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Clomiphene Citrate

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Clomiphene Citrate, Clomiphene, Clomid

  • See Also
  1. Female Infertility
  • Indications
  • Fertility
  1. Stimulate Ovulation
    1. See Female Infertility
    2. Anovulatory Bleeding (Metrorrhagia)
    3. Oligo-Ovulation
  2. Luteal Phase defect
  3. Unexplained Infertility
  • 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
  • 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
  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
  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)
  • 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
  • Precautions
  1. Confirm no Male Infertility (normal semanalysis)
  • Efficacy
  1. Pregnancy rate 60% in 4 months of use
  • Resources
  1. Clomiphene Citrate (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=be399623-6400-475d-93d3-1dedd4d43017
  • References
  1. (2013) Fertil Steril 100(3): 631-7 [PubMed]
  2. Lindsay (2015) Am Fam Physician 91(5): 308-14 [PubMed]