Calling everyone who is living with Gyno or had personal experience with gyno

[Daz69]

Gynaecomastia is the development of breast tissue in males. It's a side-effect often associated with anabolic androgenic steroid use/abuse, although it's not all that prevalent in healthy males. One study with low-dose testosterone (200 mg/week of an ester amounting to roughly 140 mg of actual testosterone) showed a prevalence of roughly 8% and likely in athletes and people using steroids for aesthetic purposes the incidence is significantly lower for various reasons including lower body-fat (adipose tissue is a primary source of aromatase, the enzyme that converts testosterone to estrogen) and the use of higher doses. Higher doses lead to higher circulation of androgens for an equal amount of aromatase that converts testosterone to estrogen. Androgens are capable of inhibiting the estrogen-induced proliferation of mammary epithelial cells and abolish estrogen-induced augmentation of ER-  expression. They also further promote pro-apoptotic (cell-killing) effects in a wide variety of breast cancer cell lines.

1.Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. Fertil Steril. 1996 Mar;65(3):626-36.

2.Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J. 2000 Sep;14(12):1725-30.

 

3. Kandouz M, Lombet A, Perrot JY, Jacob D, Carvajal S, Kazem A, Rostene W, Therwath A, Gompel A. Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):463-71. 

[Daz69]

for me personally the key to not getting gyno on tren is just to keep your E2 really low from the beginning. If you dont it just becomes a cluster f*ck that Nolva can't fix acutely. Both progesterone and prolactin have been shown to cause gyno and there is research showing tren accelerating breast cancer growth.

 

I'm not sure on the direct mechanics of it, but it appears high E2 with progesterone is where you don't want to be and tren accelerates whatever is happening. Keep your E2 low from the beginning and you won't get any problems imo. 

 

There is actually a drug out there that inhibits tren bidning to the progesterone receptor, I never followed up what this meant for tren sides because the study said it reduced the binding affinity of tren to AR.

 

To counter your arguement:

The fact that trenbolone has some binding affinity for the PR often lays at the basis to claims of gyno, but the truth is that while we know that trenbolone binds the PR, we have no idea whether it is an agonist or antagonist. Something some people want to bend into their own view, suggesting mixed agonist/antagonist gene expression profiles to fit their theories. We currently assume it's a progestin because of its effect on erectile dysfunction and the fact that a great many steroids in the 19-Nor line are known progestins. But the opposite is just as likely because progestins are sometimes administered to treat erectile dysfunction, and while progesterone treatment is typically known to increase body fat, no such effect is perceived with trenbolone. Quite the contrary. What people seem to forget is that it's largely irrelevant, because in vivo research in primates has shown no effect of ovariectomy (removal of progesterone) nor replacement with progesterone (pure progesterone receptor agonism) on the proliferation of breast tissue, demonstrating that no degree of agonism, whether partial or complete, would have any effect in breast tissue development. This is in contrast to the additive effect of progesterone to estrogen in murine models, but rodents have a different oestrous cycle regulation, where they have to continue breastfeeding while already being able to conceive again. The fact that no degree of PR activation had any effect, also excludes any indirect effects such as PR-mediated prolactin increases..... 

[Daz69]

The prolactin theory

Prolactin is the latest theory and pet peeve of the pseudo-scientists, most likely because progesterone was getting old, disproven [2] and was hard to make money off of since common anti-progestins are heavily regulated and hard to get a hold off, and the fact that PR inhibition has been linked with the occurance of gyno more than its treatment [26]. In my quest to find out what gave rise to this theory I actually found the man that claims to have started it, and even he failed to provide even one single reason to assume this is anything more than a hoax. It doesn't help that this person has a monetary stake in the sale of dopamine agonist drugs typically used to lower prolactin in patients irresponsive to standard treatments like androgen administration or anti-estrogen treatment, nor does his long standing reputation of making money off of people in these fraudulent manners. 

Research conducted on androgen-insensitive mammals who have been ovariectomized, castrated and/or adrenalectomized [27] demonstrate a drastic decrease in prolactin because of the removal of estrogen-producing organs, while treatment in primates with an anti-androgen [18] seems to increase prolactin. This is consistent with the known regulation of prolactin by sex steroids, showing that estrogens are needed to increase and maintain increased prolactin, and that androgens inhibit this action in vivo [28]. The theory is predominantly used to explain the action of the typical progesterone receptor-binding androgens like nandrolone and trenbolone, showing that protagonists of the prolactin theory hold some (frequently expressed) belief that the PR plays a role in the prolactin increase, but progesterone too attenuates the estrogen-mediated increase in prolactin [28,35], and repressed the downstream signaling cascade of prolactin [13,35] in the breast specifically. This ties into the known method of lactogenic induction in post-partum women, which is accompanied by a drastic drop in progesterone, because sex steroids in general inhibit the PRL activity at the PRLR [42]. Furthermore blood panels of users of anabolic androgenic steroids, including trenbolone and nandrolone, have been shown to have a slight decrease in circulating prolactin if anything, as one would expect with high androgen treatment. The one case where we do know gyno with lactation develops is in the use of low dose testosterone [29,30] and there we do in fact see a rise serum prolactin mediated by the imbalance in A:E ratio. It is also plausible to see this with improper post-cycle therapy after the use of heavily HPTA suppressing androgens (such as for example trenbolone) after cessation of the drug for some time, also linked to an imbalanced A:E ratio. 

There are two things we need to address here. The first is the activity of prolactin in benign breast tissue in males, and the second is the ability of prolactin to stimulate or cause gyno. We know that prolactin exerts its effects through the membrane bound prolactin receptor (PRLR), which then activates the Jak/stat kinase pathway in the cell leading to increased expression of target genes and that this receptor is required for the activity of prolactin [31,32]. However studies done specifically in men with gynaecomastia demonstrate that only 20% of cases are PRLR positive [33], allowing us to simply state that at least 80% of gyno cases aren't even susceptible to the effect of prolactin. This argument was frequently countered with the postulation that progestagenic effects upregulate PRLR, but it is widely documented [33,34] that there is no correlation between progesterone/PR expression and prolactin/PRLR expression. 

Having established that, we haven't even addressed whether or not prolactin can cause gyno on its own. We've already demonstrated that it has no correlation with the progesterone receptor and that androgen mediation attenuates the activity of estrogen on prolactin. There is however also evidence that there is no correlation between gyno and prolactin, with plenty of cases of hyperprolactinaemia showing no signs of gynaecomastia, and vice versa, plenty of gyno cases showing no elevation in prolactin or prolactin activity. It has been suggested several times in fact that prolactin has no real effect in breast development in the absence of estrogens [5,34], further establishing anti-estrogen treatment as the primary treatment for gyno, with or without prolactin. Taken together the probability of PRLR positive gyno that isn't responsive to estrogen management is extremely small. Combine that with the aforementioned unique dispersal of these occurrences to the places frequented by charismatic pseudo-scientists and you get the picture of a typical hoax. 

In conclusion:

Gynaecomastia is a condition that is quite rare in users of high dose androgens, such as athletes and people who use AAS for aesthetic reasons, and there are distinct factors that predict sensitivity to the condition. AAS-induced gynaecomastia, since its emergence, has been solely and successfully treated with estrogen management by laymen and medical professionals alike. Successful acute and preventive treatments for estrogenic side-effects have been established anecdotally in the community at large, and are widely supported by the existing literature. One should recognize that a certain amount of circulating estrogen has positive effects on health and well-being , as well as fat loss and possibly muscle and strength gains. For this reason it is wise to adhere to common sense and not self-administer additional pharmaceuticals for problems that aren?t there. 

When problems do arise, and you have reason to believe that you are getting gynaecomastia, go see a medical professional about the condition first and foremost. The smart thing to do at this point is also to cease use of the likely caGlobaltive agent, and start proper PCT to let yourself recover. Getting this condition while on high dose androgens could indicate underlying problems that pose severe threats to your health. Oftentimes your doctor will do no more than observe the condition at first. Most likely a preliminary blood test will already identify absolute estrogen or relative estrogen values as the culprit and treatment will be given accordingly. If your doctor refuses to treat, anti-estrogenic drugs are widely available, but if you do choose to self-administer these drugs, make sure you understand them and their correct use. If you are the person who is likely to believe aforementioned pseudo-scientists, this is especially relevant. For acute treatment the SERMs are widely documented to be effective, most notably clomiphene, tamoxifen and raloxifene.  

If risk factors are in play, or if you have suffered gynaecomastia during past AAS use, especially if it came on early, preventive treatment with aromatase inhibitors may be wiser. Keep in mind however that this will not address estrogenic problems caused by drugs that do not aromatize to estrogens but are still estrogenic in nature, such as nandrolone and oxymetholone. One should take care to avoid these drugs. Long term treatment with SERMs is acceptable as well, but usually more costly. 

References

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2.Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J. 2000 Sep;14(12):1725-30.

3. Kandouz M, Lombet A, Perrot JY, Jacob D, Carvajal S, Kazem A, Rostene W, Therwath A, Gompel A. Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):463-71. 

4. Rochefort H, Garcia M. The estrogenic and antiestrogenic activities of androgens in female target tissues. Pharmacol Ther. 1983;23(2):193-216. 

5. Ismail AA, Barth JH. Endocrinology of gynaecomastia. Ann Clin Biochem. 2001 Nov;38(Pt 6):596-607.

6. Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW. The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. J Clin Endocrinol Metab. 1984 Mar;58(3):467-72. 

7. Casey RW, Wilson JD. Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. J Clin Invest. 1984 Dec;74(6):2272-8. 

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13. Buser AC, Gass-Handel EK, Wyszomierski SL, Doppler W, Leonhardt SA, Schaack J, Rosen JM, Watkin H, Anderson SM, Edwards DP. Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Mol Endocrinol. 2007 Jan;21(1):106-25.

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15. Hofling M, L?fgren L, von Schoultz E, Carlstr?m K, S?derqvist G. Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopaGloball women. Gynecol Endocrinol. 2008 Jul;24(7):405-10.

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18.Herbert DC, Schuppler J, Poggel A, G?nzel P, El Etreby MF. Effect of cyproterone acetate on prolactin secretion in the female rhesus monkey. Cell and Tissue Research. 1977 Sep; 183 (1):51-60.

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 (2003) 111-122.

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.

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25. Blanco A, Moya L, Flores R, Ag?era E, Monterde JG. Effects of anabolic implants of oestradiol alone or in combination with trenbolone acetate on the ultrastructure of mammary glands in female lambs regarding their interference in prolactin secretion. J Vet Med A Physiol Pathol Clin Med. 2002 Feb;49(1):13-7.

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From: Peter Van Mol (Big Cat)..

[mikehutton112]

Thanks.

"If risk factors are in play, or if you have suffered gynaecomastia during past AAS use, especially if it came on early, preventive treatment with aromatase inhibitors may be wiser. Keep in mind however that this will not address estrogenic problems caused by drugs that do not aromatize to estrogens but are still estrogenic in nature, such as nandrolone and oxymetholone. One should take care to avoid these drugs. Long term treatment with SERMs is acceptable as well, but usually more costly."

 

I was of the impression that the gyno was solely because of Tren, but from the above literature I believe it could've been due to the Dbol.

On a sidenote, the studies and references cited above, most of them are over 10 years old, would that matter much?

[yeelang]