Adrenocortical secretion is up-regulated in women with polycystic ovary syndrome (PCOS), and absolute adrenal androgen (AA) excess is evident in similar to25% of these patients. We hypothesized that AA biosynthesis is an inherited trait and that, as for other inherited traits, AA biosynthesis remains stable over time. To test this hypothesis, we prospectively studied 23 off-treatment PCOS patients and seven age- and body mass index-matched control women on two separate occasions 3-5 yr apart (45.0+/-19.0 months and 47.4+/-21.3 months, respectively; P>0.05). All subjects underwent an acute adrenal stimulation using 0.25 mg ACTH-(1-24), and dehydroepiandrosterone (DHEA), androstenedione, and cortisol (F) were measured 0 and 60 min post ACTH; basal levels of total and free testosterone (T), SHBG, and DHEA sulfate (DHEA-S) were also assessed. Among PCOS patients, the mean DHEA-S levels during the repeat study were significantly lower when compared with the initial assessment (170+/-107 mug/dl vs. 134+/-79 mug/dl, respectively; P=0.02). However, only patients with initial DHEA-S levels above the median ( high DHEA-S) experienced a net decrease in the levels of this metabolite (252.5+/-99.2 mug/dl vs. 174.3+/-82.5 mug/dl; P=0.001) over the time of the study; patients with initial DHEA-S levels in the lower half ( low DHEA-S) did not experience a change in DHEA-S (94.6+/-28.9 mug/dl vs. 97.7+/-56.5 mug/dl; P=0.85).