Clomiphene Citrate

Aka: Clomiphene Citrate, Clomiphene, Clomid

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II. Indications: Fertility

  1. Stimulate Ovulation
    1. See Female Infertility
    2. Anovulatory Bleeding (Metrorrhagia)
    3. Oligo-Ovulation
  2. Luteal Phase defect
  3. Unexplained Infertility

III. Contraindications

  1. Absolute
    1. Pregnancy
    2. Liver disease
    3. Ovarian Cysts
    4. Possible Ovarian Cancer
  2. Relative
    1. Ovarian Cyst formation
    2. Ovarian Hyperstimulation
    3. Hormonal adverse effects
    4. Multiple Gestation
    5. Visual disturbances

IV. Mechanism

  1. Very similar to Tamoxifen
  2. History
    1. Synthesized in 1956 as possible hormonal contraceptive
    2. FDA approved for Anovulation in 1967
  3. Two stereoisomers
    1. Enclomiphene (62%): Anti-Estrogen (trans form)
    2. Zuclomiphene (38%): EstrogenAgonist (cis form)
  4. Functions as anti-Estrogen at Hypothalamus
    1. Competitively inhibits Estrogen receptors
    2. Blunts negative feedback of endogenous Estrogen on the pituitary
    3. Allows for unabated GnRH secretion
    4. Increases pituitary sensitivity to GnRH
      1. Enhanced Luteinizing Hormone (LH) release
      2. Enhanced Follicle Stimulating Hormone (FSH) release
  5. Affects Follicular and Luteal Phases
    1. Prolongs preovulatory Follicular Phase
    2. Preserves normal 14 day Luteal Phase and a functional corpus luteum
    3. Increases preovulatory follicles
  6. Negative effects
    1. Curtails uterine volume and endometrial lining
    2. Reduces quality and quantity of Cervical Mucus

V. Dosing: Infertility due to Ovulatory Dysfunction

  1. Assumes normal evaluation
  2. Clomid on cycle days 3 to 7
    1. Starting dose: 50 mg orally daily for 5 days
    2. If Ovulation does not occur
      1. Increase Clomid dose on subsequent cycles to 100 mg PO for 5 days
      2. Maximum dose: 150 mg daily
    3. If symptoms or large ovaries on 50 mg
      1. Decrease Clomid dose to 25 mg orally for 5 days on subsequent cycles
  3. Intercourse started before Ovulation (Day 10)
    1. Intercourse every other day at mid-cycle
    2. Urine LH-timed intercourse
  4. Confirm Ovulation
  5. Consider evaluation for Ovarian Hyperstimulation
    1. Consider Luteal Phase pelvic exam
    2. Consider Ultrasound monitoring
  6. Limit to 6 Clomid cycles
    1. Continue lowest ovulatory Clomid dose for 3 cycles
  7. If Polycystic Ovary Disease
    1. Metformin (Glucophage) 1500 mg daily
      1. Initial studies were promising and did increase Ovulation rates
      2. However does not increase the live birth rate
      3. Lord (2003) BMJ 327: 951 [PubMed]
      4. Sun (2013) Arch Gynecol Obstet 288(2): 423-30 [PubMed]
    2. Consider adding 0.5 mg Dexamethasone nightly
  8. If no conception
    1. See Female Infertility
    2. Infertility specialist referral if no conception after 6 cycles
    3. Consider hysterosalpingogram
    4. Consider Transvaginal Ultrasound monitoring

VI. Dosing: Amenorrhea prior to Protocol

  1. Provera 10 mg orally daily for 5 days
  2. Cycle starts on first day of withdrawal bleeding
  3. Start Clomid on cycle day 3 or day 5 (see above)

VII. Adverse Effects

  1. Multiple Pregnancy: 7.5%
  2. Birth defects: 0.1 to 0.5% Incidence
    1. Similar rate in normal pregnancies
  3. Mild Ovarian Hyperstimulation: 13%
  4. Venous Thromboembolism
  5. Increased Ovarian Cancer risk (in patients remain Nulliparous)
    1. Trabert (2013) Fertil Steril 100(6): 1660-6 [PubMed]
  6. Other common effects
    1. Decreased Cervical Mucus
    2. Hot Flushes
  7. Other less common
    1. Pelvic Pain
    2. Nausea
    3. Mastalgia
    4. May exacerbtae premenstrual symptoms

VIII. Precautions

  1. Confirm no Male Infertility (normal semanalysis)

IX. Efficacy

  1. Pregnancy rate 60% in 4 months of use

X. Resources

  1. Clomiphene Citrate (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=be399623-6400-475d-93d3-1dedd4d43017

XI. References

  1. (2013) Fertil Steril 100(3): 631-7 [PubMed]
  2. Lindsay (2015) Am Fam Physician 91(5): 308-14 [PubMed]

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Related Studies

Cost: Medications

clomiphene citrate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOMIPHENE CITRATE 50 MG TAB Generic $0.77 each
clomid (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOMID 50 MG TABLET $3.76 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Ontology: Clomiphene Citrate (C0546859)

Definition (NCI) The citrate salt form of clomiphene, a triphenylethylene nonsteroidal ovulatory stimulant evaluated for antineoplastic activity against breast cancer. Clomiphene has both estrogenic and anti-estrogenic activities that compete with estrogen for binding at estrogen receptor sites in target tissues. This agent causes the release of the pituitary gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to ovulation. (NCI04)
Definition (PDQ) The citrate salt form of clomiphene, a triphenylethylene nonsteroidal ovulatory stimulant evaluated for antineoplastic activity against breast cancer. Clomiphene has both estrogenic and anti-estrogenic activities that compete with estrogen for binding at estrogen receptor sites in target tissues. This agent causes the release of the pituitary gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to ovulation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39542&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39542&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C379" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002996
SnomedCT 387346007, 325762006, 62353003
English Citrate, Clomiphene, 2-[p-(2-Chloro-1,2-diphenylvinyl)phenoxy]triethylamine Citrate (1:1), clomiphene citrate (medication), clomiphene citrate, CLOMIPHENE CITRATE, Clomiphene Citrate [Chemical/Ingredient], citrate clomiphene, clomifene citrate, clomiPHENE Citrate, 2-[p-(2-Chloro-1,2-diphenylvinyl)phenoxy]triethylamine Citrate, Clomiphene citrate, Clomifene citrate, Clomiphene citrate (product), Clomiphene citrate (substance), Clomiphene citrate [dup] (substance), Clomiphene Citrate, ClomiPHENE Citrate
French Citrate de clomifène
Spanish citrato de clomifeno (producto), citrato de clomifeno (sustancia), citrato de clomifeno
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Clomid (C0591268)

Definition (CHV) brand name of a fertility drug
Definition (CHV) brand name of a fertility drug
Definition (CHV) brand name of a fertility drug
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002996
English Clomide, clomid, clomid [brand name], clomide, Clomid
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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