Estriol, the Safest Estrogen

Estriol is a Safe and Effective Hormone for Menopausal Women with Hot Flashes and Vaginal Dryness

Estriol is a type of estrogen made by the ovaries. It is one of the primary hormones of pregnancy and as a hormone replacement therapy it has been used in Europe for many decades. Until the advent of bioidentical hormone replacement therapy (BHRT), estriol was rarely used in the U.S., because the pharmaceutical industry here is not interested in a nonpatentable medicine, no matter how safe and effective it is.

In a review of estriol in the 1980s, Dr. Robert Greenblatt, one of the foremost researchers in hormone therapy at the time, commented that “the ability of estriol to relieve vasomotor symptoms [hot flashes] and to improve vaginal maturation [prevent vaginal dryness] without inducing notable side effects, is sufficient reason for it to be included in the management of the postmenopausal syndrome.” In other words, he felt that estriol should be considered as an effective and safe form of HRT because it prevents menopausal symptoms like hot flashes without causing side effects so common to conventional estrogen replacement therapy.

Estriol Protects Against Breast and Uterine Cancers
That estriol is a very useful form of ERT wasn’t news to Professor Henry Lemon. He and other clinical scientists had been saying this for over 30 years. In fact Dr. Lemon stated in a 1966 article published in the Journal of the American Medical Association that “Estriol offers a nontoxic, physiologic antagonist for ovarian estrogens, inducing little or no endometrial proliferation in postmenopausal women, which together with progesterone might simulate the protective effect of pregnancy upon subsequent breast cancer risk.” In other words, estriol could be used as a form of ERT to protect the uterus and breast from cancer.

Estriol as a Replacement Estrogen in Breast Cancer Survivors
Dr. Lemon also researched how effective estriol is in treating women who already have breast cancer. His rationale was that estriol, unlike estradiol or estrone, had not been shown in animal studies or human clinical trials to stimulate the uterus or breast cells, therefore making it an ideal candidate for ERT in very high risk women whose breast tumors were estrogen sensitive. A clinical trial of 2.5 to 5 mg per day of estriol therapy in 28 premenopausal and postmenopausal breast cancer patients demonstrated that estriol induced remission or arrest of metastatic tumors in six (37 percent) of the women.

Estriol Prevents Vaginal Atrophy and Urinary Tract Infections
At menopause a common problem is degeneration of the vaginal lining, which can make intercourse painful, and renders the vagina more susceptible to invasion by bacteria, causing urinary tract infections. Several studies clearly show that a vaginal estriol cream can prevent such urinary tract infections in postmenopausal women, and this is estriol's primary use in Europe.

Estriol Does Not Cause Blood Clots
A very serious problem with using estradiol or estrone in a minority of women (1 out of 5,000) is that it increases the risk of death due to deep vein thromboembolism, which means the formation of life-threatening blood clots in the veins. Estriol, on the other hand, has very little effect on the blood clotting factors. Doses as high as 8 mg per day have not been found to increase the risk of blood clotting. Dr. Lemon also noted that estriol did not cause any problems related to thromboembolism in his clinical study exploring the use of estriol for treatment of menopausal symptoms in breast cancer patients. This was also the consensus of a review committee that met in the 1980s to review the clinical efficacy of estriol.

Estriol Protects the Skin From Aging
It is well recognized that the time around menopause is associated with more rapid aging of the skin. Estrogens are important for the structural proteins collagen and elastin, which give the skin elasticity and structure, as well as hyaluronic acid, a naturally occurring “moisture retainer” under the skin. Studies published in the mid to late 1990s demonstrated that estriol, applied as a skin cream directly to the face, remarkably reversed wrinkling and other problems of skin aging associated with the onset of menopause.

How to Take Estriol
The typical oral dose used in Western Europe is 2 to 5 mg daily, but because much of it is “dumped” by the liver immediately, this may only ultimately amount to ½ to 1 mg of estriol actually getting into the body.

Many clinicians use an estriol cream that delivers 2 to 5 mg. When made as a cream, the pharmacist should indicate on the container how much cream it takes to provide the 2 to 5 mg of estriol. When you deliver estriol to your body via a cream, it is delivered in a much steadier fashion, whereas given orally it is subject to all the variables of how the digestive system and the liver are working from hour to hour.

An estriol cream that delivers 0.5 mg, used every other day, has been shown to be very effective for treating vaginal atrophy and urinary tract infections. Published studies show that 0.5 mg estriol delivered every other day for 2 weeks, is adequate for most women, and this is how estriol is used by most women in Europe. The reason that estriol is used only every other day is because it doesn’t clear from the body as fast as the other estrogens and therefore one dose will last for two days. Using it every day can result in excessively high levels. Although estriol does not absorb through the skin as rapidly as estradiol or estrone, studies have shown that topical delivery of estriol is about twenty times more efficient than oral delivery.

Note to Reader: This article was excerpted in part from the book What Your Doctor May Not Tell You about Breast Cancer, by John R. Lee, M.D., Dr. David Zava and Virginia Hopkins, which has a detailed chapter on estriol and a complete list of references on estriol research.