Trifolium pratense (Red Clover) Exhibits Estrogenic Effects In Vivo in Ovariectomized Sprague-Dawley Rats

Author: Joanna E. Burdette, Jianghua Liu, Dan Lantvit, Eula Lim, Nancy Booth, Krishna P. L. Bhat, Samad Hedayat, Richard B. Van Breemen, Andreas I. Constantinou, John M. Pezzuto, Norman R. Farnsworth and Judy L. Bolton

Publication: J. Nutr. 132:27-30, 2002

During menopause, the levels of natural estrogens decline resulting in typical menopause symptoms, including hot flushes, vaginal atrophy and increased risk of osteoporosis, heart problems and Alzheimer’s disease. Hormone replacement therapy is prescribed to menopausal women but increases the risk of breast and endometrial cancer. Many menopausal women are looking for alternative treatment with natural products such as isoflavones. It is known that red clover contains several isoflavones including genistein, daidzein, biochanin A and formononetin. A previous study by Nestel et al entitled Isoflavones from Red Clover improve systemic arterial compliance but not plasma lipids in menopausal women and published in The Journal of Clinical Endocrinology and Metabolism (1999) showed that red clover isoflavones improved arterial elasticity and cardiovascular health.

The purpose of this study was to investigate the estrogenic and anti-estrogenic activity of red clover extracts on rats. The red clover extract, which contained 15 percent isoflavones, was administered to ovariectomized rats during a period of 3 weeks. The rats were divided in two groups: rats who took only red clover extract and rast who took red clover extract and estrogen (17 beta estradiol).

The researchers found that red clover extract exerted estrogenic effects including increase in uterine weight and differentiated vaginal cells. The red clover extract increased uterine weight dose-dependently, indicating that red clover extract contains estrogen-like compounds. However, the effect was significantly lower than that of estradiol. It is known that isoflavones in red clover can bind with alpha and beta estrogen receptors. The red clover extract did not influence the effects of estradiol on uterine weight. The administration of red clover also stimulated vaginal cell differentiation and decreased body weight. Red clover did not influence the cell proliferation of the mammary glands and showed no anti-estrogenic effects in the observed tissues.

The study concluded that red clover extract has weak estrogenic effect in ovariectomized rats and did not influence the activity of estradiol.