The thing is that gyno occurs quite frequently with nandrolone, whereas I’ve yet to witness a confirmed case of trenbolone gyno. This despite the fact that both the progestagenic capacity is greater and the difference between AR and PR activation is smaller than for nandrolone. With nandrolone however we’ve been able to elucidate the mechanism of its effect. Whereas tren clearly shows the effects of a progestin in its action, nandrolone seems to exert none of the typical progestagenic effects. In fact it seems to perfectly fit the bill of an estrogenic steroid, something that was widely believed and accepted before people had access to medline. Nandrolone does aromatize, but to a much lesser degree (19). It’s also been shown to bind the estrogen receptor, but doesn’t seem to activate it unless at micromolar doses in vitro (20), something that would take massive consumption to mimic in vivo. One study however did estimate nandrolone’s estrogenic potential at 60% that of estradiol (21). With those figures a higher prevalence of gyno with this steroid than with testosterone isn’t that hard to imagine, especially when you know that the same enzyme that converts testosterone to DHT (5-alpha-reductase), the metabolite with the most profound effect on estrogen inhibition in the breast also converts nandrolone to DHN, which is a significantly WEAKER androgen (thus causing a massive A:E imbalance). But where does the estrogenic action come from ? Researchers already established (22) that aromatase, PR and ER did not play a role because the co-administration of inhibitors for each compound had no significant effect on the estrogenic potential. The elucidation of its mechanism came through a study on the synthetic steroid estren, a direct precursor to nandrolone (23). It showed that estren was able to mediate estrogenic effects by binding the AR and activating Estrogen Response Elements (ERE’s) in the DNA. Consider ERE’s like little signs that say “hey estrogen receptor, bind here and do your thing”. Apparently estren cause the AR to confuse itself with an ER. Estren however is a highly unstable metabolite, which rapidly converts to nandrolone under physiological circumstances. The time-frame of estrens effect (increased ERE activation while it is increasingly metabolized to nandrolone) and estrens low RBA to the AR compared to nandrolone clearly shows that this effect is mediated by nandrolone. So nandrolone causes estrogenic effects by binding the androgen receptor.
19. Ryan K. Biological aromatization of steroidsJ. Biol. Chem., Feb 1959; 234: 268 - 272
20. Bovee TF, Helsdingen RJ, Rietjens IM, Keijer J, Hoogenboom RL. Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types. J Steroid Biochem Mol Biol. 2004 Jul;91(3):99-109
21. J. Shields-Botella, I Duc, E. Duranti, F. Puccio, P. Bonnet, R. Delansorne, J. Paris. An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. Journal of Steroid Biochemistry & Molecular Biology 87 [Link niet meer beschikbaar].
22. J. Botella,t E. Duranti, V. Viader, I. Duc, R. Delansorne, J. Paris. Lack of Estrogenic Potential of Progesterone- or 19-Nor-progesterone-derived Progestins as Opposed to Testosterone or 19-Nor- testosterone Derivatives on Endometrial Ishikawa Cells. Steroid Biochem. Molec. Biol. Vol. 55, No. 1, pp. 77-84, 1995.
23. Centrella M, McCarthy TL, Chang WZ, Labaree DC, Hochberg RB. Estren (4-estren-3alpha,17beta-diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor. Mol Endocrinol. 2004 May;18(5):1120-30.