Vitex and cyclic mastalgia

Cyclic mastalgia is premenstrual bilateral and diffuse breast pain that presents cyclically and affects up to 80% of women in their reproductive years.

It usually presents mid to late in the luteal phase and is associated with latent hyperprolactinemia due to the insufficient inhibitory effect of dopamine on the pituitary gland.

The hypersecretion of prolactin by the pituitary gland before menstruation or in response to stressful daily stimuli can occur when the inhibitory effect of dopamine on the pituitary gland is insufficient to modulate its release.

Vitex agnus-castus is known for its dopaminergic activity and actions on latent hyperprolactinemia.

Vitex binds to dopamine-2 receptors in the brain, downregulating the activity of the the prolactin-producing cells of the anterior pituitary known as lactotropes.

It is through this dopaminergic activity that vitex indirectly enhances corpus luteum development, alleviating symptoms of premenstrual syndrome.

A systematic review AND meta-analysis published last year (2020) reviewed 25 studies (17 randomized control trials plus eight nonrandomized trials).(Ooi, Watts et al. 2020)

Vitex was effective in relieving breast pain and lowering the increased serum prolactin level in women with or without premenstrual syndromes.

The meta-analysis included only six studies (n = 718, VAC = 356, placebo = 362) and revealed a moderate effect size (SMD: 0.67, 95% CI: 0.5-0.85) favouring vitex over a placebo.

Seven trials demonstrated vitex to be a non-inferior alternative to pharmaceutical therapies for cyclic mastalgia, including dopamine agonists, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors, and hormonal contraceptives.

Vitex was safe and associated with only mild and reversible adverse events.

Active compounds
Vitex berries contain essential oils (e.g., limonene, sabinene, 1,8-cineole, iridoid glycosides (e.g., agnoside, aucubin), diterpines (e.g., vitexilactone, rotundifuran), and flavonoids (e.g., apigenin, casticin, orientin, isovitexin).

Monograph standard

• The European Union vitex herbal monograph recommends 6–12:1 dry extract with ethanol solvent (60%).
• In Australia, and other English-speaking countries, 1:5 tinctures or 1:2 extracts are more common.
• The main active dopaminergic compounds are thought to be the diterpenes. Companies may use the flavonoids agnuside and casticin as marker compounds to ensure consistency.

A review of 17 vitex products found a wide range of variation in agnuside (14% to 5054%) and casticin (3% to 1272%) content (Fukahori, Kobayashi et al. 2014)
It is hard to reconcile this finding. Surely there is an optimal quality and dosage for vitex in the treatment of PMS, mastalgia etc.

Product, Company, Extract name, mg Vitex extract:

• Mastodynon* , Bionorica - mother tincture
• Agnucaston, Bionorica, BNO 1095, 4 mg
• Prefemin (Premular in Australia), Zeller, ZE 440, 20 mg
• Monoselect Pharmextracta, 40 mg
• Femicur Schaper & Brümmer, 4 mg

• Mastodynon is a homoeopathic remedy containing: Agnus castus ø 162.0 mg, Caulophyllum thalictroides Dil. D 4 81.0 mg, Cyclamen Dil. D 4 81.0 mg, Ignatia Dil.D 6 81.0 mg, Iris Dil. D 2 162.0 mg, Lilium tigrinum Dil. D 3 81.0 mg.

• Dosages varied 4-40 mg/day with a treatment duration of 3 months in the studies included in the systemic review and meta-analysis.
• The typical liquid extract dose used in English speaking countries including Australia is 5 to 20 ml per week, or 2 ml in the morning.
• 2 ml of a 1:2 extract is 1000 mg which is a 50-fold higher dose compared to the Zeller extract Ze 440.

It is difficult to comprehend such large differences in dosing between German and English-speaking traditions. It may be due to the quality of the raw material. The Swiss company, Zeller, control the entire process from farm to finished product.

Earlier tinctures and extracts may have been based on poor quality starting materials. Australian vitex extracts are probably of high quality now but the dosing has remained high, probably just due to habitual prescribing.

The products used in clinical trials have mostly been the German and Swiss products listed above. Prefemin from Zeller is available in Australia as Premular from Flordis. If you want to use a clinically proven vitex, Premular is the obvious choice.

Vitex indications:
PMS, mastodynia/mastalgia, luteal insufficiency, menstrual bleeding disorders, amenorrhoea, oligomenorrhoea, polymenorrhoea, menorrhagia, and acne vulgaris.

References
Fukahori, M., S. Kobayashi, Y. Naraki, T. Sasaki, H. Oka, M. Seki, S. Masada-Atsumi, T. Hakamatsuka and Y. Goda (2014). "Quality evaluation of medicinal products and health foods containing chaste berry (Vitex agnus-castus) in Japanese, European and American markets." Chem Pharm Bull (Tokyo) 62(4): 379-385.