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Selective Oestrogen Receptor Modulator (SERM) / Ovulation Induction Agent Pregnancy: Contraindicated in confirmed pregnancy — must exclude pregnancy before each treatment cycle. Animal studies show skeletal abnormalities but no confirmed human teratogenicity.

Clomifene Citrate

Brand names: Clomid, Serophene

Adult dose

Dose: 50mg OD for 5 days, starting on day 2, 3, 4, or 5 of menstrual cycle. If no ovulation: increase to 100mg OD for 5 days in subsequent cycles. Maximum: 3–6 cycles at maximum dose.
Route: Oral
Frequency: Once daily for 5 days per cycle
Max: 100mg OD for 5 days per cycle; maximum 6 treatment cycles (cumulative ovarian cancer risk concern)
Indicated for anovulatory infertility (PCOS, hypothalamic-pituitary dysfunction). Anti-oestrogenic action at hypothalamus → increased FSH/LH → ovarian stimulation. Confirm ovulation by serum progesterone on day 21 (mid-luteal). Pelvic ultrasound monitoring recommended in specialist centre to detect ovarian hyperstimulation syndrome (OHSS) and multiple follicles.

Paediatric dose

Route: Oral
Frequency: Once daily for 5 days
Max: Not applicable
Not licensed and not indicated in children or adolescents. Not applicable.

Dose adjustments

Renal

No specific dose adjustment — use with caution.

Hepatic

Avoid in active hepatic disease — hepatically metabolised; contraindicated in liver dysfunction.

Clinical pearls

  • NICE NG156: clomifene first-line for ovulation induction in PCOS (if BMI 19–30) — metformin added if clomifene-resistant
  • Cumulative risk: limit to 6 cycles — concern (unproven but precautionary) regarding ovarian cancer with prolonged use
  • OHSS: mild OHSS managed conservatively (fluids, analgesia); severe OHSS (massive ovarian enlargement, ascites, electrolyte disturbance) requires hospital admission — withhold further clomifene
  • Day 21 progesterone: >30 nmol/L confirms ovulation; 16–30 nmol/L borderline; <16 nmol/L anovulatory cycle — increase dose next cycle

Contraindications

  • Liver disease
  • Ovarian cysts (other than PCOS)
  • Pregnancy
  • Abnormal uterine bleeding (uninvestigated)
  • Hormone-dependent tumours
  • Hypersensitivity to clomifene

Side effects

  • Hot flushes (anti-oestrogenic effect)
  • Ovarian hyperstimulation syndrome (OHSS — ovarian enlargement, abdominal pain, bloating)
  • Multiple pregnancy (10% twin rate; higher-order multiples rare)
  • Visual disturbances (blurring, flashes — stop immediately if occur)
  • Nausea
  • Mood disturbance
  • Headache

Interactions

  • Progesterone — used alongside to support luteal phase; not a pharmacokinetic interaction
  • No significant clinically relevant drug interactions documented

Monitoring

  • Day 21 (mid-luteal) serum progesterone (confirm ovulation)
  • Pelvic ultrasound (follicle count and size — detect OHSS and multiple follicles)
  • Pregnancy test before each cycle

Reference: BNFc; BNF 90; NICE NG156 (Fertility); RCOG OHSS Guideline 2016. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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