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  • Title: Reproductive pharmacology of LHRH and agonists in females and males.
    Author: Corbin A, Bex FJ.
    Journal: Acta Eur Fertil; 1980 Jun; 11(2):113-30. PubMed ID: 7010866.
    Abstract:
    This report reviews research supporting the anti-reproductive pharmacologic characteristics of LHRH (luteinizing hormone releasing hormone) and its agonist analogues, and their relevance to fertility regulation in the clinic. Approximately 1000 derivatives of LHRH have been synthesized since 1971. LHRH and agonistic derivatives have the ability to induce the release of pituitary LH and FSH (follicle stimulating hormone), and ovulation in a variety of animal models. These agents have been shown to produce predictable postcoital contraceptive effects, such activity and potency having been related to its basic agonist properties. This class of peptides also have the ability to 1) retard puberty; 2) disrupt the estrous cycle (delay onset of estrus and mating); 3) induce premature ovulation; 4) induce luteolysis; 5) cause ovarian and uterine regression; 6) reduce fecundity in inseminated animals; and 7) inhibit ovarian/uterine stimulation which occurs with human chorionic gonadotropin. These effects are reversible because once treatment is withdrawn, normal breeding processes resume quickly. Several LHRH agonists are also being tapped for use as a potential luteal phase-inhibiting/menses-inducing approach to contraception. In the male, however, the agonists cannot function as contraceptives due to the inappropriate dissociation between testosterone production and spermatogenesis. The antireproductive mechanisms of LHRH agonists can be traced to the 1) hypersecretion of LH; 2) dysphasic FSH and distorted prolactin secretion; 3) decrease in gonadal LH, FSH and prolactin receptors; and 4) inhibition of steroidogenesis and eventual disruption of the reproductive continuum. They may also be useful as anti-tumor agents in steroid-dependent mammary gland and prostatic neoplasms. Toxicologic, pathologic and ancillary pharmacologic studies involving varied dosing regimens show encouraging potential of selected agonists as contraceptive agents with no related side effects.
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