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Declining testosterone levels and an increase in the level of subcutaneous fatty tissue seen as part of the normal aging process can lead to gynecomastia in older males. Increased fatty tissue, a major site of aromatase activity, leads to increased conversion of androgenic hormones such as testosterone to estrogens. [ 26 ]
It does not lower androgen levels. [3] The medication can have some estrogen-like effects in men when used as a monotherapy due to increased estradiol levels. [31] [32] [33] Bicalutamide is well-absorbed, and its absorption is not affected by food. [2] The elimination half-life of the medication is around one week.
[85] [62] However, in contrast, the effects of the elevated estrogen levels remain unopposed by bicalutamide, and this is importantly involved in the feminizing side effects (e.g., gynecomastia) of the drug in men. [106] Testosterone levels decline with age in men and younger men have higher testosterone levels on average than older men. [107]
“Male breast growth is often caused by an imbalance of estrogen levels. This can result in physical discomfort, such as tenderness, pain and sensitivity in the breast area.”
Contraceptive vaginal rings and contraceptive patches likewise have been found to increase SHBG levels by 2.5-fold and 3.5-fold, respectively. [120] Birth control pills containing high doses of ethinylestradiol (>50 μg) can increase SHBG levels by 5- to 10-fold, which is similar to the increase that occurs during pregnancy. [123]
Spironolactone has been found in some studies to increase levels of estradiol, an estrogen, although many other studies have found no changes in estradiol levels. [ 109 ] [ 134 ] The mechanism of how spironolactone increases estradiol levels is unclear, but it may involve inhibition of the inactivation of estradiol into estrone and enhancement ...
In addition, spironolactone has sometimes been found to increase estradiol and cortisol levels and hence could have slight indirect estrogenic and glucocorticoid effects. The medication has also been found to interact very weakly with the estrogen and progesterone receptors , and to act as an agonist of the pregnane X receptor .
SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs. Long-term calorie restriction increases SHBG in rodents and men, while lowering free and total testosterone and estradiol and having no effect on DHEA-S , which lacks affinity for SHBG. [ 34 ]