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IMS Menopause Live

Recent studies on natural alternatives to hormone therapy

21 November, 2016

Have you noticed the increased number of publications on natural remedies for menopause symptoms in good-quality journals? The reason for these studies, in my view, is not only the alleged problematic benefit–risk balance of hormone therapy (HT) or other approved medications, but the higher awareness of women to achieve better quality of life during midlife and beyond. This may be more prominent in developing countries where traditional medicine is popular, but is certainly valid in the Western world too. The willingness of Editors of journals with a medium to high impact factor to accept such papers, provided that these meet the quality standards of the aforementioned journals, gives a tail wind to this trend. Here are a few such examples.

A randomized controlled trial (RCT) in 82 postmenopausal women compared Pueraria mirifica gel to a conjugated estrogen cream [1]. Pueraria mirifica is a widely used, herbal female hormone supplement derived from a plant found in the wild in certain regions in Thailand. Use for 12 weeks showed that Pueraria mirifica was efficacious and safe for the treatment of vulvovaginal atrophy. Yet, conjugated estrogen cream was found to be more beneficial in improving signs of vaginal atrophy and restoring vaginal epithelium at 6 and 12 weeks.

Another study included a total of 45 healthy and sexually active postmenopausal women reporting diminished libido [2]. They were randomly assigned to receive 750  mg/day of Tribulus terrestris, a flowering plant growing in many countries, or placebo for 120 days. Tribulus terrestris is usually marketed for body building, because of its testosterone-like characteristics. Results showed a significant improvement in the domains of desire (p  <  0.01), arousal/lubrication (p  =  0.02), pain (p  =  0.02), and anorgasmia (p  <  0.01) in women who used Tribulus terrestris, whereas no improvement was observed in the placebo group (p  >  0.05). Free and bioavailable testosterone levels showed a significant increase in the active treatment arm.

Schisandra chinensis comes from northern China and the Russian Far East. Its berries contain several active compounds, including lignans. Climacteric recently published the results of an RCT in 36 women, where half received an extract from Schisandra chinensis and the remaining half received placebo for 6 weeks and were followed for 12 weeks [3]. The total Kupperman Index scores were significantly lower in the Schisandra chinensis group than in the placebo group when evaluated with respect to group and time (p = 0.042).

Another commercial preparation, an ammonium succinate-based dietary supplement, or placebo, were given to 125 women with vasomotor and psychosomatic symptoms over a period of 3 months [4]. The Greene Climacteric Test and the Spielberger–Hanin test were used. Based on the Greene Test, there was a statistically significant improvement (р < 0.05) in 13 out of 21 menopausal symptoms in women who took the supplement. The Spielberger–Hanin test showed that the supplement stabilized patients' psychological state with a statistically significant decrease in anxiety, increased stress resistance and improved adaptability.

E-MHK-0103, a nutraceutical lipoprotein extracted from Atlantic Mytilus galloprovincialis, a marine mollusc, was found to have beneficial properties on hot flushes, mood swings, joint pain and bone stability associated with its glucosamine-related anti-inflammatory effect and its high content of vitamins, minerals, iron and other substances, such as selenium and vitamin E [5].


Nature around us provides ample opportunities to treat various disease conditions just by ingesting a fruit, leaves, roots or living organisms. Most of these have not been tested by modern, appropriate protocols, but are used traditionally based on generations of real-world experience. A recent review and meta-analysis in JAMA highlighted the data on plant-based therapies [6]. Most of the evaluated clinical data referred to phytoestrogens, but black cohosh and medicinal herbs were included as well. Data from 21 RCTs contributed to the meta-analysis, which showed an association of overall phytoestrogen use with a decrease in the number of daily hot flushes (pooled mean difference of changes between treatment groups, −1.31 [95% CI −2.02 to −0.61]) and in vaginal dryness scores (pooled mean difference of changes between treatment groups, −0.31 [95% CI −0.52 to −0.10]). These results reflect modest reductions in the frequency of hot flushes and vaginal dryness. The use of phytoestrogens was not associated with significant changes in 24-h night sweats. Meta-analysis of few RCTs on the use of black cohosh concluded that there was no association with changes in the number of hot flushes (pooled mean difference of changes within 24 h, −0.71 [95% CI −2.51 to 1.08]) or number of night sweats. However, one RCT which was not included in the meta-analysis did show some benefit, as was the case with two RCTs on a combination of black cohosh with other therapies. Because of the limited number of studies, it was not possible to perform meta-analysis on the associations of Chinese medicinal herbs and non-Chinese medicinal herbs with menopausal symptoms. The results of the RCTs for the association between use of Chinese medicinal herbs and menopausal symptoms were not consistent but, in general, showed no association.

A previous comprehensive review of alternative and complementary approaches to the treatment of menopause symptoms addressed a much wider spectrum of botanical hormone mediators and neurotransmitters, as well as various non-dietary methods [7]. The key points were: few botanic therapies suggested for menopause have robust evidence for efficacy and safety; pycnogenol, pollen extract, ERr731 (rhubarb extract), S-equol, and genistein may offer some symptom mitigation; soy foods offer limited symptom relief; red clover, evening primrose oil, Panax ginseng, Dioscorea, and vitamin E are ineffective. At best, botanicals decrease vasomotor symptoms by 15–30% better than placebo. The article discusses the adverse effects of each compound or extract, with a special attention to potential derangements in the clotting mechanism.

One thing becomes clear while reading the clinical data: conclusions should be based only on RCTs, rather than traditional or cultural beliefs. The huge variability in the exact contents of the plant-derived supplements and the diversity in study methodologies make it impossible to assess the available information as a whole and provide clear-cut guides to the health-care providers and customers.

Amos Pines

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Suwanvesh N, Manonai J, Sophonsritsuk A, Cherdshewasart W. Comparison of Pueraria mirifica gel and conjugated equine estrogen cream effects on vaginal health in postmenopausal women. Menopause 2016 Oct 3. Epub ahead of print
  2. de Souza KZ, Vale FB, Geber S. Efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women: a randomized, double-blinded, placebo-controlled trial. Menopause 2016;23:1252-6
  3. Park JY, Kim KH. A randomized, double-blind, placebo-controlled trial of Schisandra chinensis for menopausal symptoms. Climacteric 2016;19:574-80
  4. Radzinskii VE, Kuznetsova IV, Uspenskaya YB, et al. Treatment of climacteric symptoms with an ammonium succinate-based dietary supplement: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol 2016;32(Suppl 2):64-8 
  5. Corzo L, Rodriguez S, Alejo R, Fernandez-Novoa L, Aliev G, Cacabelos R. E-MHK-0103 (Mineraxin): a novel nutraceutical with biological properties in menopausal conditions. Curr Drug Metab 2016 Oct 14. Epub ahead of print
  6. Franco OH, Chowdhury R, Troup J, et al. Use of plant-based therapies and menopausal symptoms: a systematic review and meta-analysis. JAMA 2016;315:2554-63
  7. Taylor M. Complementary and alternative approaches to menopause. Endocrinol Metab Clin North Am 2015;44:619-48

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