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> ------------------------------

> Herbal Research Review

> Vitex agnus castus Clinical Monograph

> by Donald J. Brown, ND

> from Quarterly Review of Natural Medicine, Summer 1994

>

> c/o NPRC, Inc.

> Pioneer Building, Suite 205

> 600 First Avenue

> Seattle, WA 98104

>

> Vitex agnus castus, also known as chaste tree, is a shrub with

> finger-shaped leaves and slender violet flowers. Vitex agnus castus

> grows in creek beds and on river banks in valleys and lower foothills

> in the Mediterranean and Central Asia. The plant blooms in high summer

> and, after pollination, develops dark-brown to black fruit the size of

> a peppercorn. The fruit possess a pepper-like aroma and flavor. The

> ripe, dried fruit of Vitex agnus castus is the part of the plant used

> in medicinal preparations today.

>

> Historical Use

> The genus name Vitex is derived from the Latin " vitilium " which means

> plaiting. The flexible, but tough and hard branches were used for

> construction of wattle fences. Plinius, 1st Century A.D., has the

> earliest reference to the plant as Vitex. The species name Agnus

> castus originates from the Latin " castitas " (chastity) and the

> equating of the Greek " agnos " with the Latin " agnus " (lamb).

> Vitex agnus castus belonged to the official medicinal plants of

> antiquity and is mentioned in the works of Hippocrates, Dioscorides,

> and Theophrast. The first specific medicinal indications can be found

> in the writings of Hippocrates, 4th Century B.C. He recommends the

> plant for injuries, inflammation, and swelling of the spleen, and the

> leaves in wine for hemorrhages and the " passing of afterbirth. " In the

> " Corpus Hippocratum " he states:

> " If blood flows from the womb, let the woman drink dark red wine in

> which the leaves of the chaste tree have been steeped. A draft of

> chaste leaves in wine also serves to expel a chorion held fast in the

> womb. " Dioscorides attributed to the fruit a hot and astringent

> activity and recommended it for wild animal bites, swelling of the

> spleen, and for dropsy. Decoctions of the fruit and plant were used as

> sitz baths for diseases of the uterus.

> The English name for Vitex agnus castus, " chaste tree, " is derived

> from the belief that the plant would suppress libido in women taking

> it. In Greek cities, festivals in the honor of Demeter included a vow

> of chastity by the local women. The Catholic church in Europe

> developed a variation on this theme by placing the blossoms of the

> plant at the clothing of novice monks to supposedly suppress libido.

> It is interesting to note that another common name for Vitex agnus

> castus, " monk's pepper, " derived from the fact that monks in Southern

> Europe commonly used the fruit as a spice in their cooking.

>

> Constituents

> The majority of clinical studies with Vitex agnus castus (Vitex) have

> been performed with a tincture of the fruit. Most medical texts, as

> well as monographs in Europe, list the entire preparation as

> " medicinally active. " 1 This is an indication that the medical activity

> of the fruit is examined as a whole and that specific " active

> constituents " have not been individually isolated.

> The fruit of Vitex contains essential oils, iridoid glycosides, and

> flavonoids.2 Essential oils include limonene, 1,8 cineole, and

> sabinene.3 The primary flavonoids include castican, orientin, and

> isovitexin. The two iridoidglycosides isolated are agnuside and

> aucubin (see Figure 1).4 Agnuside serves as a reference material for

> quality control in the manufacture of Vitex extracts.

> One other report demonstrated delta-3-ketosteroids in the flowers and

> leaves of Vitex. The authors report (albeit in a somewhat vague

> manner) that this fraction of the leaves and flowers " probably "

> contained progesterone and 17-hydroxyprogesterone. Testosterone and

> epitestosterone were also presumed to be present.5 How this relates to

> the content of these substances in the fruit remains to be

> ascertained.

>

> The Menstrual Cycle: A Brief Overview

> The female menstrual cycle is controlled by a complex interplay

> between hormones of the hypothalamus, pituitary, and the ovaries (see

> Figure 2).6 The actual center of control is the hypothalamus, which

> produces a gonadotropin releasing hormone (GnRH) that stimulates the

> anterior pituitary to release the gonadotropins follicle stimulating

> hormone (FSH) and lutenizing hormone (LH). Pulsatile secretion of GnRH

> is necessary for the pituitary to respond with adequate production of

> LH and FSH. When there is continuous release or disturbance in

> pulsatile secretion, the stimulus for follicle maturation is absent,

> and sterility results.

> FSH is the primary hormone responsible for the maturation of follicles

> into fertile ova and the increased production of estrogen by the

> ovaries. LH causes release of the ovum, conversion of the follicle

> into the corpus luteum, and the subsequent production of progesterone.

> The timing of the release of these pituitary hormones, as well as

> estrogen and progesterone, during a normal menstrual cycle are

> illustrated in Figure 3. At midcycle, estrogen is at its peak and

> progesterone begins to rise. It is at this point that FSH levels

> decrease and LH levels surge to cause ovulation. In the ovary, the

> corpus luteum produces progesterone. This hormone ensures sufficient

> blood supply to the endometrium so that the fertilized ovum can

> establish itself in the uterus. If fertilization does not occur, the

> corpus luteum recedes, hormone production decreases, the endometrium

> is not sufficiently supplied with blood and menses occurs. FSH and LH

> levels decline until menses and beginning of a new menstrual cycle.

> A third hormone produced by the pituitary, prolactin, also plays an

> important role in the menstrual cycle. Prolactin is controlled by an

> inhibitory factor (PIF) produced by the hypothalamus (as opposed to

> FSH and LH which are controlled by stimulatory factors). Prolactin

> regulates the development of the mammary gland and milk secretion. In

> non-lactating women, it is critical that this hormone be in balance

> with FSH and LH. Increased production of prolactin can inhibit the

> maturation of follicles in the ovary and induce menstrual

> abnormalities and sterility. It is interesting to note that prolactin

> release is often stress-dependent. Stress reduction should always play

> a role in the management of menstrual abnormalities.

> It should also be noted that estrogen and progesterone formed by the

> ovary have a self-regulating effect on the hormones produced by the

> pituitary and hypothalamus via a feedback mechanism. Androgens, like

> testosterone, also play a part in this feedback mechanism. Disorders

> of other endocrine glands, such as the thyroid, adrenals, or pancreas,

> may also interfere with the normal functioning of this feedback

> mechanism.

>

> Corpus Luteum Insufficiency

> Corpus luteum insufficiency (also referred to as deficiency) is a

> manifestation of suboptimal ovarian function. In laboratory terms,

> corpus luteum insufficiency is usually defined as an abnormally low

> progesterone level three weeks after the onset of menstruation (serum

> progesterone below 10-12 ng/ml). This state is normal during puberty

> and at menopause. However, it is usually considered abnormal when

> occurring in women between the ages of 20 to 40 years.7

> Corpus luteum insufficiency points to abnormal formation of ovarian

> follicles, an abnormality that may be so pronounced that no secondary

> or tertiary follicles are produced with a resulting lack of ovulation

> (anovulation). Corpus luteum insufficiency also leads to a relative

> deficiency of progesterone. Insufficient levels of progesterone may

> also result in the formation of ovarian cysts.

> Corpus luteum insufficiency may result in a myriad of different

> menstrual abnormalities. Table 1 lists the most common clinical

> conditions in 1592 women diagnosed with corpus luteum insufficiency.

> Foremost are hypermenorrhea (heavy periods), polymenorrhea (abnormally

> frequent periods), and persistent anovulatory bleeding. It is

> interesting to note that secondary amenorrhea (lack of a period) may

> sometimes be observed in women with corpus luteum insufficiency.

> Disturbances of other hormones may also be associated with corpus

> luteum insufficiency. One study found hyperprolactinemia in 70% of

> cases.9 Also noted are an exaggerated response to the thyroid

> releasing hormone (TRH) test which is associated with manifest or

> latent hypothyroidism.

>

> How Does Vitex Work?

> According to Dr. Rudolf Fritz Weiss, Vitex acts on the

> diencephalohypophyseal system ­p; in other words, the hypothalamus and

> pituitary.

> Vitex increases LH production and mildly inhibits the release of FSH

> (see Figure 4). The result is a shift in the ratio of estrogen to

> progesterone, in favor of proges-terone. This is, in fact, a corpus

> luteum like hormone effect.10 The ability of Vitex to raise or

> modulate progesterone levels in the body is therefore an indirect

> effect and not a direct hormonal action.11 This is in contrast to

> other phytomedicines, like Black cohosh, frequently used in gynecology

> because of their direct binding of estrogen receptors

> ( " phyto-estrogens " ).12

> Vitex also modulates the secretion of prolactin from the pituitary

> gland. Early animal studies indicated an increase in lactation and

> enlargement of the mammary gland following administration of Vitex.13

> It is interesting to note that Vitex has been historically used as a

> lactagogue (substance to increase milk production) in lactating women

> with poor breast milk production. As we will note below, clinical

> studies have confirmed this effect.

> Current research with Vitex has indicated usefulness in

> hyperprolactinemia. In studies with rats, Vitex was shown to inhibit

> prolactin release by the pituitary gland ­p; particularly under

> stress. The mechanism of action appears to involve the ability of

> Vitex to directly bind dopamine receptors and subsequently inhibit

> prolactin release in the pituitary.14,15 Slight hyperprolactinemia is

> commonly associated with corpus luteum insufficiency.16

>

> Use of Vitex in Women's Healthcare

> The causes of menstrual disorders are multifaceted and can vary

> greatly in their manifestation. Frequently, therapeutic interventions

> must be used on a trial and error basis over the duration of a number

> of menstrual cycles to determine their efficacy. Nutritional

> interventions like vitamin B6, magnesium, and vitamin E, as well as

> phytomedicines like Black cohosh, Dong quai, and Evening Primrose oil,

> have all shown greater efficacy when used over time periods of several

> months. This reflects the gradual balancing effect that many of these

> interventions have on the female hormonal system. Vitex certainly fits

> this mold.

> The majority of clinical studies completed with Vitex have been

> non-controlled studies with large populations of female patients in

> European gynecology practices. Vitex, which has a Commission E

> Monograph in Germany, is frequently used in these practices as an

> initial intervention in a number of menstrual disorders including

> premenstrual syndrome, hypermenorrhea, polymenorrhea, anovulatory

> cycles, secondary amenorrhea, infertility, and hyperprolactinemia. As

> we will note, many of these cases can be linked to corpus luteum

> insufficiency. Vitex is also used in cases of poor lactation, uterine

> fibroids, and climacteric.

>

> Premenstrual Syndrome

> Premenstrual syndrome (PMS) is one of the most frequent complaints

> noted in gynecology practices. According to some estimates, 30 to 40%

> of menstruating women are affected by PMS.17 Table 2 lists the

> different categories for PMS and the symptoms associated with them.

> Two monitoring surveys of gynecology practices in Germany examined the

> effect of Vitex on 1542 women with a diagnosis of PMS.18 The mean age

> of the patients was 34.7 with a range of 13 to 62 years. Additional

> diagnoses noted with these patients included corpus luteum

> insufficiency (n = 1016) and uterine fibroids (n = 170). Patients were

> placed on a proprietary Vitex liquid extract known as " Agnolyt " and

> instructed to take 40 drops daily. The average duration of treatment

> was 166 days.

> The efficacy of treatment was assessed by both patients and their

> physicians. These assessments are depicted in Figures 5 and 6. In over

> 90% of the cases, symptoms were completely relieved with a report of

> side effects in only 2% of the patients (side effects are listed in

> Table 3). Only 17 of the 1542 women studied had to stop treatment due

> to side effects. Improvement in symptoms began after an average

> treatment duration of 25.3 days. 562 patients continued taking Agnolyt

> after completion of the monitoring period.

> Another study with 36 patients with a diagnosis of PMS used 40 drops

> of Vitex liquid extract ( " Agnolyt " ) daily over 3 cycles. A reduction

> was noted in physical symptoms (headaches, pressure and tenderness in

> the breasts, bloating, and fatigue), psychological changes (increased

> appetite, craving for sweets, nervousness/restlessness, anxiety,

> irritability, lack of concentration, depression, mood swings, and

> aggressiveness). Additionally, the interval of the luteal phase was

> normalized from an average of 5.4 days to 11.4 days and a diphasic

> cycle was established.19

>

> Abnormal Menstrual Cycles

> The first major clinical study on Vitex was published in 1954.

> Fifty-seven women suffering from a variety of menstrual disorders were

> given Vitex on a daily basis. Fifty patients developed a cycle in

> phase with menses while seven women did not respond. Of the fifty

> women, six women with secondary amenorrhea demonstrated one or more

> cyclic menstruations. Of nine patients with oligomenorrhea (scant or

> infrequent menstrual flow), six experienced a shortening of the

> menstrual interval and an increase in bleeding

> Most striking was a dramatic improvement in menstrual regularity among

> 40 patients with cystic hyperplasia (excessive proliferation of cells)

> of the endometrium (the mucous membrane lining the inner surface of

> the uterus). This condition is associated with a relative deficiency

> of progesterone and characterized by dysfunctional uterine bleeding.

> No side effects were observed with Vitex treatment.20

> An observational study with 126 women with menstrual disorders

> utilized 15 drops of Vitex liquid extract three times daily over

> several cycles. In 33 women suffering from polymenorrhea, the duration

> between periods lengthened from an average of 20.1 days to 26.3 days.

> In 58 patients with menorrhagia (excessive bleeding at the time of the

> period in amount or number of days), a statistically significant

> shortening of menses was achieved. Fourteen patients became pregnant

> during the study; among them were 3 women with primary infertility

> over 2, 3, and 8 years respectively, as well as 2 patients with

> secondary infertility over 4 and 15 years.21

> Twenty patients with secondary amenorrhea were admitted to a 6 month

> study using Vitex liquid extract at 40 drops daily. Laboratory

> monitoring of progesterone, FSH, LH, and pap smears were performed at

> pre-study, 3 months, and 6 months. At the end of the 6 month study,

> data was available on 15 patients. The onset of cycles with

> menstruation was observed with Vitex treatment in 10 out of the 15

> patients. The hormone values showed increased values for progesterone

> and LH, while FSH values either did not change or decreased

> slightly.22

> Propping and colleagues carried out two non-blind uncontrolled trials

> to study the effect of Vitex on corpus luteum function in a total of

> 48 infertile women of reproductive age between 23 and 39 years. The

> inclusion criteria were normal prolactin levels (below 20 ng/ml),

> normal results in the prolactin and thyroid stimulating hormone (TSH)

> stimulation tests and an abnormally low serum progesterone below 12.0

> ng/ml on the 20th day of the cycle. Treatment consisted of Vitex

> liquid extract, 40 drops daily, without any other medication for 3

> months.

> Forty-five women completed the studies (3 were excluded because of

> concurrent hormone use). The outcome of therapy was assessed by the

> normalization of the midluteal progesterone level and by correction

> (lengthening) of any preexisting shortening of the phases of the

> cycle. Treatment was deemed successful in 39 out of the 45 patients.

> Seven women became pregnant; in 25 patients, serum progesterone was

> restored to normal (> 12 ng/ml) and in 7 cases there was a trend

> toward normalization of progesterone levels.23,24

>

> Hyperprolactinemia

> As mentioned previously, Vitex has shown a modulating effect on

> prolactin. A double-blind, placebo-controlled study examined the

> effect of a proprietary Vitex preparation ( " Strotan " ) on 52 women with

> luteal phase defects due to latent hyperprolactinemia. The daily dose

> of the Vitex extract was 20 mg and the study lasted for three months.

> Hormonal analysis was performed at days 5-8 and day 20 of the

> menstrual cycle before and after three months of therapy. 37 cases

> were available for analysis (20 placebo and 17 Vitex) after 3 months

> of therapy. Prolactin release was significantly reduced in the Vitex

> group. Shortened luteal phases were normalized and deficits in

> progesterone production were normalized. No side effects were noted

> and two women in the Vitex group became pregnant.25

>

> Lactation

> As mentioned previously, Vitex has been used historically to increase

> milk production in lactating women ­p; another example of its

> modulating effect on prolactin levels. Only one controlled study

> exists examining the effect of Vitex in lactating women. Mohr found

> that lactating women with poor milk production treated with Vitex

> liquid extract were able to effectively increase production. Vitex

> often took several weeks to show results but was then used effectively

> over several months. This study and clinical use in Europe indicates

> the safety of Vitex for breast-fed infants.26

>

> Potential Indications

> Anecdotal clinical reports have indicated a potential use for Vitex in

> the management of climacteric (hot flushes) in the early stages of

> menopause.27 Other clinical observations include:

> · Uterine fibroids which are embedded into the muscle or are subserous

> may have their growth arrested by use of Vitex. Submucosal fibroids,

> however, are not likely to respond.

> · Mild cases of endometriosis for which progesterone therapy are

> indicated may respond to Vitex.

>

> How to Use Vitex

> Since the early 1950's, the standard Vitex extract used for clinical

> research and treatment in Europe has been an alcohol-based tincture of

> the fruits of the plant known as " Agnolyt. " 100 ml of the solution is

> standardized to contain 9 grams of the fruit. The recommended dosage

> is 40 drops with some liquid in the morning over several months

> without interruption. It is recommended that treatment with this

> extract be continued over several weeks after relief of symptoms is

> determined. The recent development of a solid extract equivalent of

> the tincture has allowed use by alcohol-sensitive women. The capsules

> which are 175 mg by weight, have a one-a-day recommendation also.

> It is important to note that Vitex is not a fast-acting medication. In

> cases of anovulatory cycles and infertility, treatment duration may be

> as long as 5-7 months before conception occurs. For secondary

> amenorrhea of more than two years duration, Vitex should be

> administered for at least 1.5 years. In other conditions mentioned,

> however, first indications of efficacy with Vitex are usually seen

> within one or two cycles. Extensive or complete freedom of symptoms

> usually occurs after 4 to 6 months of treatment.

>

> Is Vitex Safe?

> Human and animal studies have determined Vitex to be safe for most

> women of menstruating age. Vitex should not be used during pregnancy

> but is safe for use during lactation. Safety has not been determined

> in children. There are no known interactions with other drugs.

> Side effects noted in one large population study are listed in Table

> 3. Side effects noted in other clinical observations have included

> itching and an occasional rash. Again, these side effects are rare and

> have been noted in only 1-2 % of the patients monitored on Vitex. Some

> women also report that menstrual flow increases during Vitex

> treatment. This is often an indication of therapeutic efficacy.

>

> References

> 1. Monograph Agni casti fructus (Chaste tree fruits). Bundesanzeiger

> No. 90, May 15, 1985.

> 2. Agni cast fructus (chaste tree fruits). Commission E Monograph,

> December 2, 1992.

> 3. Kustrak, Kuftinec J & Blazevic N: The composition of the essential

> oil of Vitex agnus castus. Planta Medica 58 (Suppl l): A 681, 1992.

> 4. Gomaa CS: Flavonoids and iridoids from Vitex agnus castus. Planta

> Medica 33: 277, 1978.

> 5. Saden-Krehula M, Kustrak D & Blazevic N: Delta-3-ketosteroids in

> flowers and leaves of Vitex agnus castus. Planta Medica 56: 547, 1990.

> 6. Principles and Practice of Clinical Gynecology (Kase NG & Weingold,

> eds). John Wiley & Sons, New York, 1983.

> 7. Propping D, Katzorke T & Beliken L: Diagnosis and therapy of corpus

> luteum deficiency in general practice. Therapiewoche 38: 2992-3001,

> 1988.

> 8. Propping D, Bohnert KJ, et al: Vitex agnus-castus: Treatment of

> gynecological syndromes. Therapeutikon 5 (11): 581-5, 1991.

> 9. Muhlenstedt D, Wutke W & Schneider HPG: Short luteal phase and

> prolactin. Fertil Steril 373-4, 1977.

> 10. Weiss RF: Herbal Medicine. Ab Arcanum, Sweden, 1988.

> 11. Amann W: Removing an ostipation using Agnolyt. Ther Gegenew 104

> (9): 1263-5, 1965.

> 12. Reichert RG: Phyto-estrogens. Quart Rev Nat Med Spring 1994, pp.

> 27-33.

> 13. Amann W: Op. cit., 1965.

> 14. Sliutz G, Speiser P, et al: Agnus castus extracts inhibit

> prolactin secretion of rat pituitary cells. Horm Metab Res 25:

> 253-5,1993.

> 15. Jarry H, Leonhardt S & Wuttke W: Agnus Castus As Dopaminergous

> Effective Principle In Mastodynon N. Zeitschrift Phytother 12: 77-82,

> 1991.

> 16. Schneider HPG, Goeser R & Cirkel U: Prolactin and the inadequate

> corpus luteum. In: Lisuride and Other Dopamine Agonists. Raven Press,

> New York, 1983. pp. 113-120.

> 17. Lurie SR: The premenstrual syndrome. Obstet Gynecol 45 (4): 220-8,

> 1990.

> 18. Dittmar FW, Bohnert KJ, et al: Premenstrual syndrome: Treatment

> with a phytopharmaceutical. TW Gynakol 5(1): 60-68,1992.

> 19. Coeugniet E, Elek E & Kuhnast R: Premenstrual Syndrome (PMS) And

> Its Treatment. Arztezeitchr Naturheilverf 27 (9): 619-22, 1986.

> 20. Probst V & Roth OA: On A Plant Extract With A Hormone-like Effect.

> Dtsch Med Wschr 79 (35): 1271-4, 1954.

> 21. Bleier W: Phytotherapy in irregular menstrual cycles or bleeding

> periods and other gynecological disorders of endocrine origin.

> Zentralblatt Gynakol 81 (18): 701-9, 1959.

> 22. Losh EG & Kayser E: Diagnosis and Treatment of Dyshormonal

> Menstrual Periods In The General Practice. Gynakol Praxis 14 (3):

> 489-95, 1990.

> 23. Propping D & Katzorke T: Treatment of corpus luteum insufficiency.

> Zeits Allgemeinmedizin 63: 932-3, 1987.

> 24. Propping D, et al: Op. cit., 1988.

> 25. Milewicz A, Gejdel E, et al: Vitex agnus castus extract in the

> treatment of luteal phase defects due to hyperprolactinemia: Results

> of a randomized placebo-controlled double-blind study. Arzneim-Forsch

> Drug Res 43: 752-6, 1993.

> 26. Mohr H: Clinical investigations of means to increase lactation.

> Dtsch Med Wschr 79 (41): 1513-6, 1954.

> 27. Du Mee C: Vitex agnus castus . Aust J Med Herbalism 5 (3): 63-5,

> 1993.

-------------

Someone wrote:

> XXXX,

> Did you write this or did someone else? From my end it looks as if

> someone else wrote it and you just wrote " Thank you " but that doesn't

> make sense.

> I have a copy of the report plus a new version more geared to nurses

> which I will send to Complementary Therapies in Nursing and Midwifery

> as soon as Janina has sorted out a few queries regarding the

> references. I think that Barbara only wanted the original report to

> go to participants; however, it is being published in the Australian

> journal " Aromatherapy Today " in June.

> Both Janina's berry oil and some Turkish leaf oil were tested to see

> if they helped with menopause symptoms. They did. However, they are

> both powerful oils and should be used with care. Knowing Barbara's

> views on the matter, I don't want to say anything more for the time

> being, and I know she's away this week so can't ask what her views

> are on releasing information.

> All for now,

>

> > I heard that there has been a very positive report on the trial of

> > Vitex oil. Would anyone care to share it with this group? Are any

> > of the participants on this list and willing to share the results

> >with us? Thank you

------------

Someone wrote:

>

> RE: The sexual frustration. Seriously, I would try inhalations of e.o.

> vitex. It is a huge turn-off for men. One of the common names of this

> plant is Monk's Pepper or Chaste Tree because it is so effective at

> quelling male sexual desire that the herb was ground up and used as a

> seasoning in the monasteries.

>

> I have reports from many women who are using the oil for menopausal

> balancing that they must use it right after their mates leave the

> house so no remnant of aroma remains to irritate the man. I had two

> men bottle the two oils (0ne leaf, one berry) for a study. One had

> instant nausea and the other an instant headache. Now, bottling is

> pretty intensive inhalation--you could kick this way down for your

> client.

>

> Another testimonial came from a male colleague who did not believe the

> oil could be that effective a turn-off. He shall remain nameless, as

> his experiment was to try to masturbate while diffusing the oil. He

> found it impossible, and he said he really didn't care--just could not

> work up any excitement. That's probably more than anyone wants to

> know, but valuable information.

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