Can alcohol promote aromatization of androgens to estrogens? A review.
Increased aromatization may be a mechanism for feminization of some male alcoholics, as well as for the reported increases in plasma estrogen levels in postmenopausal women subjected to moderate alcohol consumption. Alcohol consumption-related increases in estrogen levels may in turn be partially responsible for the associated decreased risk for coronary artery disease and osteoporosis, as well as for increased risk for breast cancer. The purpose of this review is to evaluate the literature to determine whether alcohol can promote aromatization of androgens to estrogens. In male rats, chronic heavy alcohol administration (36% of total calories=12-18 g/kg/day) led to increased aromatization of androgen in the liver, but the results were equivocal for the hypothalamus. In female rats, chronic heavy alcohol administration did not promote aromatization in the hypothalamus exposed to alcohol in utero. In human placental tissue, although ex vivo alcohol administration (less or more than 72 g/day) did not affect the rate of aromatization, in vitro incubation of choriocarcinoma cells with 5-50 mM of alcohol increased estradiol secretion, which could be due to increased aromatization. In in vitro human ovarian granulosa cell studies, alcohol increased, had no effect on, or decreased estradiol secretion, and in one study, 20 mM of alcohol significantly increased aromatization of androstenedione to estrogens. These results may not be fully relevant to normal human ovary because in both studies cells were heavily luteinized by gonadotropins. A study of ovariectomized rats shows that only heavy chronic alcohol intake (4.4 g/kg/day) for 10 weeks can increase plasma estradiol levels and uterine weight, which could be due to increased aromatization or delayed clearance of estradiol. In conclusion, chronic heavy alcohol administration can result in aromatization of androgens in male rat liver. It is not clear whether moderate alcohol intake can produce a similar effect in the liver nor whether alcohol can potentiate aromatization of androgens in other tissue or organs of male rats. In females, the available information is not adequate to evaluate the effect of alcohol on aromatization. Further studies are required in both genders to evaluate the ability of alcohol (moderate vs. heavy dose) to promote aromatization of androgens to estrogens.
Purohit
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Division of Basic Research, Biomedical Research Branch, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Suite 402, 6000 Executive Boulevard, Bethesda, MD 20892-7003, USA. vpurohit@willco.niaaa.nih.gov
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D003327:Coronary Disease / Q000517:prevention & control; D004967:Estrogens / Q000097:blood / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D017698:Postmenopause; D011247:Pregnancy; D011301:Preoptic Area / Q000187:drug effects / Q000201:enzymology; D051381:Rats
D000728:Androgens; D004967:Estrogens; D000431:Ethanol; D001141:Aromatase