Coumestrol

Coumestrol and other phytoestrogens have been shown to have an effect on sexual behavior in rats by antagonizing the action of estrogen within the brain; male rats that nursed from females with coumestrol in their diets were both less likely to mount a female rat and less likely to ejaculate, despite producing normal levels of testosterone. Exposure produced similar decreases of sexual behavior in female rats, as a result of the disruption of estrogen dependent gene expression in the brain. Effects were seen in three areas of the hypothalamus, the ventromedial nucleus, the paraventricular nucleus, and the medial preoptic area, all of which play a role in sexual behavior and sexual activity.[12][13] Female rats that were exposed to coumestrol neonatally did not adopt the lordosis position as much as those that were not exposed to coumestrol.[14]

Coumestrol has been shown to accelerate the onset of puberty in mice.[11] Exposure to coumestrol immediately after birth resulted in an initial increase in uterine weight. However, continued exposure inhibited the growth of the uterus and decreased levels of estrogen receptors within uterine tissue. The rats also showed altered vaginal development including cornification and metaplasia of vaginal tissue, and delayed opening of the vagina.[13] When neonatal female mice were treated with coumestrol, similar reproductive irregularities occurred, and at 22 months old, atypical collagen distribution was observed in the uterine wall.[14] When 2 day old male Wistar rats are injected with coumestrol daily, they exhibit a decrease in size in the lumens of their seminiferous tubules and germ cells go through increased rates of apoptosis. When bulls graze on pastures containing coumestrol, metaplasia occurs in the prostate and bulbourethral glands, and sperm maturation is suppressed. Female cows that consumed alfalfa experienced lower pregnancy rates and spontaneous abortions, as well as abnormal estrogen levels during pregnancy.[15] A high coumestrol diet has also been shown to induce early development of the vulva and udder of female lambs. In addition to these anatomical abnormalities, exposure to coumestrol has also been shown to alter the estrus cycle of a number of animals, including cows and sheep, resulting in lower rates of fertility.[10]

Coumestrol has been shown to decrease bone resorption and promote the mineralization of bone in vitro and in vivo; daily injections of coumestrol were shown to reduce bone loss in rats who had undergone an ovariectomy.[13]

Coumestrol has been shown to have clastogenic properties at a certain concentration.. Studies have shown that coumestrol is a mutagen and induces formation of micronuclei in hamster cells of the V79 cell line as well as human lymphoblastoid cells in a dose-dependent manner. Exposure to coumestrol also causes single stranded breaks in hamster DNA, compromising genome stability.[16]

Studies have shown that coumestrol has beneficial properties on carbohydrate metabolism in ovariectomized rats, decreasing glycogen levels in skeletal muscle. There is also data indicating that coumestrol lowers plasma cholesterol levels in chicks. These results point to a possibility of coumestrol having a positive role to play against human obesity and diabetes in the future.[17]

Coumestrol and other phytoestrogens are sometimes used as a substitute for hormone therapy in the treatment of menopausal symptoms such as hot flashes and night sweats. However, studies have indicated that phytoestrogen-enriched foods and supplements are not necessarily effective against these symptoms.[18] In addition, studies indicate that coumestrol and other phytoestogens have an antiestrogenic effect in the brain and, as a result, do not produce the mental health benefits which are seen in estrogen replacement therapy.[12]

Coumestrol and other phytoestrogens have also been investigated as a possible substitute for hormone therapy and chemotherapy in breast cancer patients. The results of various studies regarding the use of phytoestrogens in treating breast cancer have been somewhat contradictory and ambiguous, and as a result, researchers cannot clearly define phytoestrogens like coumestrol as being chemoprotective agents or potentially having negative effects, such as inducing further growth of existing breast cancer tumors by activating ERα receptors.[19] Researchers at Georgetown University Medical Center have investigated this matter and concluded that phytoestrogens may be used as an effective treatment for breast cancer because of their apoptotic properties, but that it is only safe to do so after menopause, when women have a much lower level of estrogen in their bodies, or when used conjunctively with anti-estrogen therapies.[20]