Progestogen (Retroprogesterone) Pregnancy: Category B — extensive use in threatened miscarriage without evidence of teratogenicity; no masculinisation of female fetuses (unlike some older progestogens)

Dydrogesterone

Brand names: Duphaston

Adult dose

Dose: Threatened/recurrent miscarriage: 10 mg three times daily until 12-16 weeks gestation; Luteal phase support (IVF): 10 mg three times daily; Endometriosis: 10 mg BD from D5-25; HRT: 10 mg daily D15-28 of cycle

Route: Oral

Frequency: Two or three times daily (indication-dependent)

Max: 30 mg/day

Retroprogesterone structure — orally active progestogen with high selectivity for progesterone receptor and no oestrogenic/androgenic effects; well tolerated in early pregnancy

Paediatric dose

Dose: Not established for paediatric indications N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not indicated in paediatrics

Dose adjustments

Renal

No dose adjustment required

Hepatic

Avoid in severe hepatic impairment or history of hepatic tumours

Paediatric weight-based calculator

Patient weight (kg)

Not indicated in paediatrics

Clinical pearls

PRISM trial (Coomarasamy et al. NEJM 2019): oral dydrogesterone 10 mg TDS significantly improved live birth rate vs placebo in threatened miscarriage with first-trimester bleeding (72% vs 67% — NNT ~20); particularly effective in women with ≥1 prior miscarriage
PRISM subgroup: greatest benefit in recurrent miscarriage history (≥3 prior losses) with live birth rate 76% vs 57% — now forms basis of NICE and RCOG guidance recommending dydrogesterone in threatened miscarriage
Structural advantages over vaginal progesterone: oral route (better adherence vs pessaries), no vaginal discharge, active metabolite 20α-dihydrodydrogesterone also binds PR — distinct pharmacology from conventional progestogens
Retroprogesterone classification: inverted C-ring structure relative to progesterone — preserves high PR selectivity with minimal off-target receptor activity; explains better tolerability profile vs norethisterone
NICE NG126 (2020): dydrogesterone or vaginal progesterone recommended for threatened miscarriage in women with first-trimester bleeding + previous miscarriage; routine use in uncomplicated threatened miscarriage remains controversial

Contraindications

Undiagnosed vaginal bleeding
Severe hepatic impairment
Known or suspected hormone-dependent tumours
Known hypersensitivity

Side effects

Headache
Nausea
Spotting/irregular bleeding
Breast tenderness
Mood changes (less progestogenic side effects than norethisterone)

Interactions

Enzyme inducers (rifampicin, anticonvulsants) — may reduce dydrogesterone efficacy
Oestrogens — used in combination for HRT and cycle support

Monitoring

Pregnancy viability scan (6-8 weeks)
Fetal heartbeat confirmation
Symptom response (bleeding)

Reference: BNFc; BNF 90; PRISM trial (Coomarasamy et al. NEJM 2019); PROMISE trial (Coomarasamy et al. NEJM 2015); NICE NG126; RCOG Recurrent Miscarriage Guideline (2023); SPC Duphaston. Verify against your local formulary and the latest BNF before prescribing.