The androgen receptor (AR) is part of a superfamily of nuclear receptors. The AR has a diverse set of downstream effects on male phenotype and sexual function, muscle mass and strength, bone density, hematopoiesis, cognition, and metabolism. Testosterone replacement therapy (TRT) to treat male hypogonadism utilizes exogenously administered testosterone to activate the AR. However, TRT is known to have potential risks, including erythrocytosis, dyslipidemia, prostatic hypertrophy, hepatotoxicity, impaired fertility, aromatization of testosterone to estrogen, and testicular atrophy. Selective androgen receptor modulators, also known as SARMs, are compounds that have shown tissue-selective activation of the AR. These compounds potentially offer the ability to treat hypogonadal conditions where activating the AR in the bone, muscle, or brain is desired while sparing undesired effects in tissues such as the prostate, liver, or bone marrow. Currently, there is a dearth of data in human subjects regarding the treatment of male hypogonadism with SARMs. However, from animal models and preliminary studies of SARMs in humans, there appears to be a possible role for SARMs in the hypogonadal man, and their efficacy and safety warrant further study.

Knowledge of the anatomy and physiology of the hypothalamic-pituitary-gonadal axis is paramount for the understanding and management of hypogonadism in men. Although the definition of hypogonadism may seem elusive, there is a framework to assist with the diagnosis once a history, physical examination, and appropriate lab testing are obtained. There are a number of treatment options to consider with their associated risks and benefits.

Given the wide spectrum in practice standards and patterns, array of covered versus out-of-pocket conditions, and role of adjunct streams of revenue, the business landscape of men’s health is diverse. Fundamental to the fiscal success of many providers is the efficacy of direct to consumer marketing in the setting of inelastic demand for solutions to aging, erectile dysfunction (ED), and Peyronie’s disease; this has created enormous markets surrounding supplemental testosterone, online platforms for ED treatment, and out-of-pocket products such as platelet-rich plasma, stem-cell therapy, and shock wave treatments. The contemporary story of men’s health has been defined by the gender health gap; uncovering the link between coronary artery disease (CAD) and ED unveiled a touchpoint for establishing holistic men’s health. University and large hospital systems have the infrastructure to support comprehensive Men’s Health Centers and have therefore maximized the downstream revenue associated with prescriptions, long-term screening, and future hospitalizations.

Exogenous testosterone functions as a male contraceptive. As a result, men treated with testosterone who desire fertility will need help when trying to restore or preserve fertility. In this chapter, we provide a framework for counseling and managing hypogonadal men who desire fertility. We explore strategies ranging from cessation of exogenous testosterone to using human chorionic gonadotropin, selective estrogen receptor modulators, aromatase inhibitors, or recombinant follicle-stimulating hormone with or without testosterone to preserve Sertoli and Leydig cell function. Furthermore, we provide strategies to maintain fertility while starting testosterone and clinical pathways for a hypogonadal man to recover fertility based on his desired timeline for a pregnancy.

Men with spinal cord injury often suffer from erectile dysfunction, ejaculatory dysfunction, infertility, and hypogonadism. Restoration of sexual and reproductive functions is a top priority and efficient treatment modalities exist. Erectile dysfunction can be treated with phosphodiesterase-5 inhibitors and if unsuccessful intracavernosal injections can be tried. When injections fail a penile implant can ultimately be an option. Anejaculation and the resulting infertility are treated in a stepwise approach with penile vibratory stimulation, electroejaculation and surgical sperm retrieval followed by assisted reproduction. Assisted ejaculation is an effective and safe procedure but carries a risk of autonomic dysreflexia, especially in men with injuries at the level of T6 or above. Autonomic dysreflexia is an unregulated and uncontrolled response of the sympathetic nervous system but it can be safely managed. Hypogonadism is more prevalent in men with spinal cord injury compared to the general population and testosterone replacement therapy can be beneficial for alleviating symptoms of low testosterone, but testosterone-related spermatogenic suppression needs to be considered in men who wish to initiate a pregnancy.