Effect of Excess Endogenous Androgens on Bone Density in Young Women

Abstract

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.

Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case–controlled study (ENIGI)

“…The anabolic effect of testosterone on female body composition and bone metabolism is further supported by research in women with endogenous hyperandrogenism and postmenopausal women on testosterone therapy. A higher regional muscle mass (29), higher trabecular vBMD (30,31), and aBMD at the lumbar spine (32,33) as well as larger cortical bone size (31) and aBMD at cortical sites (whole body (32,34) and femoral neck (33)) were described in women with endogenous hyperandrogenism and/or hirsutism. Similarly, exogenous testosterone added to hormonal replacement therapy in postmenopausal women resulted in higher lean body mass and muscle mass (35,36) and increased hip (35,37) and spine aBMD (35, 38) after 2 years compared with estrogen treatment alone.…”

Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

“…Furthermore, the nonaromatizable androgen 5a-dihydrotestosterone has been shown to stimulate bone growth in osteopenic ovariectomized rats (24). In pre-and postmenopausal women, endogenous androgen levels correlate with BMD (25,26). Furthermore, a study comparing estrogen to a synthetic androgen in postmenopausal osteoporotic women showed that both steroids were equally effective in reducing bone resorption (27).…”

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

“…Amenorrheic women with unusually high androgen concentrations appear to escape the detrimental skeletal effects of estrogen deficiency (8), as do some elite female athletes with extremely intense levels of weight-bearing activities, including figure skaters (9) and gymnasts (10). There is other evidence of the potential positive role androgens may play in skeletal health in women.…”

“…Perimenopausal women with higher testosterone concentrations have slower rates of bone loss than those with lower concentrations, independent of their estrogen status (7). Premenopausal women with androgen excess have higher than normal bone mass with or without (8,11) normal menstrual cycling.…”