What it is
Phyto-SERMs are plant-derived, nonsteroidal compounds that bind to estrogen receptors. Common sources include red clover isoflavones (such as biochanin A) and soy isoflavones (such as daidzein). Isoflavones bind more strongly to estrogen receptor beta than to estrogen receptor alpha and have both estrogen-agonist and estrogen-antagonist properties. For DT56a (Femarelle), a tofu-derived extract, tissue-selective activity (estrogen-like in bone and vascular tissue but not in the uterus) has been shown mainly in studies of rats and cultured cells.
Rhapontic rhubarb extract (ERr 731) is another plant extract sold in the US for menopause symptoms. NAMS 2023 describes it as having estrogenic properties without being an estrogen, and does not recommend it: in its main trial only 7 of 55 women in the placebo group completed the study, which limits the conclusions.
Research and approval status
Phyto-SERM supplements are sold over the counter as dietary supplements. Under the Dietary Supplement Health and Education Act (DSHEA), the FDA is not authorized to approve dietary supplements for safety and effectiveness before they are marketed. The evidence varies by extract. A 2021 meta-analysis of 8 red clover RCTs found a statistically significant reduction of 1.73 hot flushes per day versus placebo, and the authors said further well-designed studies are needed. A Cochrane review of 43 phytoestrogen RCTs (4,364 participants) found no conclusive evidence that phytoestrogen supplements reduce the frequency or severity of hot flushes and night sweats. For Femarelle, a DT56a extract, an observational study of 631 women reported that 80.7% had “better” or “much better” hot flashes after four weeks, but there was no placebo group. The NAMS 2023 position statement does not recommend supplements, herbal remedies, or soy foods/extracts for hot flashes and night sweats.
Side effects and cautions
Phyto-SERMs act on estrogen receptors, so talk with a doctor before combining them with prescription SERMs, hormone therapy, or other medicines. Soy is among the eight most common food allergens, and NAMS notes that reactions range from bloating and loose stools to anaphylaxis, so people with a soy allergy should avoid soy-based products. Side effects of soy may include bloating, constipation, diarrhea, and nausea. Red clover extracts have been used in clinical studies for up to 2 years and appear to be well tolerated.
Where to get it
Red clover, soy isoflavone, and other phyto-SERM supplements are sold over the counter and online without a prescription. Check our provider directory for clinics near you.
