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Cited by 66Hypothalamic control of reproductive hormonesOvarian function and disordersReproductive Health and Contraception

Dose-Dependent Inhibition of Pituitary-Ovarian Function during Administration of a Gonadotropin-Releasing Hormone Agonistic Analog (Nafarelin)*

MONROE, SCOTT E., BLUMENFELD, ZEEV, ANDERYKO, JANICE L., SCHRIOCK, ELDON, HENZL, MILAN R., JAFFE, ROBERT B.·1986·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-63-6-1334
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Abstract

To determine if treatment with the GnRH agonistic analog nafarelin could reliably block ovulation while only partially disrupting ovarian estrogen production, three degrees of pituitary-ovarian inhibition were investigated. Thirty-two women with ovulatory menstrual cycles were given 125 micrograms (group (Gp) I), 250 micrograms (Gp II), or 1000 micrograms (Gp III) nafarelin daily by intranasal spray. Twenty-seven women completed 6 months of treatment. Basal serum FSH concentrations decreased (P less than 0.01) in all groups. Suppression of serum LH was dose dependent and significant (P less than 0.01) only in Gps II and III. Pituitary desensitization to nafarelin developed in all groups. Peak LH responses to nafarelin decreased by about 70% (Gps I and II) and 95% (Gp III). Basal serum estradiol levels after 1 month of treatment were approximately 70 pg/ml (Gp I) and 25 pg/ml (Gps II and III). Serum estradiol levels increased acutely in Gps I and II, but not in Gp III, in response to each dose of nafarelin. Thus, average daily estradiol levels in Gp II were higher than those in Gp III. Serum testosterone and androstenedione levels decreased slightly (P less than 0.05; Gp II) or by 50% (P less than 0.01; Gp III) during treatment. The effects of nafarelin on ovulatory function also were dose-dependent. In Gp I there were four ovulations (progesterone, greater than 4 ng/ml) and seven instances of luteinization (progesterone, 2-4 ng/ml) during 73 months of nafarelin administration. In contrast, there were no ovulations during 58 and 44 months in Gps II and III, respectively. After discontinuance of nafarelin, ovulatory menstrual function returned rapidly in all women. In summary, inhibition of pituitary-ovarian function by daily intranasal nafarelin administration is dose dependent. Gonadotroph sensitivity to 125 micrograms is variable, and there is inconsistent inhibition of ovulation. Daily doses of 250 or 1000 micrograms analog reliably inhibit ovulation, but are associated with either moderate (Gp II) or marked (Gp III) reduction of ovarian estradiol secretion. The effects of these reduced levels of circulating estradiol on bone are not known. Further investigation, with dosage adjusted according to individual patient sensitivity, may lead to the development of a clinically acceptable contraceptive which consistently inhibits ovulation while maintaining serum estradiol levels sufficient to prevent osteoporosis.

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Crossref · 10.1210/jcem-63-6-1334

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  • A modified menstrual cycle model based on the Margolskee 2011 model was used with optimal control theory to determine the minimum total exogenous estrogen/progesterone dose and timing of administration to induce anovulation.

    “Utilized optimal control theory on a modified menstrual cycle model (based on Margolskee 2011 model) to determine the minimum total exogenous estrogen/progesterone dose and timing of administration to induce anovulation (absence of ovulation)”

    From A Survey of Mathematical Modeling of Hormonal Contraception and the Menstrual Cycle (2024) · cites this paper as [62]

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Authors
MONROE, S. E., BLUMENFELD, Z., ANDERYKO, J. L., SCHRIOCK, E., HENZL, M. R., & JAFFE, R. B.
Affiliations
University of California, San Francisco (US)
ORCID
BLUMENFELD, ZEEV
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1986-12
Volume
63
Issue
6
Pages
1334-1341
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-63-6-1334
OpenAlex
W2075860102
Cited by
66
References
19
Citations by year
2024: 1 · 2022: 1 · 2016: 2 · 2014: 1 · 2012: 2
FWCI
4.35
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-3-2831, N01-HD-0-2811)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
Keywords
nafarelin, ovulation inhibition, dose-dependent effects, luteinization, follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, androstenedione, intranasal administration, female contraception, ovulation induction
MeSH terms
Administration, Intranasal, Adult, Androgens, Dose-Response Relationship, Drug, Endometrium, Estradiol, Female, Gonadotropins, Pituitary, Humans, Gonadotropin-Releasing Hormone, Menstruation, Ovary, Ovulation, Pituitary Gland, Thyrotropin, Nafarelin

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