The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Clomiphene citrate: mechanism(s) and site(s) of action—a hypothesis revisited
Open accessAbstract
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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“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]
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“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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Cites
The Neuroendocrine Control of the Menstrual Cycle
Knobil, E. (1980) · Elsevier eBooks · doi:10.1016/b978-0-12-571136-4.50008-5 · Cited by 1,285
Absence of oestradiol concentration in cell nuclei of LHRH-immunoreactive neurones
Shivers, B. D., Harlan, R. E., Morrell, J. I., & Pfaff, D. W. (1983) · Nature · doi:10.1038/304345a0 · Cited by 531
CARMEL, P. W., ARAKI, S., & FERIN, M. (1976) · Endocrinology · doi:10.1210/endo-99-1-243 · Cited by 482
Trounson, A. O., Leeton, J. F., Wood, C., Webb, J., & Wood, J. (1981) · Science · doi:10.1126/science.7221557 · Cited by 379
Pituitary and Gonadal Hormones in Women during Spontaneous and Induced Ovulatory Cycles
ROSS, G. T., Cargille, C. M., LIPSETT, M. B., Rayford, P. L., Marshall, J. R., Strott, C. A., & Rodbard, D. (1970) · Elsevier eBooks · doi:10.1016/b978-0-12-571126-5.50005-4 · Cited by 373
Estradiol-Concentrating Neurons: Topography in the Hypothalamus by Dry-Mount Autoradiography
Stumpf, W. E. (1968) · Science · doi:10.1126/science.162.3857.1001 · Cited by 298
The agonistic-antagonistic properties of clomiphene: A review
Clark, J. H., & Markaverich, B. M. (1981) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(81)90055-3 · Cited by 220
Richards, J. S. (1975) · Endocrinology · doi:10.1210/endo-97-5-1174 · Cited by 210
Pfaff, D. W., Gerlach, J. L., McEwen, B. S., Ferin, M., Carmel, P. W., & Zimmerman, E. A. (1976) · The Journal of Comparative Neurology · doi:10.1002/cne.901700302 · Cited by 166
Adashi, E. Y., & Hsueh, A. J. W. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)65107-9 · Cited by 160
Self-citation
Research works printed but not linked: 6
- Holtkamp, 1962, Effects of clomiphene: animal data and interpretation, Fertil Steril (Abstr), 13, 110
- Kheifets, 1973, Treatment of menstrual function disorders and female infertility of endocrine origin with chlorotrianisene, Akush Ginekol (Mosk), 49, 36
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Cited by
Sorted by citations
Diagnosis and Management of Infertility: A Review
Carson, S. A., & Kallen, A. N. (2021) · JAMA · doi:10.1001/jama.2021.4788 · Cited by 1,294
Mitwally, M. F. M., & Casper, R. F. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(00)01705-2 · Cited by 800
PROGNOSTIC ASSESSMENT OF FEMALE FECUNDITY
Navot, D., Rosenwaks, Z., & Margalioth, E. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92439-1 · Cited by 390
Assessment and management of polycystic ovary syndrome: Summary of an evidence-based guideline
Teede, H. J., Misso, M. L., Deeks, A. A., Moran, L. J., Stuckey, B. G. A., Wong, J. L. A., Norman, R. J., Costello, M. F., & Groups, O. B. O. T. G. D. (2011) · Medical Journal of Australia · doi:10.5694/mja11.10915 · Cited by 379
Mitwally, M. F. M. (2003) · Human Reproduction · doi:10.1093/humrep/deg311 · Cited by 344
Metadata
- 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)
- 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
- hybrid
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › 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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