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Abstract
Polycystic ovary syndrome (PCOS) is a phenotypically heterogenous disorder that was first described by Stein and Leventhal in 1935 as a classic triad of amenorrhea, obesity and hirsutism. Diagnostic criteria to establish PCOS are controversial, involving two among the following three Rotterdam’s criteria: first, clinical and/or sings of hyperandrogenism, second, a chronic absence of ovulation and finally, third, the increase of ovarian volume and/or the presence of at least 12 follicles in the 2- to 9-mm range in each ovary, detected by ultrasonograpy (Rotterdam ESHRE/ASRM, 2004). Other clinical and biochemical characteristics associated with PCOS include gonadotropin abnormalities (elevated LH pulse amplitude and frequency with usually increased LH-FSH ratio) and metabolic abnormalities (peripheral insulin resistance with hyperinsulinemia independent of obesity). Polycystic ovary syndrome affects approximately 5% of all reproductive age women and is a major cause of infertility. A potential new therapy for anovulatory infertility associated with PCOS is administration of an insulin-sensitizing agent. Current clinical protocols involve an orderly step-by-step approach to ovulation inducyion that includes weight loss, clomiphene, gonadotropins, ovarian surgery and assisted reproductive techniques or IVF/ICSI. The first line of treatment is weight loss for patients with an elevated body mass index. Studies have shown that as little as 5% loss of total body weight is often associated with an increased number of ovulatory cycles. On the basis of the theory that hyperinsulinemia impedes ovulation and may be an important contributor to the pathophysiology of PCOS, it is postulated that insulin sensitizers might improve the endocrine imbalances associated with PCOS, resulting in an increase in ovulatory menstrual cycles and pregnancy. Metformin is an oral biguanide anti-hyperglycemic drug used for decades in Europe for the treatment of non insulin-dependant diabetes. It is a category B drug for pregnant women and is used by some clinicians to treat diabetes in pregnant women (Nestler et al, 1998). Metformin lowers blood glucose mainly by inhibiting blood glucose production and by enhancing peripheral glucose uptake. Metformin enhances insulin sensitivity at the post receptor level and stimulates insulin-mediated glucose disposal. Recent research suggests that metformin may increase the number of ovulatory cycles in women with PCOS, especially in conjunction with clomiphene. In our study, we aimed at assessing the effect of metformin therapy in lean and obese PCOS women. Thirty four PCOS women were included in this study. They were divided into two groups: Lean cases: body mass index < 25 kg/m .
Obese cases: body mass index > 30 kg/ m .
All women were subjected to clinical examination, anthropometric measures, hormonal assays and transvaginal ultrasonographic examination before treatment and hormonal assays are repeated again six months after treatment. For all cases of the study, metformin therapy was administered in a dose of 500 mg three times daily for six months. As regarding the results of the three months period o metformin therapy, the followings was observed:
A significant improvement in the clinical measures of the PCOS women e.g. menstrual disturbances.
8 lean women (50.0%) and 4 obese women (22.2%) ovulated.
6 lean women ( 37.5%) and 3 obese women (16.6%) conceived. These results were in agreement with most but not all investigators concerned with the effect of metformin on ovulation and pregnancy.