1 Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and 2 Department of Internal Medicine, Division of Endocrinology, S1hhiye 06100 Ankara, Turkey
Dear Sir,
We appreciate the interest of De Leo and la Marca in our manuscript (Yarali et al., 2002). We did not note a significant change in insulin sensitivity with metformin pretreatment. However, there was a significant increase in spontaneous ovulation rate with metformin compared with placebo. We therefore postulated that significant restoration of ovulation by metformin might be due to its direct effect on the ovaries. We should stress that the exact molecular biological mechanism(s) of action of metformin on the ovary, if present, is not known.
The only significant change associated with metformin treatment was a decrease in free testosterone levels. As we have stressed in our paper, the lack of data on sex hormone-binding globulin is a limitation.
The study by Stadtmauer et al. (Stadtmauer et al., 2001) is an IVF-based retrospective study. The rationale, protocol and drugs used in the context of IVF are totally different from that of the low-dose step-up protocol. Therefore, it is not appropriate to compare the results of this study with ours and De Leos study (De Leo et al., 1999
).
Further well-designed appropriately powered prospective randomized studies are clearly warranted to delineate the role of insulin sensitizing drugs to restore ovulation in patients with polycystic ovary syndrome.
Notes
3 To whom correspondence should be addressed E-mail: yarali{at}ada.net.tr
References
De Leo, V., la Marca, A., Ditto, A. et al. (1999) Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome. Fertil. Steril., 72, 282285.[ISI][Medline]
Stadtmauer, L.A., Toma, S.K., Riehl, R.M. and Talbert, L.M. (2001) Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil. Steril., 75, 505509.[ISI][Medline]
Yarali, H., Yildiz, B.O., Demirol, A. et al. (2002) Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Hum. Reprod., 17, 289294.