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Clinical white paper

Hormone Balance: formulation and evidence review

A formulation and evidence summary for healthcare professionals and informed readers.

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

PDF · 4 pages Read the full white paper (PDF) Open the complete formulation and evidence review

Executive summary

Hormone Balance was designed around the relationship between metabolic signaling, micronutrient status, cardiovascular markers, mood, and cycle health. The formula combines B vitamins, zinc, magnesium, berberine phytosome, grape seed proanthocyanidins, and passionflower to support several connected systems rather than focusing only on sex-hormone pathways.

The evidence base includes epidemiology, mechanistic work, meta-analyses, and human interventions on individual compounds. Semaine also completed a registered, third-party observational study of the finished formula. That open-label study can describe changes observed over two months, but it cannot establish a placebo-controlled effect.

Formulation rationale

Why support metabolic hormones

The paper begins with a root-level design question: symptoms often described in everyday language as hormone concerns can sit alongside insulin sensitivity, blood pressure, nutritional status, sleep, and mood. Rates of insulin resistance rise during the menopause transition, and magnesium and zinc status are linked to metabolic signaling. This led to a formula built for reproductive years and beyond.

Berberine phytosome was selected to support glucose metabolism with greater bioavailability and a lower raw-extract load. Grape seed extract broadens the design toward vascular and antioxidant support. B vitamins, magnesium, and zinc invest in common nutrient pathways, while passionflower adds support for calm through its relationship with GABA signaling. The formula is intended to accompany nutrition, movement, sleep, and clinician-led care.

Formula at a glance

IngredientForm / amountRole in the formula
B1, B6, B9, B12 Thiamine HCl; pyridoxine HCl; methylfolate; methylcobalamin Folate sufficiency, homocysteine metabolism, and nervous-system support
Zinc 20 mg elemental zinc as zinc glycinate monohydrate Bioavailable mineral support for metabolic signaling and skin health
Magnesium 19 mg elemental Sucrosomial magnesium A GI-conscious form supporting normal nerve, muscle, and metabolic function
Berberine 80 mg from 250 mg berberine phytosome Bioavailability-focused support for glucose metabolism
Grape seed extract 180 mg Enovita, more than 95% proanthocyanidins Vascular and antioxidant support
Passionflower 80 mg extract, more than 4% vitexin Support for calm and normal GABA signaling

See current product facts

Published literature

The evidence base

Nineteen cited publications connect the formula's design objectives to the underlying literature. The page groups the most decision-relevant evidence below, while the numbered list preserves the full source trail from the paper.

  • Metabolic perspectiveEpidemiology and reviews

    Wang and Long establish the overlap between blood-pressure and metabolic markers; Lejsková and Sowers place those changes in the menopause transition. This matters because the formula was designed around connected metabolic systems.

  • Berberine and cycle healthHuman intervention context

    The paper draws on intervention literature connecting insulin sensitivity with cycle-related metabolic health. A phytosome form was chosen to increase exposure without the raw-extract levels commonly associated with GI effects.

  • Magnesium and zincNutrient-status and mechanism studies

    Workinger describes the difficulty of assessing magnesium status, while Kostov reviews magnesium in insulin secretion and signaling. These sources support investing in nutrient sufficiency as part of the design.

  • Grape seed proanthocyanidinsMeta-analyses of randomized studies

    Zhang pooled 16 randomized trials on blood-pressure changes, and Feringa evaluated cardiovascular risk markers. Together they support a standardized, proanthocyanidin-rich extract for vascular and antioxidant roles.

  • Mood and nervous-system supportHuman and mechanistic context

    The literature links metabolic markers with mood and supports a multi-system design. Passionflower was included for its relationship with GABA signaling, not as a substitute for mental-health care.

Finished-formula evidence

Our own study

In a third-party observational open-label study of 45 women over two months, participants reported significant perceived improvement in mood swings, time to fall asleep, energy, and anxiety. The study also found significant improvement in fasting insulin (p<0.05) and total cholesterol and lipid profile (p<0.001).

Participants were recruited based on self-reported mood changes, low energy, food cravings, or sleep difficulty, and completed surveys plus at-home dried-blood-spot testing. With no placebo group, the study describes changes observed during use and does not establish causation.

Funding disclosure: This 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
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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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