Premenstrual Syndrome (PMS) is a common condition, affecting up to 90% of women at some point in their reproductive lifetime. Symptoms can range from mild and inconvenient to severe and disabling. The pathophysiology of PMS is complex but is thought to occur due to interactions between the hypothalamic–pituitary–ovarian (HPO) axis, neurotransmitter signalling, inflammatory pathways, glycaemic control, and stress physiology.¹ Pathways include:

• Elevated prolactin levels or increased sensitivity to prolactin impairs progesterone and dopamine production and function (indirectly);
• Fluctuating oestrogen and progesterone levels in the luteal phase alter neurotransmitters including gamma-aminobutyric acid (GABA), serotonin, norepinephrine, epinephrine, and endogenous opioids;
• Fluctuating progesterone levels alter insulin signalling, leading to altered glucose metabolism;
• Catecholamine alterations and stress activate the sympathetic nervous system, which increases the intensity of uterine contractions during menses.¹

This leads to a combination of physical and psychological symptoms, including changes in appetite, weight gain, abdominal pain, back pain, low back pain, headache, swelling and tenderness of the breasts, nausea, constipation, anxiety, irritability, anger, fatigue, restlessness, mood swings and crying.¹

Why Combination Therapy Matters in PMS

PMS symptoms rarely occur in isolation, and for many patients, single-agent interventions offer incomplete relief. Strategically combining herbs and nutrients can allow clinicians to address overlapping drivers of symptoms and mechanisms concurrently, improving both symptom coverage and patient outcomes.

Key Herb–Nutrient Synergies

Mood Support

Elevated prolactin levels (hyperprolactinaemia) can often present with premenstrual emotional difficulties, namely depressed mood, anxiety, decreased libido, irritability, and hostility.^2,3 Diterpenes in Chaste Tree (Vitex agnus-castus) are dopaminergic compounds⁴ that bind to lactotropes in the pituitary gland and suppress the release of prolactin.⁵ A meta-analysis of randomised controlled trials found that women taking Chaste Tree were significantly more likely to experience relief of PMS symptoms including irritability, mood, anger, headaches, bloating, and breast fullness) compared to those taking placebo (p=0.0004).⁶ Chamomile (Matricaria chamomilla) has anti-anxiety, anti-inflammatory, antioxidant, and antispasmodic properties.⁷ The flavonoid, apigenin, is a potential phytoprogestin and researchers suggest its progesterogenic action may help explain Chamomile’s effectiveness in relieving premenstrual mood symptoms. Other flavonoids are also known to interact with neurotransmitter systems and produce sedative, anxiolytic and antidepressant effects. Antispasmodic properties can also relieve painful cramps associated with menstruation.⁷ Vitamin B6 is an important coenzyme in the biosynthesis of the neurotransmitters gamma-aminobutyric acid (GABA), dopamine, serotonin, adrenaline and noradrenaline,⁸ explaining its clinical use for stress and mood support.⁹ Vitamin B6 also modulates steroid hormone activity (particularly progesterone),¹⁰ supporting hormonal balance. Zinc deficiency is associated with neuropsychological symptoms such as depression, anxiety, and irritability, likely through glucocorticoid-mediated disturbance in glutamatergic neurotransmission.¹¹ A meta-analysis found that zinc supplementation was superior to placebo in relieving psychological and physical symptoms of PMS.¹²

Mastalgia

Latent hyperprolactinaemia is associated with cyclical mastalgia, which can be alleviated by the dopaminergic/prolactin-inhibiting action of Chaste Tree. A meta-analysis demonstrated that Chaste Tree was efficacious in reducing breast pain intensity and lowering elevated serum prolactin levels in women with or without PMS. Chaste Tree treatment was deemed comparable in effect to pharmaceutical therapies, but with fewer reported side effects.¹³ Additionally, a randomised controlled trial showed that Chamomile can lessen the intensity of mastalgia pain, comparable to the anti-inflammatory drug mefenamic acid.¹⁴

Sugar Cravings and Glycaemic Control

PMS is associated with changes in insulin regulation, dysglycaemia and subsequent sugar and carbohydrate cravings in the luteal phase. Increased sugar intake is associated with worsening PMS. Chromium plays an important role as a co-factor in all insulin-regulated activities including carbohydrate, lipid and protein metabolism. It is an essential component of glucose tolerance factor, a compound that helps regulate blood sugar.¹⁵

Pain and Inflammation

Evidence suggests that increased inflammation and decreased antioxidant status may be evident in women with PMS.¹⁶ Ginger (Zingiber officinale) is known to have anti-inflammatory and pain-relieving effects. A meta-analysis found Ginger is more effective than placebo in relieving menstrual pain, with a similar efficacy to anti-inflammatory medications. Thanks to its digestive effects, Ginger may also relieve associated nausea, vomiting and diarrhoea during menstruation.¹⁷ Chamomile’s antispasmodic and anti-inflammatory properties can also relieve painful cramps associated with menstruation. A systematic review found that Chamomile may effectively relieve menstrual pain and reduce heavy menstrual bleeding.¹⁸ Zinc may offer additional pain-relieving support, with a meta-analysis finding that zinc supplementation was effective and safe in the relief of dysmenorrhoea and menstrual pain.¹⁹

Takeaway for Practice

A synergistic herb–nutrient approach allows clinicians to address PMS as the complex, multi-factorial condition it is. By matching formulations to symptom patterns, practitioners can achieve more consistent and clinically meaningful outcomes.

References

1. Gudipally PR, Sharma GK. Premenstrual Syndrome. [Internet] Treasure Island (FL): StatPearls Publishing; 2025 Jan [cited 2026 Jan 20]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560698/

2. Sobrinho LG. Emotional aspects of hyperprolactinemia. Psychother Psychosom. 1998;67(3):133-139. DOI: 10.1159/000012273

3. Kellner R, Buckman MT, Fava M, Fava GA, Mastrogiacomo I. Prolactin, aggression and hostility: a discussion of recent studies. Psychiatr Dev. 1984;2(2):131-138.

4. Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlová-Wuttke D. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Phytomedicine. 2003 May;10(4):348-357. DOI: 10.1078/094471103322004866

5. Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol. 1994;102(6):448-454. DOI: 10.1055/s-0029-1211317

6. Csupor D, Lantos T, Hegyi P, Benkő R, Viola R, Gyongyi Z, et al. Vitex agnus-castus in premenstrual syndrome: A meta-analysis of double-blind randomised controlled trials. Complement Ther Med. 2019 Dec;47:102190. DOI: 10.1016/j.ctim.2019.08.024.

7. Khalesi ZB, Beiranvand SP, Bokaie M. Efficacy of chamomile in the treatment of premenstrual syndrome: a systematic review. J Pharmacopuncture. 2019 Dec;22(4):204-209. DOI: 10.3831/kpi.2019.22.028.

8. Braun L, Cohen M. Herbs & natural supplements – an evidenced-based guide. 4^th ed. Volume 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015.

9. Durrani D, Idrees R, Idrees H, Ellahi A. Vitamin B6: a new approach to lowering anxiety, and depression. Ann Med Surg (Lond). 2022 Oct;82:104663. DOI: 10.1016/j.amsu.2022.104663.

10. Allgood VE, Cidlowski JA. Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily. J Biol Chem. 1992 Feb;267(6):3819-3824.

11. Rafalo A, Sowa-Kucma M, Pochwat B, Nowak G, Szewczyk B. Zinc deficiency and depression. In: Erkekoglu P, Kocer-Gumusel B. Nutritional deficiency [Internet]. Vienna: IntechOpen; 2016 [cited 2023 May 10]. Chapter 1. DOI: 10.5772/61450.

12. Haider S, Sajjad M, Zahid M. A systematic review and meta-analysis examining the role of zinc supplementation in ameliorating physical and psychological manifestations of premenstrual syndrome in young females. Eur J Obstet Gynecol Reprod Biol. 2025 May 22;312:114082. DOI: 10.1016/j.ejogrb.2025.114082. 

13. Ooi SL, Watts S, McClean R, Pak SC. Vitex agnus-castus for the treatment of cyclic mastalgia: a systematic review and meta-analysis. J Womens Health. 2020;29(2). DOI: 10.1089/jwh.2019.7770

14. Sharifi F, Simbar M, Mojab F, Alavi Majd H. Comparison of the effects of Matricaria chamomila (chamomile) extract and mefenamic acid on the intensity of mastalgia associated with premenstrual syndrome. Women’s Health Bulletin, 2014;1(2):1-5. DOI: 10.17795/whb-20042

15. Hechtman L. Clinical naturopathic medicine. 2nd ed. Chatswood NSW: Elsevier Australia; 2019.

16. Granda D, Szmidt MK, Kaluza J. Is premenstrual syndrome associated with inflammation, oxidative stress and antioxidant status? a systematic review of case-control and cross-sectional Studies. Antioxidants (Basel). 2021 Apr 14;10(4):604. DOI: 10.3390/antiox10040604

17. Moshfeghinia R, Salmanpour N, Ghoshouni H, Gharedaghi H, Zare R, Cramer H, et al. Ginger for pain management in primary dysmenorrhea: a systematic review and meta-analysis. J Integr Complement Med. 2024 Nov 1;30(11):1016-30. DOI: 10.1089/jicm.2023.0799

18. Niazi A, Moradi M. The effect of chamomile on pain and menstrual bleeding in primary dysmenorrhea: A systematic review. Int J Community Based Nurs Midwifery. 2021 Jul;9(3):174.

19. Hsu TJ, Hsieh RH, Huang CH, Chen CS, Lin WY, Huang YC, Lin JH, Huang KT, Liu YL, Tsai HM, Ho DR. Efficacy of zinc supplementation in the management of primary dysmenorrhea: A systematic review and meta-analysis. Nutrients. 2024 Nov 28;16(23):4116. DOI: 10.3390/nu16234116