Ovarian Hyperthecosis: In Vivo and In Vitro Correlations of the Androgen Profile

A 36-year-old patient with secondary amenorrhea and progressive frank virilization was found by histologic examination to have ovarian hyperthecosis. Baseline androgenic investigation revealed a selective increase in testosterone (T) production rate (3.1 mg/day), which was associated with an increase in both plasma T concentration (total and unbound) and metabolic clearance rate (MCR) of T (2156 liters/day). There was a marked concentration gradient for circulating plasma T between each ovarian vein and the peripheral veins (right ovarian, 50 ng/ml; left ovarian, 21 ng/ ml). After bilateral wedge resection there was a rapid decrease in the total and unbound T levels as well as in the MCR of T, which remained normal for at least 6 months. By then the patient had stopped shaving and was menstruating normally. In vitro incubation studies of fragments from each ovary revealed incorporation of [ H]-dehydroepiandrosterone and [H]-progesterone into [H]-T in the range reported for normal human ovarian stroma, and short-term cellular culture suggested a normal morphology and steroidogenesis. It is concluded that in this patient with ovarian hyperthecosis, the observed increased ovarian T production resulted more from an increase in the amount of stromal-thecal tissue than from a functional biochemical defect in the latter.