Side Effects of clomiphene: A Synthesis of Findings from 30 Studies

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Original Abstract of the Article

Main Research Findings

Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. 4 Letrozole is a more effective drug than clomiphene citrate for ovulation induction, and it has fewer side effects. 5 28 However, letrozole is associated with a risk of congenital malformations in fetuses, so its use in women seeking pregnancy should be cautious. 28

Reasons for Side Effects

Clomiphene citrate acts on estrogen receptors to stimulate the release of estrogen from the ovaries. 1 Increased estrogen levels can promote ovulation but can also cause various side effects. 1

Common Side Effects

Visual Disturbances

Visual disturbances have been reported as a side effect of clomiphene citrate. 20 Visual disturbances may be due to the effect of clomiphene citrate on the optic nerve. 20

Gastrointestinal Symptoms

Gastrointestinal symptoms have been reported as a side effect of clomiphene citrate. 14 Gastrointestinal symptoms may be due to the effect of clomiphene citrate on the gastrointestinal tract. 14

Neuropsychiatric Symptoms

Neuropsychiatric symptoms have been reported as a side effect of clomiphene citrate. 20 Neuropsychiatric symptoms may be due to the effect of clomiphene citrate on the brain. 20

Other

Various other symptoms have been reported as side effects of clomiphene citrate. 21 17 27 29 30 Side effects of clomiphene citrate vary widely, and not everyone experiences them. 21 17 27 29 30

Countermeasures for Side Effects

Visual Disturbances

If you experience visual disturbances, stop taking clomiphene citrate and consult your doctor. 20

Gastrointestinal Symptoms

If you experience gastrointestinal symptoms, stop taking clomiphene citrate and consult your doctor. 14

Neuropsychiatric Symptoms

If you experience neuropsychiatric symptoms, stop taking clomiphene citrate and consult your doctor. 20

Other

If you experience any other side effects, stop taking clomiphene citrate and consult your doctor. 21 17 27 29 30

Comparison Between Studies

Commonalities

Multiple studies have confirmed that clomiphene citrate is effective in treating infertility due to oligo-ovulation or anovulation. 4 23 7 Studies have reported that clomiphene citrate can cause side effects such as visual disturbances, gastrointestinal symptoms, and neuropsychiatric symptoms. 20 14

Differences

The frequency and severity of side effects of clomiphene citrate vary across studies. 21 17 27 29 30 This is likely due to factors such as the age and health status of the study participants, the dosage of clomiphene citrate, and other factors. 21 17 27 29 30

Caution for Application in Real Life

Clomiphene citrate is an effective drug for the treatment of infertility, but it is important to be aware of the risk of side effects. 4 23 7 5 28 If you are considering taking clomiphene citrate, consult with your doctor to understand the risks and benefits and make appropriate treatment choices. 4 23 7 5 28

Limitations of Current Research

Research on the side effects of clomiphene citrate is not yet sufficient. 21 17 27 29 30 In particular, research on long-term side effects is limited. 21 17 27 29 30

Future Research Directions

Further research is needed on the long-term side effects of clomiphene citrate and the mechanisms by which side effects occur. 21 17 27 29 30 Comparative studies with other ovulation induction drugs are also important. 28

Conclusion

Clomiphene citrate is an effective drug for the treatment of infertility, but it is associated with the risk of side effects. 4 23 7 5 28 If you are considering taking clomiphene citrate, consult with your doctor to understand the risks and benefits and make appropriate treatment choices. 4 23 7 5 28

Literature analysis of 30 papers
Positive Content
23
Neutral Content
5
Negative Content
2
Article Type
3
2
4
6
29
1.

Clomiphene citrate for unexplained subfertility in women.

Author: HughesE, CollinsJ, VandekerckhoveP

Subfertility treatment
Headaches
Hot flashes
Mood swings
Multiple pregnancy
Ovarian cancer
Visual disturbances

Clomiphene citrate is effective in treating sub-fertility associated with oligo-ovulation. However, it is associated with an elevated multiple pregnancy rate of approximately 10%. Other side effects include hot flashes, mood swings, headaches, and visual disturbances. The potential for increased ovarian cancer risk is a concern.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

6.

Therapeutic approach for metabolic disorders and infertility in women with PCOS.

Author: MorganteG, MassaroM G, Di SabatinoA, CappelliV, De LeoV

Insulin sensitivity
PCOS treatment
Hyperandrogenism
PCOS

Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting women. Treatment options include lifestyle changes, oral contraceptives, and insulin-sensitizing drugs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Comparative Evaluation of Sildenafil Citrate and Estrogen as an Adjuvant Therapy for Treatment of Unexplained Infertility in Women.

Author: AltyarAhmed E, BoshraMarian S, Abou WardaAhmed Essam, ShawkeySherwet M, Abdallah Mohamed SalemSara, SarhanRania M, SarhanNeven

Endometrial thickness
Pregnancy rates
Headache

Adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and increase pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where infertility has lasted less than two years.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation.

Author: SolimanGhareb M, FetihGihan, AbbasAhmed M

Infertility treatment

This study focused on developing and characterizing thermosensitive gels for vaginal administration of sildenafil as a potential treatment for endometrial thinning caused by clomiphene citrate use in women with type II eugonadotrophic anovulation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

13.

Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial.

Author: RagniGuido, Levi-SettiPaolo E, FadiniRubens, BriganteClaudio, ScarduelliClaudia, AlagnaFederica, ArfusoVeronica, Mignini-RenziniMario, CandianiMassimo, PaffoniAlessio, SomiglianaEdgardo

Improved pregnancy chances
Lower cost

This randomized controlled trial compared clomiphene citrate to gonadotropins for ovarian stimulation in women with compromised ovarian reserve undergoing IVF. Although the gonadotropin group had more oocytes retrieved and higher embryo transfer rates, delivery rates were similar between the groups. However, the cost per delivery was significantly lower with clomiphene citrate.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Comparison of the effects of Ginger extract with clomiphene citrate on sex hormones in rats with polycystic ovarian syndrome.

Author: AtashpourShekoufeh, Kargar JahromiHossein, Kargar JahromiZahra, MaleknasabMozhgan

Improved hormonal secretion
Side effects of clomiphene

Ginger extract at higher doses was more effective than a lower dose of ginger extract and clomiphene citrate in improving sexual hormone imbalance in a polycystic ovarian syndrome (PCOS) rat model.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism.

Author: KrzastekSarah C, SharmaDevang, AbdullahNatasha, SultanMark, MachenG Luke, WenzelJessica L, EllsAlex, ChenXizhao, KavoussiMehraban, CostabileRaymond A, SmithRyan P, KavoussiParviz K

Improved testosterone
Reduced hypogonadal symptoms

Clomiphene citrate is a drug that can help raise testosterone levels in men. Further research is needed to understand the long-term effects of this drug.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

16.

Ovulation induction in young girls with menometrorragia: a safe and effective treatment.

Author: FulghesuAnna Maria, MagniniRoberta, PiccalugaMaria Paola, PorruCristina

Infertility treatment
Ovulation induction

This article discusses the use of clomiphene, a drug used to induce ovulation in women with infertility, as a potential treatment for menometrorrhagia, a condition characterized by abnormal uterine bleeding.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review.

Author: GundewarTejas, KuchakullaManish, RamasamyRanjith

Male sub-fertility treatment
Decreased sperm parameters

Clomiphene citrate treatment for male subfertility can lead to paradoxical decline in semen parameters in up to 24% of patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

20.

Clomiphene citrate-induced visual hallucinations: a case report.

Author: VenkateshRamesh, GujralGaganjeet Singh, GuravPrachi, TibrewalShailja, MathurUmang

Ovulation induction
Illusory palinopsias

Polycystic ovary syndrome (PCOS) is a common cause of infertility. Clomiphene citrate is a first-line treatment for ovulation induction in women with PCOS. This case report describes a rare side effect of illusory palinopsias, a visual disturbance, in a patient with PCOS who was taking clomiphene citrate. The report highlights the importance for gynecologists and their patients to be aware of this potential side effect.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Clinical review: The use of aromatase inhibitors for ovulation induction and superovulation.

Author: PavoneMary Ellen, BulunSerdar E

Anovulation treatment

This study discusses the use of clomiphene citrate for ovulation induction and the potential benefits of alternative agents, such as aromatase inhibitors, due to clomiphene's antiestrogenic side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

23.

Comparison of the effects of letrozole and clomiphene citrate for ovulation induction in infertile women with polycystic ovary syndrome.

Author: NahidL, SirousK

Ovulation induction

This study compared the efficacy of letrozole and clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS).

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

24.

Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review.

Author: O'RourkeTimothy K, WosnitzerMatthew S

OPIAD treatment
OPIAD effects

This review explores the pathophysiology, diagnosis, and management of opioid-induced androgen deficiency (OPIAD), including the use of testosterone replacement therapy (TRT) and potential future research directions.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

25.

Clomiphene citrate for male infertility: A systematic review and meta-analysis.

Author: HuijbenManou, HuijsmansRoel L N, LockM Tycho W T, de KempVincent F, de KortLaetitia M O, van BredaJetske H M K

Male infertility treatment

Male infertility is a common problem worldwide. Clomiphene citrate is a medication that can help women ovulate, but we need more research to determine if it can improve sperm quality in men.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

26.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

Author: TaylorFrederick, LevineLaurence

Hypogonadism treatment
Male infertility treatment

Clomiphene citrate is a cost-effective treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects compared to testosterone gel replacement therapy.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

28.

Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis.

Author: PundirJyotsna, AchilliChiara, BhidePriya, SabatiniLuca, LegroRichard S, RombautsLuk, TeedeHelena, CoomarasamyArri, ZamoraJavier, ThangaratinamShakila

Ovulation induction
Congenital malformations

Letrozole is an aromatase inhibitor increasingly used for ovulation induction. Despite its effectiveness, many clinicians are reluctant to use it due to a strong-label warning about congenital malformation risk to the fetus.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

29.

Adnexal torsion in a woman undergoing ovarian hyperstimulation with clomiphene citrate therapy: a case report and review of the literature.

Author: ShiauChii-Shinn, HuangYu-Hsin, ChangMing-Yang, LoLiang-Ming, HsiehT'sang-T'ang, HsiehChia-Lin

Ovulation induction
Adnexal torsion

This case report describes a rare adverse event of unilateral adnexal torsion following ovulation induction with clomiphene citrate. Despite laparoscopic unwinding, the adnexum became hemorrhagic, requiring resection. This highlights a potential complication associated with clomiphene citrate, emphasizing the importance of careful monitoring and timely intervention.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
LetterA written message for communication and exchange of information between individuals.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

30.

Acute myocardial infarction associated with clomiphene citrate in a young woman.

Author: AvşarŞahin, ÖzAhmet, Köken AvşarAydan, KayaAdnan, BörklüEdibe Betül

Ovulation induction
MI

This case report describes a 36-year-old woman who experienced a myocardial infarction (MI) after being prescribed clomiphene citrate for infertility. Though clomiphene citrate is generally considered safe, this case highlights the potential for serious side effects, especially in patients with risk factors for coronary artery disease.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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