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  • Title: Anti-LHRH and anti-pituitary gonadotropin vaccines: their development and clinical applications.
    Author: Thau R.
    Journal: Scand J Immunol Suppl; 1992; 11():127-30. PubMed ID: 1514027.
    Abstract:
    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. Long-lasting, safe, and inexpensive reversible methods of birth control that allow administration by non medical personnel are acutely needed. Among immunological approaches several contraceptive vaccines are the targets of clinical trials, and anti hormone vaccines are the most promising. The method for women is based on active immunization against human chorionic gonadotropin (hCG). Immunization against luteinizing hormone releasing hormone (LHRH) prevents endogenous LHRH from binding to pituitary receptors thereby disrupting the menstrual cycle and ovulation and suppressing not only sperm production but also testosterone synthesis. In females, immunization against LHRH appears less promising. The results from numerous animal studies suggest that active immunization against LHRH is a promising method in men, but the libido must be maintained by concomitant administration of exogenous androgen. Immunization against LHRH suppresses serum testosterone levels, thus the first clinical trials involving men with prostate carcinoma commenced in several countries show that high levels of anti-LHRH antibodies can be induced. In luteinizing hormone (I.H.) vaccine development immunization against LH in males is not superior to the LHRH vaccine, since anti-LH in males is not superior to the LHRH vaccine, since anti-LH antibodies suppress testosterone. Active immunization of females against species-specific LH can block ovulation and results in distribution of cyclicity and suppression of ovarian steroidogenesis which could lead to undesirable long-term effects. Various hCG vaccines are now in clinical trials. In follicle stimulating hormone (FSH) vaccine preparation for clinical trials in men, acute and subacute animal toxicity studies were performed in rats and monkeys with no indication of adverse effects. In rhesus an crab-eating monkeys consistent infertility did not arise after active immunization against FSH, but the bonnet monkey was encouraging.
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