INCREASED FREE TESTOSTERONE BUT NORMAL 5-ALPHA-REDUCED TESTOSTERONE METABOLITES IN OBESE PREMENOPAUSAL WOMEN

OBJECTIVE The alm of the study was to investigate whether the absence of increased 5-alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN As in hyperandrogenicity there generally exists evidence for increased 5-alpha-reductase activity, we measured, as parameters of 5-alpha-reductase activity, plasma levels of 5-alpha-androstane-3-alpha,17-beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTs Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS Compared to controls, mean free testosterone levels were increased (P<0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P<0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P<0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P<0.01), in the normal range in obese hirsute, and decreased in obese women (P<0.01). CONCLUSIONS These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.