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Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone


This article reviews the clinical uses of agonists and antagonists of luteinizing-hormone-releasing hormone (LHRH), also known as gonadotropin-releasing hormone. In particular, the state of the art treatment of breast, ovarian and prostate cancer, reproductive disorders, uterine leiomyoma, endometriosis and benign prostatic hypertrophy is reported. Clinical applications of LHRH agonists are based on gradual downregulation of pituitary receptors for LHRH, which leads to inhibition of the secretion of gonadotropins and sex steroids. LHRH antagonists immediately block pituitary LHRH receptors and, therefore, achieve rapid therapeutic effects. LHRH agonists and antagonists can be used to treat uterine leiomyoma and endometriosis; furthermore, both types of LHRH analogs are used to block the secretion of endogenous gonadotropins in ovarian-stimulation programs for assisted reproduction. The preferred primary treatment of patients with advanced, androgen-dependent prostate cancer is based on the periodic administration of depot preparations of LHRH agonists; these agonists can be likewise used to treat estrogen-sensitive breast cancer in premenopausal women. LHRH antagonists have been successfully used to treat prostate cancer and benign prostatic hypertrophy. Since receptors for LHRH are present on a variety of human tumors, (notably breast, prostate, ovarian, endometrial and renal cancers), cytotoxic therapy that targets these tumors with hybrid molecules of LHRH might be possible in the near future. Analogs of LHRH are now a well-established means of treating sex-steroid-dependent, benign and malignant disorders.

Key Points

  • Luteinizing-hormone-releasing hormone (LHRH) agonists induce a hypogonadotropic state by depletion of receptors for LHRH on pituitary gonadotrophs

  • LHRH antagonists achieve a hypogonadotropic state by blockade of pituitary LHRH receptors

  • LHRH agonists are a well-established treatment for sex-steroid-dependent cancers such as breast cancer and prostatic carcinoma

  • LHRH agonists are also widely used to treat benign, sex-steroid-dependent disorders, such as uterine leiomyoma and endometriosis

  • LHRH agonists and antagonists are used in the field of reproductive medicine to prevent premature luteinizing-hormone surges in controlled ovarian-stimulation cycles

  • Cytotoxic, hybrid analogs of LHRH might be used to treat cancers that express receptors for LHRH

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Figure 1: Mode of action of agonists, antagonists and cytotoxic analogs of LHRH.


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Correspondence to Jörg B Engel.

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Competing interests

AV Schally received grant support from the Medical Research Service of the Veterans Affairs Department, and a grant from Zentaris GmbH (Frankfurt, Germany) to Tulane University. JB Engel declared he has no competing interests.

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Engel, J., Schally, A. Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Rev Endocrinol 3, 157–167 (2007).

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