Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.
OBJECTIVE
To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone.


METHODS
Randomized controlled double-blind trial.


METHODS
A referral center in Caracas, Venezuela.


METHODS
One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention.


METHODS
One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo.


METHODS
Frequencies of ovulation and serum free T after 6 months.


RESULTS
Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone.


CONCLUSIONS
These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.
Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Jean-Patrice
JP
Baillargeon
Daniela J
DJ
Jakubowicz
Maria J
MJ
Iuorno
Salomon
S
Jakubowicz
John E
JE
Nestler
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D008687:Metformin / Q000008:administration & dosage*; D010060:Ovulation / Q000187:drug effects*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000077154:Rosiglitazone; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014687:Venezuela
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D012738:Sex Hormone-Binding Globulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D008687:Metformin