Enclomiphene citrate

Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity‐related functional androgen deficiency.

To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity‐related functional androgen deficiency.

A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim‐and‐fill analysis were used to assess publication bias.

Seven studies met the inclusion criteria providing information on 292 men with obesity‐related functional androgen deficiency treated with clomiphene citrate (12.5–50 mg daily) or enclomiphene citrate (12.5–25 mg daily) for 1.5–4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I2 = 69%, pfor heterogeneity = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I2 = 4%, pfor heterogeneity = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I2 = 0%, pfor heterogeneity = 0.66). No publication bias was revealed by Egger's test and trim‐and‐fill analysis. No treatment‐related unexpected findings regarding safety profile were registered.

Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity‐related functional androgen deficiency. Further long‐term studies are warranted to define clinical reflections of the selective estrogen receptor modulators‐induced increase in testosterone levels and to better clarify the safety profile.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC.  Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropin levels and TMSC.