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Luteinizing Hormone Releasing Hormone and Analogues: Conceptive and Contraceptive Potential

Chapter
Part of the Progress in Hormone Biochemistry and Pharmacology book series (PRHO, volume 1)

Abstract

The isolation and identification of luteinizing hormone releasing hormone (LHRH) had immediate and far reaching implications concerning the diagnosis and treatment of infertility. The availability of synthetic LHRH that was identical in physical, chemical and biological properties to the natural peptide has allowed, over the past nine years, the extensive evaluation of these potential applications. However, in terms of the utility that was originally conceived, progress has proceeded more slowly and success has been less complete than initially anticipated. In this regard, LHRH has been found to be a useful diagnostic adjunct to existing methods but not as a primary means of differentiating hypothalamic and hypophysial dysfunction. Moreover, therapeutic use of LHRH in theoretically appropriate situations, such as in treatment of delayed puberty, oligospermia and hypothalamic anovulation, generally has produced discouraging results. The identification by pharmacokinetic studies of the short half-life (≈ 4 min) of LHRH in humans suggested that the problems that were being encountered may be related to inadequate dosages, length of exposure and bioavailability. However, more involved LHRH treatment regimens employing frequent administration or continuous infusion, quite often in conjunction with established therapies, or use of various highly potent and longacting agonistic derivatives of the parent compound, have done little to improve the success rate of this pro-fertility approach. In fact, it has become apparent that LHRH and its agonists possess a pharmacologic profile that, in marked contrast to initial concepts, is anti-reproductive in nature. Characterization of this paradoxical anti-reproductive property has included, in laboratory studies, the ability of these LH-releasing agents to induce luteolysis and terminate pregnancy, reduce fecundity, retard puberty, and to inhibit spermatogenesis and, in clinical studies, inhibition of ovulation and disruption of luteal function. Furthermore, evaluation of a wide variety of LHRH derivatives has revealed a direct correlation between agonist (LH release) and anti-reproductive potencies. This association, aside from explaining the limited success of their pro-fertility application, has generated considerable interest in the agonists as a new class of potential contraceptive agents.

Keywords

Luteinizing Hormone Luteinizing Hormone Release Hormone Luteinizing Hormone Release Luteinizing Hormone Release Hormone Luteinizing Hormone Release Hormone Analog 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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