Rankings / Hormones & Endocrine
Estetrol (E4) for menopause
Hormones & Endocrine · Native estrogen (NEST)
Tier B
Bottom line
Read Off Label grades Estetrol (E4) for menopause as B (6.6/10) based on strong evidence, med-high benefit magnitude, and a med-risk safety profile.
Estetra/Mithra (Donesta; licensed to Gedeon Richter).
Studied, labeled, or reported-use context: Oral 15-20 mg/day (menopause trials) — Rx; not individualized guidance.
What the evidence says
Estetra/Mithra (Donesta; licensed to Gedeon Richter). E4COMFORT I and II Phase 3 (n~640): significant reductions in moderate-severe vasomotor symptom frequency and severity at weeks 4 and 12 vs placebo. Already approved as the contraceptive Nextstellis/Drovelis. Menopause launch expected 2026, an option for women with synthetic-HRT contraindications. Industry-sponsored.
Mechanism
Estetrol, a native fetal estrogen with tissue-selective estrogen-receptor activity and minimal hepatic impact, apparently with lower thrombotic-marker effect than synthetic or conjugated estrogens.
Studied, labeled, or reported dose & route
Oral 15-20 mg/day (menopause trials)
This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.
Citations
A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.
Common questions
- What does the evidence show about Estetrol (E4) for menopause's effects?
- Read Off Label rates the evidence for Estetrol (E4) for menopause as Strong and the benefit magnitude as med-high, producing an overall grade of B (6.6/10). Estetra/Mithra (Donesta; licensed to Gedeon Richter).
- What safety findings are reported for Estetrol (E4) for menopause?
- Estetrol (E4) for menopause has a med risk profile in the database. Med (estrogen-class thrombotic/breast/endometrial considerations; apparently milder than synthetic estrogens) Legal status: Rx (approved as contraceptive; menopause indication Phase 3 / filing).
- What doses or routes are reported for Estetrol (E4) for menopause?
- Oral 15-20 mg/day (menopause trials) This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
- How does Estetrol (E4) for menopause work?
- Estetrol, a native fetal estrogen with tissue-selective estrogen-receptor activity and minimal hepatic impact, apparently with lower thrombotic-marker effect than synthetic or conjugated estrogens.
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.