The red clover plant (Trifolium pretense, purple clover, trefoil, cow clover, meadow clover) is a perennial legume. Its red and purple flower tops are used medicinally. The flower top contains isoflavonoids (biochanin A, daidzein, formononetin, and genistein), flavonoids (pectolinarin and trifolin), volatile oil (containing furfural), saponins, coumarins (coumarin, medicagol, and coumestrol), salicylic acid, minerals, vitamins, phytoalexins, carbohydrates, and fats. Historically, Chinese medicine has taken advantage of its expectorant properties, while Russians have used it to relieve bronchial asthma. Red clover has been used to treat skin conditions such as psoriasis and eczema, but its mechanism of action for this skin improvement is unknown. The herb has also been used in the past to treat breast cancer. It has been shown to have chemoprotective, antispasmodic, and hormone replacement properties.

The isoflavones have an estrogenic effect on the body. Like soy phytoestrogens, these isoflavones may function as SERMs. It has been shown that isoflavones can have an antiestrogenic effect on premenopausal women but can have an estrogen-like effect on postmenopausal women who have low levels of endogenous estrogen. They have an affinity for the beta-estrogen receptors that are common in the heart, vasculature, bones, and bladder. The estrogenic effects may be useful for symptoms of menopause, including hot flashes, and for prevention of osteoporosis. It is controversial whether the isoflavones have any effect on bone mineral density. Also, these hormonal effects can improve the decreasing arterial compliance seen in postmenopausal women. Red clover may be indirectly involved in lowering cholesterol and producing an increase in bile acid excretion.

There are several red clover products on the market, including tea, powder blossom, powder tops, tablets, capsules, and extracts. Red clover is also available in combination with other herbs; such products include Promensil, Rimostil, Super Fem, and Avlimil.

In 2003, a 12-week clinical trial examined the use of red clover isoflavones in menopausal women who were experiencing at least five hot flashes a day. Researchers randomly assigned 250 women to Promensil 82 mg, Rimostil 56 mg, or placebo. The results provided some evidence for a biological effect of Promensil, but neither supplement had a clinically important effect on hot flashes or other symptoms of menopause. Another study performed in Amsterdam investigated the effectiveness of Promensil versus placebo in reducing hot flashes. This trial included 30 menopausal women experiencing more than five hot flashes a day. Treatment with Promensil 80 mg/day resulted in a significant decrease (about 44%) in hot flashes, compared to placebo.

Women with hormone-sensitive diseases or a history of breast cancer should avoid red clover because of its synthetic estrogen properties. It is contraindicated with the use of any other hormone therapy, such as oral contraceptives or any estrogen or progesterone compounds. It could have additive or antagonistic effects on therapy. Because red clover contains a coumarin component, it causes an increased risk of bleeding when used with anticoagulants, aspirin, or other blood-thinning herbs (e.g., ginkgo, ginger, garlic). Adverse reactions include headache, nausea, vaginal spotting, and some muscle pain and rash-like reactions. No serious side effects have been reported. Peak concentrations of these phytoestrogens vary from four to eight hours after intake, and they are excreted within 24 hours.

The usual dose of red clover is 4 g of the flower top three times daily. There are many dosage forms available. Traditionally, the dried herb is used as a tea prepared by steeping 4 g of dried flower tops in 150 mL of hot water for 10 to 15 minutes. The patient may drink up to three cups daily. The herb is available in capsule and tablet form, and patients should follow the directions on the product package labels closely. Taken as a fluid extract (1:1 in 25% alcohol), the dose is 1.5 to 3 mL three times daily.

Conclusion

The herbs discussed in this article have a long history of use as foods, spices, and medicine. Soy, black cohosh, dong quai, chasteberry, red clover, and sage are hormonal herbs that are possibly effective in treating menopausal symptoms because of their estrogenic activity. Valerian, a nervine herb, may be effective for sleep disorders, tension, and anxiety associated with menopause.

These herbs are considered relatively safe and effective if taken in recommended amounts. However, clinical safety and efficacy cannot be established completely due to insufficient evidence.As with all herbal medicines, the clinical trials conducted to date have been small, and many are flawed.

Menopausal women use many alternative therapies that do not have clinical data supporting efficacy claims. Pharmacists should provide their patients with as much information as possible regarding the uses, side effects, and interactions of these products. Always check a reliable herbal medicine reference for drug, disease state, and herbal interactions. These references include Natural Medicines Comprehensive Database, Facts and Comparisons Review of Natural Products, and Micromedex.

Pharmacists should also make the following recommendations to their patients regarding the use of herbal products:

• Inform your health care provider and pharmacist of which herbal supplements you take.
• Keep a list of herbal products that you use and take it with you to medical appointments.
• If you are thinking of starting herbal therapies, consult with your health care provider and pharmacist to ensure that the products will not interact with other medications you are taking.
• Never take more than the recommended dose listed on the label.
• Do not use a product that does not have the manufacturer’s name, address, and telephone number on the label.
• Avoid taking products that do not have expiration dates or lot numbers on the label.
• Avoid taking products that have an expiration date that is not at least one year from the purchase date.

Pharmacists should encourage their patients to provide the information on herbal products that they have found on the Internet so that the pharmacists can assist in evaluating its accuracy and validity. Pharmacists are in a unique position to assist the consumer in this area of health care and should become informed so that they may provide the best care to their patients.

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