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Clinical white paper

Peri/Menopause Essentials: formulation and evidence review

This page is a condensed, citation-preserving summary; the linked PDF is the complete document.

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Executive summary

This page is a condensed, citation-preserving summary of the full white paper; the linked PDF is the complete document.

We designed Peri/Menopause Essentials around a whole-body transition in which cardiovascular, metabolic, vasomotor, and bone-related physiology changes over time.[1][5][7][8] Red clover provides 50 mg standardized isoflavones, while olive and bergamot provide polyphenols for cardiometabolic and healthy-aging support.

Why we chose three polyphenol sources

We selected 250 mg red clover standardized to 20% isoflavones because systematic reviews and human studies examine isoflavones across menopause-transition and bone contexts.[10][17][22] The 50 mg isoflavone serving is close to the 40 mg used in a randomized bone-density study.[17] We added 50 mg olive fruit extract and 100 mg bergamot phytosome yielding 40 mg polyphenolic fraction because human and population research evaluates these polyphenol sources in cardiometabolic and healthy-aging contexts.[25][27][28]

Formula and dose rationale at a glance

IngredientForm / amountRole in the formula
Red clover extract 250 mg standardized to 20% isoflavones, providing 50 mg Four-isoflavone source selected for transition and bone-health research
Olive fruit extract 50 mg Opextan, double-standardized polyphenols Cardiovascular, brain, and healthy-aging support
Bergamot 100 mg phytosome providing 40 mg polyphenolic fraction Bioavailability-focused cardiometabolic support

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The evidence we used

Our 29-source review includes epidemiology, receptor research, systematic reviews, and randomized interventions; these sources vary in directness and do not substitute for controlled finished-formula evidence.[10][20][25][1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

  • Transition contextReviews and observational studies

    Cardiovascular and metabolic markers change across menopause.[1][5][8]

  • IsoflavonesSystematic review and human studies

    Reviews and trials informed red-clover selection and dose.[10][17][19]

  • Receptor activityMechanistic and safety research

    Isoflavones interact preferentially with estrogen receptor beta in mechanistic work; clinical safety requires separate evidence.[20][11][12]

  • Olive polyphenolsRandomized and cohort evidence

    A 12-month intervention and a US cohort provide different forms of healthy-aging evidence.[25][27]

  • BergamotSystematic review

    A systematic review evaluated bergamot and lipid-profile outcomes in humans.[28]

Our observational finished-formula study

In our third-party, open-label study, 42 women ages 40 to 57 used the formula for three months and completed the validated Menopause Rating Scale monthly.[30] At month three, 93% reported improvement in hair quality, sexual satisfaction, physical and mental exhaustion, and brain fog; 90% reported improvement in hot flashes, night sweats, and irritability; and 88% reported improvement in anxiety.[30] Every reported symptom decreased at p<0.001; counts showed 69% fewer daily hot flashes and 80% fewer nighttime sweats.[30] With no placebo group, these participant-reported changes do not establish causation.[30]

Funding disclosure: The study was independently conducted by Citrus Labs and funded by Semaine.

See the full study design, results, and limitations

Full references

  1. Rosano GMC, et al. Menopause and cardiovascular disease. Climacteric. 2007;10 Suppl 1:19-24.Review
  2. Zhang Y. Cardiovascular diseases in American women. Nutr Metab Cardiovasc Dis. 2010;20:386-393.Review
  3. Wang Y, Wang QJ. Prevalence of prehypertension and hypertension among US adults. Arch Intern Med. 2004;164:2126-2134.Epidemiology
  4. Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension. J Clin Hypertens. 2011;13:244-251.Review
  5. Lejsková M, et al. Menopause and population changes in insulin resistance. Climacteric. 2011;14:83-91.Observational
  6. Maas AHEM, Franke HR. Women's health in menopause with a focus on hypertension. Neth Heart J. 2009;17:68-72.Review
  7. Ji MX, Yu Q. Primary osteoporosis in postmenopausal women. Chronic Dis Transl Med. 2015;1:9-13.Review
  8. Carr MC. Emergence of metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88:2404-2411.Review
  9. Sowers M, et al. Insulin resistance and hormone interactions in premenopausal and perimenopausal women. J Clin Endocrinol Metab. 2003;88:4904-4910.Observational
  10. Chen LR, et al. Isoflavone supplements for menopausal women: systematic review. Nutrients. 2019;11.Systematic review
  11. Fritz H, et al. Soy, red clover, isoflavones, and breast cancer: systematic review. PLoS One. 2013;8:e81968.Systematic review
  12. Powles TJ, et al. Red clover isoflavones in women with a family history of breast cancer. Menopause Int. 2008;14:6-12.Human safety
  13. Sathyapalan T, et al. Soy isoflavones and cardiovascular risk markers in early menopause. Nutr Metab Cardiovasc Dis. 2018;28:691-697.Human clinical
  14. Nestel P. Isoflavones and cardiovascular risk and functions. Curr Opin Lipidol. 2003;14:3-8.Review
  15. Terzic MM, et al. Red clover-derived isoflavones and serum lipid profile. J Obstet Gynaecol Res. 2009;35:1091-1095.Human clinical
  16. Hannan MT, et al. Risk factors for longitudinal bone loss. J Bone Miner Res. 2000;15:710-720.Cohort study
  17. Atkinson C, et al. Phytoestrogen isoflavones and bone density: randomized placebo-controlled trial. Am J Clin Nutr. 2004;79:326-333.Randomized trial
  18. Clifton-Bligh PB, et al. Red clover isoflavones, lipid and bone metabolism. Menopause. 2001;8:259-265.Randomized trial
  19. North American Menopause Society. Role of soy isoflavones in menopausal health. Menopause. 2011;18:732-753.Society report
  20. Kuiper GG, et al. Phytoestrogen interaction with estrogen receptor beta. Endocrinology. 1998;139:4252-4263.Mechanistic
  21. Setchell KD. Soy isoflavones as selective estrogen receptor modulators. J Am Coll Nutr. 2001;20:354S-362S.Review
  22. Lambert MNT, et al. Isoflavone formulations and bone resorption: systematic review and meta-analysis. Am J Clin Nutr. 2017;106:801-811.Meta-analysis
  23. Lefèvre-Arbogast S, et al. Polyphenol intake and long-term dementia risk. Neurology. 2018;90:e1979-e1988.Cohort study
  24. Filik L, Ozyilkan O. Olive-oil consumption and cancer risk. Eur J Clin Nutr. 2003;57:191.Epidemiology
  25. Filip R, et al. Olive polyphenol extract in postmenopausal women with osteopenia. J Nutr Health Aging. 2015;19:77-86.Randomized trial
  26. Gorzynik-Debicka M, et al. Olive oil and plant polyphenols. Int J Mol Sci. 2018;19.Review
  27. Guasch-Ferré M, et al. Olive oil and total and cause-specific mortality in US adults. J Am Coll Cardiol. 2022;79:101-112.Cohort study
  28. Lamiquiz-Moneo I, et al. Bergamot and lipid profile in humans: systematic review. Crit Rev Food Sci Nutr. 2020;60:3133-3143.Systematic review
  29. Salehi B, et al. Naringenin: review of clinical trials. Pharmaceuticals. 2019;12.Review
  30. Semaine Health. Peri/Menopause Essentials white paper, v6. Observational open-label study and results.Finished-formula observational

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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