The effects of continuous androgen secretion on the hypothalamic-pituitary axis in woman: Evidence from a luteinized thecoma of the ovary

Hyperandrogenic states in women are often accompanied by disruption of gonadotropin secretion. However, the role of androgens per se in the pathogenesis of this abnormality is poorly understood. We report a woman with a virilizing ovarian tumor in whom the effects of continuous androgen secretion on the hypothalamic-pituitary axis were investigated in detail. A 29-yr-old woman with previously normal reproductive function, including prior fertility, was evaluated for amenorrhea and hirsutism. She had elevated peripheral serum levels of testosterone (T; 337-500 ng/dl) and androstenedione (A; 258-353 ng/dl). Her serum LH level was above the normal follicular phase range and was hyperresponsive to LHRH, whereas the FSH level was below normal early follicular phase levels and increased minimally in response to LHRH. A luteinized thecoma of the left ovary, shown by catherization of the ovarian venous blood to be secreting both T and A, was removed. Postoperatively, serum T and A levels returned to normal, and the patient had a normal ovulatory menstrual cycle in the 30 days after the operation, documented by daily determinations of plasma estradiol, progesterone, and gonadotropin levels. A repeat LHRH test in the follicular phase of the second postoperative menstrual cycle was completely normal. This case indicates that the characteristic abnormalities of gonadotropin secretion observed in hyperandrogenic states such as polycystic ovarian disease can result from chronic androgen secretion by an ovarian tumor and that normal folliculogenesis and gonadotropin secretion can be promptly restored by the elimination of the androgen excess.