GnRH Antagonists in Men

Abstract

GnRH is a decapeptide, secreted from the hypothalamus in a pulsatile fashion, that regulates the synthesis and secretion of pituitary gonadotropins (1–9). In contrast, synthetic GnRH agonists or antagonists inhibit gonadotropin secretion and subsequently gonadal function (10, 11). Since synthetic agonist analogs were shown to suppress gonadotropin secretion after an initial phase of stimulation (12–17), several studies were performed aiming toward modulation of androgen secretion and the development of a male contraceptive (18–24). GnRH agonists can effectively suppress secretion of gonadal steroids (25–28), but during the initial 2–3-week period of administration a transient stimulation of LH release occurs, resulting in an increase in gonadal steroid levels, which can in some cases induce a flare of the underlying disease. Agonists failed, however, to effectively and consistently suppress spermatogenesis (29–32). Oligospermia was achieved by most men in these studies, but only very few men reached azoospermia (33). This failure of GnRH agonists can be attributed to incomplete suppression of serum FSH immunoreactivity and bioactivity (34) and to the fact that, during longterm agonist administration, FSH serum levels tend to return toward baseline (35).