Trenbolone acetate: estrogenic and progestogenic activity

Trenbolone is often advertised as a "pure" androgen with no estrogenic side effects. In fact, the picture is more complicated: the drug really does not convert into estradiol, but actively interacts with the progesterone receptor. The editorial explains what this means for the breast, hormones and libido, and where the data ends and the speculation begins.

Why is this question confusing?

In steroid pharmacology, the "estrogenicity" of a drug can mean two different things. The first is the ability of the molecule to transform into estrogens under the action of the aromatase enzyme. The second is the ability of the molecule itself or its metabolites to directly activate estrogen receptors. These properties are often confused, and hence contradictory statements arise.

Progestogenic activity is a separate third dimension. It means that the substance binds to the progesterone receptor and triggers part of its effects. For testosterone, this property is practically not expressed, but for derivatives of 19-nortestosterone, which include nandrolone and trenbolone, it is well known.

Since estrogens, progestins and androgens interact in tissues, for example in the mammary gland and hypothalamus, the effect of a particular drug depends on the general hormonal background of a person. Therefore, unequivocal answers such as "trenbolone does not cause gynecomastia" do not correspond to the complexity of biology.

In addition, the situation is complicated by the lack of research on humans. Much of the information on the receptor activity of trenbolone has been obtained in vitro and in animal experiments, and clinical observations are mainly case reports.

Aromatization: what is not happening

Aromatase converts testosterone to estradiol by changing the structure of the A ring of the steroid molecule. Trenbolone has a system of conjugated double bonds in positions 4, 9, and 11, which makes the molecule a poor substrate for this enzyme. In a review, Yarrow et al. (2010) described trenbolone as an androgen with reduced estrogenic activity that does not undergo aromatization at clinically relevant scales.

This has a practical consequence: the use of trenbolone does not increase, but usually decreases the level of estradiol in men. After all, suppressing one's own testosterone also reduces the amount of substrate for aromatase. Low estradiol in men is also undesirable: it is associated with a decrease in libido, deterioration of the condition of bones and lipid profile.

The absence of aromatization also means the absence of estrogenic fluid retention characteristic of testosterone in large doses. That is why the visual effect of "dryness" became part of the drug's reputation. However, behind this there is a less noticeable price - the loss of cardioprotective and bone-protective effects of estrogens.

It is also worth remembering that some immunoassays for estradiol can give inaccurate results against the background of synthetic steroids. In such a situation, it is better to entrust the interpretation of hormonal tests to a doctor who knows about taking drugs.

Progestogenic activity: what the data say

The most frequently cited source is the study by Bauer et al. (2000), which compared the affinity of different anabolics for the human androgen receptor, sex hormone-binding globulin (GHB), and the bovine progesterone receptor. Trenbolone showed high affinity for both the androgen and progesterone receptors, while binding to HGH was weak.

It is important to understand the limitations of such data. Affinity to the receptor in a test tube is not equal to the strength of action in the body: it is affected by the concentration of the free substance, metabolism, and the presence of cofactors in a specific tissue. In addition, the bovine, not the human, progesterone receptor was used in the work.

However, the very fact of progestagen activity is consistent with what is known about 19-nortestosterone derivatives. Some of them, such as norethisterone, are even used in medicine precisely as progestins. So the hypothesis about the effect of trenbolone on progesterone receptors in humans looks biologically plausible.

Progestins themselves suppress the secretion of gonadotropins in the pituitary gland. Therefore, the progestagen action probably deepens the suppression of the hormonal axis, which already causes the androgenic activity of trenbolone.

Gynecomastia, prolactin and libido

Gynecomastia — growth of the glandular tissue of the mammary gland in men — occurs when the balance between estrogenic stimulation and androgenic inhibition of this tissue is disturbed. Progesterone in the physiology of the mammary gland enhances the effect of estrogens on proliferation. Hence the theoretical possibility that progestin against the background of even normal estradiol can contribute to gynecomastia.

There are no direct clinical studies in the literature that would prove that trenbolone causes gynecomastia through progesterone receptors. There are case reports of consumers who used several drugs at the same time, which does not allow establishing the cause. The editors consider it correct to formulate this as a plausible but unproven hypothesis.

An increase in prolactin is often associated with trenbolone in the sports environment. The scientific connection here is even less obvious: progestins are not classic stimulators of prolactin secretion, and data on trenbolone are limited. Hyperprolactinemia can be caused by many factors, so it should be diagnosed in a laboratory, and not "inferred" from the name of the drug.

Decreased libido and erectile problems on the background of trenbolone most likely have several reasons: suppression of own testosterone, low estradiol, possible effect on the central nervous system. Each of them requires a separate assessment by a doctor.

Comparison with other androgens

To better understand the place of trenbolone, it is useful to compare it to testosterone and nandrolone, the two most studied injectable androgens. The following is a qualitative characteristic shared by pharmacological reviews.

The table shows that trenbolone combines the strongest androgenic signal with a pronounced progestogenic effect and an almost complete absence of estrogenic. Such a combination is not "ideal" - it is simply different, and each of its components has its own consequences.

Nandrolone, the closest "relative" of trenbolone, also has progestogenic activity and is associated with similar complaints. However, nandrolone has the clinical history and data from patient studies that trenbolone lacks.

Testosterone, on the other hand, has the most "physiological" profile: part of its action is realized through estradiol and DHT, as in natural conditions. That is why it is the only first-line androgen in replacement therapy.

• Aromatization: practically absent - estradiol does not increase, but often decreases.
• Progestogenic effect: confirmed in vitro, clinical significance in humans has not been fully studied.
• Gynecomastia and prolactin: the connection is plausible, but not proven; diagnosis is only laboratory.

Editorial conclusion

Trenbolone Acetate does not aromatize, so it does not increase estradiol and does not cause estrogenic fluid retention. At the same time, it can reduce estradiol to undesirably low values.

The progestogenic activity of trenbolone has been confirmed in laboratory studies and probably deepens the suppression of the hormonal axis. Its role in the development of gynecomastia and changes in prolactin remains a hypothesis without reliable clinical evidence.

Any symptoms on the part of the mammary gland, a decrease in libido or an erection is a reason to consult an endocrinologist, and not to use other prescription drugs on your own.

We recommend also reading: "Effect of Trenbolone Acetate on own testosterone production (hypothalamic–pituitary–gonadal axis suppression)", "Myths about Trenbolone Acetate: what is true and what is not" and "Mechanism of action of Trenbolone enanthate: effect on androgen receptors and protein synthesis".

References

1. Bauer ER, Daxenberger A, Petri T, Sauerwein H, Meyer HH. Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor. APMIS. 2000;108(12):838–846.
2. Yarrow JF, McCoy SC, Borst SE. Tissue selectivity and potential clinical applications of trenbolone (17β-hydroxyestra-4,9,11-trien-3-one): a potent anabolic steroid with reduced androgenic and estrogenic activity. Steroids. 2010;75(6):377–389.
3. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
4. 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.
5. Braunstein GD. Gynecomastia. N Engl J Med. 2007;357(12):1229–1237.
6. Nieschlag E, Behre HM, Nieschlag S (eds). Testosterone: Action, Deficiency, Substitution. 4th ed. Cambridge University Press; 2012.