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Chaste tree

vitexagnuscastus
Vitex agnus-castus
Verbenaceae
Chaste tree, Monk's pepper, vitex
Fruit

Vitex is a favourite herbal medicine widely used by European and North American herbalists.

Vitex is most commonly used for female disorders associated with the menstrual cycle including:

  • Premenstrual syndrome (PMS)
  • Irregular menstruation
  • Fluid retention
  • Breast soreness
  • Pre-menstrual dysphoric disorder
  • Beneficial effects have also been seen in acne, post traumatic epilepsy, mouth ulcers, and herpes simplex (cold sores and genital herpes), which worsen before menstruation.

Breast pain is one of the specific indications for Vitex agnus-castus and a number of papers have attempted to explain the mechanism, suggesting that the prolactin-suppressive effect is likely to be due to a mixture of clerodane-type diterpenes, which bind to recombinant DA2-receptor protein, and suppress prolactin release from cultivated lactotrophs in vitro and also in vivo in animal experiments. These substances are almost identical to dopamine in their prolactin-suppressive properties.

In men, the symptoms of hyperprolactinemia include infertility, impotence, and galactorrhea.

Safety of Vitex is derived from long-standing medicinal use. Studies on acute and repeat-dose toxicity, genotoxicity and reproductive/developmental toxicity have not found anything suggesting any safety risks.

Vitex lowers prolactin levels, and is not considered to be safe during pregnancy or lactation.

Treatment with Vitex in a daily dose of 40 mg extract is well tolerated.

Preparations of Vitex intended for adults and adolescents over 12 years of age have been on the market in the Member States for more than 30 years without any indication of serious risks.

vitex3

Vitex is a deciduous shrub native to European, Mediterranean and Central Asian countries.

It has slender, finger-like leaves, purple-black berries, and belongs to the Verbenaceae family.

It is a deciduous shrub of free spreading habit, young shoots covered with a fine grey down; leaves opposite, composed of five to seven radiating leaflets borne on a main stalk 1 to 2 1/2 inches long, leaflets linear, lance-shaped, toothed, dark green above, grey beneath with a very close felt; stalks of leaflets 1/4 inch or less long- flowers fragrant, produced in September or October, in whorls on slender racemes 3 to 6 inches long, sometimes branched; the berries somewhat like peppercorns, dark purple, half-covered by their sage-green calyces, yellowish within, hard, having an aromatic odour; taste warm, peculiar.

The pharmacological effects of herbal extracts are not due to an isolated component or mechanism. Therefore the whole extract must to be considered as the active principle.

Vitex agnus castus contains the following main constituents: 1-6

  • Iridoid glycosides (around 1 %): aucubin andagnusid,
  • Diterpenoids: halimane-type diterpenoids : vitetrifolin B and C viteagnusinsA and B, labdane-typediterpenoids:viteagnusinsC,D,E,F,G,andH, viteagnusin I.
  • Lipophilic flavonoids: Casticin [5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavon] (around 0.7-1.8 %), kaempferol, quercetagetin,vitexin,
  • Alkaloids:viticin,
  • Volatile oils with mainly monoterpenes and sesquiterpenes: bornylacetate, 1,8 cineol, limonen, α-pinen and β-pinen,
  • Essential fatty acids: palmitic acid, oleic acid, linoleic acid, stearicacid.

aucubin

Figure 1: Constituents of Vitex agnus-castus L., fructus: Aucubin

agnuside

Figure 2: Constituents of Vitex agnus-castus L., fructus: Agnuside

casticin

Figure 3: Constituents of Vitex agnus-castus L., fructus: Casticin.

References

1.         Hajdú Z, Hihmann J, Forgo P, et al. Diterpernoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents. Phytother.Res. 2007;21  391-394.

2.         Ono M, Yamasaki T, Konoshita M, et al. Five new diterpenoids, viteagnusins A--E, from the fruit of Vitex agnus-castus. Chem.Pharm.Bull.(Tokyo). 2008;56(11):1621-1624.

3.         Choudhary MI, Jalil S, Nawaz SA, Khan KM, Tareen RB. Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus. Phytother.Res. 2009;23(9):1336-1339.

4.         ESCOP. Agni casti fructus. In: Phytotherapy ESCo, ed. ESCOP Monographs. The Scientific Foundation for Herbal Medicinal Products. Stuttgart: Thieme-Verlag; 2009.

5.         Ono M, Eguchi K, Konoshita M, et al. A new diterpenoid glucoside and two new diterpenoids from the fruit of Vitex agnus-castus. Chemical & pharmaceutical bulletin. 2011;59(3):392-396.

6.         Li S, Qiu S, Yao P, Sun H, Fong HH, Zhang H. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction. Evidence-based complementary and alternative medicine : eCAM. 2013;2013:432829.

monkspepperVitex has been used as a medicinal plant for centuries. Hippocrates (450 BC) suggested it be used to treat injuries, inflammations, enlargement of the spleen and to help the uterus expel the afterbirth.

Others around this time used it to reduce headache and fever and to stimulate perspiration, to dispel wind and flatulence and to stop diarrhoea.

Dioscorides (50 AD) recommended Vitex for inflammation of the uterus; in Persia, it was used to cure insanity, madness and epilepsy; and Pliny (first century AD), used the berries to promote menstruation, reduce fever and headaches, to stimulate perspiration and to promote lactation in new mothers.

Vitex was also used ‘to cool passions’ - some said it was infallible, others claimed it had stimulating properties, but this may have depended on gender (and many of the old herbals were lacking in information on this point).

The dried fruits have a peppery taste and were used in monasteries as a condiment, supposedly to suppress libido - a common name for Vitex is monk’s pepper.

In Rome, the Vestal Virgins carried twigs of it as a symbol of chastity. The eclectics in the 19th century used a tincture of berries for impotence and ‘sexual melancholia’, but whether this was for men, women or both sexes is unclear.

vitex2Vitex is most commonly used for female disorders associated with the menstrual cycle including:

  • Premenstrual syndrome (PMS)
  • Fluid retention
  • Breast soreness
  • Pre-menstrual dysphoric disorder
  • Beneficial effects have also been noted in acne,1 post‑traumatic epilepsy,2 mouth ulcers,3 and herpes simplex (cold sores and genital herpes),4which worsen before menstruation.

Preparations of Vitex agnus castus (chaste tree) are a popular treatment for the managementof female reproductive disturbances including corpus luteum insufficiency, menopausal symptoms, and pre-menstrual syndrome (PMS).

Small randomized controlled trials indicate that vitex may be helpful in hyperprolactinemia, cyclical breast pain and PMS.

The Premenstrual Syndrome is defined as the cyclic, repeated occurrence of psychic lability accompanied by physical symptoms such as mastodynia, edema and weight gain during the luteal phase.

Depressive mood, lack of concentration, irritability and anxiety are the dominant psychic symptoms. These symptoms culminate during the premenstrual phase and disappear at the onset of menstrual bleeding. The complaints are of variable degree.

Pre-menstrual dysphoric disorder

Pre-menstrual dysphoric disorder is a severe type of pre-menstrual disorder in which mood symptoms predominate and which responds favourably to the class of antidepressants known as SSRIs.

A single blind study was undertaken to compare the efficacy of the SRI fluoxetine with Vitex agnus-castus extract because both are known to favourably influence severe PMS symptoms. After a period of two months to screen patients for suitability, 41 patients with PMDD according to DSM-IV were recruited into the study. The patients were randomised to fluoxetine or Vitex for two months. The outcome measures showed there was no statistically significant difference between the groups with respect to the rate of responders, however, while fluoxetine was more effective for psychological symptoms, the Vitex extract was more effective for physical symptoms.5

References

1.         Amann W. Besserung der Akne vulgaris nach Agnus castus (Agnolyt). Ther.Gegenwart. 1967;106  124-126.

2.         Ecker G. ‘Pramenstruelles syndrom als schrittmacher einer posttraumatischen epilepsie’. Landarzt. 1964;40:872-874.

3.         Hillebrand H. Die Behandlung der prämenstruellen Stomatitis aphthosa ulcerosa mit Agnolyt. Landarzt. 1964;40  1577.

4.         Albus GA. Herpes simplex recidivans als fragmentäres Zeichen eines prämenstruellen Syndroms. Z.Hautkrankh.Geschlechtskrankh. 1964;36  220-223.

5.         Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum.Psychopharmacol. 2003;18(3):191-195.

capsulesThe HMPC assessment report (2010) supports the well established use of the dry extract (6-12:1) of whole, ripe, dried fruit Vitex agnus-castusL., extraction solvent: ethanol 60%(m/m), 20mg per day corresponding to 180 mg drug per day on average, in the treatment of premenstrual syndrome.1

The ESCOP monograph recommends preparations of Chaste tree fruits equivalent to 30- 40 mg of the drug daily or up to 240 mg of the drug daily in patients suffering from PMS for oral administration in adults. Therapeutic indications, recommend by ESCOP, comprise the premenstrual syndrome (PMS) including symptoms such as mastodynia or mastalgia, and menstrual cycle disorders such as polymenorrhoea, oligomenorrhoea or amenorrhoea.2

The Clinical Overview represents and estimates the relevant clinical data of chaste tree fruits (Agni casti fructus) dried extracts on the basis of the German Commission E monograph (Commission E, 1992), the ESCOP monograph (ESCOP, 2003), the draft of the HMPC monograph on traditional medicinal use (HMPC, 2010) and relevant literature selected by international database search (Pubmed, Embase, Cochrane, Medline).

During the peri-menopausal phase, Vitex has been observed to regulate the menstrual cycle, perhaps by initiating more regular ovulation. It can be useful for peri-menopausal women with menstrual irregularities and/or pre-menstrual symptoms, and appears to normalise elevated FSH levels, as well as menstrual cycle regularity in some cases.

Vitex should be started in the early part of the cycle, preferably prior to ovulation, and is usually given as a single dose in the morning. For full benefit, Vitex is usually prescribed between three and nine months. Longer-term administration is necessary in some cases and there are reports of women taking Vitex for up to 16 years without ill effects.3

Positive changes to the menstrual cycle are usually evident in the first month; however, some women initially report longer or shorter cycles than usual until stabilisation occurs.

References

1.         HMPC. Assessment report on Vitex agnus-castus L., fructus London  EMA; 2010.

2.         ESCOP. Agni casti fructus. In: Phytotherapy ESCo, ed. ESCOP Monographs. The Scientific Foundation for Herbal Medicinal Products. Stuttgart: Thieme-Verlag; 2009.

3.         Dittmar FW, Böhnert KJ, Peeters M, Albrecht M, Lamertz M, Schmidt U. Prämenstruelles Syndrom. Behandlung mit einem Phytopharmakon. TW Gynäkologie. 1992;5  60-68.

safetySafety of Vitex is derived from long-standing medicinal use.

Studies on acute and repeat-dose toxicity, genotoxicity and reproductive/developmental toxicity have not found anything suggesting any safety risks.

Vitex lowers prolactin levels, and is not considered to be safe during pregnancy or lactation.

Treatment with Vitex in a daily dose of 40 mg extract is well tolerated.

Preparations of Vitex intended for adults and adolescents over 12 years of age have been on the market in the Member States for more than 30 years without any indication of serious risks.

The most frequent adverse events noted were nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash.1 An article in a British medical journal reported that a woman on her fourth cycle of a drug-free in vitro fertilisation (IVF) program, who self-administered Vitex (dose not stated), produced increased numbers of ovarian follicles and developed symptoms suggestive of mild ovarian hyperstimulation (symptoms not stated).2

An observational study of 56 women reported the following adverse events (only those with more than one mentioning are listed here): not specified (12), nausea (8), allergy (2), diarrhoea (3), weight gain (3), stomach trouble (4), anomalies of the length of menstruation (4), acne (2), exanthema (2), erythema (2), headache (3).3,4

Herb−drug interactions

Dopamine antagonists Vitex agnus-castus appears to have dopaminergic activity.

In vitro research has found a potent binding inhibition of ethanolic Vitex agnus-castus extracts for dopamine D2 and opioid receptors.

Spiperone, a psychoactive drug which is a selective D2 dopamine receptor antagonist, has been shown to antagonise the effects of Vitex.5

Antagonistic interactions between Vitex and dopamine antagonists are thus possible. Fertility drugs Vitex is often used for improving fertility associated with elevated prolactin levels.

There has been a report of a woman on her fourth cycle of a drug-free in vitro fertilisation (IVF) program, who self-administered Vitex (dose not stated), who produced increased numbers of ovarian follicles and developed symptoms suggestive of mild ovarian hyperstimulation (symptoms not stated).2

There is a theoretical risk of hyperstimulation when Vitex is given concurrently with FSH analogues.

As a rule, a woman who has not yet been on IVF treatment should not be given Vitex until her response to the particular drug regimen has been observed. A poor response can be an indication of the need for concurrent Vitex and drug prescriptions.

If the IVF regimen is changed, the same rule applies. The use of Vitex with patients undergoing IVF treatment should be under the guidance of a qualified herbalist with experience in the concurrent treatment of women on IVF, and in particular, with experience in timing the use of herbs to coincide with the most advantageous outcomes in terms of ovum numbers.

Hormone therapy

The use of Vitex while women are taking hormonal preparations such as HT or any of the commonly prescribed progestin drugs such as medroxyprogesterone acetate (Provera), norethisterone (Primulet), dydrogesterone (Duphaston) and danazol (Danocrine) has not been studied. While no adverse effects are expected, use of Vitex with these hormone therapies should be under the guidance of the prescribing practitioner.

References

1. Daniele C, Thompson CJ, Pittler MH, Ernst E. Vitex agnus castus: a systematic review of adverse events. Drug Saf. 2005;28(4):319-332.

2. Cahill DJ, Fox R, Wardle PG, Harlow CR. Multiple follicular development associated with herbal medicine. Hum.Reprod. 1994;9(8):1469-1470.

3. Loch EG, Kaiser E. Diagnostik und Therapie dyshormonaler Blutungen in der Praxis. GynÑkol.Praxis. 1990;14 489-495.

4. Loch EG, Bîhnert KJ, Peeters M, Schmidt U, Lamertz M. Die Behandlung von Blutungsstîrungen mit Vitex agnus-castus-Tinktur. Frauenarzt. 1991;32 867-870.

5. Meier B, Berger D, Hoberg E, Sticher O, Schaffner W. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. 2000;7(5):373-381.

vitex5Most pharmacological data were raised using ethanol or methanol extracts. Inhibitory influence on the prolactin release and dopaminergic (dopamine-agonistic) effects was seen by different working groups.

From the data seen there are opposite results concerning binding to oestrogen receptor (more preferential binding to β- or α-receptor) or not.

Furthermore there are some references concerning β-endorphin-like activity (via µ-opiate receptor binding).

Effects on hyperprolactaemia

Breast pain is one of the specific indications for Vitex agnus-castus and a number of papers have attempted to explain the mechanism, suggesting that the prolactin-suppressive effect is likely to be due to a mixture of clerodane-type diterpenes, which bind to recombinant DA2-receptor protein, and suppress prolactin release from cultivated lactotrophs in vitro and also in vivo in animal experiments.

These substances are almost identical to dopamine in their prolactin-suppressive properties.1

In men, the symptoms of hyperprolactinemia include infertility, impotence, andgalactorrhea.

A comparative evaluation of bromocriptine and Vitex agnus-castus concluded that Vitex performed similarly to bromocriptine with respect to lowering serum prolactin and reducing breast pain, and also offered the advantages of better patient compliance and lower cost. The authors concluded that Vitex be used as a first-line treatment option for cyclic mastalgia and mild hyperprolactinaemia.2

Dopamine receptor binding

Vitex has been shown to inhibit prolactin secretion by competitively binding to dopamine receptors, but does not appear to affect LH or FSH levels. In rat studies, an active dopamine-like principle in Vitex was shown to bind to the lactotrope cells from rat pituitary in vitro, inhibiting prolactin release.3

A potent binding inhibition for dopamine D2 and opioid receptors was observed, suggesting a dopaminergic effect of Vitex and additional pharmacological actions via opioid receptors. Vitex may improve PMS symptoms via interaction with opiate receptors and modulation of specific ß endorphins, which have been shown to declinein the pre-menstrual phase of the cycle. This decline is proportional to symptom severity such as anxiety, food cravings, and physical discomfort.4

Oestrogen receptor binding

In a receptor binding assay performed with recombinant human oestrogen receptor, an ethanol extract of Vitex agnus-castus showed a preferential binding to oestrogen receptor β over oestrogen receptor α.5 The oestrogenic compounds of this extract were identified as the flavonoids penduletin and apigenin.6

Opiate receptor binding

A later in vitro study identified agonistic activity exhibited Vitex at the mu-opiate receptor.7

Doperminergic effects

The LH secretion from the anterior pituitary of mammals is controlled by many neurotransmiters such as dopamine. Therefore, the probable effects of  anhydroalcoholic Vitex agnus castus extract on the male reproductive physiology and its interaction with dopaminergic system on LH and testosterone were investigated in male mice.

The following doses of Vitex extract were used:65, 165, 265, 365 and 465 mg/kg. Bromocriptine as a dopamine receptor agonist (5, 10, 20 mg/kg and haloperidol as a dopamine receptor antagonist (1, 1.5, 2, 2.5, 3 mg/kg) were administered.

Intraperitoneal injections were applied in all experiments, once a day for 30 days. The control group remained in tact and the sham group received vehicle. LH and testosterone, showed significant decrease in bromocriptine group and haloperidol increased these hormones.

Vitex extract decreased significantly the LH and testosterone levels. The coadministration of Vitex extract and bromocriptine decreased LH and testosterone. Coadministration of Vitex extract and haloperidol decreased LH and testosterone levels. These results suggest that dopamine regulates the gonadotroph-leydig cells axis.8

Oestrogenic activity

The oestrogenic activity of ethanolic extract of Vitex agnus-castus fruits was studied in two dose levels (0.6 and 1.2 g/kg) by the vaginal smear, and uterine weight methods fornormal and ovariectomized female rats.

Vitex extract induced significant increase in th uterine weight of ovariectomized rats at two dose levels comparable to that of controlgroup.

Significant increases in plasma progesterone and total estrogens levels were shown at the two dose levels when compared to that of control group.

Further, the Vitex extractinducedsignificant reduction in luteinizing and plasma prolactin hormones.9

References

  1. Carmichael AR. Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence? Evid.Based Complement Alternat.Med. 2008;5(3):247-250.
  2. Kilicdag EB, Tarim E, Bagis T, et al. Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and mastalgia. Int J Gynaecol Obstet. 2004;85(3):292-293.
  3. 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.
  4. Meier B, Berger D, Hoberg E, Sticher O, Schaffner W. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. 2000;7(5):373-381.
  5. Christoffel V, Spengler B, Jarry H, Metten M, Wuttke W. Selective estrogenic activity of extract BN 1095 from Vitex agnus-castus frutis. Arch Pharm Pharm Med. 2002;335(1):137.
  6. Jarry H, Sprengler B, Wuttke W, Christoffel V. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. Maturitas. 2006;55 S26-S36.
  7. Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ. Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. J.Ethnopharmacol. 2006;106(2):216-221.
  8. Nasri S, Oryan S, Rohani AH, Amin GR. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Pak.J.Biol.Sci. 2007;10(14):2300-2307.
  9. Ibrahim NA, Shalaby AS, Farag RS, Elbaroty GS, Nofal SM, Hassan EM. Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt. Nat.Prod.Res. 2008;22(6):537-546.

 

vitex4Clinical trials have shown that Vitex is capable of correcting a range of menstrual irregularities,1 including amenorrhoea,2 and especially when associated with cyclic changes caused by latent hyperprolactinaemia.3

Latent hyperprolactinaemia

This syndrome is characterised by lower than normal progesterone secretion and normal to mildly elevated prolactin levels and is thought to cause a spectrum of menstrual disorders ranging from the typical PMS symptoms, to altered menstrual cycle lengths, to complete absence of ovulation and menstruation. Its causative factors are not entirely understood, but seem to be related to an alteration of HPO axis activity.

In one trial, 13 women with elevated prolactin levels and irregular cycles were given Mastodynon N (a German herbal preparation containing Vitex extract). Following a decrease in prolactin levels, normal cycles returned in all cases. 3

In another study, 52 women with luteal phase defects due to latent hyperprolactinaemia took part in a double-blind, placebo-controlled study. They were given a daily dose of 20 mg of Vitex. Prolactin levels were normalised after three months, and deficits in the luteal progesterone production were corrected. There were no side effects and two of the women treated with Vitex became pregnant.4

Meczekalski  et al. (2015) described a patient with mild hyperprolactinemia and menstrual disorders (oligomenorrhea) who presented with relative hypoestrogenism in laboratory tests. Magnetic resonans excluded the presence of pituitary adenoma. Because patient developed a bromocriptine intolerance, a Vitex extract was prescribed. The vitex therapy was effective, with symptoms relief and improvement of hormonal tests.5

PMS

A multicentre open trial investigated the efficacy and tolerance of Vitex in 1,634 patients suffering from PMS. A specific questionnaire was developed for determining the effect of Vitex on the four characteristic PMS symptom complexes of depression, anxiety, craving and fluid retention.

After three menstrual cycles, 93 per cent of patients reported a decrease in the number of symptoms or symptom complexes or even cessation of PMS complaints, and 85 per cent of physicians rated the treatment as good or very good. The severity and frequency of breast pain was reduced after three months.

The majority of patients assessed the tolerance of Vitex as good or very good. Adverse drug reactions were suspected in only 1.2 per cent of patients, but none were serious.6

In a prospective multicentre trial, the efficacy of a Vitex agnus-castus extract was investigated in 43 patients with PMS. The patients took 20 mg extract daily for three menstrual cycles. Symptoms in three post-treatment cycles were compared to baseline cycles before administration of the herb, using a menstrual distress questionnaire as the self-assessment tool.

At the end of the study, symptoms were reduced in the late luteal phase by 47.2 per cent. While symptoms gradually returned after treatment cessation, a difference from baseline remained for up to three cycles.7

A double-blind, placebo-controlled trial compared Vitex 20 mg with placebo in 170 women with PMS over three menstrual cycles. Women undertook self-assessment of symptoms. The study showed that Vitex was an effective and well tolerated treatment for the symptom relief of PMS for the majority of participants.8

A double-blind, placebo-controlled study of 178 women found that treatment with Vitex over three menstrual cycles significantly reduced general PMS symptoms. The dose used was one 20 mg tablet daily of a dry Vitex extract. Women in the treatment group experienced significant improvements in symptoms, including irritability, depression, headache, and breast tenderness.8

Another study enrolling 221 patients concluded that Vitex was an effective and well-tolerated treatment of moderate to severe PMS. From the 221 patients, 118 provided full data, and 109 completed the treatment phase. The severity of the PMS symptoms consistently decreased during treatment, on average from 22.8 score points during the baseline cycle to 10.2 during the third cycle. Response to treatment was found in 67.8 per cent of the women during the third treatment cycle.9

A prospective multicentre, placebo-controlled study which enrolled 217 Chinese women for treatment with Vitex 40 mg or placebo, found Vitex to be safe, well tolerated and effective for moderate to severe PMS as compared to placebo.10

Dante and Facchinetti (2011) reviewed the use of herbal preparations for the treatment of premenstrual syndrome.

Systematic literature searches were performed in electronic databases, covering the period January 1980 to September 2010. Randomised controlled clinical trials (RCTs) were included. Papers quality was evaluated with the Jadad' scale.

A further evaluation of PMS/PMDD diagnostic criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10 of them were included. The heterogeneity of population included, study design and outcome presentation refrained from a meta-analysis.

Vitex agnus-castus was the more investigated remedy (four trials, about 500 women), and it was reported to consistently ameliorate PMS better than placebo. None of the examined herbs (including Vitex) was associated with major health risks – the only adverse event mentioned for Vitex was headache in both, the study and the placebo group. 11

Breast pain (mastalgia)

Benefits were also seen in a double-blind trial that enrolled 160 women with cyclic breast pain. The women were given Vitex, a progestogen, or placebo, and were followed for at least four menstrual cycles.12

The results again suggested that Vitex was superior to placebo.

A double-blind, placebo-controlled study examined the tolerability and efficacy of Vitex agnus-castus extract for pre-menstrual mastalgia, with treatment or placebo given over three menstrual cycles. Mastalgia during at least five days of the cycle before the treatment was the strict inclusion condition. The results showed the intensity of the cyclical breast pain diminished in the Vitex group and the herb was well tolerated.13

Dinc et al. (2014) examined the efficacy of vitex compared with flurbiprofen in the treatment of cyclic mastalgia. is described as a diffuse, periodic and bilateral breast pain that can not be localized.

One hundred and fourteen premenapousal patients younger than 40 years old with a complaint of cyclic mastalgia and without any clinical, family or ultrasonography findings were analyzed prospectively. VAS scores were accepted as full recovery whit a score of zero, as significant healing when the score improved more than 50%, as mild-moderate healing when the improvement was less than 50% and as no healing in case of no improvement.

The mean age in group 1 was 28.29+/-5.81, and in group 2 was 29.09+/-4.49. The mean number of days with pain was 6.0+/-1.70 days in group 1, and was 6.3+/-1.63 in group 2. There was no significant difference in VAS scores between the two groups after treatment.14

This stduy found that both vitex and flurbiprofen significantly reduce the complaints of cyclic mastalgia and have acceptable side-effects. There is no proven superiority over each other.

Dysmenorrhoea (painful menstruation

Aksoy et al. (2014) used a case-control study to compare the efficacy of ethinyl estradiol/drospirenone and Vitex in women with severe primary dysmenorrhea by measuring uterine artery blood flow via Doppler ultrasonography.

A total of 60 women with severe primary dysmenorrhea and 30 healthy women (control) were included in this study. Thirty patients were treated with ethinyl estradiol 0.03 mg/drospirenone (group 1) and another 30 were treated with Fructus agni casti (group 2) during three menstrual cycles.

Before and at the end of third month of therapy visual analog scale (VAS) scores, pulsatility index (PI), resistance index (RI) of uterine artery were recorded before and after receiving therapy on the first day of the menstrual cycle.

  • Mean PI and RI values in patients with severe primary dysmenorrhea were significantly higher than in the control groups on the first day of the menstrual cycle (P < 0.0001).
  • Mean PI and RI values were significantly lower after the treatment in both groups compared to before values (P < 0.001 for both).

After using the drugs for three menstrual cycles, VAS scores were significantly dropped in both groups compared to before treatment values (P < 0.0001 for both); however, there were no significant differences in terms of Doppler findings between group 1 and 2.15

This study found that the effectiveness of Vitex was similar to that of ethinyl estradiol/drospirenone in patients with primary dysmenorrhea.

Abnormal menstrualcycles

The term“lutealinsufficiency” describes an endocrinal disorder of themenstrual cycle with a shortened progestational stage and a decreased progesterone level in blood. It is a possible cause forfemale sterility.

Numerous open studies have found a positive effect of the use of vitex in regulating the menstrual cycle.

In an open trial, 1,592 women (averageage of 32) with corpus luteum insufficiency presenting as hypermenorrhea, polymenorrhea,secondaryamenorrhea, dysmenorrhea, PMS anovulation, sterility, menorrhagia, and disturbed menstruation received Vitex (40 drops daily) for six months.

61% of the patients reported a good outcome, and physicians noted that 33% of patients were free of complaints and that there was a positive response to treatment in 51% of the patients.16

Vitex has been shown to be benefical in several different types of abnormal menstrual cycle including luteal phase defect and latent hyperprolactaemia4, Intrauterine device (IUD)-induced bleeding17, amenorrhoea, oligomenorrhoea and menorrhagia.18,19

Systemic review of the use of vitex in women’s health

Van die et al. (2013) conducted a systematic review to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.

Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials.

Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.

Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia.

For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex.

In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17beta-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia.

Adverse events with Vitex were mild and generally infrequent.

The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.

Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia.20

Premenstrual dysphoric disorder (PMDD)

Atmaca et al. (2003) compared the efficacy of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), with that of the Vitex extract.

After a period of 2 screening months to screen the patients for suitability, 41 patients with PMDD according to DSM-IV were recruited into the study.

The patients were randomized to fluoxetine or AC for 2 months of single-blind, rater- blinded and prospective treatment period.

The outcome measures included the Penn daily symptom report (DSR), the Hamilton depression rating scale (HAM-D), and the clinical global impression-severity of illness (CGI-SI) and -improvement (CGI-I) scales.

At endpoint, using the clinical criterion for improvement, a similar percentage of patients responded to fluoxetine (68.4%, n = 13) and AC (57.9%, n = 11). There was no statistically significant difference between the groups with respect to the rate of responders.

This preliminary study suggests that patients with PMDD respond well to treatment with both fluoxetine and Vitex. However, fluoxetine was more effective for psychological symptoms while the extract diminished the physical symptoms.21

Ciotta et al. (2011) found that Vitex extract was effective in the treatment of PMDD. The effeicacy was comparable to fluoxetine. No side effects from Vitex treatment was recorded.22

References

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