Men desire fatherhood through natural (not assisted) conception or its prevention through reliable contraception. Men participate widely in fertility treatments and contraceptive practices, yet options to regulate fertility are limited. Decades of animal and human studies provide a good understanding of the hormonal regulation of spermatogenesis and its therapeutic manipulation. Natural fertility can be restored in hypogonadotropic hypogonadism using gonadotrophin therapy. However, most infertility arises from primary spermatogenic failure (1oSG) for which a cause can be identified in a minority (Klinefelters, Yq microdeletions, testicular damage). For idiopathic 1oSG new genetic causes are emerging as are environmental and infective impacts. Assisted reproductive treatments (ART), especially intracytoplasmic sperm injection, effectively ‘bypass’ the male reproductive defect, by using viable sperm retrieved from semen or testis. ART outcomes are now similar to female factor aetiologies. Currently half of ART treatment relate solely, or partly, to male factors. Although reassuring to date, assessment of the heath of ART offspring is a continuing responsibility.
Conversely, a global demand also exists for new safe, effective and reversible male contraceptive options. Male hormonal contraception (MHC) relies on gonadotrophin suppression by exogenous androgens, often combined with progestin, while maintaining virilisation. The loss of FSH action and a 100-fold reduction in intratesticular testosterone (iTT) levels profoundly impairs spermatogenesis, particularly meiotic progression and sperm release. Over 3-6 months sperm densities fall to <1 million/ml with contraceptive efficacy similar to female methods. Inadequate suppression in ~5% of men probably results from residual iTT action. Recovery occurs over 6 -12 months depending on the formulation. Despite decades of encouraging translational studies, including multinational trials under the auspices of the WHO, development has stalled due to industry concerns about the risk: benefit (registration costs, liability, side effect profile, market size). Limited public sector research continues.