Anti-LHRH and anti-pituitary gonadotropin vaccines: their development and clinical applications

Active immunization against hormones involved in the regulation of reproduction is a promising approach to immunocontraception. The hypothalamic peptide, LHRH, controls the synthesis and release of the pituitary gonadotropins, LH and FSH, which regulate gonadal steroidogenesis, sperm production, follicular development and ovulation. Immunizing female primates against LHRH or LH induces infertility, but also disrupts the menstrual cycle. Immunization against the beta subunit of the placental hormone, chorionic gonadotropin (hCG), or its fragment prevents pregnancy without interfering with menstrual cycles or ovulation. hCG vaccines have reached the stage of clinical trials. FSH and LHRH have been tested for immunocontraception in male primates. While active as well as passive immunization against FSH reduced spermatogenesis severely, azoospermia could not be achieved consistently. Immunization against LHRH effectively suppressed spermatogenesis in rats and rabbits. Normal sexual behaviour was maintained by concomitant androgen administration. Fertility was restored when antibody titres declined and no adverse effects were observed. A number of LHRH vaccine preparations are being tested in men in several countries, including the United States. Since the LHRH vaccine reduces serum testosterone levels the first clinical studies involve men with prostate cancer. These trials will be followed by immunization of normal men if the antibody response is sufficient and no adverse effects are observed.