Estriol, or E3, the weakest of the estrogens that occurs naturally only in high circulating levels during pregnancy, is very popular in the alternative community. It is often promoted as the ideal estrogen, a natural alternative providing all of the benefits of hormone therapy with none of the risks. This assumption is not supported by the literature, as the research on estriol is limited. In one study examining the use of estriol over 12 months, 53 women were given 2 mg daily. They reported good symptom relief and satisfaction, and histiologic evaluation of the endometrium revealed no hyperplasia or atypia. Bone mineral density showed no change (98). In another study examining the effect of estriol, 64 women were followed for 24 months. There were four treatment arms: 2.0 mg E3 plus 2.5 mg medroxyprogesterone acetate, 0.625 mg of conjugated estrogen plus 2.5 mg medroxyprogesterone acetate, 1 μg of 1-alpha hydroxy vitamin D3, and 1.8 g calcium lactate containing 250 mg of elemental calcium. Outcome measures were taken at baseline, 6, 12, 18, and 24 months, and included the following assessments: bone mineral density at third lumbar vertebrae, serum levels of osteocalcin, total alkaline phosphatase, and urinary ratios of calcium/creatinine and hydroxyproline/creatinine. The findings revealed decreased bone mineral density in the vitamin D and calcium groups and no decrease in the conjugated estrogen and E3 groups. Osteocalcin and alkaline phosphate was decreased or without change in the conjugated estrogen and E3 groups, and was increased in the vitamin D3 and calcium groups. Urinary calcium/creatinine ratios were decreased with E3 and conjugated estrogen, and there was no decrease with the use of vitamin D3 and calcium. Urinary hydroxyproline/creatinine ratios were decreased in the conjugated estrogen group, unchanged in the E3 and vitamin D3 groups, and increased in the calcium group. Uterine bleeding was significantly less in the E3 group compared with the conjugated estrogen group, with 2.4 days compared with 13 days per person. In conclusion, the study supported the finding that a bone-preserving effect occurred with E3 when compared with conjugated estrogen (99).
It was proposed that estriol might have anticarcinogenic activity. Unlike estradiol, estriol is not carcinogenic in rodent models, reduces uterine growth, and enhances phagocytic activity. After one or more pregnancy, estriol excretion significantly increases in comparison with nulliparous women. This may or may not be linked to the increased risk of breast and ovarian cancer in nulliparous women. In a study following over 84,000 Finnish women, oral and transdermal estradiol was associated with a slightly increased risk of breast cancer (2 to 3 additional cases per 1,000 women across 10 years), while oral estriol and vaginal estrogens were not associated with an increased risk (100).
Oral estriol appears to provide symptom relief and to stimulate breast and endometrial tissue less than estradiol (101). It may prove to have mildly beneficial effects on bone. It appears to exert estrogenic effects on the endometrium and to have no effect or mild effects on lipids. No clinical interventional trials exist on the effect of oral estriol use on the breast.