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Cited by 249Estrogen and related hormone effectsOvarian function and disordersReproductive Biology and Fertility

Clomiphene citrate: mechanism(s) and site(s) of action—a hypothesis revisited

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Wallach, Edward E., Adashi, Eli Y.·1984·Fertility and Sterility
DOI 10.1016/s0015-0282(16)48069-6
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Abstract

It has now been 28 years since the synthesis of clomiphene citrate (CC) by Dr. Frank P. Palopoli,l, 2 then a synthetic chemist with the William S. Merrell Company.However, despite intense basic and clinical research and a cumulative bibliography now approaching 8000 contributions, the mechanism(s) and site(s) of action of CC have only been partially clarified.This knowledge gap is particularly striking in view of the widespread and highly successful use of CC worldwide.Indeed, the clinical utility of CC has recently been further enhanced through its introduction as a primary agent in the management of luteal phase dysfunction 3 and its application in the area of in vitro fertilization. 4It is the intent of this presentation to critically explore the current hypothesis underlying the mechanism(s) and site(s) of action of CC and to propose its expansion and modification in keeping with recently accumulated experimental data.

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  • Clomiphene citrate inhibits oestradiol receptors binding in the hypothalamus and pituitary, blocking negative feedback, which increases gonadotrophin-releasing hormone, FSH, and stimulates follicular growth and ovulation.

    “It inhibits oestradiol receptors binding in the hypothalamus and pituitary, blocking negative feedback. This hypothalamus release from negative inhibition increases gonadotrophinreleasing hormone, which in turn increases FSH and stimulates follicular growth and ovulation. 217”

    From Assessment and management of polycystic ovary syndrome: Summary of an evidence-based guideline (2011) · cites this paper as [217]

  • Clomiphene citrate results in ovulation in most patients (60%-90%), but the pregnancy rates are disappointing (10%-40%).

    “Clomiphene citrate is easy to use and results in ovulation in most patients (60%-90%), but the pregnancy rates are disappointing (10%-40%).”

    From A new era in ovulation induction (2006) · cites this paper as [7]

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Research works printed but not linked: 1

  1. Clark JH, McCormack SA, Kling R, Hodges D, Hardin JW: Effect of clomiphene and other triphenylethylene de- rivatives on the reproductive tract in the rat and baboon. In Hormones and Cancer, Edited by S JacobeUi, RJB King, HR Lindner, ME Lippman. New York, Raven Press, 1980, p 295

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Authors
Wallach, E. E., & Adashi, E. Y.
Affiliations
University of Maryland, Baltimore (US)
ORCID
Adashi, Eli Y.
Venue
Fertility and Sterility
Publisher
Elsevier BV
Published
1984-09
Volume
42
Issue
3
Pages
331-344
ISSN
0015-0282 (ISSN-L)
DOI
10.1016/s0015-0282(16)48069-6
OpenAlex
W138858130
Cited by
249
References
85
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 5
FWCI
4.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Fertility and Sterility (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
clomiphene citrate, mechanism of action, site of action, in vitro fertilization, ovulation induction
MeSH terms
Animals, Aromatase, Binding Sites, Clomiphene, Estrogen Antagonists, Estrogens, Female, Follicle Stimulating Hormone, Ovarian Follicle, Humans, Hypothalamus, Luteinizing Hormone, Neurosecretory Systems, Ovary, Ovulation, Pituitary Gland, Progesterone, Receptors, Estrogen, Structure-Activity Relationship, Rats, In Vitro Techniques

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