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

Abstract

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.

LHRH receptor expression in sarcomas of bone and soft tissue

“…To sustain this positive and growing trend, further and newer treatment methods must be perceived and instituted. Recent relevant advances encompass the development of three types of analogs of luteinizing hormone releasing hormone (LHRH) and the discovery of expression of receptors for the hypothalamic releasing hormones, including those for LHRH (LHRH-R), in cancer cells [6][7][8][9]. In various studies, analogs of other neurohormones (e.g.…”

Effect of Goserlin Acetate and Oxidative Stress in Iraqi Women with Recurrenceof Endometriosis

“…LHRHa are 50-100 times more potent than LHRH. In addition, they have a longer duration of action due to increased receptor affinity and greater biological stability [5].Estrogens have been shown to have in vitro antioxidant effects on membrane phospholipid peroxidation [6]. The antioxidant activity of estrogens is associated with the phenol structure of estradiol and its metabolites [7].Oxidative stress (OS) substances may have a contributive role in the pathogenesis of endometriosis through the activation of macrophages.…”

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

“…These are peptide analogs of hypothalamic hormones: luteinizing hormone-releasing hormone (LHRH), growth hormone-releasing hormone (GHRH), somatostatin, and analogs of other neuropeptides such as bombesin and gastrin-releasing peptide. The receptors for these peptides have been found to be widely distributed in the human body, including in many types of cancers (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The regulatory functions of these hypothalamic hormones and other neuropeptides are not confined to the hypothalamo-hypophyseal system or, even more broadly, to the central nervous system (CNS).…”

“…In particular, GHRH can induce the differentiation of ovarian granulosa cells and other cells in the reproductive system and function as a growth factor in various normal tissues, benign tumors, and malignancies (2-4, 6, 11, 14-18). Previously, we also reported that antagonistic cytototoxic derivatives of some of these neuropeptides are able to inhibit the growth of several malignant cell lines (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

“…The dismal outcome of this malignancy demands great efforts to find improved methods of treatment (1). Many compounds have been synthesized in our laboratory in the past few years that have proven to be effective against diverse malignant tumors (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These are peptide analogs of hypothalamic hormones: luteinizing hormone-releasing hormone (LHRH), growth hormone-releasing hormone (GHRH), somatostatin, and analogs of other neuropeptides such as bombesin and gastrin-releasing peptide.…”