Adrenocortical secretion of dehydroepiandrosterone in healthy women: Highly variable response to adrenocorticotropin

Excess adrenal androgen (AA) levels are observed in 25-50% of women with th e polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent sel ection bias. Thus, it is possible that AA secretion among the general popul ation is highly variable, and that those women who are predisposed to secre ting greater amounts of AA have a greater probability of having PCOS. We no w hypothesize that the levels of AAs are highly variable among normal nonhy perandrogenic women, and that this heterogeneity is the result of a variabl e response of AAs to ACTH stimulation. To test this hypothesis we prospecti vely studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1-24) in 56 healthy eumenorrheic n onhirsute 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/m(2) (18.2-46.2 kg/m(2)). Baseline s amples and poststimulation samples were assayed for DHA and F. The basal an d ACTH-stimulated levels of DHA, but not those off, were negatively correla ted with age, although neither the basal nor ACTH-stimulated responses of D HA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. DeltaF; r = -0.54; P < 0.0 01), whereas there was no significant relationship between basal DHA. and < Delta>DHA. We also compared the intersubject variability (coefficient of va riation) for basal and stimulated levels of DHA and F. For basal (DHA(0)), 60 min (DHA(60)), and net increment in (Delta DHA) DHA levels, the coeffici ents of variation were 67.9%, 61.4%, and 76.0%, respectively; for F-0, F-60 , and DeltaF, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in Delta DHA was significantly higher, and the variance in F,, was signifi cantly lower than that in all other variables; DHA(0), DHA(60), F-0, and De ltaF had similar variances. In conclusion, in our population of healthy reproductive-aged women we obse rved that both basal and ACTH-stimulated levels of DHA after ACTH-(1-24) st imulation had significantly greater intersubject variance (similar to 60-70 %) compared with the basal and poststimulation levels of F (similar to 15-4 0%). These data support the hypothesis that among normal women, AA (i.e. DH A) levels are highly variable compared to those of F. In addition, the inte rsubject variability in DHA levels is at least in part due to a variable re sponse of AAs to ACTH stimulation. Whether the AA. excess frequently observ ed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.