Bioidentical Estriol: Uses, Safety and How It Compares to Estradiol

What is estriol?

Your body makes three main estrogens:

• Estradiol (E2), the most potent, made by the ovaries during the reproductive years
• Estrone (E1), the main estrogen after menopause, made largely in fat tissue
• Estriol (E3), the weakest, produced in large amounts by the placenta during pregnancy and present at low levels otherwise

"Bioidentical estriol" is lab-made estriol with the same structure as the hormone your body produces, usually manufactured from plant starting materials. Estriol binds estrogen receptors more weakly and leaves them faster than estradiol, which is why it is often called "gentle." That makes it useful for some local symptoms, but less effective for whole-body symptoms like hot flashes.

In the US, there is no FDA-approved estriol product. It is prescribed through compounding pharmacies, either alone (often as a vaginal cream) or blended with estradiol in "biest." In parts of Europe and elsewhere, licensed vaginal estriol creams, pessaries and gels are widely used.

What is estriol used for?

Vaginal dryness and genitourinary syndrome of menopause

Low estrogen thins the tissues of the vagina, vulva and urethra, causing dryness, burning, pain with sex and urinary symptoms, together called genitourinary syndrome of menopause (GSM). Vaginal estrogen is the most effective treatment for moderate to severe GSM (Menopause Society 2020). A Cochrane review found vaginal estrogen preparations, including estriol, improved symptoms compared with placebo, without clear differences between preparations (Lethaby 2016). A systematic review of 22 studies of vaginal estriol found it effective with few side effects, and serum estriol did not stay raised at 6 months (Rueda 2017). For a closer look, see estriol cream for vaginal atrophy.

Recurrent urinary tract infections

In a classic randomized trial of 93 postmenopausal women with recurrent UTIs, vaginal estriol cream reduced infections from 5.9 to 0.5 episodes per woman per year compared with placebo. It lowered vaginal pH and allowed protective lactobacilli to return (Raz 1993). Side effects were minor but led some women to stop.

By the numbers

Vaginal estriol and recurrent UTIs

0.5UTI episodes per woman per year on vaginal estriol creamSource: Raz 1993

5.9UTI episodes per woman per year on placeboSource: Raz 1993

Skin

Estriol creams are sometimes marketed for skin aging. Evidence is limited to small studies, and applying a hormone to the face on a daily basis still exposes your body to it. This is not a well-established use.

Hot flashes

Estriol at vaginal doses does not reliably relieve hot flashes and night sweats. Systemic estradiol is the estrogen with strong evidence for those symptoms; see the hormone replacement therapy guide.

Estriol vs. estradiol: how do they compare?

Is estriol safe?

Low-dose vaginal estriol appears to be well tolerated, with minimal and short-lived effects on blood levels (Rueda 2017). But estriol is still an estrogen, and route and dose matter:

• Oral estriol stimulates the uterine lining. In a large Swedish case-control study, taking 1 to 2 mg of oral estriol daily for at least 5 years was associated with about 3 times the risk of endometrial cancer and 8 times the risk of atypical hyperplasia. Vaginal low-potency estrogens showed only weak associations (Weiderpass 1999). Women with a uterus using systemic estriol may need a progestogen.
• Compounded products vary. Because estriol is only available compounded in the US, strength and purity depend on the pharmacy, and there is no FDA review or standard patient labeling. ACOG recommends FDA-approved hormone therapy over compounded preparations when an FDA-approved option meets your needs (ACOG 2023).
• Breast cancer history. If you have had breast cancer, especially if you take an aromatase inhibitor, any vaginal estrogen, including estriol, should be discussed with your oncology team first.
• "Natural" creams. Over-the-counter creams that claim to contain estriol are not regulated as medicines; you can't be sure what dose, if any, they contain.

By the numbers

Oral estriol and the uterine lining

About 3×endometrial cancer risk with 1 to 2 mg oral estriol daily for 5+ yearsSource: Weiderpass 1999

8×risk of atypical hyperplasia with the same long-term oral useSource: Weiderpass 1999

How is vaginal estriol usually used?

Vaginal estrogen regimens, estriol included, typically start with a nightly "loading" phase of about two weeks, then drop to a maintenance dose two or three times a week. Many women notice less dryness and burning within a few weeks, with fuller improvement over two to three months. Because GSM tends to return when treatment stops, vaginal estrogen is usually continued long-term at the lowest dose that keeps symptoms controlled.

A few practical points:

• Apply it at bedtime so it stays in place.
• Use a separate lubricant for sex; estrogen cream is not a lubricant, and a partner can absorb a small amount.
• Mild irritation or discharge in the first weeks is common; persistent burning, bleeding or spotting should be checked.
• You can use vaginal estrogen alongside systemic hormone therapy if dryness persists, which is common.

What about biest and triest?

Biest (estriol plus estradiol, often in an 80:20 ratio) and triest (adding estrone) are compounded blends marketed as gentler than estradiol alone. There is no good evidence that they are safer. Their effect on hot flashes comes mostly from the estradiol portion, and they carry the same need for a progestogen if you have a uterus. Our guide to bioidentical vs. synthetic hormones covers compounded blends in more detail.

Which option is right for you?

If your main symptoms are vaginal dryness, pain with sex or recurring UTIs, low-dose vaginal estrogen is the usual first step. FDA-approved vaginal estradiol creams, tablets, inserts and rings are available, and some women prefer compounded estriol. Moisturizers and lubricants help too. See genitourinary syndrome of menopause for all the options.

If hot flashes, night sweats and poor sleep are the problem, you need systemic estrogen, and estradiol is the one with strong evidence. FDA-approved patches, gels and pills with oral progesterone are one route. Amie's clinicians prescribe Amie HRT+, a compounded cream with estradiol and progesterone (no estriol), with the strength chosen by a licensed clinician. It is not FDA-approved, and the clinician will decide whether it's appropriate for you.

The bottom line