Estriol
Estriol is the weakest of the three natural estrogens, used primarily as topical vaginal therapy (Ovestin cream, pessaries) for postmenopausal urogenital atrophy. Its weak systemic effect and short half-life make it suited for local relief with minimal systemic exposure.
- Chemical formula
- C18H24O3
- CAS number
- 50-27-1
- ATC code
- G03CA04
- Molecular weight
- 288.39 g/mol
- Drug class
- Estrogen (weak)
- Also known as
- Ovestin, Ovestinon, Trimovate, E3
What is it?
Estriol (E3) is the weakest of the three natural human estrogens (alongside estradiol E2 and estrone E1) and is produced in large amounts during pregnancy. As medication, it is used primarily topically in the vagina for postmenopausal urogenital atrophy. Marketed as Ovestin (Aspen, formerly Organon) and Ovestinon in Europe and Latin America; it is widely available there but not in the United States, where vaginal estradiol products dominate. Authorised generic estriol cream and pessaries are widely available in the markets where it is licensed.
Mechanism of action
Estriol binds estrogen receptors but with shorter receptor occupancy and weaker activation than estradiol, producing a 'weak' estrogenic effect. In the vagina, this is sufficient to reverse urogenital atrophy — restoring vaginal mucosa, normalising pH, reducing dryness, dyspareunia and recurrent urinary tract infections — without producing significant systemic estrogenic effects at typical maintenance doses. The short receptor occupancy is the basis of estriol's reputation as a 'safer' estrogen for local use.
Pharmacokinetics
Vaginal estriol is rapidly absorbed across the atrophic mucosa initially, then absorption falls as the mucosa thickens. Plasma levels peak 1–2 hours after vaginal application but remain low at maintenance doses. The plasma half-life is short (~6 hours). Hepatic conjugation predominates with renal excretion of conjugates. Oral estriol is also available in some markets (Trimovate) but absorption is unreliable and oral use is uncommon.
Indications
Estriol vaginal preparations are approved for treatment and prevention of urogenital atrophy and recurrent urinary tract infections in postmenopausal women, and in some markets for vaginal preparation before pelvic surgery. According to current menopause guidelines, vaginal estrogen (estriol or estradiol) is the most effective treatment for urogenital atrophy when local symptom relief is sufficient and systemic HRT is not needed.
Safety profile
Vaginal estriol is well tolerated. Common adverse effects are local: vaginal irritation, discharge or pruritus in the first weeks. Systemic effects (breast tenderness, breakthrough bleeding) are uncommon at maintenance doses but can occur with higher induction doses. Endometrial hyperplasia risk is low at typical doses, and most current guidelines do not require concomitant progestogen for low-dose vaginal estriol — a notable simplification compared with systemic estrogen HRT in women with an intact uterus.
Products containing this ingredient
Frequently asked questions
Is estriol safer than estradiol for vaginal atrophy? ▾
Both estriol and estradiol are effective vaginal estrogens with low systemic exposure at maintenance doses. Estriol's shorter receptor occupancy may produce slightly less endometrial stimulation, which is one reason it is positioned as a 'mild' option. Both are considered safe at typical low maintenance doses without concomitant progestogen. According to current menopause guidelines, choice depends on regional availability and patient preference.
Why is estriol not approved in the United States? ▾
Estriol has been used in Europe since the 1970s but the manufacturer never submitted an FDA approval application, partly because the regulatory bar for new estrogen products was high and the US market favoured estradiol products. According to current US menopause guidelines, US prescribers do not have access to FDA-approved estriol and use vaginal estradiol (Estrace cream, Vagifem tablets, Estring ring) instead.
Do I need progesterone with vaginal estriol? ▾
At typical low-dose maintenance regimens, vaginal estriol does not require concomitant progestogen even in women with an intact uterus, because endometrial absorption is minimal. According to the prescribing information, this differs from systemic HRT (oral or transdermal estrogen) where progestogen is required for endometrial protection. Higher-dose induction regimens may warrant individual assessment.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.