Endocrine Abstracts

Men actively participate in family planning and fertility treatments. Much is now understood about the hormonal regulation of spermatogenesis and its therapeutic manipulation. Hypogonadotropic hypogonadism is uncommon but provides the opportunity to restore natural fertility using gonadotrophin therapy. Prenatal-onset (e.g. Kallmann’s), cryptorchidism and small testes predict a poorer spermatogenic response compared to post pubertal onset cases; natural fertility occurs in ~70 and >90%, respectively. Most infertility arises from poor spermatogenesis; a defined cause is apparent in the minority (Klinefelters, Yq microdeletions, testicular damage) with most cases being unexplained. Genetic causations are emerging from translational studies using clinical DNA databases. The management of idiopathic male infertility has been transformed by the development of intracytoplasmic sperm injection. When viable sperm are retrievable from the semen or the genital tract, success rates in men previously considered sterile are similar to those of age-matched couples with other aetiologies.

On the other hand a demand exists for new safe, effective and reversible male contraceptive options. Male hormonal contraception relies on gonadotrophin suppression by exogenous androgens, often combined with progestin, while maintaining virilisation. Spermatogenesis is impaired by loss of FSH action and a 100-fold reduction in intratesticular testosterone levels. 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 intratesticular androgen action. Despite decades of encouraging translational studies, including a recent multinational trial sponsored by the WHO and CONRAD, development has stalled with the withdrawal of industry support due to uncertainty about the risk:benefit ratio (registration costs, product liability, side effect profile and market size). It is unrealistic to expect 100% applicability, acceptability and efficacy without side effects. Public sector supported research continues especially the use of selective androgen response modulators and the identification of non-hormonal approaches.