Randomized trial of effect of metformin on some endocrine and metabolic parameters in women with insulin resistance related polycystic ovarian syndrome

ABSTRACT

To evaluate the effect of metformin [3-6 months therapy] on the clinical, endocrinal, metabolic, and ovulatory performance in women with insulin resistance-related polycystic ovarian syndrome [PCOS]. 60 women with insulin resistant polycystic ovarian syndrome [PCOS] were included and divided equally between clomiphene citrate [100 mg daily for five days], metformin [500 mg tablet 3 times per day] and combined clomiphene citrate and metformin treatments for 3-6 months. All the women had a fasting insulin level of > 10 micro U/ml and an accumulated insulin level [area under the curve for insulin during a 2-hour, 75-g oral glucose tolerance test] of > 5,000 micro U/ml/min. The primary outcome variable was the rate of ovulation. Our secondary outcome variables included clinical variables [menstrual pattern, body weight, BMI, hirsuitism score], endocrine variables [levels of LH, FSH, testosterone, SHBG] and metabolic variables [fasting glucose, fasting insulin, accumulated insulin level, LDL, HDL, cholesterol, triglycerides]. Statistical analysis included X2, Fisher exact for count variables and the ANOVA test for parametric continuous data. Kolmogoroy-Smirnov test was used to examine he distributional characteristics of the continuous variable. The significance level was chosen at P <.05. Patients who were treated with Metformin and Clomiphene have a significantly higher ovulation rate [69. 7%] than those treated with clomiphene [35.5%] or metformin alone [44.5%]. Clomiphene therapy was associated with significant reduction of oligomenorrhea and amenorrhea, significant increase in tile frequency of regular cycles and significant increase in the serum progesterone level but no significant difference regarding the other clinical and endocrine parameters nor any effect on the metabolic parameters. The use of metformin either alone or in addition to clomiphene was associated with significant reduction of body weight, BMI, hairsuitism and the frequency of amenorrhea/oligomenorrhea. Regarding the endocrine parameters, it's associated with significant reduction of LH level, testosterone level and sign increase in SHBG and serum progesterone level. It's also associated with significant reduction of the fasting glucose level, fasting insulin level, AUC insulin, total cholesterol, triglycerides, LDL and significant increase in HDL. There was no difference among the three study groups as regards the body weight, BMI, hairsuitism score, frequency of regular menses, serum FSH level, serum progesterone level, fasting glucose level and serum LDL level. Patients who were treated with either Metfarmin or Metformin and Clomiphene, had a significant lower level of LH/FSH ratio, testosterone, fasting insulin level, AUC insulin, total cholesterol and serum triglycerides level, and significant higher level of SHBG and serum HDL. This study concluded that metformin plus clomiphene is more effective than clomephine alone in inducing ovulation in patients with insulin-resistant PCOS. Moreover, it's more effective in reducing the testosterone level, normalizes the glucose tolerance and improves lipid profile