The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase m clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50% of breast cancers and 80% of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.

Original languageEnglish
Pages (from-to)1364-1379
Number of pages16
JournalHuman Reproduction
Volume9
Issue number7
StatePublished - Aug 3 1994
Externally publishedYes

Fingerprint

Hormone Antagonists
Hormones
Gonadotropin-Releasing Hormone
Cancer
Neoplasms
Breast Neoplasms
Hypophysectomy
Analogue
Castration
Endometrial Neoplasms
Breast Cancer
Ovarian Cancer
Sex Cord-Gonadal Stromal Tumors
Cells
Clinical Trials
Gastrin-Releasing Peptide
Breast cancer
Bombesin
Oncology
Chemotherapy

Keywords

  • Breast
  • Cancer
  • Endometrium
  • LHRH analogues
  • Ovary

ASJC Scopus subject areas

  • Physiology
  • Developmental Biology
  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Rehabilitation

Cite this

The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. / Emons, G.; Schally, Andrew V.

In: Human Reproduction, Vol. 9, No. 7, 03.08.1994, p. 1364-1379.

Research output: Contribution to journalArticle

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abstract = "The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase m clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50{\%} of breast cancers and 80{\%} of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.",
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