Effect of Excess Endogenous Androgens on Bone Density in Young Women

To determine whether endogenous androgens influence bone density in young women, we studied 27 normal women and 19 women with androgen excess, as defined by increased serum bioavailable testosterone (bio T) concentrations. The women ranged from 21-48 yr of age. The 2 groups were comparable with respect to age, anthropomorphic measures, nutrition, gynecological history, and serum cortisol and estradiol levels. Trabecular (lumbar) and cortical (radial) bone density were quantitated by computerized tomography and single photon absorptiometry, respectively. Serum obtained during the follicular phase of the cycle was assayed for bio T, total T, dehydroepiandrosterone sulfate, androstenedione (Adione), and 3 alpha-androstanediol glucuronide (3-Adiol-G). Trabecular bone density was significantly higher in the androgen excess group [172 +/- 7 (+/- SE) vs. 153 +/- 5 mg/mL; P = 0.03]; controlling for serum Adione (but not for serum bio T, total T, dehydroepiandrosterone sulfate, or 3 alpha-androstanediol glucuronide, or 3-Adiol-G) abolished this difference. Similarly, serum Adione correlated more strongly than the other androgens with trabecular bone density (r = 0.31; P = 0.03). Average cortical bone density was not higher in the androgen excess group (0.740 +/- 0.014 vs. 0.722 +/- 0.008 g/cm2; P = 0.27). Among the 27 normal women, cortical density was correlated to serum bio T (r = 0.47; P = 0.01) and total T (r = 0.53; P = 0.004), but not to the other androgens. We conclude that supraphysiological levels of endogenous androgens are associated with increased trabecular bone density in young women. Serum Adione appeared to be the best marker for the impact of androgen on trabecular density. Among normal women, cortical bone density was related to serum T.