Male factor infertility is found in approximately 40% of couples. Spermatogenesis is a complex process and given the intricacies of hormone effects and multiple feedback pathways, even subtle alterations in these processes can lead to male subfertility. In theory, medical management of male subfertility addresses underlying endocrine abnormalities or hormone imbalances to possible improve spermatogenesis, fertility, and chances of natural conception.
When male factor infertility is found in approximately 40% of couples who are unable to conceive after 12 months of unprotected intercourse, it is surprising how infrequently appropriate evaluation and management of suspected male factor subfertility is performed. Hormone therapy for male factor infertility is an overlooked and underutilized treatment modality that can significantly impact clinical outcomes of infertile couples. In this paper, we discuss various endocrinopathies associated with male subfertility and review the latest evidence for hormone based therapies.
Although there is controversy regarding the role of routine hormonal screening in all subfertile males and the efficacy of hormone manipulation in male factor infertility is variable, diligent evaluation and appropriate treatment may be beneficial and avoid the costs and morbidity associated with artificial reproductive technologies (ART).
Looking ahead, several studies suggest hormone levels are heritable including androgen receptor polymorphism and trinucleotide repeats and may predispose particular individuals to subfertility. Pharmacogenomic studies evaluating phenotypic variations among individuals are needed to better understand the response to hormone manipulators in infertile men. Future research will evaluate the genetic framework and clinical implications of these polymorphisms and mutations in large cohorts of men. We believe information derived from large population databases and biobanks will help drive and enhance this research. Better sequencing technologies and pharmacogenetic data collection will help develop a better evidence based, personalized approached to therapy using an individual’s genetic profile to determine efficacy and success of certain treatments.
Authors: Darshan P. Patel, MD, Jason Chandrapal, MD, MS. James M. Hotaling, MD, MS.