Reply: Metformin in therapy naïve patients with polycystic ovary syndrome
Department of Obstetrics and Gynaecology,
Centre for Reproductive Medicine, Academic Medical Center,
University of Amsterdam,
PO Box 22700, 1100 DE Amsterdam,
The Netherlands
1 Correspondence address. E-mail: e.moll{at}amc.uva.nl
The literature on metformin and polycystic ovary syndrome includes a lot of confusing information about the type of patient and the type and amount of medication. Our review attempted to clearly distinguish the type of patients, therapies and comparisons. One of the comparisons is clomiphene versus clomiphene plus metformin. When we look at these data, there is no doubt that metformin does not have an additional role next to clomiphene in naïve patients in reaching a live birth. The pooled relative risk for live birth was 1.0 (95% CI 0.82–1.3; three trials with 664 women). Two studies reported multiple pregnancy rates (Moll et al., 2006
; Legro et al., 2007). After combining these data no significant difference was seen (RR 0.38; 95% CI 0.09–1.5; 193 women).
The suggestion of excluding the articles of Khorram et al. (2006) and Sahin et al. (2004) is not correct. Khorram et al. randomized patients between metformin plus clomiphene and clomiphene alone. Metformin was started in the same cycle as was clomiphene. Sahin et al. did treat the patients with metformin 3 months prior to administrating clomiphene, but all patients also received clomiphene, which also makes the comparison justifiable. Both these studies together counted for 52 of 985 patients (5%) in this particular comparison.
Obviously, there is no argument against more data as the estimation of the truth will thereby improve.
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Khorram O, Helliwell JP, Katz S, Bonpane CM, Jaramillo L. Two weeks of metformin improves clomiphene citrate-induced ovulation and metabolic profiles in women with polycystic ovary syndrome. Fertil Steril (2006) 85:1448–1451.[CrossRef][Web of Science][Medline]
Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosmon GG, et al. Cooperative Multicenter Reproductive Medicine Network. (2007) Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med (2007) 356:551–566.
Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ (2006) 332:1485. 2006.
Sahin Y, Yirmibes U, Kelestimur F, Aygen E. The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol (2004) 113:214–220. 2004.[CrossRef][Web of Science][Medline]
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