Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea

Abstract

Context: Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population.

Objective: Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women.

Design and setting: We conducted a cross-sectional study at a general clinical research center.

Study participants: A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls.

Main outcome measures: Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed.

Results: Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass.

Conclusions: Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women.

Fig. 1

Mean total and free testosterone levels are lower in women with anorexia nervosa not receiving oral contraceptives (AN − E) and women with anorexia nervosa receiving oral contraceptives (AN + E) than in normal-weight women with hypothalamic amenorrhea (HA) and healthy controls of reproductive age (HC); mean free testosterone and DHEAS levels are lower in AN + E than AN − E; DHEAS levels were not lower than normal in AN − E. *, P < 0.05 compared with HC and HA; **, P < 0.05 compared with AN − E, HC, and HA.