Dose-dependent response to long-term clomiphene citrate in male functional hypogonadotropic hypogonadism

男性功能性促性腺激素低下性性腺功能减退症对长期服用枸橼酸氯米芬的剂量依赖性反应

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Abstract

SUMMARY: Functional hypogonadotropic hypogonadism is a relatively common condition in middle-aged to elderly men that can significantly impair quality of life. Besides lifestyle optimisation, androgen replacement remains the mainstay of treatment; however, its adverse effects on spermatogenesis and testicular atrophy are undesirable. Clomiphene citrate is a selective oestrogen receptor modulator that acts centrally to increase endogenous testosterone without affecting fertility. Although it has demonstrated effectiveness in shorter-duration studies, its longer-term outcomes are less well-documented. In this study, we report the case of a 42-year-old male with functional hypogonadotropic hypogonadism who sustained an excellent dose-dependent, titratable clinical and biochemical response to clomiphene citrate with no known adverse effects for 7 years to date. This case highlights that clomiphene citrate has potential as a safe and titratable longer-term treatment option, and the need for further randomised control trials in therapy options to normalise androgen status. LEARNING POINTS: Functional hypogonadotropic hypogonadism is a relatively common, but likely underdiagnosed, condition in middle-aged to older males. Testosterone replacement is the current mainstay of endocrine therapy but can cause sub-fertility and testicular atrophy. Clomiphene citrate is a serum oestrogen receptor modulator that acts centrally to increase endogenous testosterone production without affecting fertility. It has potential as a safe and efficacious longer-term treatment option that can be titrated to increase testosterone and relieve clinical symptoms in a dose-dependent manner. Longitudinal prospective studies as randomised control trials evaluating alternatives to exogenous testosterone are required.

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