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Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge.
Hum Reprod 1997; 12(3):430-5HR

Abstract

The determination of the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists in blocking the luteinizing hormone (LH) surge and luteal function is important for our understanding of the control of the menstrual cycle and for clinical application. GnRH antagonists have failed to block the LH surge reliably in the non-human primate. The aim of the study was to utilize high dose GnRH antagonist treatment administered during the late follicular phase of the menstrual cycle to block the pre-ovulatory LH surge. It was postulated that the LH surge would be prevented in all animals, but if this failed subsequent luteal function would be blocked by continued suppression of LH, since the early corpus luteum is susceptible to inhibition by GnRH antagonist treatment. A group of 16 adult female stumptailed macaques (Macaca arctoides) with regular menstrual cycles were selected. The GnRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-(Hci)6, Lys(iPr)8,D-Ala10]GnRH (Antarelix) (concentration 10 mg/ml) was administered as three daily s.c. injections, at a dose of 1 mg/kg on days 11, 12 and 13 of the follicular phase of the menstrual cycle. Of nine macaques in which it was judged that the treatment was commenced within 1 day of the expected LH surge (serum oestradiol >400 pmol/l), six demonstrated a decline in serum oestradiol concentrations, a total block of the LH/follicle stimulating hormone (FSH) surge and inhibition of ovulation as judged by an absence of a rise in progesterone concentrations. In the three other animals in this category, a partial LH surge occurred, but this failed to result in a functional corpus luteum. In a further three animals treatment was initiated on the day of the LH surge, and again there was absence of a subsequently functional corpus luteum. These results show that GnRH is involved at the time of the mid-cycle LH/FSH surge in the non-human primate. Initiation of high dose GnRH antagonist treatment during the periovulatory period abolishes luteal function irrespective of its effects upon the LH surge because of its long-term action and resultant withdrawal of luteal support.

Authors+Show Affiliations

MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9130734

Citation

Fraser, H M., et al. "Initiation of High Dose Gonadotrophin-releasing Hormone Antagonist Treatment During the Late Follicular Phase in the Macaque Abolishes Luteal Function Irrespective of Effects Upon the Luteinizing Hormone Surge." Human Reproduction (Oxford, England), vol. 12, no. 3, 1997, pp. 430-5.
Fraser HM, Lunn SF, Morris KD, et al. Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge. Hum Reprod. 1997;12(3):430-5.
Fraser, H. M., Lunn, S. F., Morris, K. D., & Deghenghi, R. (1997). Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge. Human Reproduction (Oxford, England), 12(3), pp. 430-5.
Fraser HM, et al. Initiation of High Dose Gonadotrophin-releasing Hormone Antagonist Treatment During the Late Follicular Phase in the Macaque Abolishes Luteal Function Irrespective of Effects Upon the Luteinizing Hormone Surge. Hum Reprod. 1997;12(3):430-5. PubMed PMID: 9130734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge. AU - Fraser,H M, AU - Lunn,S F, AU - Morris,K D, AU - Deghenghi,R, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 430 EP - 5 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 12 IS - 3 N2 - The determination of the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists in blocking the luteinizing hormone (LH) surge and luteal function is important for our understanding of the control of the menstrual cycle and for clinical application. GnRH antagonists have failed to block the LH surge reliably in the non-human primate. The aim of the study was to utilize high dose GnRH antagonist treatment administered during the late follicular phase of the menstrual cycle to block the pre-ovulatory LH surge. It was postulated that the LH surge would be prevented in all animals, but if this failed subsequent luteal function would be blocked by continued suppression of LH, since the early corpus luteum is susceptible to inhibition by GnRH antagonist treatment. A group of 16 adult female stumptailed macaques (Macaca arctoides) with regular menstrual cycles were selected. The GnRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-(Hci)6, Lys(iPr)8,D-Ala10]GnRH (Antarelix) (concentration 10 mg/ml) was administered as three daily s.c. injections, at a dose of 1 mg/kg on days 11, 12 and 13 of the follicular phase of the menstrual cycle. Of nine macaques in which it was judged that the treatment was commenced within 1 day of the expected LH surge (serum oestradiol >400 pmol/l), six demonstrated a decline in serum oestradiol concentrations, a total block of the LH/follicle stimulating hormone (FSH) surge and inhibition of ovulation as judged by an absence of a rise in progesterone concentrations. In the three other animals in this category, a partial LH surge occurred, but this failed to result in a functional corpus luteum. In a further three animals treatment was initiated on the day of the LH surge, and again there was absence of a subsequently functional corpus luteum. These results show that GnRH is involved at the time of the mid-cycle LH/FSH surge in the non-human primate. Initiation of high dose GnRH antagonist treatment during the periovulatory period abolishes luteal function irrespective of its effects upon the LH surge because of its long-term action and resultant withdrawal of luteal support. SN - 0268-1161 UR - https://www.unboundmedicine.com/medline/citation/9130734/Initiation_of_high_dose_gonadotrophin_releasing_hormone_antagonist_treatment_during_the_late_follicular_phase_in_the_macaque_abolishes_luteal_function_irrespective_of_effects_upon_the_luteinizing_hormone_surge_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/12.3.430 DB - PRIME DP - Unbound Medicine ER -