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Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Qualifying studies
Minimum requirements
Systematic review or meta-analysis of human trials
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
RDBPC human trials
1 study

Approximately 50.3% to 82.1% of women going through menopause experience hot flashes and night sweats. (21) To help manage symptoms, 40-50% of women rely on the use of complementary therapies such as plant-based supplements. (8)

Plant compounds called phytoestrogens have been found to have similar structures and functions when compared to the hormones within humans. (1) Estradiol is an estrogen steroid hormone that naturally drops throughout a woman’s life cycle. Decreases in estradiol levels create vasomotor instability, which contributes to hot flashes. Utilizing plant compounds is theorized to help compensate for the estradiol drops through a woman’s life cycle. (1)

Lower rates of postmenopausal symptoms have been observed in Asian women. This is thought to be due to the high dietary intake of soybeans, which contain isoflavones. Isoflavones are thought to work as a phytoestrogen and have a high binding affinity to estrogen beta receptors. (5) This sheds light on the mechanism behind how phytoestrogens are able to reduce hot flash frequency and vaginal dryness scores. (8)

Based on the current research findings, the ingredients in the protocol below have demonstrated efficacy in improving hot flashes associated with menopause.


40-80 mg, total isoflavones per day (dosing varies based on isoflavone), minimum 12 weeks (5)(7)(14)(15)(19)

  • A meta-analysis of 17 trials found reduced frequency (20.6%) and severity (26.2%) of hot flashes when compared to placebo; further analysis found isoflavones with 18.8 mg of genistein were twice as effective for reducing frequency of hot flashes (18)
  • Daidzein-rich isoflavone supplementation in doses of 40 mg and 60 mg improved frequency of hot flashes by 43% and 41% after 8 weeks, and 52% and 51% after 12 weeks, respectively, when compared to 32% and 39% with placebo, without any alteration of endogenous sex hormones or thyroid hormones (14)
  • For acute menopausal symptoms, 60 mg of isoflavones for six weeks decreased hot flashes by 57% and night sweats by 43%, with no other changes in serum levels of lipoproteins, estradiol, and follicular stimulating hormones when compared to that of placebo (5)
  • Mean number of hot flushes decreased by 36.2% and 41.2 % in treatment group compared to 24.0% and 29.3% with placebo at week 6 and 12, respectively (7)
  • Red clover isoflavones decreased Kupperman Index score at three months and number of hot flushes at one month compared to that of placebo, with no effects on cardiovascular risk markers (15)
  • Hot flush frequency decreased in a pooled mean analysis when compared to that of placebo while having no statistically significant reported side effects (4)
Isoflavones in the Fullscript catalog

St. John’s wort (Hypericum perforatum)

900 mg, three times per day, minimum of 12 weeks (2)(1) or as directed (6)

  • Women aged 40 to 65 with 3 or more hot flashes per day experienced better quality of life as shown by improvements in baseline questionnaire after 3 months of supplementation (2) 
  • Supplementation produced a significant decrease in Kupperman Index scores as demonstrated by a decrease in the frequency and intensity of hot flashes when compared to that of placebo (6)
  • Peri- and post-menopausal women receiving SJW extract experienced decreased duration, frequency, and severity of hot flashes compared to placebo, as measured by the Blatt-Kupperman index for climacteric symptoms (1)
St. John's wort in the Fullscript catalog
  • Menopausal vasomotor symptoms reduced by 26% in pooled analysis  (17)
  • All three treatment groups (black cohosh, estradiol valerate/progesterone, and estradiol valerate/medroxyprogesterone acetate) experienced decreased Kupperman menopause scores after 3 months; the black cohosh group experienced the lowest incidence of breast tenderness at 12.9% (vs. 36.7% and 14.3%, respectively) and vaginal bleeding at 6.5% (vs. 26.7% and 82.1%, respectively) (20)
  • In a trial of 122 menopausal women lasting 12 weeks, women with an initial Kupperman Index equal or greater than 20 experienced a 47% reduction in scores from a dried ethanolic extract group, compared to 21% in the placebo group (9)
  • In a trial of 120 menopausal women lasting 6 months, both the black cohosh and fluoxetine treatment groups experienced significantly decreased Kupperman Index and Beck’s depression scale scores; however, monthly scores for hot flushes and night sweats decreased by 85% in the black cohosh group, compared to 62% in the fluoxetine group (16)
Black cohosh in the Fullscript catalog

Rhubarb extract – ERr 731

4 mg, once per day, 12 weeks (13)(12)(11)

  • Menopause Rating Scale (MRS) decreased overall as shown by a decrease in number and severity of hot flushes in treatment group when compared to placebo (13)
  • Total score for MRS II decreased as shown by decrease in severity of hot flushes, and increase of menopause-specific quality of life; no adverse effects were found as shown by a lack of findings through endometrial biopsies, bleeding, weight changing, blood pressure and heart rate (12)
  • Number of hot flushes experienced averaged less than 1.4 per day with long-term use (48 weeks) of ERr 731 with no clinically significant adverse events (11)
Rhubarb extract in the Fullscript catalog

Vitamin E

400-800 IU, total per day, minimum 4 weeks (21)(3)

  • Severity score and frequency of hot flashes was significantly decreased when compared to placebo (21)
  • Reduced frequency of hot flashes by one per day compared to placebo following crossover analysis (3)
Vitamin E in the Fullscript catalog


The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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  1. Abdali, K., Khajehei, M., & Tabatabaee, H. R. (2010). Effect of St John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause , 17(2), 326–331. (B)
  2. Al-Akoum, M., Maunsell, E., Verreault, R., Provencher, L., Otis, H., & Dodin, S. (2009). Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause , 16(2), 307–314. (C)
  3. Barton, D. L., Loprinzi, C. L., Quella, S. K., Sloan, J. A., Veeder, M. H., Egner, J. R., Fidler, P., Stella, P. J., Swan, D. K., Vaught, N. L., & Novotny, P. (1998). Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 16(2), 495–500. (C)
  4. Chen, M.-N., Lin, C.-C., & Liu, C.-F. (2015). Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric: The Journal of the International Menopause Society, 18(2), 260–269. (A)
  5. Cheng, G., Wilczek, B., Warner, M., Gustafsson, J.-A., & Landgren, B.-M. (2007). Isoflavone treatment for acute menopausal symptoms. Menopause , 14(3 Pt 1), 468–473. (B)
  6. Eatemadnia, A., Ansari, S., Abedi, P., & Najar, S. (2019). The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial. Complementary Therapies in Medicine, 45, 109–113. (C)
  7. Ferrari, A. (2009). Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms. The Journal of Obstetrics and Gynaecology Research, 35(6), 1083–1090. (B)
  8. Franco, O. H., Chowdhury, R., Troup, J., Voortman, T., Kunutsor, S., Kavousi, M., Oliver-Williams, C., & Muka, T. (2016). Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis. JAMA: The Journal of the American Medical Association, 315(23), 2554–2563. (A)
  9. Frei-Kleiner, S., Schaffner, W., Rahlfs, V. W., Bodmer, C., & Birkhäuser, M. (2005). Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial. Maturitas, 51(4), 397–404. (B)
  10. Gao, L., Zheng, T., Xue, W., Wang, Y., Deng, Y., Zuo, H., & Sun, A. (2018). Efficacy and safety evaluation of Cimicifuga foetida extract in menopausal women. Climacteric: The Journal of the International Menopause Society, 21(1), 69–74. (C)
  11. Hasper, I., Ventskovskiy, B. M., Rettenberger, R., Heger, P. W., Riley, D. S., & Kaszkin-Bettag, M. (2009). Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause , 16(1), 117–131. (C)
  12. Heger, M., Ventskovskiy, B. M., Borzenko, I., Kneis, K. C., Rettenberger, R., Kaszkin-Bettag, M., & Heger, P. W. (2006). Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause , 13(5), 744–759. (B)
  13. Kaszkin-Bettag, M., Ventskovskiy, B. M., Solskyy, S., Beck, S., Hasper, I., Kravchenko, A., Rettenberger, R., Richardson, A., & Heger, P. W. (2009). Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Alternative Therapies in Health and Medicine, 15(1), 24–34. (C)
  14. Khaodhiar, L., Ricciotti, H. A., Li, L., Pan, W., Schickel, M., Zhou, J., & Blackburn, G. L. (2008). Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause , 15(1), 125–132. (B)
  15. Mainini, G., Torella, M., Di Donna, M. C., Esposito, E., Ercolano, S., Correa, R., Cucinella, G., Stradella, L., Luisi, A., Basso, A., Cerreto, F. V., Cicatiello, R., Matteo, M., & De Franciscis, P. (2013). Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. Clinical and Experimental Obstetrics & Gynecology, 40(3), 337–341. (C)
  16. Oktem, M., Eroglu, D., Karahan, H. B., Taskintuna, N., Kuscu, E., & Zeyneloglu, H. B. (2007). Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Advances in Therapy, 24(2), 448–461. (C)
  17. Shams, T., Setia, M. S., Hemmings, R., McCusker, J., Sewitch, M., & Ciampi, A. (2010). Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Alternative Therapies in Health and Medicine, 16(1), 36–44. (A)
  18. Taku, K., Melby, M. K., Kronenberg, F., Kurzer, M. S., & Messina, M. (2012). Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause , 19(7), 776–790. (A)
  19. Van de Weijer, P. H. M., & Barentsen, R. (2002). Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas, 42(3), 187–193. (C)
  20. Zheng, T.-P., Sun, A.-J., Xue, W., Wang, Y.-P., Jiang, Y., Zhang, Y., & Lang, J.-H. (2013). Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women. Chinese Medical Journal, 126(11), 2034–2038. (C)
  21. Ziaei, S., Kazemnejad, A., & Zareai, M. (2007). The effect of vitamin E on hot flashes in menopausal women. Gynecologic and Obstetric Investigation, 64(4), 204–207. (B)

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