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Aromatase Inhibitor — Ovulation Induction Pregnancy: Contraindicated in pregnancy — teratogenic; use only in non-pregnant women attempting conception

Letrozole (Ovulation Induction)

Brand names: Femara

Adult dose

Dose: 2.5-5 mg once daily for 5 days (days 2-6 of cycle)
Route: Oral
Frequency: Once daily for 5 days
Max: 7.5 mg/day (5 days)
First-line ovulation induction for PCOS (NICE NG68). Off-label use (not licensed for ovulation induction in UK). Typically cycle days 2-6; monitoring with USS follicle tracking. Typical starting dose 2.5 mg; increase to 5 mg if no response

Paediatric dose

Dose: Not applicable N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not applicable — adult female indication

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment in mild-moderate impairment; use with caution in severe

Paediatric weight-based calculator

Not applicable — adult female indication

Clinical pearls

  • NICE NG68 (Fertility): Letrozole now recommended as first-line ovulation induction for anovulatory PCOS — superior to clomifene for live birth rate (NEJM 2014 Legro trial: 27.5% vs 19.1% cumulative live birth)
  • Mechanism: aromatase inhibition reduces oestrogen synthesis — hypothalamic-pituitary feedback reduces, increasing FSH release and stimulating follicular development
  • Lower multiple pregnancy rate than clomifene — monofollicular development more common; important counselling point
  • Off-label use: letrozole is not licensed for ovulation induction in UK (licensed for breast cancer) — informed consent required; prescribe after specialist fertility review
  • Teratogenicity: ensure patient not pregnant before each cycle; contraception required if not attempting conception immediately

Contraindications

  • Pregnancy (teratogenic)
  • Premenopausal women with oestrogen receptor-positive breast cancer (different licensed indication)
  • Breastfeeding

Side effects

  • Hot flushes
  • Headache
  • Nausea
  • Joint pain
  • Multiple pregnancy (lower risk than clomifene)
  • Ovarian hyperstimulation (lower risk than FSH)

Interactions

  • Tamoxifen (reduces letrozole efficacy)
  • Oestrogens (antagonise effect)

Monitoring

  • Transvaginal ultrasound follicle tracking
  • LH surge / ovulation confirmation
  • Pregnancy test after cycle

Reference: BNFc; BNF 90; NICE NG68 (Fertility); Legro et al. NEJM 2014; ESHRE/ASRM PCOS Guidelines 2023. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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