Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.
BACKGROUND
Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.


OBJECTIVE
The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.


METHODS
We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.


METHODS
The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy.


METHODS
One hundred nonobese primary infertile anovulatory women with PCOS participated.


METHODS
We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.


METHODS
The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.


RESULTS
The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).


CONCLUSIONS
Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.
Palomba
Stefano
S
Department of Gynecology and Obstetrics, University Magna Graecia of Catanzar, Via Nicolardi 188, 80131 Naples, Italy. stefanopalomba@tin.it
Orio
Francesco
F
Falbo
Angela
A
Manguso
Francesco
F
Russo
Tiziana
T
Cascella
Teresa
T
Tolino
Achille
A
Carmina
Enrico
E
Colao
Annamaria
A
Zullo
Fulvio
F
D000328:Adult; D000858:Anovulation / Q000188:drug therapy*; D002996:Clomiphene / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008687:Metformin / Q000627:therapeutic use*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011247:Pregnancy; D011446:Prospective Studies
D002996:Clomiphene; D008687:Metformin