I was interested so I asked our pharmacist(involved in drug development and responsible for some of the compounds in our newest thermogenic Plus product..release is soon) on staff for supplement development for his feedback.
what he had to say:
The fact is that the etiology with much of gynecomastia is unknown, so how can one say, "this or that definitely doesn't play a role" when no one knows how exactly most gynecomastia is formed for certain. That, along with the fact that progestins have been shown to cause gynecomastia in men and the association of progesterone with gynecomastia in one study, it would be very naive and incorrect to assume that not only does it play no role in gynecomastia, whether directly or indirectly, but that it actually combats it when there are data to the contrary.
Granted, in the majority of cases, gynecomastia is induced by estrogens, either elevated serum levels or high localized production (though this has yet to be advanced beyond a hypothesis), there are many cases of idiopathic gynecomastia which do not fit with such diagnostic criteria. It's certainly reasonable that progesterone can play a role in gynecomastia. As big of a role player as estrogens? Certainly not. But to assume it plays no role and is actually beneficial is wrong.
A recent paper in NEJM points out a few things:
There is no uniformity of opinion regarding what biochemical evaluation, if any, should be performed in a patient with asymptomatic gynecomastia. The diagnostic tests for patients with symptomatic gynecomastia of recent onset for which no cause is discerned on the basis of the history or physical examination (Figure 3) have a low yield; however, a prospective cost–benefit analysis in this population has not been performed. In a retrospective study of 87 men with symptomatic gynecomastia, 16% had apparent liver or renal disease, 21% had drug-induced gynecomastia, and 2% had hyperthyroidism, whereas 61% were considered to have idiopathic gynecomastia. Forty-five of the 53 patients in the group with idiopathic gynecomastia underwent endocrine testing, of whom only 1 patient (2%) was found to have an endocrine abnormality — an occult Leydig-cell testicular tumor.51
Finally, since the excessive aromatization of androgens to estrogens has been shown to be present in many patients with gynecomastia, it is unclear why aromatase inhibitors have not been more successful in the treatment of these patients or in the prevention of the development of gynecomastia in patients with prostate cancer treated with antiandrogens.
Gut. 1982 Apr;23(4):276-9.
Progesterone, prolactin, and gynaecomastia in men with liver disease.
Farthing MJ, Green JR, Edwards CR, Dawson AM.
Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids.
Acta Endocrinol (Copenh). 1980 Oct;95(2):265-70. Links
Sebum production and plasma testosterone levels in man after high-dose medroxyprogesterone acetate treatment and androgen administration.
Novak E, Hendrix JW, Chen TT, Seckman CE, Royer GL, Pochi PE.
PIP: In 47 healthy male volunteers, the administration of 100 mg of oral (MPA) medroxyprogesterone acetate daily for 42 consecutive days caused a modest 16.7% decrease in sebum production from a baseline mean of 2.28 mg to a posttreatment mean of 1.90 mg. This represented a considerably smaller decrement than had been reported in the literature. Immediately following the period of MPA administration, the addition of daily oral doses of either 50 mg of fluoxymesterone, methyltestosterone, or calusterone to the 100 mg daily dose of MPA for 42 additional days resulted in the return of sebum production to essentially presuppression values. A statistically significant decrease in serum testosterone levels from a pretreatment mean of 862 ng/100 ml to a posttreatment mean of 251 ng/100 ml, was seen in all groups treated during the first 42 days with 100 mg of MPA daily (P0.05). The addition of 50 mg of fluoxymesterone, methyltestosterone, or calusterone to the 100 mg of MPA for another 42 day period caused a further decrease in serum testosterone levels (P0.001); the fluoxymesterone-MPA combination produced the greatest decrease of serum testosterone levels, from a pretreatment mean value of 932.8 ng/100 ml (Day 1), to a posttreatment mean value of 70.6 ng/100 ml (Day 85). The daily dose of 20 mg of MPA for 42 consecutive days caused less suppression of serum testosterone levels (from 831 ng/100 ml to a mean of 585 ng/100 ml) than 100 mg of MPA from 831 ng/100 ml to a more than that of placebo (pretreatment mean of 886 ng/100 ml to a posttreatment mean of 871 ng/100 ml). Except for changes in hemoglobin, hematocrit, and haptoglobin values, no other medically significant changes were seen in the routine screening chemistries and urine analyses for any of the drug groups. These changes were not unexpected, as they are known to occur with androgen therapy. Of potentially clinical importance was the absence of any effect of antithrombin-3 levels during the study period. No major side effects were reported other than in 1 patient who developed gynecomastia of his right breast on Day 42 of MPA therapy. After his being removed from the study, the gynecomastia disappeared rapidly.
