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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
- Schreiber, 1966, Studies with 14C-labeled clomiphene citrate, Clin Res, 14, 287
- Kitai, 1984, Direct ovarian effects of clomiphene citrate in the rabbit, Fertil Steril, 41, 6S
- Stahler, 1975, Direct effect of clomiphene on the ovary examined with an in vitro perfusion system of the human ovary, Arch Gynaekol, 219, 585
- Schultz, 1968, The intracellular distribution of [14C] Clomid (MRL-41) in various organs of the immature female guinea pig, Hoppe Seylers Z Physiol Chem, 349, 15
Cited by
Sorted by citations
Items 201–249 of 249
Strigini, F. A. L., Collins, W. P., Whitehead, M. I., Melis, G. B., FIORETTI, P., & Campbell, S. C. (1986) · Fertility and Sterility · doi:10.1016/s0015-0282(16)49513-0 · Cited by 1
Meyer-Wittkopf, M., Birkenfeld, A., & Beier, H. M. (1989) · Archives of Gynecology and Obstetrics · doi:10.1007/bf02417671 · Cited by 1
Taymor, M. L. (1990) · Springer eBooks · doi:10.1007/978-1-4613-0627-6_26 · Cited by 1
Moramezi, F., Saadati, N., & Aboutalebi, Z. (2015) · Jentashapir Journal of Health Research · doi:10.5812/jjhr.27174
Medical and Endocrine Therapy of the Infertile Male
Sokol, R. Z. (1997) · Springer eBooks · doi:10.1007/978-1-4612-1848-7_10
Diagnostik und Therapie des polyzystischen Ovarsyndroms
Ortmann, O. (1998) · Springer eBooks · doi:10.1007/978-3-642-58738-2_3
Gemelización en Poecilia reticulata causada por citrato de clomifeno
Rodríguez-Varela, A. D. C., Cruz-Gómez, A., & Vázquez-López, H. (2009) · Dialnet (Universidad de la Rioja)
Antihormone in der Gynäkologie
Breckwoldt, M. (1989) · Springer eBooks · doi:10.1007/978-3-642-74784-7_477
Endokrinologie, Orthologie, Funktionsdiagnostik und funktionelle Störungen des Endometriums
Löning, T. (2001) · Spezielle pathologische Anatomie · doi:10.1007/978-3-642-56781-0_19
New advances and new horizons in assisted reproduction
Bdolah, Y., & Laufer, N. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139003254.014
Wallach, E. E. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.03.080
Self-citationChang, C., Hu, H.-J., Tang, H.-C., & Sun, L.-T. (1992) · Aquaculture · doi:10.1016/0044-8486(92)90035-j
Ovarian Stimulation: Clomiphene Citrate
Gianfortoni, J. G. (2004) · Elsevier eBooks · doi:10.1016/b0-12-475570-4/00963-x
8 Ovulation induction for luteal phase defects and luteal phase defects after ovulation induction
Li, T. C., & Warren, M. A. (1993) · Baillière s Clinical Obstetrics and Gynaecology · doi:10.1016/s0950-3552(05)80137-3
Chang, Y., Lee, J. Y., Moon, S. Y., Kim, J. G., & Yoon, B. H. (1988) · Asia-Oceania Journal of Obstetrics and Gynaecology · doi:10.1111/j.1447-0756.1988.tb00102.x
Investigation of the Female Partner
Messinis, I. E., & Templeton, A. (1994) · Springer eBooks · doi:10.1007/978-1-4471-1029-3_7
The Histopathological Changes in Rat Ovary and Endometrium Following Long Term Clomiphene Treatment
ÖZDEMİR, M., Erol, A. Y. G., CEVRİOĞLU, A. S., & Dılek, F. H. (2015) · Turkiye Klinikleri Journal of Medical Sciences · doi:10.5336/medsci.2015-45930
Recent Treatment Strategies for Polycystic Ovary Syndrome
Lee, H. (2015) · Journal of Korean Diabetes · doi:10.4093/jkd.2015.16.3.194
Antihormone in der Gynäkologie
Breckwoldt, M. (1989) · Archives of Gynecology and Obstetrics · doi:10.1007/bf02417623
Aromatase Inhibitors in the Treatment of Unexplained Female Infertility
Sekhon, L. H., Rekawek, P., & Grunfeld, L. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2140-9_26
Ovarian Stimulation with Clomiphene Citrate
Gianfortoni, J. G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95857-4
Letrozol zur Ovulationsinduktion bei PCOS
Doblinger, J., & Griesinger, G. (2017) · Gynäkologische Endokrinologie · doi:10.1007/s10304-017-0128-0
SERMs’ Effect on the Neuroendocrine System and the Reproductive Organs
Santoro, N. F., & Kovács, P. (2002) · Humana Press eBooks · doi:10.1007/978-1-59259-157-2_10
General Concepts of Endocrine Manipulation of Assisted Reproduction
Fasouliotis, S. J., & Laufer, N. (2003) · Elsevier eBooks · doi:10.1016/b978-012053642-9/50030-2
Les modulateurs sélectifs des récepteurs aux œstrogènes : à propos de deux exemples
Letombe, B., Catteau-Jonard, S., & Robin, G. (2019) · Elsevier eBooks · doi:10.1016/b978-2-294-75965-9.00016-7
Comparision of tamoxifene v/s clomiphene citrate in ovulation induction
Sharma, V. M., Tekani, D., & Airao, B. B. (2020) · International Journal of Clinical Obstetrics and Gynaecology · doi:10.33545/gynae.2020.v4.i1c.456
Hellebaut, S., Meerschaut, F. V., & Vandekerckhove, F. (2020) · Tijdschrift voor Geneeskunde · doi:10.47671/tvg.76.20.039
Physical activity and cardiovascular disease risk in women with polycystic ovary syndrome
Woodward, A. (2021) · Sheffield Hallam University · doi:10.7190/shu-thesis-00398
Rabe, T., Gör, Ü. B., Urbancsek, J., & Runnebaum, B. (1994) · Springer eBooks · doi:10.1007/978-3-662-07633-0_11
Gibson, M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1436-1_35
Lecomte, P., & Lecomte, C. (2000) · EMC - Ginecología-Obstetricia · doi:10.1016/s1283-081x(00)71877-7
von Bruchhausen, F., Ebel, S., Frahm, A. W., Hackenthal, E., Albinus, M., Ali, H.-F., Ali, S. L., Amschler, G., Amschler, U., Angerer, E. V., et al. (1993) · Springer eBooks · doi:10.1007/978-3-642-57995-0_3 · Cited by 1
Legro, R. S. (2018) · Springer eBooks · doi:10.1007/978-3-319-45534-1_9
Lecomte, P., & Lecomte, C. (2006) · EMC - Gynécologie · doi:10.1016/s0246-1064(00)00030-x
Shoham, Z., & Howles, C. M. (2012) · Informa Healthcare eBooks · doi:10.3109/9781841849737.037 · Cited by 1
Effects of Clomiphene citrate on the histological structure of the Iraqi domestic chicken’s ovaries
(2019) · University of Thi-Qar Journal · doi:10.32792/utq/utj/vol13/3/5
The Management of Unexplained Infertility
Zayed, F., & Abu‐Heija, A. (1999) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199911001-00038
Oral Agents for Ovulation Induction
Narin, R. (2022) · Düzce Tıp Fakültesi Dergisi · doi:10.18678/dtfd.1185208
Quarde, A. (2023) · Wiley eBooks · doi:10.1002/9781119863564.ch6
Diagnostik Therapie bei gestörter Ovarfunktion
Strowitzki, T. (2024) · Springer eBooks · doi:10.1007/978-3-662-65517-7_6
Nutraceuticals and Infertility
Sureda, A., Monserrat-Mesquida, M., & Tejada, S. (2024) · Food bioactive ingredients · doi:10.1007/978-3-031-76481-3_10
Kaļva, A., & Briģis, Ģ. (2025) · World Medical & Health Policy · doi:10.1002/wmh3.70032
Zhou, N., Xu, J., Liu, L., Yang, Y., Fan, X., & Ren, H. (2025) · Clinical Therapeutics · doi:10.1016/j.clinthera.2025.07.025
Ovarian stimulation with clomiphene citrate
Peigné, M., Sonigo, C., & Robin, G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00268-5
Velupulai, P., Karim, A., Ahmad, M. F., & Abu, M. A. (2024) · Malaysian Journal of Medicine and Health Sciences · doi:10.47836/mjmhs20.5.19
Hoehne, C. L., Lohner, A., Salim, Y., Terhart, M., Andersen, W., Angerhöfer, C., Moltrecht, R., Scheuerecker, F., MaassenVanDenBrink, A., & Raffaelli, B. (2026) · The Journal of Headache and Pain · doi:10.1186/s10194-026-02325-y
Zhu, W., Chen, D., 詹雪君, Li, Q., Deng, S., Chen, D., Yingling, F., Liang, J., He, C., & Shen, X. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1888569
Understanding and Addressing Anovulatory Infertility
Violette, C. J., & Eaton, J. L. (2026) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2026.08.003
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
