Developments in the control of testicular function

Abstract

Clinicians and clinical investigators have developed improved means for controlling testicular function in men. New and refined approaches for stimulation and inhibition of the hypothalamic-pituitary-testicular axis are now available. This chapter reviewed the most successful ways to inhibit the reproductive axis in men and its current application to the treatment of precocious puberty, metastatic prostate cancer, benign prostate hyperplasia and as prospective male contraceptives. Safe, effective and reversible medical approaches to male contraception are now approaching reality. Azoospermia and severe oligozoo/azoospermia can now be accomplished in the majority of men with combined GnRH antagonists and replacement doses of testosterone. Androgens and androgen-progestogen concentrations will induce azoospermia in over 90% of Asian men and azoospermia or severe oligospermia in Caucasian ethnic groups. Field trials are ongoing to determine whether testosterone administration will be more effective than condoms as contraceptives. True precocious puberty can now be managed more effectively than in the past by suppression of gonadotropin secretion with GnRH analogues. Precocious puberty due to other causes can be treated more effectively with inhibitors of steroidogenesis and blockers of androgen action. Metastatic prostate cancer, previously treatable with either castration or oestrogens, is now amenable to suppression of androgen secretion. GnRH analogues are given either alone or combined with blockers of androgen action. While significant palliative effects are observed with endocrine ablative therapy in most men with Stage C or D prostate cancer, modest increases in duration of survival may be seen. Benign prostate hyperplasia was previously approachable only with surgical intervention. Recent data have suggested that medical treatment with 5 alpha-reductase inhibitors and/or selective alpha-adrenergic blockers may offer non-surgical alternatives in some patients. More data are needed to determine the role of medical management of this common disorder.

PIP: Recent approaches to inhibiting testicular function for the purposes of male contraception, treatment of precocious puberty, and palliation of prostatic disease (prostatic carcinoma and benign prostatic hypertrophy) are addressed. By refined approaches inhibition of testicular function can be achieved at points of the reproductive axis, including the hypothalamus, pituitary testis, and peripheral sites of androgen action. Azoospermia and severe oligozoo/azoospermia can be achieved with combined gonadotropin releasing hormone (GnRH) antagonists and replacement doses of testosterone. In recent developments with reversible hormonal agents, the use of gonadotropin inhibitors for male contraception was based on observations that hypophysectomized and hypogonadotropic men (deficient in luteinizing hormones [LH] and follicle stimulating hormone [FSH] are aznoospermic. Long term suppression of LH and FSH with steroids and GnRH analogues has proven to be reversible with discontinuation of medication suggesting that inhibitors of LH and FSH secretion would prove to be effective and reversible male contraceptive agents. Steroid hormones suppress gonadotropin output and secondarily suppress testicular function including the production of spermatozoa. The androgen testosterone enanthate in doses of 200 mg every week suppressed LH and FSH concentrations to 50% of pretreatment baseline. True precocious puberty can be managed more effectively by suppression of gonadotropin secretion with GnRH analogues. Metastatic prostate cancer, previously treatable with either castration or estrogens, now responds to suppression of androgen secretion. Benign prostate hyperplasia previously manageable only by surgery can respond favorably to 5 alpha-reductase inhibitors and/or selective alpha-adrenergic blockers in some patients according to recent data.