Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome.
OBJECTIVE
In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS.


METHODS
Double-blind, randomized, placebo-controlled trial.


METHODS
Academic reproductive endocrinology clinic.


METHODS
Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC.


METHODS
Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months.


METHODS
The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens.


RESULTS
Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change.


CONCLUSIONS
Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.
Ghazeeri
Ghina
G
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis 38163, USA.
Kutteh
William H
WH
Bryer-Ash
Michael
M
Haas
Derek
D
Ke
Raymond W
RW
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002996:Clomiphene / Q000008:administration & dosage*; D003894:Deamino Arginine Vasopressin / Q000031:analogs & derivatives* / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D010062:Ovulation Induction; D010919:Placebos; D011085:Polycystic Ovary Syndrome / Q000628:therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D000077154:Rosiglitazone; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood; D013844:Thiazoles / Q000008:administration & dosage*; D045162:Thiazolidinediones
D001786:Blood Glucose; D002996:Clomiphene; D003894:Deamino Arginine Vasopressin; D019314:Dehydroepiandrosterone Sulfate; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D000077154:Rosiglitazone; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D013844:Thiazoles; D045162:Thiazolidinediones; C010097:DCDAVP