The best clinical trial data on the hormone have to do with its ability to halt MS. Two major studies randomized women with MS to estriol or placebo and the the results were remarkable. The hormone eradicated >80% of the brain lesions in women with MS (lesions where the immune system is specifically attacking the myelin sheath around the neuron) and prevented the formation of news ones. This benefit was sustained as long as the participants were on the active drug. Cognitive function was also improved. As of now, it is unknown if these benefits are due to estriol’s DIRECT actions in the brain or if it’s due to estriol’s effect on the inflammatory immune response.

This is in stark contrast to “other” estrogens, which have been shown in clinical trials to be harmful to the brain in women without MS. Premarin (an estrogen mixture composed predominantly of estrone sulfate) increases the risk of stroke and dementia; it also causes a loss of brain tissue volume in the hippocampus and frontal lobe based on MRI studies. Premain, with and without progestin, also raises the risk of breast cancer, heart attacks, and gallbaldder disease. Now many people believe that this is because Premarin or conjugated equine estrogen is not “bio-identical”. That’s only partially true – Premarin contains many estrogens, some of which are foreign substances to the human body, namely equilin. But its main component is estrone sulfate, which is the dominant estrogen in postmenopausal women. Estrone is readily converted/convertible to estradiol in a woman’s body. And there are also small amounts of estradiol in Premarin. So while the source of Premarin is no doubt *GROSS*, it’s not wholly “unnatural”.

Proponents of estradiol should also be aware that this potent hormone carries serious risks. Having too much estradiol over a lifetime, whether a woman had more menstrual cycles or is obese, is a major risk factor for certain cancers and probably heart disease and cognitive decline. The clinical trials on estradiol have all been disappointing – women with a history of stroke or heart diseases had more cardiac events on the drug. Low dose estradiol in patch form also caused memory problems in a trial of women with osteoporosis.
(Excess estradiol in MEN is also hazardous.)

Which brings us back to the estriol question. This hormone deserves far more attention and study than it gets. Women need an alternative therapy for menopausal symptoms. Major trials should be done to look at whether this “weak” estrogen can globally benefit women. It’s not unreasonable to think that it might. We know that it is neurologically beneficial to women with MS and HAS to be present in sufficient quantities to protect the health of a pregnant woman and her fetus and to depose the potentially harmful effects of supraphysiological levels of estradiol that accompany a pregnancy.