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Published on: August 13, 2019
Selective modulation of estrogen receptor in obese men with androgen deficiency: A systematic review and
Daniele Tienforti1, Chiara Castellini1, Francesca Di Giulio1
1Department of Clinical Medicine, Life, Health and Environmental Sciences, Andrology Unit, University of L'Aquila, L'Aquila, Italy.
Background:
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.
Objective:
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.
Materials And Methods:
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.
Results:
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.
Discussion And Conclusion:
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.
Insights
Selective estrogen receptor modulators, such as clomiphene citrate and enclomiphene citrate, effectively increase testosterone levels in men with obesity-related functional androgen deficiency. These treatments offer a safe alternative to testosterone replacement therapy.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Pharmacology
Background:
- Obesity-related functional androgen deficiency is a growing concern.
- Selective estrogen receptor modulators (SERMs) show promise for treating hypogonadism.
- Limited data exist on SERMs for obesity-related androgen deficiency.
Approach:
- Systematic review and meta-analysis of seven studies.
- Included 292 men with obesity-related functional androgen deficiency.
- Analyzed testosterone level changes with clomiphene or enclomiphene citrate.
Key Points:
- Both clomiphene and enclomiphene citrate significantly increased testosterone levels.
- Pooled estimates showed substantial testosterone increases (e.g., 11.56 nmol/L with clomiphene).
- No publication bias or unexpected safety concerns were identified.
Conclusions:
- SERMs (clomiphene, enclomiphene) are effective and safe for obesity-related functional androgen deficiency.
- These agents represent a viable alternative to testosterone replacement therapy.
- Further long-term research is needed to clarify clinical implications and safety.
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