Estriol is not as well known or as frequently prescribed as other types of estrogen but it is an effective treatment for many post-menopausal women. It can be applied locally to treat vaginal atrophy associated with menopause. It has failed to gain widespread use in the United States mostly due to the prevalence of estradiol as the main type of estrogen hormone therapy and the fact that it cannot be patented. However a compounding pharmacy can make estriol in creams and suppositories for local application and many women are prescribed topical estriol for vaginal use.

Vaginal Symptoms of Menopause

Almost half of women will experience vaginal atrophy symptoms after menopause. These symptoms include urinary tract infections, vaginal infections, and vaginal dryness.  These vaginal changes are due to decreased levels of estrogen – which is an important hormone for women. Other symptoms may include burning and irritation, pain during sex, and bleeding. There are other contributing risk factors to developing genitourinary symptoms of menopause including smoking, which decreases blood flow to the vagina and inhibits estrogen. Having had a vaginal birth at any time may reduce the risk of these symptoms. Having regular sexual activity with or without a partner is a preventative measure as it can also improve blood flow and elasticity of the vagina.

There are a variety of over-the-counter remedies for many vaginal symptoms of menopause – moisturizers and lubricants for treating vaginal dryness, for example. However these are not treatments, only ways of managing symptoms. Treatment with estrogen can help restore a balanced hormone level and improve genitourinary symptoms for many women. Localized estrogen therapy is usually the first choice of treatment.

What is Estriol?

Estriol is a naturally occurring estrogen – an essential type of hormone for a woman’s health. The major estrogen excreted by the ovaries is estradiol (E2), with the secondary estrogens being estrone (E1) and estriol (E3). Estriol actually plays an essential role in pregnancy when it becomes the dominant estrogen. During pregnancy, the placenta produces estriol. It promotes the growth of the uterus and prepares a woman’s body for giving birth. By looking at estriol levels, it is also possible to get a better idea of a baby’s health as it is an indication of how the baby is producing hormones. When a woman is not pregnant, levels of estriol are generally lower. Measuring levels of this hormone can help determine when birth may happen.

Estriol has low bioavailability when it is taken orally. In oral form it has around 10% of the bioavailability it has when applied vaginally. Because of its low oral bioavailability it is often prescribed as a vaginal cream or suppository. Estriol is sometimes considered a “weaker” estrogen than other forms like estradiol but it should not be disregarded. It is possible that for certain menopausal symptoms like vaginal atrophy it may be the most effective treatment with the lowest incidence of side effects.

Studies have shown that estriol can treat hot flashes when taken daily and reduce the frequency of urinary tract infections, urinary urgency, and leakage. It can help restore a normal vaginal flora and reduce vaginal atrophy. Importantly, it can do this without the side effect of endometrial proliferation which is a risk with estrogen therapy (usually estradiol). Besides treating menopause symptoms, estriol is also being studied as a treatment for multiple sclerosis. Its potential effectiveness for this condition was discovered when pregnant women with MS were found to experience decreased relapse rates.

Vaginally Applied Estriol

In a systematic literature review that examined a variety of studies of estrogen therapy, it was determined that vaginally applied estriol appeared to be safe and effective for women who had risk factors associated with systemic estrogen therapy. Estriol vaginal creams have been shown to reduce patient reported vaginal dryness as well as objective markers of improvement like pH measurements.

When estriol is applied vaginally, the amount of estrogens circulating in the blood stream is lower than when systemic forms of estrogen are given.  Vaginally applied estriol enters the blood stream and has a peak concentration one hour after it is applied. After that, circulating levels quickly return to baseline. Studies have not shown systemic effects on the breast with vaginally applied estriol in post menopausal women. Endometrial proliferation is also not common after using locally applied estriol, as it may be with estradiol taken orally.

Vaginal estriol has been shown to help regulate vaginal pH, which helps prevent infections. In a study of 93 postmenopausal women, it was shown that estriol decreased vaginal pH from 5.5 to 3.8. The rate of vaginal colonization of potentially harmful bacteria went from 67% to 31% in treated patients. The adverse reactions of vaginal itching and burning were mild and occurred in a minority of the treated patients.

For vaginal symptoms of menopause, the first treatment of choice is usually vaginally applied estrogen. Localized application of estrogen can reduce some of the risk of taking estrogen in other ways like oral tablets and transdermal patches that result in more systemic effects. While estriol is considered a weaker estrogen when it is naturally produced in the body, as a treatment it may potentially be ideal for managing vaginal atrophy after menopause.

Forms of Topical Estriol

Cream

Estriol can be compounded in a cream in a variety of strengths.

Example strengths:

• 05mg, 1mg, 1.5mg, 2mg, 3mg, or 4mg per gram estriol cream
• 0.05%, 0.2%, 0.3%, 0.5%, or 1% estriol cream

Suppositories

Estriol vaginal suppositories are another treatment option for local administration.

Example strengths: 0.1mg, 0.5mg, 1mg, or 2mg estriol suppositories

Combination Formulations

A compounding pharmacy is able to combine different pharmaceutical ingredients into one formulation. A formulation can be made that includes estriol along with DHEA, progesterone, or testosterone.

Example combinations:

• Estriol 1mg, DHEA 10mg per gram cream
• Estriol 1mg, Progesterone 150mg per gram cream
• Estriol 1mg, Testosterone 1.5mg per gram cream

Articles

• The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review – Climacteric (opens in new window)
• A Controlled Trial of Intravaginal Estriol in Postmenopausal Women with Recurrent Urinary Tract Infections – The New England Journal of Medicine (opens in new window)
• Vaginal and Urinary Symptoms of Menopause – JAMA Patient Page (opens in new window)
• Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition – Clinical Trial (opens in new window)