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Clinical white paper

Hormone Balance: formulation and evidence review

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

By Matt Crane, PhD, Co-Founder & Chief Science Officer · Last reviewed July 2026

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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 Hormone Balance around connected metabolic, micronutrient, vascular, and cycle-related pathways because insulin resistance is associated with hypertension and increases during the menopause transition.[2][4] Our formula provides B vitamins, zinc, magnesium, berberine phytosome, grape seed extract, and passionflower as nutritional support across reproductive years and beyond.

In our registered, third-party, open-label observational study, 45 participants used the formula for two months; reported comfort, fasting insulin, and lipid measures improved, but the uncontrolled design cannot establish causation.

Formulation rationale

Why we support metabolic pathways

We began with evidence that insulin resistance can coincide with menstrual irregularity, mood symptoms, fatigue, inflammation, and elevated blood pressure.[6][7][8][9][10] We therefore designed support for connected pathways rather than concentrating only on sex hormones.

We chose 19 mg elemental Sucrosomial magnesium because magnesium status is difficult to assess and magnesium participates in insulin secretion and signaling.[15][16] We chose 180 mg standardized grape seed extract because meta-analyses evaluated blood pressure and cardiovascular risk markers.[17][18] We use 80 mg berberine from 250 mg phytosome to reduce raw-extract load while following the source paper's bioavailability rationale.

Formula and dose rationale at a glance

IngredientForm / amountRole in the formula
B1, B6, B9, B12 20 mg thiamine HCl; 20 mg pyridoxine HCl; 680 mcg DFE calcium L-5-methyltetrahydrofolate; 4 mcg cyanocobalamin Folate, homocysteine, and nervous-system nutrient support
Zinc 20 mg elemental zinc as zinc glycinate monohydrate Bioavailability-focused mineral support
Magnesium 19 mg elemental Sucrosomial magnesium GI-conscious mineral support
Berberine 80 mg from 250 mg berberine phytosome Bioavailability-focused glucose-metabolism support
Grape seed extract 180 mg Enovita, more than 95% proanthocyanidins Vascular and antioxidant support
Passionflower 80 mg flower extract, more than 4% vitexin Botanical support for calm

See current product facts

Published literature

The evidence we used

Our review connects epidemiology, mechanisms, and human interventions to design objectives; evidence for an ingredient does not prove an effect of the finished formula.[1][17][1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]

  • Metabolic contextEpidemiology and reviews

    Half of US adult women in the cited survey had hypertension or prehypertension, and later work describes overlap with insulin resistance.[1][2]

  • Menopause transitionObservational

    Insulin resistance increased across the transition in the cited population study.[4]

  • MagnesiumReview and mechanism

    Reviews describe assessment limits and roles in insulin secretion and signaling.[15][16]

  • Grape seed extractMeta-analyses

    Randomized-trial meta-analyses evaluated blood-pressure and cardiovascular-marker outcomes.[17][18]

Finished-formula evidence

Our observational finished-formula study

We registered NCT05328609 as an independent, open-label observational study; 45 participants with self-reported mood changes, low energy, food cravings, or sleep difficulty used the formula for two months.[20] Participants completed surveys and at-home dried-blood-spot tests at baseline, repeated surveys, and a final blood test.[20] The source reports significant perceived improvements in mood swings, sleep onset, energy, and anxiety, plus fasting insulin at p<0.05 and lipid profile at p<0.001.[20] Because there was no placebo group, these observations do not establish causation.[20]

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. Wang Y, Wang QJ. Prevalence of prehypertension and hypertension among US adults. Arch Intern Med. 2004;164:2126-2134.Epidemiology
  2. Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension. J Clin Hypertens. 2011;13:244-251.Review
  3. Silvestris E, et al. Obesity as disruptor of female fertility. Reprod Biol Endocrinol. 2018;16:22.Review
  4. Lejsková M, et al. Menopause and population changes in insulin resistance. Climacteric. 2011;14:83-91.Observational
  5. Fabbrocini G, et al. Low glycaemic diet and metformin therapy in acne. Clin Exp Dermatol. 2016;41:38-42.Human clinical
  6. Glintborg D, et al. Metabolic risk factors in women with PCOS. Clin Endocrinol. 2010;73:732-738.Observational
  7. Kan C, et al. Depression and insulin resistance: systematic review and meta-analysis. Diabetes Care. 2013;36:480-489.Meta-analysis
  8. Vgontzas AN, et al. Fatigue, visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab. 2000;85:1151-1158.Observational
  9. Ruiz-Núñez B, et al. Lifestyle, nutrition, and chronic low-grade inflammation. J Nutr Biochem. 2013;24:1183-1201.Review
  10. Zhou MS, et al. Link between insulin resistance and hypertension. Diabetol Metab Syndr. 2014;6:12.Review
  11. Lee JK, Smith AD. Metformin as adjunct therapy for acne vulgaris. Dermatol Online J. 2017;23.Human clinical
  12. AlHussain F, et al. Metformin and depression symptoms in women with PCOS. Patient Prefer Adherence. 2020;14:737-746.Human clinical
  13. Sowers M, et al. Insulin resistance and hormone interactions in premenopausal and perimenopausal women. J Clin Endocrinol Metab. 2003;88:4904-4910.Observational
  14. Orio F, Palomba S. Guidelines for diagnosis and treatment of PCOS. Nat Rev Endocrinol. 2013;10:130-132.Guideline review
  15. Workinger JL, et al. Challenges in the diagnosis of magnesium status. Nutrients. 2018;10.Review
  16. Kostov K. Magnesium deficiency and mechanisms of insulin resistance. Int J Mol Sci. 2019;20.Review
  17. Zhang H, et al. Grape seed extract and blood pressure: meta-analysis of 16 randomized trials. Medicine. 2016;95:e4247.Meta-analysis
  18. Feringa HHH, et al. Grape seed extract and cardiovascular risk markers: meta-analysis. J Am Diet Assoc. 2011;111:1173-1181.Meta-analysis
  19. Amsellem M, et al. Endotelon in premenstrual syndrome: multicenter study. Tempo Medical. 1987;282:46-51.Human clinical
  20. Semaine Health. Hormone Balance white paper, v7. Pilot clinical trial and results.Finished-formula observational
Read the full white paper (PDF)View the clinical evidenceSee current product facts

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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