Hirsutism, Polycystic Ovarian Disease, and Ovarian 17-Ketosteroid Reductase Deficiency

We studied an 18-year-old woman with progressive hirsutism, secondary amenorrhea, and polycystic ovarian disease. Excess androstenedione was secreted by the ovaries, most likely because of a genetic deficiency of ovarian 17-ketosteroid reductase, the enzyme that converts androstenedione to testosterone. Markedly elevated basal plasma levels of androstenedione, estrone, and testosterone were regulated by gonadotropin but not by ACTH. The rate of androstenedione production in the patient's blood at base line and after administration of dexamethasone was very high (10.0 to 11.6 mg per day; value in control women with hirsutism, <4.1 mg per day), where-as her blood production of testosterone was 0.64 to 0.7 mg per day, similar to or higher than that in control women with hirsutism. The fractional blood conversion ratio of androstenedione to testosterone was normal (5.6 percent). Thus, 88 to 93 percent of the testosterone in the blood was derived from the peripheral conversion of androstenedione, and very little testosterone was secreted by the ovaries. These in vivo biochemical data suggest that the patient had a deficiency of ovarian 17-ketosteroid reductase activity but normal pubertal activity. The patient's two younger sisters with peripubertal symptoms of androgen excess also had elevated serum levels of androstenedione. We propose that the increased secretion of androstenedione in the three siblings in this family was probably due to a genetic deficiency of ovarian 17-ketosteroid reductase. (N Engl J Med 1987; 316: 1295–301.), THE existence of 17-ketosteroid reductase, which converts the precursor hormone androstenedione to the product hormone testosterone and converts estrene to estradiol in human adrenal and gonadal tissue, is well known. Furthermore, a genetic defect or deficiency in this enzyme in testicular tissue is a well-defined cause of male pseudohermaphroditism due to the insufficient production of testosterone beginning in early fetal life.^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24} This enzyme deficiency is rarely diagnosed at birth.^19,20 More frequently, it is discovered at or after puberty in genetic males (raised as males) during assessments of gynecomastia and incomplete male genital development.^8,24 In genetic males raised as females,^5,9,21,22 severe….