Effects of Pioglitazone Versus Metformin on Metabolism and Ovulation in PCOS

Abstract

BRIEF BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting 5-10% of women of reproductive age. It is characterized by insulin resistance, hyperinsulinemia, hyperandrogenism and polycystic ovaries. PCOS is the most common cause of female infertility and increases risk of endometrial cancer, type-2 diabetes and cardiovascular problems. Pioglitazone and Metformin are insulin sensitizing oral hypoglycemic drugs used for treating PCOS related infertility. OBJECTIVES: To evaluate and compare the effects of pioglitazone and metformin on metabolism and ovulation among PCOS infertile women. SUBJECTS, MATERIALS AND METHODS: In this randomized open prospective clinical trial after RRC and ERC approval eighty diagnosed PCOS infertile women with ages 20-40 years (Rotterdam criteria 2003) were enrolled from the infertility clinic of a private hospital of Karachi. Written informed consent was taken from all patients and they were divided into two groups with 40 individuals. Group A received tablet Pioglitazone 30 mg once daily per orally while Group B received tablet metformin HCl 500 mg thrice daily per orally for three months. Escalation to required dose was done in one week time. Both groups were advised for 30-60 minute walk daily, avoidance of excess sugars, oily food and red meat from their diet along with pharmacotherapy. Patients were subjected to evaluation of body weight, BMI, waist and hip circumference, W/H ratio, cyclical regularity, F-G scoring, estimation of blood pressure, serum FSG, FSI, G/I ratio, FSH, LH, testosterone, prolactin, progesterone, TSH, lipid profile, hs-CRP, CBC, LFTs with transvaginal ultrasound at baseline. At day 90 all parameters were evaluated again with the exception of FSH, LH, testosterone, prolactin, TSH and transvaginal ultrasound. RESULTS: Patients in both groups were equally matched with the exception of body weight and BMI. This is caused by recruitment of more obese patients in Group B on account of computer generated randomization list. The mean weight in Group A was 68.90 ± 10.39 kg versus 76.03 ± 9.82 kg in Group B at baseline. 2 In Group A statistically significant reduction was produced in systolic blood pressure that remained within the normal limits of adult blood pressure range. Weight, BMI, waist and hip circumference and W/H ratio showed non-significant results at day 90. F-G score, acanthosis nigricans, male pattern baldness and cyclical regularity showed significant improvement at day 90. FSG, FSI, G/I ratio, HDL, LDL, VLDL, cholesterol, triglycerides, hs-CRP, progesterone, Hb, hematocrit, MCV, MCH, MCHC, serum enzymes ALT, AP and AST showed statistically significant results at day 90. Weight gain was found in 9(29.03%) patients. In Group B weight, BMI, F-G score, cyclical regularity, FSG, FSI, G/I ratio, HDL, LDL, VLDL, cholesterol, triglycerides, hs-CRP, progesterone, Hb, hematocrit, serum enzymes GGT, ALT, AP and AST showed statistically significant results at day 90. Weight gain was found in only 2(6.6%) patients. Upon comparison Pioglitazone produced more beneficial effects on carbohydrate metabolism with more profound increase in serum progesterone level and less deleterious effects on the liver function profile. It produced more number of pregnancies (4v/s2) during treatment period of three months. Metformin produced more beneficial effects on lipid and protein metabolism. Metformin produced more reduction in body weight, BMI, waist to hip ratio, diastolic blood pressure and more improvement in cyclical regularity. CONCLUSION: Pioglitazone and Metformin have produced significant effects on metabolism and ovulation within their respective group indicating clinical efficacy for treating PCOS infertile women. Upon comparison, Pioglitazone is found to be superior to Metformin due to more pronounced effect on ovulation. It offers alternate treatment option in PCOS infertile women.