Herbs Used to Treat Menopause Symptoms:  A Review of Favorable Human Studies.

Pictured – Menopause Symptoms

By: Kathy Sadowski, Master of Science Degree in Aromatherapy, Registered Aromatherapist, LMT, RYT

Menopause is a natural process all women go thru beginning at about the age of fifty.  Symptoms of menopause include hot flashes, night sweats, menstrual cycle changes, vaginal dryness and thinning, bone density loss, mood swings, weight gain, and more. Research in the past twenty years has indicated the use of synthetic hormones to treat menopausal symptoms may come with dangerous side effects such as increased chances of heart attack, stroke, and cancer.  More women have turned to herb based phytoestrogens to treat the symptoms.  This paper provides an overview of the favorable human based studies on herbs to treat menopause. Potential plants include: soy and its isoflavone constituent, black cohosh, red clover, anise and fennel along with the anethole constituent, flaxseed, chasteberry, evening primrose, licorice, sage, passionflower, and valerian.   Also discussed are dosages based on the studies and potential side effects of each herb.  Mentioned in the appendix are studies showing no improvement in symptoms compared to the placebo.

Research Methods

Human studies with favorable results were searched for in google scholar and PubMed.  Meta analyses were found which reviewed multiple studies. Studies in which an herb was not more effective than the placebo in treating menapausal symptoms are listed in Appendix 1.

Results

Menopause happens when a woman’s ovaries stop releasing eggs, and less estrogen and progesterone are produced at around the age of 50 years (FDA, 2017).  Symptoms of menopause can include: hot flashes and night sweats, changes in frequency and length of menstrual cycle, vaginal drying and thinning, bone density loss (osteoporosis), mood swings, hair loss, cardiovascular disease, urinary incontinence, and weight gain.  Synthetic hormones used to treat menopause may pose a variety of health concerns.  Several studies have shown the following risks:  increased chances of blood clots, heart attacks, stroke, breast cancer, endometrial cancer, and gallbladder disease (FDA, 2017).   One study, called The Women’s Health Initiative (WHI), lasted 15 years and studied 161,800 postmenopausal women, finding hormone replacement therapy increased heart disease and the risk was not worth the benefits of reducing menopausal symptoms (Writing Group for the Women’s Health Initiative Investigators, 2002). Side effects of taking synthetic hormones can also include: bloating, breast tenderness, headaches, nausea, mood changes, and vaginal bleeding (WebMD, 2016).   More women have turned to herbs to treat menopause symptoms with less harsh side effects.  When treating with herbs, it is important to know their effectiveness based on research beyond just anecdotal evidence as well as the proper dosage and any known contraindications.

Plant estrogens, called phytoestrogens, are produced by plants such as legumes and certain whole grains and seeds.  Phytoestrogen may stimulate and/or block estrogen in the body, reacting differently than the actual estrogen hormone by affecting the estrogen receptors, and each individual will absorb and metabolize phytoestrogens in different ways, varying the response and health effects (Setchell et al, 2003). Phytoestrogens taken in food quantities are generally considered safe, but quantities taken as a medical herb supplement are still being researched (The National Women’s Health Network, 2015).

Soy (Glycine max)

This legume of the Fabaceae family is useful for its isoflavone content, and of all the plants reviewed, soy showed the most promising research for reducing menopausal symptoms.  Soy can be taken as a food, such as a vegetable protein, milk beverage, flour, or cereal, or there are also isolated isoflavone supplements available.  As a food, soy has been taken daily in Asian countries with little side effects for thousands of years (National Women’s Health Network, 2015).  Fermented soy products like miso and soy sauce are easier for the body to digest and absorb isoflavone content (Hutchins, Slavin, & Lampe, 1995).  As soy milk, 10-80 grams of milk with an isoflavone content of  40-120 mg daily can be taken (Ulbricht, 2010).  In Asian countries where women eat about 50-100 mg of soy isoflavones per day, incidences of hot flashes are about 50% lower than among American women who eat an average of less than 1 mg per day (Thomas et al, 2014). However, due to its estrogenic effect, soy taken in large quantities, and especially taken as an isoflavone supplement, should be avoided with hormone sensitive conditions (Ulbricht, 2010).  Some research has suggested excessive intake of soy isoflavones can increase breast cancer recurrence.  However, a 2013 systematic review of 131 articles including 40 RCTs, 11 trials, and 80 observational studies found a lack of evidence of harm, but indicated more studies are necessary to confirm the safety of use of over 100 mg of isoflavones a day in women who have had breast cancer (Fritz et al, 2013).

Research has shown that the effectiveness of soy taken to relieve hot flashes may be related to a patient’s ability to convert the isoflavone: daidzein to S-equol (Newton et al, 2015).  Related to menapausal research, a review of 55 articles and 16 studies summarized that soy isoflavones showed slight and slow effects on reducing menopause hot flashes (Li, Lv, Xu, & Zheng, 2015).  In another meta-analysis of 17 randomized, controlled trials it was concluded that isoflavones reduced hot flushes in menopausal women (Howes, Howes, & Knight, 2006).  Below is a list of favorable studies:

• A double blind randomized placebo controlled study of 51 women over twelve weeks showed 60 mg of isoflavones daily reduced hot flashes and night sweats by 57% and 43%, respectively (Cheng et al, 2007).
• In a randomized, double-blind crossover trial with 51 women, soy intake significant reduced lipid and lipoprotein levels, blood pressure, and menopausal symptoms (Washburn, Burke, Morgan, Anthony, 1999).
• In a double-blind, parallel, multicenter, randomized placebo-controlled trial of 104 postmenopausal women, soy powder added to the daily diet significantly reduced hot flushes (Albertazzi et al, 1998).
• In a 6-month, randomized, double-blind controlled trial of 79 women, a supplement of 120 mg of soy isoflavones reduced symptoms of menopause (Kaari et al, 2006).

 Black Cohosh (Actaea racemosa)

This is a woodland perennial shrub growing to eight feet tall with white cluster flowers and large serrated leaves.  Roots and rhizomes are black in color during the Autumn season, and this is the part of the plant used for herbal therapy.  It has been widely used in Europe to treat hot flashes, and found in a USA supplement called Remifemin (The National Women’s Health Network, 2015).  The Remifemin tablet contains 1or 2 mg of 27-deoxyactein and is taken twice daily for menopausal symptoms (Ulbricht, 2010).  In preparing the herb, the dosage is 40 – 200 mg per day of the dried rhizome, divided into three times a day; long term use has not been studied thus it is not recommended for longer than six months until further research (Ulbricht, 2010).  Possible contraindications are related to its hormone like action, and it may be inappropriate for women with hormone sensitive conditions, as well as liver disorders (Ulbricht, 2010).  Based on a meta-review of research, black cohosh was deemed inappropriate for use during pregnancy and lactation due to a potential labour-inducing effect, hormonal effect, emmenagogue effect, and anovulatory effect (Dugoua et al, 2006).  In addition, it may interfere with the following medications:  tamoxifen, chemotherapy drugs, blood pressure medications, lipitor, aspirin, blood thinners, hepatotoxic drugs, and cytochrome P450 3A4 (Petersen, 2016 & Natural Medicines, 2017).  Overuse may also cause gastrointestinal upset (Natural Medicines, 2017).  In addition, there is a possibility that excessive use of black cohosh may be associated with liver toxicity (Mahady et al, 2008).

A few meta-reviews on black cohosh were found.  In 2010, nine randomized placebo controlled trials were reviewed and data showed that black cohosh improved symptoms of menopause, with more research on the effectiveness and safety of the herb being warranted (McCusker, 2010).   A review of eight human studies showed black cohosh to be safe and effective in treating menopausal symptoms (Lieberman, 1988).  Below is a list of several more human studies on black cohosh:

• In a randomized double blind trial of 304 patients, hot flashes were reduced in menopausal women with a 40 mg tablet of black cohosh extract taken daily for 12 weeks (Osmers et al, 2005).
• In a six month controlled, randomized, double-blinded parallel group study, black cohosh extract improved menopause symptoms without an estrogen-like effect (Liske et al, 2002).
• A randomized trial of 82 women demonstrated that black cohosh reduced hot flashes, night sweats, and depression in menopausal women (Saghafi et al, 2013).
• Black cohosh as the commercial product Remifemin reduced hot flashes in women with a low level of toxicity (Pockaj et al, 2004).
• In a Chinese three month randomized double blind controlled study with 244 participants, Cimicifuga racemosa extract at 40 mg a day was effective and safer than the drug tibolone in treating menopausal symptoms (Bai et al, 2007).
• In a randomized study of forty-nine patients, a daily blend of 60 mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, for 24 weeks reduced the frequency of menstrually associated migraine headaches (Burke, Olson, & Cusack, 2002).
• An herbal combination of black cohosh and St. John’s wort reduced menopausal symptoms in a double-blind randomized placebo-control study of 301 women (Uebelhack et al, 2006).

Red Clover (Trifolium pratense) 

The purple round flower head of this common perennial weed of the Fabaceae family has been used historically as a menopausal symptoms remedy.  Biochanin, formononetin, and genistein are three phytoestrogenic isoflavones found in red clover.  In studies, between 40 – 160 mg of red clover isoflavones (as in the product Promensil) have been taken per day (Ulbricht, 2010).  The fresh flowers can also be prepared as decoction to extract the minerals by simmering one ounce of fresh herbs in a stainless steel pot with one pint of water until it reduces to ¾ of a pint of water.  Cool, strain, and store in the refrigerator for up to three days (Petersen, 2016).  Adult dosage for the decoction is up to 4 Tablespoons up to 4 times a day (Petersen, 2016).  As far as possible contraindications, red clover may increase the risk of bleeding and interfere with anticoagulant medications and aspirin due to coumarin and isoflavone content (Natural Medicines, 2016).  It may also interfere with antiretroviral drugs, estrogen containing medications, diabetic medications, and drugs that metabolize in the liver (Natural Medicines, 2016).  It can have possible adverse interactions with the following diseases: breast cancer, hormone cancers, hormone conditions, coagulant disorders, protein deficiencies, and surgery (Natural Medicines, 2016).

Promising research has warranted the possible use of red clover to treat hot flushes.  In a meta-analysis reviewing seventeen articles, it was concluded that there is a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women with no adverse side effects for short term use and no evidence on long term use (Coon, Pittler, & Ernst, 2007).  In a double blind, randomized, placebo controlled study with 30 women of the product Promensil®, hot flashes were reduced with a supplement of 80 mg of red clover isoflavones per day (van de Weijer & Barentsen, 2002).  In a clinical randomized, triple-blind trial conducted on 72 menopausal women,it reduced menopausal symptoms at a dose of 45 mg of red clover isoflavones capsules per day for eight weeks (Salehi et al, 2013).  Unfortunately, some of the human studies on this subject were poorly designed or short in duration and there have been other published studies with conflicting results; further research is necessary (Ulbricht, 2010).

The Anethole Constituent (as in Anise and Fennel)

This phenol methyl ether is found in the essential oil of certain plants of the Apiaceae family such as anise (Pimpinella anisum) and fennel (Foeniculum vulgare). It is also found in licorice and star anise, both of different plant families.  In a study of essential oils of eleven Pimpinella species with anethole as a major compound, even the species with the low anethole still showed estrogenic activity (Tabanca et al, 2004).  A 1980 article by Albert-Puleo discusses fennel and anise, and its main constituent of anethole as an active estrogenic agent that can be used to increase milk secretion, promote menstruation, facilitate birth, alleviate male climacteric, and increase libido.

Related to menopause, a double-blind clinical trial of 72 women who took 330 mg capsules of Pimpinella anisum three times a day for four weeks demonstrated a reduction in hot flashes (Nahidi, Kariman, Simbar, & Mojab, 2012).  In a double blind randomized controlled trial on 60 postmenopausal women, a vaginal cream with fennel applied once a day for eight weeks reduced vaginal atrophy (Yaralizadeh et al, 2016).  In a triple-blind, placebo-controlled trial, 90 postmenopausal women took 100mg of fennel twice a day for 8 weeks and showed significant reduction in menopausal symptoms (Rahimikian et al, 2017).

Natural Standards indicates there is not enough available research to determine a  safe internal dose of anise (Ulbricht, 2010).  Fennel can be maken as a tea up to three times a day by crushing fennel seeds and steeping 2 grams with 6 ounces of boiled water for 5-10 minutes (Petersen, 2016).  As it relates to the essential oil, anise and fennel should be avoided with estrogen dependent cancers, sensitive skin, and may affect the strength of some birth control pills (Lis-Balchin, 2006, & WebMD, n.d.).  The oils should also be avoided during pregnancy and breastfeeding (Ulbricht, 2010).  As an oil: it is not advised to exceed a maximum dose of 3 drops, three times per day, for over two weeks as anethole and phenolic ethers can reduce circulation and cause disorders to the circulatory and nervous system (Petersen, 2015).  Further, Pimpinella anisum caused neuronal hyper-excitability in snails and could be contraindicated in those with epilepsy (Janahmadi et al, 2008).  Epileptic seizures were reported with use of fennel oil (Ulbricht, 2010)

Flaxseed (Linum usitatissimum)

Also called linseed, flax comes from a small weed of the Linaceae family.  One tablespoon of dried flax, whole or bruised, can be mixed with a glassful of water and taken up to three times per day (Natural Standard, 2010). Flaxseed at a dose of 40 g per day for two months reduced mild menopausal symptoms and lowered glucose and insulin levels in  25 hypercholesterolemic menopausal women in a randomized crossover study  (Lemay et al, 2002).  Excessive use of flaxseed may cause gastrointestinal discomfort, fullness, and flatulence.  Further, flax may affect the absorption of the following medications and conditions:  acetaminophen, antibiotics, anticoagulants, antiplatelets, antidiabetes meds, antihypertensives, estrogens, furosemide, ketoprofen, metoprolol, bleeding disorders, diabetes, gastrointestinal obstructions, hormone related cancers and conditions, hypertension, hypotension, and high blood sugar (Natural Standard, 2016). ​The linamarin constituent found in the raw flaxseed, if taken in excess, can cause poisoning (Petersen, 2016).

 Chasteberry (Vitex agnus-castus) 

 These berries come from the chaste tree, a perennial deciduous aromatic tree of the Verbenaceae family.  A dose of about 4 mg of dried extract or 600 mg of dried fruit have been taken daily (Natural Standard, 2010).  The essential oil from the leaf of chaste berry showed reduced menopausal symptoms (Lucks, Sorensen, & Veal, 2002).  Another study of sixty postmenopausal women that was randomized, double blind, and placebo controlled, showed chasteberry taken for eight weeks reduced hot flushes (Abbaspoor, Hajikhani, & Afshari, 2011).   Chasteberry should be avoided with hormone sensitive cancers, in vitro fertilization, Parkinson’s, and psychotic disorders including Schizophrenia (Natural Medicines, 2016).  In addition, it may interfere with the following drugs:  contraceptives, dopamine agonists, estrogens, metoclopramide, and antipsychotics (Natural Medicines, 2016).

Licorice (Glycyrrhiza glabra) 

The root and rhizomes of this perennial plant from the Fabaceae family are used.  Glycyrrhizic acid is a constituent of the plant that can be unsafe in excess, and deglycyrrhizinated liquorice (DGL) has had the glycyrrhizin content removed (Ma et al, 2009). A dosage used has been DGL tablets of 380-1140 mg taken three times a day, licorice powder root at a dose of 1-4 g total in a day, divided into three doses (Natural Standard, 2010).  ​Excessive doses may cause sodium retention and potassium depletion (ACHS, 2017).  Further, it could interfere with the following medications: antihypertensives, cisplatin, corticosteroids, cytochrome substrates, digoxin, diuretics, estrogens, ethacrynic acids, furosemide, midazolam, warfarin, cardiac glycosides, laxatives, grapefruit juice, potassium, and testosterone (Natural Standard, 2016).  Research has shown some potential in the use of licorice to treat menopausal symptoms.  In a randomized, double blind, clinical trial study with 60 menopausal women, licorice was more effective than hormone replacement in reducing the duration of hot flashes (Menati, Khaleghinezhad, Tadayon, & Siahposh, 2014).  Licorice showed estrogenic activity that reduced menopausal symptoms over hops related to its liquiritigenin content (Hajirahimkhan et al, 2013).

Sage (Salvia officinalis) 

Sage of the Lamiaceae family has been used for centuries in Europe as a medicinal herb (Ulbricht, 2010).  A dosage of  120 mg of sage extract (along with 60- mg of alfalfa extract) was taken safely in a study daily for up to three months to treat menopause (Ulbricht, 2010).  In a multicenter clinical trial of 71 patients, a fresh sage preparation taken daily for eight weeks reduce hot flushes (Bommer, Klein, & Suter, 2011).   In a randomized controlled triple blind trial of 84 women, sage reduced the frequency of hot flashes in menopausal women (Sadeghi et al, 2013).  As an essential oil, it is not intended for internal use, can cause skin irritation, and should be avoided with the fragile population (Lis-Balchin, 2006).  Sage, cedar, thuja, and hyssop essential oil showed convulsant and neurotoxic activity in mice related to the constituents camphor, thujone, thuja, and pinocamphone (Millet et al, 1981).

Evening Primrose (Oenothera biennis) 

Evening primrose of the Onagraceae family is a plant whose flower blooms in the evening. In a randomized clinical trial of 56 menopausal women using 500 mg of encapsulated evening primrose oil twice a day for six weeks, hot flashes and other menopausal symptoms were reduced (Farzaneh, Fatehi, Sohrabi, & Alizadeh, 2013).  Evening primrose should be avoided with seizure disorders, mental illness medications, and two weeks before surgery with anesthesia; it may also interfere with medications to treat blood pressure, mental illness, depression, blood thinners, and arthritis (Ulbricht, 2010).

Passion Flower (Passiflora incarnata) 

passionflower

Passion flower of the Passifloraceae family is a vine like plant that has beautiful, aromatic, purple, Summer flowers.  While there is not enough clinical evidence to recommend the best dose, up to two grams daily of the dried herb, or 1-4 mL of the tincture at 3-4 times a day, and teas or infusions have been taken (Ulbricht, 2010).  In this randomized clinical trial of 54 women, passion flower reduced hot flashes (Kazemian, Sereshti, Forouzandeh, & Akbari, 2006).  Use of the herb has caused drowsiness, and may interfere with some medications (Ulbricht, 2010).

Valerian Root (Valeriana officinalis) 

This plant’s rhizomes and roots have shown to be useful in the treatment of insomnia.  Hot flashes were also reduced in two human studies.  Adult dosage is up to three times a day of the following: up to 3 mL of a fluid extract, up to 1 tsp of a powder, up to 6 Tbsp of an infusion, and up to 5 mL of a tincture (Petersen, 2016).  Studies have shown it safe taken in short term time periods up to 28 days (Natural Medicines, 2016).  In a double blind clinical trial performed on 48 women, valerian was effective in treating hot flashes (Kazemian, Banaeian, Parvin, & Delaram, 2006).  In another double blind clinical trial, 68 menopausal women took 255 mg valerian capsules 3 times a day for 8 weeks and showed that valerian effectively reduced hot flashes compared to placebo (Mirabi & Mojab, 2013).

Discussion

Of all the plants reviewed, soy seems to have the most research demonstrating safe use over the long term to treat menopausal symptoms.  Additional herbs have promising research, like black cohosh and red clover, but more is necessary.  Below is a summary:

• Soy has been eaten safely as food for centuries by Asian countries with statistical evidence showing that Asian women have much lower menopausal symptoms. More research is necessary on the use of supplements of isolated isoflavone in terms of safety and effectiveness.
• Black cohosh has a good amount of research demonstrating a small reduction in symptoms, but there is not enough research on the possible health effects of long term use. It is not advised to take supplements long term, and with hormone sensitive conditions, liver conditions, and other medical issues.
• Red clover had research showing improved symptoms, but the studies are of short duration and small sample size. Commercial supplements are available, but more research is necessary.  It is not advisable to take for an extended period of time and with certain health conditions.
• Other herbs mentioned in this paper show potential, but more research is necessary and include:
  • Anise and Fennel and the anethole constituent
  • Flaxseed
  • Chaste berry
  • Licorice
  • Sage
  • Evening primrose
  • Passion flower
  • Valerian root

Conclusion

 More women, concerned about risks of synthetic hormones, are turning to herbs to treat menopausal symptoms.  There have been some good human studies demonstrating the use of soy, black cohosh, and other herbs in reducing symptoms, but more research is necessary.  Many of the studies have a small number of participants or the herbs are administered for a short duration of time.  There are also conflicting studies demonstrating no improvement in symptoms compared to the placebo.  Further, it is important for women to be aware of the proper dose and possible contraindications with taking herbs.  Dosages as taken like food from dietary sources are safer than manufactured supplements with higher amounts of isolated constituents.  As in soy, people have been eating it as food for thousands of years with little risk of side effects; while it is still unknown what the risk of phytoestrogen supplements may have on health, and especially hormone sensitive conditions.  Further, the effectiveness of phytoestrogens in treating menopause may be different across individuals based on genetics, diet, and lifestyle.

Appendix 1

List of human studies on herbs to treat menopause with outcomes no better than placebo:

• Isoflavones (red clover) did not reduce hot flushes. From:  Baber, R. J., Templeman, C., Morton, T., Kelly, G. E., & West, L. (1999). Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric, 2(2), 85-92.
• Promensil containing isoflavones from clover did not have a clinically significant effect on hot flushes. From:  Tice, J. A., Ettinger, B., Ensrud, K., Wallace, R., Blackwell, T., & Cummings, S. R. (2003). Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. Jama, 290(2), 207-214.
• Black cohosh and red clover did not reduce menopausal symptoms compared to the placebo. From:  Geller, S. E., Shulman, L. P., Van Breemen, R. B., Banuvar, S., Zhou, Y., Epstein, G., … & Bolton, J. L. (2009). Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause (New York, NY), 16(6), 1156.
• Red clover did not significantly improve menopausal symptoms. From:  Del Giorno, C., Da Fonseca, A. M., Bagnoli, V. R., de Assis, J. S., Soares Jr, J. M., & Baracat, E. C. (2010). Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopausal women. Rev Assoc Med Bras, 56(5), 558-62.
• Eating muffins with flaxseed did not reduce hot flashes. From:  Lewis, J. E., Nickell, L. A., Thompson, L. U., Szalai, J. P., Kiss, A., & Hilditch, J. R. (2006). A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause, 13(4), 631-642.
• Eating flaxseed rich food did not reduce postmenopausal symptoms more than placebo. Should have went for the chocolate muffin.  From:  Simbalista, R. L., Sauerbronn, A. V., Aldrighi, J. M., & Arêas, J. A. (2010). Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. The Journal of nutrition, 140(2), 293-297.
• Soy isoflavones in a diet did not reduce menopause symptoms. From:  Germain, A. S., Peterson, C. T., Robinson, J. G., & Alekel, D. L. (2001). Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause, 8(1), 17-26.
• A supplement containing soy isoflavones and A racemosa did not reduce menopasual symptoms. From:  Verhoeven, M. O., van der Mooren, M. J., van de Weijer, P. H., Verdegem, P. J., van der Burgt, L. M., & Kenemans, P. (2005). Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Menopause, 12(4), 412-420.

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