Metformin and polycystic ovarian syndrome
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Metformin and Polycystic Ovarian Syndrome (PCOS)
Introduction to PCOS and Metformin
Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by irregular or absent ovulation, elevated levels of male hormones (androgens), and insulin resistance, often leading to hyperinsulinemia. This condition is associated with increased risks of cardiovascular disease and diabetes mellitus. Metformin, an insulin-sensitizing agent, has been widely studied for its potential benefits in managing PCOS symptoms, particularly anovulation and metabolic disturbances .
Metformin for Ovulation Induction
Metformin vs. Placebo
Research indicates that metformin may improve live birth rates compared to placebo, although the evidence quality is low. Metformin also appears to increase clinical pregnancy and ovulation rates significantly. However, it is associated with a higher incidence of gastrointestinal side effects . For instance, metformin was found to improve live birth rates (OR 1.59) and clinical pregnancy rates (OR 1.98) compared to placebo, but with a notable increase in gastrointestinal disturbances (OR 4.00).
Metformin Combined with Clomiphene Citrate (CC)
When combined with clomiphene citrate (CC), metformin may enhance clinical pregnancy and ovulation rates compared to CC alone. However, the combination therapy also increases the likelihood of gastrointestinal side effects. The evidence on whether this combination improves live birth rates remains inconclusive . Studies show that the combination therapy group had higher clinical pregnancy rates (OR 1.62) and ovulation rates (OR 1.65) but also experienced more gastrointestinal side effects (OR 4.26).
Metformin vs. Clomiphene Citrate
Comparing metformin directly with CC, the findings for live birth rates are inconsistent. In obese women, metformin appears less effective, while non-obese women might benefit more from metformin, although the evidence is of very low quality . For example, obese women had lower birth rates with metformin (OR 0.30), whereas non-obese women showed a possible benefit (OR 1.71).
Metformin and Lifestyle Modifications
Combining metformin with lifestyle modifications, such as diet and exercise, has shown promising results in managing PCOS. This combination is associated with lower BMI, reduced subcutaneous adipose tissue, and improved menstrual regularity compared to lifestyle modifications alone . Studies indicate that lifestyle plus metformin significantly reduces BMI (MD -0.73 kg/m²) and increases menstrual cycles (MD 1.06) over six months.
Metformin in Assisted Reproductive Techniques (ART)
Metformin's role in improving outcomes for women with PCOS undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is still under investigation. While metformin may reduce the incidence of ovarian hyperstimulation syndrome (OHSS), its effect on live birth rates remains uncertain. The evidence suggests that metformin might increase clinical pregnancy rates in long GnRH-agonist protocols but not in short GnRH-antagonist protocols. For instance, metformin reduced OHSS incidence (RR 0.46) but showed mixed results on live birth rates depending on the stimulation protocol used.
Metformin and Combined Oral Contraceptive Pills (COCP)
When comparing metformin with combined oral contraceptive pills (COCP), metformin is found to be inferior in reducing androgen levels but superior in lowering insulin and triglyceride levels. Combination treatment with metformin and COCP may offer biochemical benefits by targeting both hyperinsulinemia and hyperandrogenism. For example, metformin lowered insulin levels (-27.12 pmol/l) and triglycerides (-0.15 mmol/l) compared to COCP.
Conclusion
Metformin shows potential benefits in managing PCOS, particularly in improving ovulation and clinical pregnancy rates. However, its effectiveness in increasing live birth rates is less clear, and it is associated with gastrointestinal side effects. Combining metformin with lifestyle modifications or other treatments like CC may enhance its efficacy. Further research is needed to clarify its role in assisted reproductive techniques and long-term management of PCOS.
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