Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome.
To test the hypothesis that insulin plays a role in the hyperandrogenism of obese women with polycystic ovary syndrome, we conducted a prospective study in which the androgen status of five obese women with polycystic ovary syndrome was assessed on two occasions: before and after 10 days of oral diazoxide (100 mg, three times daily) administration. Fasting serum insulin levels decreased from 177 +/- 45 (+/- SE) to 123 +/- 43 pmol/L (P less than 0.01) and insulin release in response to 100 g oral glucose administration decreased from 223.0 +/- 29.2 to 55.6 +/- 7.9 nmol.min/L (P less than 0.002) after diazoxide administration. At the same time, serum total testosterone fell from 2.5 +/- 0.4 to 2.1 +/- 0.3 nmol/L (P less than 0.007), serum testosterone not bound to sex hormone-binding globulin fell from 1.9 +/- 0.3 to 1.4 +/- 0.2 nmol/L (P less than 0.01), and the molar ratio of serum androstenedione to serum estrone fell from 25.7 +/- 7.7 to 16.6 +/- 5.5 (P less than 0.04). Serum sex hormone-binding globulin levels increased slightly but not significantly from 13.2 +/- 1.0 to 21.7 +/- 4.1 nmol/L. Serum androstenedione, dehydroepiandrosterone sulfate, estradiol, estrone, and progesterone concentrations did not change, nor did basal or GnRH-stimulated serum LH and FSH concentrations. These results suggest that hyperinsulinemia in obese women with polycystic ovary syndrome may directly increase serum testosterone levels.
Nestler
J E
JE
Department of Internal Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Barlascini
C O
CO
Matt
D W
DW
Steingold
K A
KA
Plymate
S R
SR
Clore
J N
JN
Blackard
W G
WG
D001786:Blood Glucose / Q000032:analysis; D003981:Diazoxide / Q000008:administration & dosage*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000097:blood / Q000209:etiology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000150:complications*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003981:Diazoxide