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.
Baillargeon
Jean-Patrice
JP
Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Jakubowicz
Daniela J
DJ
Iuorno
Maria J
MJ
Jakubowicz
Salomon
S
Nestler
John E
JE
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