The effect of clomiphene citrate, herbal mixture, and herbal mixture along with clomiphene citrate on clinical and para-clinical parameters in infertile women with polycystic ovary syndrome: a randomized controlled clinical trial

Introduction: To evaluate the effect of a herbal mixture (i.e., Mentha spicata, Zingiber officinale, Cinnamomum zeylanicum, and Citrus sinensis) alone and in combination with clomiphene citrate (CC) compared to CC on the treatment of polycystic ovary syndrome (PCOS). Material and methods: This single-blind randomized clinical trial was conducted on 60 infertile participants with PCOS who were randomly divided into three groups. After spontaneous or progestin-induced withdrawal bleeding, group 1 (n = 20) received routine treatment with CC (50-150 mg) for three menstrual cycles from the 3rd to 5" day of menstruation for 5 days while group 2 (n = 20) and group 3 (n = 20) received herbal mixture capsules 700 mg/day and the herbal mixture along with CC for 3 months, respectively. Finally, several related parameters were measured, including the level of sex steroids, homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile (primary outcomes), thyroid hormones, and clinical features. The analysis was based on intention-to-treat analysis. Results: No statistically significant differences were observed between the groups in terms of socio-demographic characteristics. However, after adjustment for baseline, luteinizing hormone (aMD = 4.9; 95% CI: 3.7-6.2), luteinizing hormone/follicle-stimulating hormone (aMD = 0.9; 95% CI: 0.7-1.2), total testosterone (aMD = 0.12; 95% CI: 0.2 to 0.01) in group 2 and free testosterone (aMD = 6.0; 95% CI: 9.7 to 2.3) in group 3 revealed a significant difference compared to group 1. In addition, HOMA-IR in group 2 (aMD = 1.3; 95% CI: 2.4 to 0.2) decreased significantly compared to group 1. Further, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol decreased significantly in group 2 (aMD =-21.8; 95% CI:-31.5 to-12.1; aMD =-29.9; 95% CI:-47.9 to-12.0; aMD =-21.2; 95% CI:-31.3 to-11.1; aMD =-5.1; 95% CI:-7.5 to-2.7) and group 3 (aMD =-18.3; 95% CI:-27.4 to-9.2; aMD =-26.9; 95% CI:-43.8 to-9.9; aMD =-21.4; 95% CI:-31.1 to-11.7; aMD =-5.9; 95% CI:-8.3 to-3.6) compared to group 1, respectively. However, high-density lipoproteins cholesterol in group 2 (aMD = 6.8; 95% CI: 2.9-10.7) and group 3 (aMD = 10.7; 95% CI: 7.2-14.7) increased remarkably compared to group 1. Overall, clinical outcomes improved significantly in all groups (p < 0.05). Conclusions: In general, the herbal mixture along with CC was found to improve free testosterone, HOMA-IR, lipid profile, and clinical features of PCOS women.