LAUSR

BACKGROUND Although selective estrogen receptor modulators (SERMs) have been proposed as a treatment for men with central functional hypogonadism, only few data have been produced in men with obesity-related functional androgen deficiency (ORFAD). OBJECTIVE To determine whether and to what extent SERMs are an effective and safe therapy in men with ORFAD. MATERIALS AND METHODS A thorough search of PubMed, Web of science, Scopus and Cochrane Library databases was performed to identify studies comparing testosterone (T) levels before and after treatment with SERMs in men with ORFAD. Mean differences (MDs) with 95% coefficient intervals (CIs) were combined using random effects models. Funnel plot, Egger's test and trim-and-fill analysis were used to assess publication bias. RESULTS Seven studies met the inclusion criteria providing information on 292 men with ORFAD treated with clomiphene citrate (CC, 12.5-50 mg daily) or enclomiphene citrate (EC, 12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in T levels both with CC (MD: 11.56 nmol/L; 95% CI: 9.68, 13.43; I2 = 69%, Pfor heterogeneity = 0.01) and EC (MD: 7.50 nmol/L; 95% CI: 6.52, 8.48; I2 = 4%, Pfor heterogeneity = 0.37). After the exclusion of one study on severe obese men, who exhibited the highest response rate to CC, the heterogeneity disappeared (MD: 10.27 nmol/L; 95% CI: 9.39, 11.16; I2 = 0%, Pfor heterogeneity = 0.66). No publication bias was revealed by the Egger's test and trim-and-fill analysis. No SERMs-related unexpected findings regarding safety profile were registered. DISCUSSION AND CONCLUSION Treatment with CC and EC may be an effective and safe alternative to T replacement therapy in men with ORFAD. Further long-term studies are warranted to define clinical reflections of the SERMs-induced increase in T levels and to better clarify the safety profile. This article is protected by copyright. All rights reserved.