Effect of obesity on the response to acute adrenocorticotropin stimulation in eumenorrheic women.

OBJECTIVE

Alterations in adrenocortical biosynthesis, as measured by the steroid response to acute adrenocorticotropic hormone (ACTH) stimulation, have frequently been reported in female hyperandrogenism. These patients are also commonly obese, which may account for some of these abnormalities. The object of this study was to test the hypothesis that obesity alters the adrenal response to acute adrenal stimulation.

DESIGN

A prospective study of healthy premenopausal women of varying weights.

SETTING

University-based clinical research center.

PATIENTS

Fifty-seven healthy, eumenorrheic, nonhirsute female volunteers were studied, 30 weighing between 90% and 110% (normal-weight) and 27 weighing greater than 120% (obese) their ideal body weight.

INTERVENTIONS

All subjects underwent a 60-minute acute intravenous ACTH-(1-24) stimulation test in the follicular phase (days 3 to 8) of the menstrual cycle.

MAIN OUTCOME MEASURES

The basal levels of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone (T), sex hormone-binding globulin (SHBG), estrone, estradiol, prolactin, and the luteinizing and follicle-stimulating hormone ratio were measured. Basal and poststimulation levels of androstenedione (A), dehydroepiandrosterone (DHEA), 17 alpha-hydroxyprogesterone (17 alpha-OHP), 17-hydroxypregnenolone (17-PREG), 11-deoxycortisol (S), and cortisol (F) were also obtained, and the net increments after stimulation were calculated.

RESULTS

Normal-weight and obese women did not differ in age, height, or waist-hip ratio. Obese volunteers demonstrated lower circulating SHBG, 17-PREG, and S levels, and S/F ratio, but a higher free T and DHEAS/DHEA levels. No other differences were observed in either basal or adrenal response measures, with the exception of the net increment in A, which was almost twofold higher in obese volunteers (P less than 0.001).

CONCLUSIONS

Obesity in eumenorrheic nonhirsute women is associated with lower circulating SHBG activity and higher free T and DHEAS/DHEA levels. No significant difference in adrenocortical response to acute ACTH-(1-24) stimulation was observed between obese and normal-weight women, with the exception of a higher net adrenal output of A. It does not appear that the abnormal adrenal stimulation results frequently observed in hyperandrogenic women are a consequence of their obesity.