Empiric medical therapy with hormonal agents for idiopathic male infertility

INTRODUCTION: Infertility affects approximately 15% of all couples, and male factor contribute to up to 50% of cases. Unfortunately, the cause of male infertility is unknown in about 30% of these cases. Infertility of unknown origin is classified as idiopathic male infertility when abnormal semen parameters are present. Despite not having a definable cause, these men may respond to treatment. This review focuses on the use of empiric hormonal therapies for idiopathic male infertility. METHODS: A detailed PubMed/MEDLINE search was conducted to identify all publications pertaining to empiric use of hormonal therapies in the treatment of idiopathic male infertility using the keywords “idiopathic,” “male infertility,” “empiric treatment,” “clomiphene,” “SERM,” “gonadotropin,” “aromatase inhibitor,” and “androgen.” These manuscripts were reviewed to identify treatment modalities and results. RESULTS: Gonadotropins, androgens, aromatase inhibitors, and selective estrogen receptor modulators (SERMs) have all been used with varying results. The studies on these treatments are of variable quality. The most well-studied agents are the SERMs which show a modest increase in semen parameters and pregnancy rates. Aromatase inhibitors are most effective in non-idiopathic patients. Gonadotropin treatment is limited by their inconvenience and relative ineffectiveness in this population. Testosterone suppresses spermatogenesis and should not be used to treat infertility. CONCLUSION: Gonadotropins, SERMs, and aromatase inhibitors may improve semen parameters and hormone levels in men with idiopathic infertility with the best results from SERMs. Testosterone should never be used to treat infertility. Large multicenter randomized controlled studies are needed to better determine the success of empiric use of hormonal therapy on pregnancy rates.