Metenolone acetate: oestrogens and progestogens

One of the most frequently asked questions about any anabolic steroid is whether it “aromatizes” and has progestogenic effects like nandrolone. For metenolone acetate, the answers seem simple: no and almost no. But these answers hide nuances that are often missed. The editors explain why metenolone does not convert to oestrogens, what is known about its interaction with the progesterone receptor, and why the absence of oestrogens is not always an advantage.

How steroids acquire oestrogenic activity

An anabolic steroid can affect the oestrogen system in two ways. The first and main one is aromatization, that is, the conversion of androgen into oestrogen by the enzyme aromatase (CYP19A1). Thus, testosterone becomes oestradiol, and androstenedione becomes estrone. Aromatase is active in adipose tissue, brain, bone, liver, and testes.

The second way is the direct interaction of the steroid molecule itself or its metabolites with oestrogen receptors. This occurs less frequently and is usually of minor importance, but weak oestrogenic activity of metabolites has been described for some synthetic androgens.

Progestogenic activity — the ability to bind to the progesterone receptor — is considered separately. The most famous example among anabolic steroids is nandrolone and its derivatives, which, due to the absence of a 19-methyl group, are structurally similar to synthetic progestins.

To understand which group metenolone belongs to, you need to look at its structure and what enzymes can work with it.

Why metenolone is not aromatized

Aromatase converts the A ring of the steroid into an aromatic ring characteristic of oestrogens. For this, she needs a specific substrate — an androgen with a 3-keto-4-ene structure, like testosterone. Metenolone is a 5α-reduced derivative of DHT: it does not have a double bond in position 4, instead it has a C1–C2 double bond and a 1-methyl group.

DHT and its derivatives are not aromatase substrates, a well-known fact of steroid biochemistry described in pharmacological reviews, including Kicman (2008). Accordingly, metenolone does not form oestradiol, and the effect on the level of oestrogens in the blood can only be indirect.

This indirect effect works by suppressing its own hormonal axis. When metenolone reduces LH secretion, the testes produce less testosterone and therefore less substrate for aromatase. Therefore, against the background of non-aromatized androgens, the level of oestradiol in men may not increase, but decrease.

That is why drugs that block aromatase do not make pharmacological sense for metenolone. They do not affect its effect, but only additionally reduce oestradiol, formed from its own testosterone.

Progestogenic activity: comparison with nandrolone

The progesterone receptor is structurally related to the androgen receptor, and some synthetic steroids are able to interact with both. For nandrolone and its derivatives (19-nortestosterone), the progestogenic activity is well described and is associated with the absence of a methyl group in position 19.

Metenolone retains the 19-methyl group like testosterone and DHT. Therefore, from the point of view of structural logic, pronounced progestogenic activity is not expected for it. In the pharmacological literature, metenolone is not classified as a steroid with a significant progestogenic effect.

It is worth noting: we did not find systematic modern studies that would quantitatively evaluate the binding of metenolone to the progesterone receptor in human tissues. Therefore, the statement "virtually no progestagen activity" is based on structure and clinical experience, not on precise measurements.

The practical significance of this issue is related to the fact that progestins potentially increase the suppression of gonadotropins and can affect breast tissue. For metenolone, these mechanisms are probably irrelevant, but inhibition of the axis through the androgen receptor still occurs.

Reverse: oestrogen deficiency

In men, oestradiol is a complete and necessary hormone. Clinical observations of men with aromatase deficiency or oestrogen receptor mutations have shown that oestrogens are important for the closure of growth zones and bone mineralization. A study by Finkelstein et al. (2013) in the New England Journal of Medicine showed that some of the effects previously attributed to testosterone, particularly on fat mass and sexual function, are mediated by oestradiol.

When own testosterone is suppressed and the source of androgenic action is a non-aromatized steroid, oestradiol levels may drop below optimal levels. Possible manifestations are a decrease in libido, mood deterioration, complaints from the joints, adverse changes in lipids.

The degree of oestradiol reduction is individual and depends on how suppressed the own axis is. It can be evaluated only in the laboratory, using sensitive methods for determining oestradiol, because standard immunoassays in the male range are inaccurate.

This aspect is often missed in popular descriptions, where the lack of aroma is presented only as an advantage.

Gynaecomastia and Water Retention: What's Really About Them

Gynaecomastia is an increase in glandular breast tissue in men caused by an imbalance between oestrogenic and androgenic stimulation. Metenolone itself does not form oestradiol, so the classic "oestrogenic" mechanism is atypical for it.

However, there are several scenarios in which gynaecomastia is possible. The first is the period after withdrawal, when own testosterone has not yet recovered, and the balance of androgens and oestrogens is shifted. The second is the simultaneous use of aromatized steroids. The third is a counterfeit product containing another substance.

• Oestrogen-type water retention is not characteristic of metenolone.
• The visual "dryness" of the muscles is related to the lack of aromatization, and not to a special anabolic effect.
• Gynaecomastia is possible indirectly - due to hormonal imbalance or impurities.
• Any lump in the breast area requires a doctor's examination, not self-medication.

A review by Pope et al (2014) notes that gynaecomastia is one of the most common presenting symptoms in anabolic steroid users and that it can become persistent, requiring surgical treatment.

Therefore, the low probability of oestrogenic effects when using real metenolone does not equal the complete absence of the risk of gynaecomastia in real conditions.

Editorial conclusions

Metenolone acetate as a derivative of DHT does not aromatize and does not have significant progestogenic activity - this follows from its structure and is consistent with clinical experience.

The lack of oestrogenic effects has a reverse side: against the background of suppression of own testosterone, oestradiol in men can decrease, which affects bones, lipids, libido and well-being.

Gynaecomastia is atypical for genuine metenolone, but is possible due to hormonal imbalance after withdrawal, drug combinations, or counterfeits.

The editors advise you to also familiarize yourself with the materials on the mechanism of action of metenolone acetate, on the suppression of the hormonal axis and on a complete overview of its side effects.

List of used literature

1. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
2. Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011–1022.
3. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
4. Kuhn CM. Anabolic steroids. Recent Prog Horm Res. 2002;57:411–434.
5. Nieschlag E, Behre HM, Nieschlag S (eds). Testosterone: Action, Deficiency, Substitution. 4th ed. Cambridge University Press; 2012.
6. Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–1279.