Mechanisms of Action
The mechanisms of action of Agnus Castus are not fully understood but its principal pharmacological effect on the body is the inhibition of prolactin secretion. Various studies have indicated that the seeds produce a modulating effect on the hypothalamus-pituitary system, and hence promote hormonal balance and a regular menstrual cycle. Therapeutic properties are credited to its indirect actions on prolactin and progesterone, in particular.
Agnus Castus increases progesterone by increasing luteinizing hormone (LH) and inhibiting follicle-stimulating hormone (FSH) and prolactin levels. 1,2 It can also increase dopamine activity in the brain, which also results in a reduction of prolactin release. Studies have shown central dopaminergic activity in vitro and in vivo.3-5
Prolactin and Dopamine
Prolactin is a hormone made by the pituitary gland and causes the breasts to grow and produce milk during pregnancy and after childbirth. Levels are, hence, normally elevated in pregnant and breastfeeding women. Higher than normal levels of prolactin in women who are neither pregnant or lactating are associated with infertility, irregular menstruation, loss of libido and other menstrual disorders.
One of the key regulators of the production of prolactin is the hormone dopamine, which is produced by the hypothalamus. Dopamine suppresses the pituitary secretion of prolactin via the dopamine receptor 2. Hence, more dopamine means less prolactin.
Agnus Castus has been shown to influence dopaminergic activity and subsequently has prolactin-lowering effects.1-3 It has also been shown to bind opiate receptors, which in turn promotes dopamine activity.1,4,5 The chemical components of Agnus Castus, casticin and the diterpenes, in particular, are believed to reduce elevated prolactin levels.6,7
One study showed that the diterpene clerodadienol binds dopamine receptors and suppresses prolactin release as effectively as dopamine.6 Furthermore, animal studies suggest that casticin inhibits estradiol stimulation of prolactin secretion via suppression of pituitary α-estrogen receptor mRNA expression.
Oestrogen and Progesterone
High levels of oestrogen and/or low levels of progesterone are believed to play a crucial part in many disorders associated with hormone imbalance.
Oestrogen dominance is a term that refers to having an excess of oestrogen in the body in relation to progesterone. Many women are in a state of oestrogen dominance and can hence suffer with the symptoms associated with it such as PMS (discussed further below), irregular menstruation, heavy bleeding, fibroids, endometriosis, depression, anxiety, irritability and so on.
What causes oestrogen dominance?
Medications such as hormonal contraceptives, obesity (fat cells produce extra oestrogen), gut dysbiosis, chronic stress, exposure to xenoestrogens (chemicals that mimic the behavior of oestrogens), and HRT. Poor excretion of oestrogen is also a common factor. Supporting the liver is important and can help it to safely detoxify and help clear oestrogen. A liver cleansing herb such as milk thistle can be beneficial and will help eliminate toxins and compounds that the body does not need.
The health and regularity of the bowel is also key. Supporting the gut and maintaining regular bowel movements also allows oestrogen to be excreted adequately.
Progesterone is responsible for maintaining pregnancy, monthly menstruation, and helps prepare the female body for conception. It has been described as ‘natures valium’ due to its relaxing effects. Low levels can be caused by many factors and can cause a number of menstrual disorders. Low progesterone can often be due to irregular ovulation.
Progesterone production can be supported and increased using herbal support.1 Agnus Castus stimulates the pituitary to produce LH which in turn signals the ovaries to produce more progesterone. It may therefore help to boost the production of progesterone naturally, improving the oestrogen to progesterone ratio, resulting in hormonal balance.
PMS
PMS is often a sign of hormone imbalance and oestrogen dominance. It refers to a variety of emotional, behavioral, and physical symptoms that occur up to two weeks before the onset of menses.1 It is characterized by physical symptoms such as menstrual cramps, headaches, skin problems and breast tenderness; and emotional symptoms including irritability, mood swings depression and anxiety. It is estimated that as many as 30% of women can experience moderate to severe PMS and between 3 and 8 % of women in the UK suffer from premenstrual dysphoric disorder (PMDD)2, a severe form of PMS, which can have a significant impact on life. PMS symptoms have been linked with a low level of progesterone.
A clinical survey published in 1992 evaluated the effect of an Agnus Castus preparation on 1,542 women diagnosed with PMS. Treatment of 40 drops daily lasted an average of 166 days. Both physicians and patient assessed efficacy, with 90 percent reporting relief of symptoms, after an average treatment duration of 25.3 days.3
In other clinical trials, Agnus Castus reduced many symptoms associated with PMS, especially breast pain, irritability, depression and low mood, irritability, and headache.
Amenorrhea and Menstrual Disorders
A healthy menstrual cycle depends on the proper balancing of hormone levels. Agnus Castus has been shown to correct menstrual irregularities, including amenorrhea (the absence of menstruation), specifically when caused by latent hyperprolactinemia (a condition in which a person has higher-than-normal levels of the hormone prolactin in the blood) owing to its ability to inhibit prolactin secretion.1
Luteal phase disorder is primarily caused by progesterone deficiency in the first phase of the menstrual cycle. An RCT of women with luteal-phase defect menstrual cycle irregularities attributable to elevated prolactin found that 20 mg of Vitex lowered prolactin levels and normalized menstrual cycles after 3 months.
Menopause
The hormone-balancing effects of Agnus Castus may also help to alleviate the unpleasant symptoms of menopause. In one study, vitex oils were given to 23 women in menopause. Women reported improved menopause symptoms, including better mood and sleep.
Fertility
A regular menstrual cycle is important for conception, and menstrual cycle disorders can be one reason why some women have problems conceiving. This can be due to too much prolactin and too little progesterone. Agnus Castus has been shown to help regulate both.
An RCT compared the use of Agnus Castus and other supportive nutrients to placebo in 93 women with infertility. After 3 months, progesterone levels in women taking Agnus Castus had increased compared with those receiving placebo. Furthermore, 13 of the 53 women became pregnant compared with none in the placebo group.
Polycystic Ovarian Syndrome (PCOS)
PCOS is a complex endocrine disorder and is said to affect around 6-8% of the female population in the reproductive age.1 It is caused by an imbalance of the female sex hormones and higher levels of hormones called androgens (e.g., testosterone and androstenedione). It is characterized by polycystic ovaries, lack or absence of ovulation and excessive presence of the male sex hormones. This can lead to irregular menstrual cycles, hirsutism (excessive hair growth), skin problems and infertility. In conditions like PCOS, Agnus Castus is helpful in restoring ovulation and regulating progesterone levels.
Agnus Castus helps to regulate prolactin, FSH, and LH, which may then regulate and balance testosterone levels, as well as levels of other reproductive hormones.2 This can be therapeutic in women with PCOS and elevated androgens.
Contraindications
Agnus Castus should not be used by anyone undergoing infertility treatment and is also not recommended by anyone on birth control. It should not be used by pregnant and breastfeeding women. There are no reported drug interactions but given its dopaminergic effects, the herb could potentially interfere with drugs that affect dopamine levels.
With a long traditional history of use, Agnus Castus can be a beneficial botanical alternative to address female hormonal imbalances and a range of symptoms associated with them.
References
Mechanism of Action
1.Brown D. (1994) Vitex agnus castus clinical monograph. Quarterly Review of Natural Medicine. 2:111–21.
1. PG, M. et al. (1996) “The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects,” Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 104(6), pp. 447–453.
2. et al. (2000) “Pharmacological activities of Vitex agnus-castus extracts in vitro,” Phytomedicine : international journal of phytotherapy and phytopharmacology, 7(5), pp. 373–381.
3. Roemheld-Hamm, B. (2005) “Chasteberry,” American Family Physician, 72(5), pp. 821–824.
4. Wuttke W. (1996). Dopaminergic action of extracts of Agnus Castus. Forschende Komplementarmedizen. 3:329–30.
Prolactin and Dopamine
5. et al. (2000) “Pharmacological activities of Vitex agnus-castus extracts in vitro,” Phytomedicine : international journal of phytotherapy and phytopharmacology, 7(5), pp. 373–381.
6. Roemheld-Hamm, B. (2005) “Chasteberry,” American Family Physician, 72(5), pp. 821–824.
7. Wuttke W. (1996). Dopaminergic action of extracts of Agnus Castus. Forschende Komplementarmedizen. 3:329–30.
8. DE, W. et al. (2011) “Opioidergic mechanisms underlying the actions of Vitex agnus-castus L,” Biochemical pharmacology, 81(1), pp. 170–177.
9. DE, W. et al. (2006) “Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS,” Journal of ethnopharmacology, 106(2), pp. 216–221.
10. W, W. et al. (2003) “Chaste tree (Vitex agnus-castus)–pharmacology and clinical indications,” Phytomedicine : international journal of phytotherapy and phytopharmacology, 10(4), pp. 348–357.
11. G, S. et al. (1993) “Agnus castus extracts inhibit prolactin secretion of rat pituitary cells,” Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 25(5), pp. 253–255.
12. Q, Y. et al. (2010) “Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro,” Acta pharmacologica Sinica, 31(12), pp. 1564–1568.
Oestrogen and Progesterone
13. NA, I. et al. (2008) “Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt,” Natural product research, 22(6), pp. 537–546.
PMS
1. A, R. (2003) “A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder,” Psychoneuroendocrinology, 28 Suppl 3(SUPPL. 3), pp. 39–53.
2. Yonkers, K. A., O’Brien, Prof. P. M. S. and Eriksson, Prof. E. (2008) “Premenstrual syndrome,” Lancet, 371(9619), p. 1200.
3. Dittmar, F. W (1992) Premenstrual Syndrome (PMS): Treatment with a Phytopharmaceutical. Gynäkol. 5(1):60-68.
4. R, S. (2001) “Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study,” BMJ (Clinical research ed.), 322(7279), pp. 134–137.
5. C, L. et al. (1997) “Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine,” Phytomedicine : international journal of phytotherapy and phytopharmacology, 4(3), pp. 183–189.
6. D, B. et al. (2000) “Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS),” Archives of gynecology and obstetrics, 264(3), pp. 150–153.
7. EG, L., H, S. and N, B. (2000) “Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus,” Journal of women’s health & gender-based medicine, 9(3), pp. 315–320.
Amenorrhea
1. Vitex Agnus-Castus – an overview | ScienceDirect Topics. Available at: https://www.sciencedirect.com/topics/medicine-and-dentistry/vitex-agnus-castus (Accessed: July 22, 2021).
2. [Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study] – PubMed (1993). Available at: https://pubmed.ncbi.nlm.nih.gov/8369008/ (Accessed: July 22, 2021).
Menopause
1. L. (2003) “Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154],” Complementary therapies in nursing & midwifery, 9(3), pp. 157–160.
Fertility
1. Chaste Tree Berry (Vitex agnus castus 2) – Restorative Medicine. Available at: https://restorativemedicine.org/library/monographs/chaste-tree-berry-vitex-agnus-castus-2/#sdendnote15sym (Accessed: July 22, 2021).
2. LM, W., ML, P. and AS, T. (2006) “Double-blind, placebo-controlled study of Fertilityblend: a nutritional supplement for improving fertility in women,” Clinical and experimental obstetrics & gynecology, 33(4), pp. 205–208.
PCOS
1. Saul, S. (2017) “Effects of vitex agnes castus on hormonal imbalances in Polycystic Ovary Syndrome,” International Journal of Basic & Clinical Pharmacology, 6(8), pp. 2051–2055.
2. S, N. et al. (2007) “The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice,” Pakistan journal of biological sciences: PJBS, 10(14), pp. 2300–2307.