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Adrenocortical Secretion of Dehydroepiandrosterone in Healthy Women: Highly Variable Response to Adrenocorticotropin¹

Departments of Obstetrics and Gynecology (R.A., R.P., L.R.B.), Medicine (R.A.), and Biostatistics (L.M.F.), University of Alabama, Birmingham, Alabama 35233; and Department of Gynecology and Obstetrics, The Johns Hopkins University College of Medicine (H.A.Z.), Baltimore, Maryland 21287

Address all correspondence and requests for reprints to: Ricardo Azziz, M.D., Department of Obstetrics and Gynecology, University of Alabama, 618 South 20th Street, OHB 549, Birmingham, Alabama 35233-7333. E-mail: razziz{at}uabmc.edu

Abstract

Excess adrenal androgen (AA) levels are observed in 25–50% of women with the polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent selection bias. Thus, it is possible that AA secretion among the general population is highly variable, and that those women who are predisposed to secreting greater amounts of AA have a greater probability of having PCOS. We now hypothesize that the levels of AAs are highly variable among normal nonhyperandrogenic women, and that this heterogeneity is the result of a variable response of AAs to ACTH stimulation. To test this hypothesis we prospectively studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1–24) in 56 healthy eumenorrheic nonhirsute healthy women with a mean age of 28.9 yr (range, 20–37 yr.) and a mean body mass index (BMI) of 29.2 kg/m² (18.2–46.2 kg/m²). Baseline samples and poststimulation samples were assayed for DHA and F. The basal and ACTH-stimulated levels of DHA, but not those of F, were negatively correlated with age, although neither the basal nor ACTH-stimulated responses of DHA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. F; r = -0.54; P < 0.001), whereas there was no significant relationship between basal DHA and DHA. We also compared the intersubject variability (coefficient of variation) for basal and stimulated levels of DHA and F. For basal (DHA₀), 60 min (DHA₆₀), and net increment in (DHA) DHA levels, the coefficients of variation were 67.9%, 61.4%, and 76.0%, respectively; for F₀, F₆₀, and F, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in DHA was significantly higher, and the variance in F₆₀ was significantly lower than that in all other variables; DHA₀, DHA₆₀, F₀, and F had similar variances.

In conclusion, in our population of healthy reproductive-aged women we observed that both basal and ACTH-stimulated levels of DHA after ACTH-(1–24) stimulation had significantly greater intersubject variance (60–70%) compared with the basal and poststimulation levels of F (15–40%). These data support the hypothesis that among normal women, AA (i.e. DHA) levels are highly variable compared to those of F. In addition, the intersubject variability in DHA levels is at least in part due to a variable response of AAs to ACTH stimulation. Whether the AA excess frequently observed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.

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