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

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.