hours. Another problem is the 200mg plus per administration necessary to realize margin of the effectiveness that the sterile parental (injectable) prescription preparation affords, and long term cost.

Like many other higher priced aromatase inhibitors, there is no doubt that Formestane acetate in a sterile preparation will show up somewhere before the printing of this column. The only question is purity of the substrates used and the reliability of the company manufacturing the product. Naturally it will need to be offered as a sterile oral product as Synthol has, and some will of course opt to not follow the label instructions.

I am currently following the favorable progress of one such product and will keep you informed once the results are in. It is Aromabolan by HM Gear and can be found mostly on-line and some Max Muscle stores. Their home site is www.hmgear.com.

Reference Materials

Effects of treatment with megestrol acetate, aminoglutethimide, or formestane on insulin-like growth factor (IGF) I and II, IGF-binding proteins (IGFBPs), and IGFBP-3 protease status in patients with advanced breast cancer. J Clin Endocrinol Metab 1996 Jun;81(6):2216-21    

Effect of two-4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer. Breast Cancer Res Treat 1994;30(2):127-32    

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. J Steroid Biochem Mol Biol 1997 Nov-Dec;63(4-6):261-7

The luteinizing hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: effects on bone metabolism markers. J Steroid Biochem Mol Biol 2000 Dec 1;75(1):65-73    

Estrogen suppression in males: metabolic effects. J Clin Endocrinol Metab 2000 Jul;85(7):2370-7  Nemours Research Programs at the Nemours Children's Clinic, Jacksonville, Florida 32207, USA.

Effect of tamoxifen on lipoprotein(a) and insulin-like growth factor-I (IGF-I) in healthy women. Eur J Cancer 1999 Apr;35(4):596-600 FIRC Chemoprevention Unit, European Institute of Oncology, Milan, Italy.

Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI Lady Davis Research Institute, and Department of Medicine, McGill University, 3755 Cote St. Catherine Road, Montreal, Quebec H3T 1E2, Canada. Clin Cancer Res 1996 Dec;2(12):2037-42

Davies JH et al. Effects of 4-hydroxyandrost-4-ene-3,17-dione and its metabolites on 5 alpha-reductase activity and the androgen receptor. J Enzyme Inhib. 1992;6(2):141-7.

Second generation aromatase inhibitor--4-hydroxyandrostenedione BREAST CANCER RESEARCH AND TREATMENT ,   30(1):81-87 1994

The effect of aromatase inhibitor 4-hydroxyandrostenedione on steroid receptors in hormone-dependent tissues of the rat JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY ,   52(1):71 1995

LACK OF EVIDENCE FOR AROMATASE IN HUMAN PROSTATIC TISSUES EFFECTS OF 4 HYDROXYANDROSTENEDIONE AND OTHER INHIBITORS ON ANDROGEN METABOLISM CANCER RESEARCH,   49(23):6551-6555 1989

DOSE-RELATED ENDOCRINE EFFECTS AND PHARMACOKINETICS OF ORAL AND INTRAMUSCULAR 4 HYDROXYANDROSTENEDIONE IN POSTMENOPAUSAL BREAST CANCER PATIENTS CANCER RESEARCH ,   49(5):1306-1312 1989

Effects of aromatase inhibitor 4-hydroxyandrostenedione and other compounds in the 7, 12-dimethylbenz(a)anthracene-induced breast carcinoma model CANCER RESEARCH ,   42(8 Suppl):3360s-3364s 1982

The influence of 4-hydroxy-4-androstene-3,17-dione on androgen metabolism and action in cultured human foreskin fibroblasts. J Steroid Biochem. 1987 Jan;26(1):131-5.