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Hormone · Profile

Clomiphene

Clomid · Clomifene · Serophene

Hormone ManagementApproved
MW
406g/mol
Formula
C26H28ClNO

Clomiphene citrate is a non-steroidal ovulatory stimulant classified as a selective estrogen receptor modulator, primarily produced in laboratories for medical use. Researchers primarily study it for its role in inducing ovulation in women with conditions such as polycystic ovary syndrome (PCOS) and for its off-label use in male hypogonadism. Key findings from clinical studies indicate that clomiphene citrate can effectively promote ovulation in women with anovulatory infertility, although its efficacy may be lower compared to other treatments like gonadotropins. Additionally, studies suggest that clomiphene may enhance endogenous testosterone production in men with low testosterone levels, potentially improving fertility outcomes. Current research continues to explore its safety profile, optimal use in various populations, and the potential benefits of combination therapies, highlighting its clinical relevance in reproductive medicine.

Overview

Übersicht

Clomiphene, also known as Clomid, Clomifene, or Serophene, is a synthetic non-steroidal compound. It is primarily used in the management of infertility in both women and men. Clomiphene belongs to the class of selective estrogen receptor modulators (SERMs) and is not naturally produced in the body. It is typically administered orally in the form of clomiphene citrate. Researchers have extensively studied clomiphene for its role in ovulation induction, particularly in women with polycystic ovary syndrome (PCOS) and other forms of anovulatory infertility. It is also investigated for its potential benefits in treating male hypogonadism and improving spermatogenesis. Clomiphene acts by binding to estrogen receptors in the hypothalamus, blocking the negative feedback of estrogen, and thereby increasing the release of gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This stimulation leads to ovulation in women and increased testosterone production in men. Pharmacokinetically, clomiphene is well absorbed orally, with a half-life that varies due to its isomeric forms. It undergoes hepatic metabolism and is excreted primarily in feces. Clinically, clomiphene is widely used as a first-line treatment for female infertility due to anovulation and is also employed off-label for male hypogonadism. It is approved by various regulatory bodies for specific indications, although its long-term safety profile continues to be evaluated in ongoing research.

Chemical profile

Chemische Struktur

Chemical structure of Clomiphene
FormelC26H28ClNO
Molekulargewicht406g/mol
CAS-Nummer911-45-5
PubChem CID2800
Mechanism

Wirkmechanismus

Clomiphene acts on estrogen receptors in the hypothalamus, blocking estrogen's negative feedback. This inhibition leads to increased secretion of gonadotropins (FSH and LH), promoting ovulation in women and testosterone production in men.

Mechanism

Signalweg

Clomiphene citrate primarily acts as a selective estrogen receptor modulator (SERM) by competitively binding to estrogen receptors in the hypothalamus, thereby blocking the negative feedback of estrogen on gonadotropin-releasing hormone (GnRH) secretion. This leads to increased secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary, stimulating ovarian follicle development and ovulation. The exact downstream signaling pathways involved in this process, including the specific roles of the cAMP/PKA pathway and other hormonal interactions, are not fully understood.

Half-Life & Pharmacokinetics

POOral

Half-life varies due to isomeric forms, approximately 5-7 days

Clomiphene consists of two isomers, zuclomiphene and enclomiphene, which have different half-lives, contributing to its prolonged effect.

Storage

Temperature

Store at room temperature (15-30C)

Light

Protect from light

Form

Stable as a tablet form for extended periods

Notes

Ensure packaging is sealed to maintain stability

Solubility

Löslichkeit

Clomiphene citrate is slightly soluble in water and more soluble in ethanol.

Legal Status

🇩🇪DE

Verschreibungspflichtig (prescription only); not a controlled substance under BtMG.

🇺🇸US

FDA approved for female infertility; prescription required; not a controlled substance.

🇦🇺AU

TGA Schedule 4 (prescription only medicine).

🇬🇧UK

Prescription only medicine (POM) under MHRA regulations.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Open Questions

Offene Forschungsfragen

Current evidence is limited regarding the long-term efficacy and safety of clomiphene citrate, particularly in its off-label use for male hypogonadism, where its comparative effectiveness against testosterone replacement therapy remains unclear. Further research is needed to explore the benefits of combination therapies involving clomiphene citrate and other agents, as well as to establish its effectiveness in diverse populations, including those with varying hormonal profiles. Additionally, larger randomized controlled trials are necessary to validate the findings on clomiphene citrate's role in ovulation induction compared to newer agents like letrozole, especially in women with PCOS and those who have failed previous treatments.

77 Research Publications

4,999

Total Citations

26

Human/RCT

6.5

Avg. Influence

2024

Latest

Sort
Filter
#01

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

HumanInfluence46.0
974
The study demonstrated that clomiphene citrate is superior to metformin in achieving live births among infertile women with polycystic ovary syndrome, although multiple pregnancies were a noted complication.
#02

Metformin in polycystic ovary syndrome: systematic review and meta-analysis.

ReviewInfluence34.0
768
The study demonstrated that metformin effectively improves ovulation and pregnancy rates in women with polycystic ovary syndrome compared to placebo and clomiphene alone.
#03

Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.

ReviewInfluence17.0
385
The review indicated that metformin significantly improves ovulation rates and metabolic parameters in women with polycystic ovary syndrome, especially when combined with clomiphene citrate.
#04

Modern use of clomiphene citrate in induction of ovulation.

ReviewInfluence19.0
336
Researchers observed that clomiphene citrate effectively induces ovulation in anovulatory women, with pregnancy rates similar to those in the normal fertile population, although obesity negatively impacts response rates.
#05

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

HumanInfluence12.0
273
The study demonstrated that adding metformin to clomiphene citrate does not significantly improve ovulation rates in women with polycystic ovary syndrome compared to clomiphene alone.
#06

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

HumanInfluence13.0
261
The study found that while letrozole resulted in fewer multiple gestations compared to gonadotropins, it also led to lower live birth rates compared to both gonadotropin and clomiphene treatments.
#07

Development, pharmacology and clinical experience with clomiphene citrate.

ReviewInfluence12.0
226
Researchers observed that clinical outcomes in clomiphene citrate cycles are influenced by factors such as follicle size and endometrial thickness, with pregnancy rates remaining consistent over multiple cycles.
#08

Clomiphene and anti-oestrogens for ovulation induction in PCOS.

ReviewInfluence12.0
215
The review indicated that clomiphene citrate is effective in increasing pregnancy rates compared to placebo, but evidence on its effects on miscarriage and live births is limited.
#09

Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial.

HumanInfluence8.0
186
The study demonstrated that clomiphene citrate and unstimulated intrauterine insemination do not significantly improve live birth rates compared to expectant management in couples with unexplained infertility.
#10

Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation.

ReviewInfluence5.0
99
The study demonstrated that clomiphene citrate effectively increases pregnancy rates compared to placebo, with no significant difference observed when compared to tamoxifen.

Clinical Trials (45)

Preclinical
Phase I
Phase II
Phase III
Approved

45

Total Trials

8,962

Total Enrolled

The Potential Biochemical Diagnosis Criteria and Therapeutic Effect Indexes: Sex Hormone Binding Globulin Levels and Free Androgen Index in Blood of Patients With Polycystic Ovary Syndrome

NCT01784380COMPLETED
Sponsor

Zhongshan Bo Ai Hospital

Enrollment

1,159

Started

2006

Primary outcome

The potentially biochemical diagnosis criteria and therapeutic effect evaluation indexes: Sex hormone binding globulin levels and free androgen index in blood of patients with polycystic ovary syndrome

The Investigators Collected 534 PCOS Patients as the Case Group,and 580 Infertile Women With Normal Ovulatory Cycle of the Control Group;At the Same Time, the Investigators Continuedly Collect Cases to October 2012, and Totally Collected 579 Patients With PCOS Altogether;534 Patients in the Cases Group and 580 Women in the Control Group Received no Measures, While 579 Patients Received Drugs;The Investigators Monitored Basic Indexes in Blood of All the Subjects in This Suvey,and Also Monitored Indexes of 579 Patients After Treatment.

Comparison of Recombinant Follicle Stimulating Hormone and the Combination of Recombinant Follicle Stimulating Hormone With Clomiphene Citrate in Stimulated Intrauterine Insemination Cycles

Sponsor

Bezmialem Vakif University

Enrollment

254

Started

2023

Primary outcome

Rate of clinical pregnancy

Infertility Unexplained

Letrozole or Combined Metformin Clomiphene Citrate (CC) for Women With CC Resistant Polycystic Ovary Syndrome

NCT00911313COMPLETED
Sponsor

Mansoura University

Enrollment

250

Started

2006

Primary outcome

Principally the ovulation rate as well as the number of growing and mature follicles, serum E2 (pg/ml), serum P (ng/mL), and endometrial thickness (mm).

Polycystic Ovary Syndrome

Letrozole or Combined Clomiphene Citrate Metformin as a First Line Treatment in Women With Polycystic Ovarian Syndrome

NCT01679574COMPLETED
Sponsor

Assiut University

Enrollment

200

Started

2009

Primary outcome

ovulation rate

Polycystic Ovary Syndrome

L-Carnitine and Clomiphene Citrate for Induction of Ovulation in Women With Polycystic Ovary Syndrome

NCT03476356COMPLETED
Sponsor

Ain Shams University

Enrollment

106

Started

2017

Primary outcome

Ovulation success by trans-vaginal ultrasound

Polycystic Ovary Syndrome

Tamoxifen Compared With Clomiphene Citrate for Women Who Had Thin Endometrium Women Under Clomiphene in a Previous Cycle

Sponsor

Shaare Zedek Medical Center

Enrollment

100

Started

2007

Primary outcome

Pregnancy rate

Infertility

Clomiphene Citrate Stair-Step Protocol

Sponsor

Ain Shams Maternity Hospital

Enrollment

60

Started

2017

Primary outcome

Occurrence of the ovulation by transvaginal ultrasound

Polycystic Ovary

Anti-Mullerian Hormone as Predictor of Ovarian Responce to Clomiphene Citrate in PCOS

Sponsor

Ain Shams University

Enrollment

40

Started

2018

Primary outcome

AMH in prediction of Ovulation in women with PCOS.

Polycystic Ovary Syndrome

Progestin-induced Endometrial Shedding in PCOS (The PIES in PCOS Study)

NCT01718444TERMINATED
Sponsor

University of Illinois at Chicago

Enrollment

27

Started

2015

Primary outcome

Live Birth

Polycystic Ovary SyndromeInfertility

Differential Effects of Clomiphene Citrate in Women Undergoing Superovulation

NCT01291056COMPLETED
Sponsor

University of Utah

Enrollment

20

Started

2010

Primary outcome

Follicular Cycle Total Behavioral Score for Calendar of Premenstrual Experiences (COPE) Self Assessment

Mood

Cost-effective Treatment of Unexplained Infertility

NCT06178523Phase 4COMPLETED
Sponsor

Batterjee Medical College

Enrollment

900

Started

2024

Primary outcome

Pregnancy outcome

Unexplained Infertility

Metformin for the Treatment of Unexplained Oligozspermia

NCT01529177Phase 4UNKNOWN
Sponsor

The Egyptian IVF-ET Center

Enrollment

600

Started

2012

Primary outcome

sperm count

Infertility

Strategies for Ovulation Induction in Anovulatory Infertile Patients With PCOS

NCT00461643Phase 4UNKNOWN
Sponsor

University Magna Graecia

Enrollment

552

Started

2007

Primary outcome

Multiple pregnancy rate

Anovulatory Infertility Related to Polycystic Ovary Syndrome

Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups

NCT07523022Phase 4ENROLLING_BY_INVITATION
Sponsor

Szeged University

Enrollment

500

Started

2024

Primary outcome

sperm DNA fragmentation

Male Infertility

Adding Prednisolone During Ovulation Induction With CC in Lean Women With CC Resistant PCOS

NCT02344888Phase 4UNKNOWN
Sponsor

Mahmoud Thabet

Enrollment

300

Started

2015

Primary outcome

Ovulation rate

InfertilityPolycystic Ovarian Syndrome

Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF

NCT02201914Phase 4UNKNOWN
Sponsor

Bioroma

Enrollment

250

Started

2014

Primary outcome

Clinical pregnancy rate

Poor RespondersIVFClomiphene CitrateGnRH AgonistGnRH Antagonist

PCOSMIC Trial - PolyCystic Ovary Syndrome, Metformin for Infertility With Clomiphene

NCT00795808Phase 4COMPLETED
Sponsor

University of Auckland, New Zealand

Enrollment

171

Started

2003

Primary outcome

Clinical pregnancy

Polycystic Ovary Syndrome

Letrozole Versus Clomifene Citrate for Ovulation Induction

NCT00478504Phase 4COMPLETED
Sponsor

University of Nottingham

Enrollment

159

Started

2007

Primary outcome

Pregnancy rate

InfertilityPolycystic Ovarian Syndrome

Phytoestrogens as an Alternative to Estradiol in Ovulation Induction in PCOS

NCT02352597Phase 4COMPLETED
Sponsor

Cairo University

Enrollment

150

Started

2013

Primary outcome

endometrial thickness

Polycystic Ovaries

Effect of Sildenafil Citrate Compared to Estrogen as Adjuvant Therapy for Unexplained Infertility

NCT05753098Phase 4COMPLETED
Sponsor

Beni-Suef University

Enrollment

148

Started

2021

Primary outcome

pregnancy rates

Subfertility, Female

Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response

NCT03400722Phase 4UNKNOWN
Sponsor

Nova Clinic, Russia

Enrollment

120

Started

2017

Primary outcome

Total number of retrieved oocytes per cycle

Infertility, FemaleOvarian StimulationIn Vitro Fertilisation

The Effect of Ethinyl Estradiol on Polycystic Ovary Syndrome Women Undergoing Intrauterine Insemination

NCT01219101Phase 4COMPLETED
Sponsor

Royan Institute

Enrollment

95

Started

2011

Primary outcome

Clinical Pregnancy rate

Infertility

Pulsatile Gonadotropin-releasing Hormone for Infertility in Non-obese Patients With Polycystic Ovary Syndrome

NCT03989024Phase 4UNKNOWN
Sponsor

RenJi Hospital

Enrollment

78

Started

2019

Primary outcome

Number of participants with ovulation recovery (according to basal body temperature, progesterone levels on cycle day 21, or ultrasonography)

Polycystic Ovary SyndromeInfertilityOvulation Disorder

Combined Letrozole and Clomid in Women With Infertility and PCOS

NCT02802865Phase 4COMPLETED
Sponsor

Rachel Mejia

Enrollment

70

Started

2016

Primary outcome

Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level

Polycystic Ovary SyndromeInfertility

Effect Clomiphene vs Clomiphene Along With Pioglitazone on Ovarian Stimulation Rate

NCT07462065Phase 4RECRUITING
Sponsor

PAEC General Hospital, Islamabad

Enrollment

62

Started

2026

Primary outcome

Ovarian stimulation rate

Infertility TreatmentPregnancy Rates

Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study

NCT01921166Phase 4COMPLETED
Sponsor

Wake Forest University Health Sciences

Enrollment

23

Started

2011

Primary outcome

Oocytes

Infertility

Myo-inositol Versus Clomiphene Citrate in PCOS

NCT04306692Phase 4TERMINATED
Sponsor

University Hospital, Ghent

Enrollment

12

Started

2020

Primary outcome

Rate of cumulative ongoing pregnancy (a pregnancy diagnosed by ultrasonic visualisation of one or more gestational sacs with fetal heart beat) after 3 treatment cycles with inositol versus clomiphene citrate for ovulation induction.

Ovulation InductionPolycystic Ovary SyndromeClomipheneInositol

Impact of Clomiphene Citrate Administration During the Early Luteal Phase on Endocrine Profile in IVF Cycles

NCT01791751Phase 4COMPLETED
Sponsor

Fundació Privada Eugin

Enrollment

10

Started

2012

Primary outcome

LH Levels (IU)

Female Infertility

Pregnancy in Polycystic Ovary Syndrome II

NCT00719186Phase 3COMPLETED
Sponsor

Yale University

Enrollment

750

Started

2009

Primary outcome

Live Birth

PregnancyPolycystic Ovary Syndrome

Assessment of the Effects of Enclomiphene Citrate on Bone Mineral Density in Men With Secondary Hypogonadism

NCT01619683Phase 3COMPLETED
Sponsor

Repros Therapeutics Inc.

Enrollment

300

Started

2012

Primary outcome

Bone Mineral Density

Effect of Treatment on Bone Mineral Density

Human Chorionic Gonadotrophin & Trigger

NCT02264847Phase 3UNKNOWN
Sponsor

Cairo University

Enrollment

200

Started

2014

Primary outcome

Ovulation rate

Ovulation Disorder

Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism

NCT01739595Phase 3COMPLETED
Sponsor

Repros Therapeutics Inc.

Enrollment

181

Started

2012

Primary outcome

Subjects With Testosterone in Normal Range After Treatment

Secondary Hypogonadism

Letrozole vs. Clomiphene Citrate in Patients With Anovulatory Infertility

NCT00610077Phase 3COMPLETED
Sponsor

Sun Pharmaceutical Industries Limited

Enrollment

55

Started

2004

Primary outcome

Ovulation rate (ovulatory cycles/ all treatment cycles) by Ultrasonography (USG).

Infertility

Letrozole vs Clomiphene Citrate for Induction of Ovulation in Women With Polycystic Ovarian Syndrome

NCT05702957Phase 2/3COMPLETED
Sponsor

Services Institute of Medical Sciences, Pakistan

Enrollment

220

Started

2016

Primary outcome

Pregnancy rate

Polycystic Ovary SyndromeInfertility

NAC in CC Resistant PCOS After LOD

NCT02775734Phase 2/3COMPLETED
Sponsor

Ain Shams University

Enrollment

144

Started

2016

Primary outcome

Biochemical pregnancy rate

Clomiphene Citrate Resistant Polycystic Ovary Syndrome

Cabergoline As An Adjuvant To Clomiphene Citrate For Management Of Unexplained Infertility

NCT03549741Phase 2/3UNKNOWN
Sponsor

Assiut University

Enrollment

120

Started

2018

Primary outcome

The number of mature follicles

Infertility

Letrozole Versus Clomiphene Citrate for Ovulation Induction in Women With Poly Cystic Ovary Syndrome ( PCOS )

NCT02551367Phase 2UNKNOWN
Sponsor

mostafa gomaa hamid halawa

Enrollment

110

Started

2015

Primary outcome

ovulation rate

AnovulationPolycystic Ovary Syndrome

Sex Hormone Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial

NCT04944836Phase 2RECRUITING
Sponsor

University of Utah

Enrollment

58

Started

2023

Primary outcome

Magnetic Resonance Imaging (MRI) tendon healing Post-op

Rotator Cuff Tears

A Multi-Center Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Body Composition and Metabolic Parameters With Diet and Exercise in Conjunction With Treatment With 12.5 mg or 25 mg Enclomiphene

NCT02651688Phase 2COMPLETED
Sponsor

Repros Therapeutics Inc.

Enrollment

50

Started

2016

Primary outcome

Change From Baseline in Lean Body Mass (LBM) at Week 48

Acquired Hypogonadotropic HypogonadismObesity

Clomid in Men With Low Testosterone With and Without Prior Treatment

NCT01904734Phase 2COMPLETED
Sponsor

Phoenix VA Health Care System

Enrollment

42

Started

2012

Primary outcome

Total serum testosterone

Hypogonadism, Male

Hypogonadotropic Hypogonadism in Obese Young Males

NCT03245827Phase 2TERMINATED
Sponsor

Sandeep Singh Dhindsa, M.D., F.A.C.E

Enrollment

9

Started

2019

Primary outcome

Serum Free Testosterone

Hypogonadism, Hypogonadotropic

Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) Response to Low Dose Clomiphene Citrate in Normally Menstruating Fertile Women

NCT01340521Phase 1/2COMPLETED
Sponsor

Milton S. Hershey Medical Center

Enrollment

25

Started

1991

Primary outcome

LH Concentration

Infertility

Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting

NCT03028532Phase 1COMPLETED
Sponsor

Stuart Willick

Enrollment

12

Started

2017

Primary outcome

The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.

Sports Drug AbuseAbuse of Steroids or Hormones

Metformin Use and Clinical Pregnancy Rate in Women With Unexplained Infertility

NCT03681197Early Phase 1UNKNOWN
Sponsor

Elham Raafat

Enrollment

170

Started

2018

Primary outcome

Clinical pregnancy rate

Infertility

Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS

NCT01909141Early Phase 1COMPLETED
Sponsor

Cairo University

Enrollment

100

Started

2013

Primary outcome

Ovulation Rate

Polycystic Ovary SyndromeInfertility

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This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer