A Comparative Clinical Study of Clomifene, Letrozole, Finasteride and Metformin in Treatment of Infertility in Women with Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy typified by oligo-ovulation or anovulation, signs of androgen excess, and multiple small ovarian cysts. PCOS is thought to be one of the leading causes of female subfertility. It has been estimated that PCOS affects 5-10% of females in reproductive age in some way. The etiology of the syndrome is complex and likely multifactorial. Aim of study: The objective of the present clinical study is to evaluate the therapeutic effect of clomifene citrate compared to letrozole when both given alone and metformin when given alone compared to finasteride when being combined with contraceptive pill in the treatment of patients with infertility secondary to PCOS. Patients and Methods:
One hundred sixty- two infertile married women at reproductive age were involved in this study during their attendance at the infertility center of maternity and pediatrics teaching hospital in Hilla city and those referred from hospital in Hilla city, Babylon Province, Iraq. Patients where collected depending on history and physical examination (including both breast and pelvic examinations) seeking for the presence of secondary sexual characteristics, features of endocrine disorders, clinical signs of hyperandrogenism such as acne and hirsuitism. At day 2 of menstrual cycle measurement of hormones including Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin, Testosterone and Thyroid Stimulating Hormone (TSH), also Fasting blood glucose (FBG), and LH/FSH ratio were done. On day 12 of menstrual cycle ultrasound examination was done transvaginally to detect the number and size of follicles. Patients were diagnosed as PCOS when they have at least two out of three of Rotterdam criteria. Then Patients were divided into four groups. Group 1 include 45 patients (80 cycles) were treated with clomifene citrate (50 mg twice daily for 5 days starting from day 2 of menstrual cycle), group 2 include 40 patients (47 cycles) were treated with letrozole (5 mg daily for 5 days starting from day 2 of menstrual cycle), group 3 include 39 patients were treated with finasteride (5 mg daily concomitantly with an oral contraceptive consisting of cyproerone acetate plus ethinyloestradiol, starting from day 5 of menstrual cycle continuously for 2 months), and group 4 include 38 patients were treated with metformin (500mg three times daily, starting from day 2 of menstrual cycle continuously for 3 months). After treatment the outcome measured (size and number of mature follicles, monofollicular cycles and ET measured at day 12 of menstrual cycle and pregnancy rate) in CC group were compared to those in letrozole group, while outcome measured in finasteride group were compared to those in metformin group. Results: In regard to the treatment with clomifene citrate and letrozole the present study found that each of the percentages of cycles responded to the treatment (resulted in mature follicles ≥17 mm in size) (70.21% versus 41.25%) and the mean number of mature follicles (1.420.66 versus 1.150.44) was significantly higher in letrozole treated group (p<0.05). While the number of monofollicular cycles (87.87% versus 63.63%) and the mean of endometrial thickness (ET) (9.68  2.73 versus 8.02  1.24 mm) was significantly higher in clomifene citrate treated group (p<0.05). Also the pregnancy rate (per cycle) was higher in clomifene citrate treated group (12.12% versus 9.09%) although there was no significant difference (p>0.05). In regard to the treatment with metformin and finasteride the present study, found that the percentage of patients responded to these drugs was higher in finasteride treated group (35.89% versus 26.315%) although significant differences were not found (p >0.05). The difference between finasteride and metformin in regard to the mean number of mature follicles per patient (1.21 0.43 versus 1.2 0.42) was insignificant (p> 0.05). The difference between the mean of ET in finasteride and metformin groups (7.261.1and 7.80 2.25 mm respectively) was also insignificant (p> 0.05). The pregnancy rate per patient was higher in metformin treated group (60% versus 21.42%); however, this difference was insignificant (p> 0.05). Conclusion: In patients with infertility secondary to PCOS we can conclude the following: 1. Letrozole (when given alone) was the better in comparison to clomifene citrate (when given alone) in regard to each of responded cycles and mean number of mature follicles whereas regarding to each of endometrial thickness, monofollicular cycles, and pregnancy rate (per cycle), clomifene citrate was the better. 2. Finasteride (when combined with contraceptive pill) was the better in comparison to metformin (when given alone) in regard to responded patients whereas regarding each of monofollicular development and ET they were comparable in both groups and regarding the rate of pregnancy (per patient) metformin was the better.