Subject: Vitex agnus castus LONG from TLFD

From: [email-masked] (Al Czap)
Date: 9 Oct 1995 19:23:08 GMT

The following is reprinted from the Townsend Letter for Doctors, by
permission.  Those with questions, or interest on the subject may call
360-385-6021 for more information.  If those reading this newsgroup find
the information interesting, the editor, Dr. Collin, has agreed to let me
post a number of articles each month from his magazine.  Let me know what
you think, flame me if you don't like the stuff.

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 ³vitilium² 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 ³castitas² (chastity) and the equating of the Greek ³agnos²
with the Latin ³agnus² (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 ³passing of afterbirth.² In the ³Corpus
Hippocratum² he states:
   ³If 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.²
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, ³chaste tree,² 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, ³monk¹s pepper,² 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 ³medicinally
active.²1 This is an indication that the medical activity of the fruit is
examined as a whole and that specific ³active constituents² 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 ³probably² 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 the 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  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 (³phyto-estrogens²).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  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 Women¹s 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 ³Agnolyt² 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 (³Agnolyt²) 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 (³Strotan²) 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  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 1950¹s, 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 ³Agnolyt.² 100 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.