The deficiency of ovarian 17-ketosteroid
reductase (17-KSR) was recently discovered to be a possible cause of polycystic
ovarian disease (PCOD) in hirsute women. Forty three patients with PCOD (age range, 18-38 yr) were reevaluated to search for a hormonal pattern that might suggest an ovarian
17-KSR deficiency.
Androstenedione,
testosterone, FSH, LH,
17-hydroxyprogesterone, and
dehydroepiandrosterone sulfate were evaluated basally on the day 17 of the menstrual cycle, when present, and after dynamic tests (
ACTH stimulation, 1 mg im for 2 consecutive days;
dexamethasone inhibition, 0.5 mg four times a day for 14 days; and
cyproterone acetate treatment, 50 mg each day for 14 days) in three successive menstrual cycles or at 30-day intervals. All patients studied presented with hyperestronemia, abnormal
gonadotropin pattern, and
hyperandrogenism, but showed different responses of
androstenedione and
testosterone to dynamic tests. In two patients the hormonal pattern suggested an ovarian
17-KSR deficiency: in fact they showed plasma values of
androstenedione (22 and 31.3 nmol/L, respectively) and
estrone (628 and 849 pmol/L, respectively) that were greatly increased compared with other patients and with controls.
Androstenedione did not increase after
ACTH stimulation (21.5 and 32.1 nmol/L, respectively) and did not decrease after
dexamethasone inhibition (21 and 29 nmol/L, respectively), but only decreased after
cyproterone acetate treatment (8 and 10.8 nmol/L, respectively). An hCG test, performed during
dexamethasone suppression, confirmed the diagnosis of ovarian 17-KSR defect in one of these two patients (patient 1). Two of three brothers of patient 1 (aged 25 and 34 yr) presented with persistent important pubertal
gynecomastia; one brother also had severe
oligospermia. These clinical findings and the high values of
androstenedione/
testosterone (0.85) and
estrone/
estradiol (4.1) ratios of baseline plasma levels compared with controls (0.18 and 2.1, respectively) suggested a partial testicular
17-KSR deficiency. Five other patients showed PCOD secondary to nonclassic
21-hydroxylase defect diagnosed on the basis of high
17-hydroxyprogesterone plasma values and highly responsive to
ACTH. The remaining 36 patients showed increased values of
androstenedione and
testosterone after
ACTH stimulation and a decrease of these two parameters after both
dexamethasone inhibition and
cyproterone acetate treatment. The discovery of the
17-KSR deficiency in men and women in the same family demonstrates genetic control of this
enzyme similar in both sexes, confirming the hypothesis that this disorder is inherited as an autosomal recessive character. Finally, it is strongly supported that ovarian 17-KSR defect may cause a syndrome closely resembling PCOD.