Frontiers in hormone therapy for male infertility

Iyad Khourdaji, Haerin Lee, Ryan P. Smith


For a significant number of couples worldwide, infertility is a harsh reality. As specialists in male infertility, much of our armamentarium lacks definitive, evidence-based therapies. For years, we have relied on manipulation of the male hormonal axis to treat those men who help carry the burden of infertility in their partnerships. Indeed, male factor infertility is the sole component of infertility in at least 20% of couples. Further compounding this dilemma is that 25% to 50% of males with infertility have no identifiable etiology and thus present a true management conundrum. This manuscript is an attempt to clarify what therapies exist for the treatment of male factor infertility. We have reviewed the relevant infertility literature honing, our focus on hormonal anomalies and their subsequent impact on fertility. Many of the therapies discussed have been utilized in practice for generations. Thus, this article attempts to provide the evidence-based literature to support the continued use of the current treatment paradigm. Furthermore, we recognize that any review beckons a discussion of what challenges and therapies await on the horizon. For instance, there has been significant interest in restoring spermatogenesis after testosterone replacement therapy (TRT). We explore the adverse long-term spermatogenic outcomes associated with TRT, which with the widespread use of TRT, will inevitably present a great challenge for male infertility specialists. Moreover, we discuss the role of varicocelectomy in the treatment of hypogonadism and infertility, review the association between growth hormone (GH) and male fertility and address the challenges presented by the rising prevalence of obesity.