Herb Of The Week - Vitex - Summary (LONG)

[Guest guest]

A summary on Vitex presented by The UIC/NIH Center for Botanical Dietary

Supplement Research in Women's Health.

This is long, and I left the LONG list of references in tact because I

think its important for folks to be able to follow up on the info and

also get an idea of some books they may want to get for their library

 

*Smile*

Chris (list mom)

 

Available Now

New Styles Of Perfume/Potion Bottles

http://www.alittleolfactory.com

 

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 

http://www.uic.edu/pharmacy/research/diet/content/scont_womens_health_ch

asteberry.htm

 

 

Summary

 

 

Vitex agnus castus, commonly known as the chaste tree, is a shrub with

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

native to the valleys and lower foothills of the Mediterranean and

Central Asia, but also is cultivated in the southern United States.

After blooming, the plant develops dark-brown to black fruit, which have

a pepper-like aroma and flavor. The ripe, dried fruit of Vitex agnus

castus is the part of the plant used commercially for the preparation of

extracts.

 

The medicinal use of Vitex began with Plinius (Pliney the Elder), in the

1st century A.D. The species name agnus castus originates from the Latin

" castitas " (chastity) and the Greek " agnos " with the Latin " agnus "

(lamb). Vitex agnus castus has a long history of use and was mentioned

in the works of Hippocrates, Dioscorides, and Paracelsus (Christie and

Walker 1997). In the 4th century B.C., Hippocrates recommended Vitex for

the treatment of injuries, inflammation, and swelling of the spleen, and

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

Dioscorides recommended it for the treatment of animal bites, swelling

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

also used as sitz baths for diseases of the uterus. The common names for

Vitex agnus castus including chaste tree or monk's pepper, were derived

from the belief that the plant suppresses libido in women, and from the

fact that European monks used the fruit as a cooking spice as well as to

suppress libido (Anon 1992).

 

 

Constituents

 

 

Many clinical studies with Vitex agnus castus have been performed using

a tincture of the dried fruit. Up to 2.0% of the fruit essential oil

contains bornyl acetate and 1,8-cineol as the primary constituents.

Flavonoids, iridoids and diterpenes represent major groups of secondary

constituents found in the fruit (Farnsworth 2002). Casticin, in

concentrations up to 0.2% is the major flavonoid, with chrysosplnetin,

chrysosplenol D, cynaroside, 5-hydroxy-3,4',6,7-tetramethoxyflavone,

6-hydroxykaempferol, isorhamnetin, luteolin, and luteolin 6-C-glycoside

derivatives being other compounds of this class. Major iridoids found

include agnuside (p-hydroxybenzoylaucubin, 0.0014%) and aucubin

(0.0013%). Diterpene constituents include vitexilactone (0.001-0.004%),

6ß,7ß-diacetoxy-13-hydroxylabda-8,14-diene, rotundifuran, vitexlabdines

A-D, and vitexlactam A.The fruit of Vitex contains essential oils,

iridoid glycosides, and flavonoids.(Farnsworth 2002) Essential oils

include limonene, 1,8 cineole, and sabinene. The primary flavonoids

include castican, orientin, and isovitexin. The two iridoidglycosides

isolated are agnuside and aucubin.

 

 

Menstrual Cycle Irregularities

 

 

The menstrual cycle is controlled by a complex interplay between

hormones of the hypothalamus, pituitary, and the ovaries (Kase and

Weingold 1983). The hypothalamus 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. 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. When there is continuous release

or disturbance in pulsatile secretion of GnRH, the stimulus for follicle

maturation is absent, and sterility results.

 

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

estrogen and progesterone, during a normal menstruation is cyclic. 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. Another 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 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 (Propping 1987). 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 (also referred to as deficiency) is thought

to be a result of suboptimal ovarian function (Propping 1987).

Clinically, 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, but is abnormal in women between

the ages of 20 to 40 years. Corpus luteum insufficiency points to

abnormal formation of ovarian follicles, and may lead to a relative

deficiency of progesterone. Corpus luteum insufficiency may result in a

number of different menstrual abnormalities, such as hypermenorrhea

(heavy periods), polymenorrhea (abnormally frequent periods), persistent

anovulatory bleeding, and occassionally secondary amenorrhea (lack of a

period). Hyperprolactinemia is also be associated with corpus luteum

insufficiency.

 

Currently, vitex is promoted for the symptomatic treatment of

gynecological disorders including corpus luteum insufficiency and

hyperprolactinemia (Merz et al., 1996; Milewicz et al., 1993),

premenstrual syndrome (PMS) (Loch et al., 2000; Meier and Hoberg 1999;

Lauritzen et al., 1997; Dittmar et al., 1992; Coeugniet et al., 1986;

Wuttke et al., 1995), menstrual irregularities (Blumenthal et al 1998,

IKS 1988, Loch et al., 1991; Loch, 1990), cyclic mastalgia (Halaska et

al., 1998; Kress et al., 1981; Kubista et al., 1983) and also to treat

hormonally-induced acne (Amann, 1975; Giss and Rothenberg 1968). It was

also used historically for treatment of endometrial hyperplasia and

secondary amenorrhea (Probst and Roth 1954); endocrine dependant

dermatoses (dermatitis dysmenorrhea symmetrica, acne vulgaris, eczema,

acne rosacea), hypermenorrhea (Bleier, 1959), infertility due to

hyperprolactinemia and luteal phase defect (Böhnert, 1990; Gerhard et

al., 1998); insufficient lactation (Mohr 1954). More recent clinical

data have indicated that vitex preparations may be used to treat fibroid

cysts and infertility, to stop miscarriages due to progesterone

insufficiency, to flush out the placenta after birth (McGuffin, et al.,

1997; Peirce, 1999) and also as a digestive aid, sedative,

anti-infective and for the treatment of hot flashes (Christie and

Walker, 1997).

 

 

Experimental Evidence

 

 

A variety of extracts of the fruit act as dopamine agonists in vitro and

in vivo. The binding of an ethanol extract of the fruit and various

extract fractions of the extract to the dopamine D2 and other receptors

were valuated both by radioligand binding studies and by superfusion

experiments (Meier et al 2000). The extract bound to the dopamine D2 and

opioid (µ and k subtype) receptors, however binding was not observed for

the histamine H1, benzodiazepine and OFQ receptor, or the serotonin

transporter. In superfusion experiments, an aqueous fraction of a

methanol extract inhibited the release of acetylcholine in a

concentration-dependent manner. In addition, the D2 receptor antagonist

spiperone antagonised the effect of the extract suggesting a

dopaminergic action mediated by D2 receptor activation (Christoffel et

al 1999). A number of fruit extracts and chromatographic fractions have

been tested in vitro for their ability to displace receptor binding

ligands in the m-, k-, d-opioid receptors (Berger 1998; Brugisser et al

1999; Meier et al 2000). The extract and a butanol, chloroform and

hexane fraction bound to the m- and k-receptors, while the aqueous

extract was more active in the d-opioid receptor. No binding in the

orphan opioid receptor was noted.

 

Several groups have demonstrated that extracts of chaste berry bind to

the estrogen receptor and have weak estrogenic effects, suggesting that

chaste berry may also affect the estrogen/progesterone balance (Berger

1998, Eagon et al 1997, Jarry et al 2000, Burdette et al 2003).

Incubation of recombinant human estrogen receptors expressed in yeast

cells with 50-200 µg/ml of a fruit extract, resulted in the binding of

the extract to ER and a dose-dependent increase in the production of

ß-galactosidase, indicating a weak estrogenic effect (Berger 1998). A

fruit extract dose-dependently bound to both ER isotypes, but binding

appeared to be more selective for ERß than ERa (Jarry et al 2000). The

extract also dose-dependently inhibited the secretion of progesterone

from human granulosa cells (hGLC) (Jarry et al 2000), an effect that is

mediated by ER, as it can be blocked by tamoxifen. Futhermore, one in

vivo study has shown that treatment of ovariectomized rats with an

undefined extract of the fruit (no dose given) increased uterine growth,

and the expression of uterine c-myc mRNA levels and liver ceruloplasm

mRNA levels, indicating an estrogenic effect (Eagon et al 1997).

 

A methanol extract of the fruit bound to both ERa and ERb, and induced

the expression of estrogen-dependent genes, progesterone receptor (PR),

and pS2 (presenelin-2) in Ishikawa cells (Liu et al 2000). Significant

binding affinity for both ERa and ERb, with a median inhibitory

concentration of 46.3 mg/ml and 64.0 mg/ml, respectively, and the

affinity for ERa and ERb was not significantly different (Liu et al

2001). Based on bioassay-guided isolation, the " estrogenic " component

from the fruit extract was identified as linoleic acid (LA), which also

bound to ERa and ERb (Burdette et al 2003). Similar to the extract, LA

also induced of the expression of the progesterone receptor (PR) mRNA in

Ishikawa cells, at a concentration of 1 µg/ml, indicating that binding

produced a biological estrogenic effect in vitro. In addition, low

concentrations of the extract or LA (10 mg/ml) up-regulate the

expression of ERb mRNA in the ER+ hormone-dependant T47D:A18 cell line,

a further indication of estrogenic activity (Burdette et al 2003).

 

 

Clinical Studies

 

 

Over 32 clinical trials have assessed the safety and efficacy of various

fruit extracts or tinctures (53-70% ethanol) for the treatment of acne,

corpus luteum insufficiency, cyclic breast pain, hyperprolactinemia,

menopausal symptoms, increasing lactation, premenstrual syndrome,

uterine bleeding disorders, and miscellaneous menstrual irregularities.

A review of all of the clinical data has been recently published by the

American Herbal Pharmacopoeia (AHP 2001). Most of the investigations are

open, uncontrolled studies investigating its effects on menstrual cycle

abnormalities or PMS. One double-blind placebo-controlled (DBPC) study

investigated a fruit extract in treatment of luteal phase defects due to

hyperprolactinemia (Milewicz et al., 1993). Two other DBPC studies

investigated a fruit extracts in treatment of PMS (Lauritzen et al.,

1997; Turner and Mills, 1993).

 

During the past 50 years at least 17 clinical studies have assessed the

effects of extracts of the fruit on a variety of menstrual cycle

disorders including amenorrhea, oligomenorrhea, polymenorrhea, corpus

luteum insufficiency and infertility (AHP 2001). Two double-blind

placebo-controlled clinical trials and several observational studies

have investigated the effect of various fruit extracts on corpus luteal

phase disfunction and infertility (Milewicz et al 1993, Gerhard et al

1998, Propping et al 1988). The products tested were all ethanol

extracts (53-70% ethanol), and the dose used in these investigations was

20 drops twice daily, 15 drops three times daily, 30 drops twice daily

or one to two tablets or capsules daily. A randomized, double-blind,

placebo-controlled trial assessed the efficacy of a dried fruit extract

on infertility (Milewicz et al 1993). The aim of the study was to

determine if elevated pituitary prolactin could be reduced and if

deficits in luteal phase length and luteal phase progesterone synthesis

was normalized. Blood for hormone analysis was taken at days 5-8 and day

20 of the menstrual cycle, before and after three months of therapy.

Latent hyperprolactinaemia was analyzed by monitoring the prolactin

release 15 and 30 min after intravenous administration of 200 mg of

thyroid hormone. Thirty-seven cases (placebo: n = 20, treatment: n = 17)

were included in the statistical analysis. After 3 months of treatment,

prolactin release was reduced, a significant increase in the length of

the luteal phase (10.5 days; P < 0.05) was observed and deficits in

luteal progesterone synthesis were eliminated. These changes only

occurred in the treatment group. All other hormonal parameters did not

change with the exception of 17 beta-estradiol, which increased during

the luteal phase was observed in the treatment group. The overall length

of the menstrual cycles did not change, suggesting that there was a

corresponding shortening of the follicular phase. Two women in the

extract group became pregnant by the end of the study. No side effects

were reported. In the second randomized, double-blind,

placebo-controlled the efficacy of a fruit extract was assessed in 96

infertile women (Gerhard et al 1998). The outcome criteria measured

included pregnancy or menstrual bleeding in women with secondary

amenorrhea or improved luteal hormone concentrations. The women were

administered 30 drops twice daily for three months. Sixty-six women

completed the study, and positive outcomes were observed in 47% of women

overall, with 61% in the treatment group and 38% in the placebo group,

however these results did not reach statistical significance (P =

0.069). In the women with amenorrhea or luteal phase dysfunction,

pregnancy resulted twice as often in the treatment group 15% versus the

placebo group (7%), however no statistical analysis was reported.

 

Two larger post-marketing trials, involving 479 women assessed the

safety and efficacy of fruit extracts for the treatment of

oligomenorrhea or polymenorrhea (Mergner 1992). The women were treated

with 30 drops of the extract twice daily and the outcome measured was

the bleeding free interval. An increase in the bleeding free interval

was observed 35 days in 187/287 women receiving treatment for

olgiomenorrhea and 26 days in 139/192 women receiving treatment for

polymenorrhea.

 

Ten open (uncontrolled) (Fersizogliou 1989; Fikentscher 1977; Fournier

and Grumbrecht 1987; Gobel 1985; Gregl 1985; Krapfl 1988; Kress and

Thanner 1981; Roeder 1976; Opitz and Liebl 1980; Schwalbe 1979) and

three randomized controlled clinical trials (Halaska et al 1999; Kubista

et al 1986; Wuttke et al 1997) have assessed the safety and efficacy of

extracts of the fruit for the treatment of cyclic mastalgia.

 

A randomized, double-blind, placebo-controlled clinical trial involving

104 women with cyclic breast pain (at least 3 cycles) assessed the

effects of a preparation of the fruit (10 g tincture containing 2 g of

crude drug in 53% ethanol-VAC) for the treatment of cyclic breast pain

(Wuttke et al 1997). The patients were treated with placebo, VAC

solution (30 drops twice daily), or VAC tablets (one tablet twice daily)

for 3 cycles. Patients assessed the intensity of breast pain once per

cycle using a Visual Analog Scale and also recorded the presence of

menstrual bleeding and the intensity of pain in a diary. Prolactin

levels were also measured during the premenstrual week of cycles 1 and

3. At the end of the third cycle of treatment, a significant reduction

in breast pain was observed in the treated patients as compared with

placebo (VAC solution, p = 0.006; VAC tablets, p= 0.007). A significant

decrease in prolactin levels (P = 0.039) was also observed in the

treatment group as compared with placebo. A second randomized,

placebo-controlled, double-blind, with a similar design compared VAC

solution (30 drops twice daily for 3 cycles) with placebo for the

treatment of 100 women (50 per group) with breast pain at least 5 days

prior to menses in the last cycle before the study (Halaska et al 1999).

The study was designed as double-blind, placebo controlled treatment

phase lasted 3 menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or

placebo. Mastalgia during at least 5 days of the cycle before the

treatment was the strict inclusion condition. For assessment of the

efficacy visual analogue scale was used. Altogether 97 patients were

included into the statistical analysis (VACS: n = 48, placebo: n = 49).

Intensity of breast pain diminished quicker with VACS group. The study

design and duration was similar to that of Wuttke et al (1997). The

results of this study showed a decrease in the VAS scores in both the

treatment and the placebo groups. However, as compared with the placebo,

the treatment group had significantly lower VAS values at the end of

each cycle (P = 0.018, 0.006, and 0.064 for cycles 1,2, and 3,

respectively).

 

In a randomized, placebo-controlled trial the effects of VAC solution

and placebo (double-blind) were compared with that of gestagen

(Lynestrenol; uncontrolled) in 160 women with mastalgia (Kubista et al

1986). A complete remission or improvement of symptoms was reported in

82.1%, 74.5%, and 36.8% of the patients in the gestagen, chaste tree,

and placebo groups, respectively. The difference in effect between

treatment groups and placebo was significant (P < 0.01). No significant

difference was found between the two active groups.

 

Premenstrual syndrome (PMS) refers to the regular occurrence of

affective symptoms such as depressive moods, irritability, anxiety,

confusion, and social withdrawal, as well as somatic symptoms including

breast tenderness or heaviness and breast pain (mastalgia), abdominal

bloating, cravings, fatigue, and headache. The syndrome affects

approximately 30 to 40% of menstruating women and is one of the most

frequent complaints noted in gynecology practices.17 Twelve clinical

trials have assessed the efficacy of extracts of the fruit for the

symptomatic treatment of PMS (Berger et al 2000; Coeugniet et al 1986;

Dittmar et al 1992; Feldmann et al 1990; Lauritzen et al 1997; Liebl

1992; Loch et al 1991; Loch et al 2000; Meyl 1991; Peters-Welte and

Albrecht 1994; Schellenberg et al 2001; Turner and Mills 1993). Of these

studies, only three were randomized controlled trials and two were

double-blinded (Lauritzen et al 1997; Schellenberg et al 2001; Turner

and Mills 1993). A positive placebo effect was ruled out by one

randomized placebo-controlled, GCP-compliant study (Schellenberg and

others 2001). In this study, patients with PMS were given either a

chaste tree fruit extract (n = 86; Z 440; 1 tablet daily) or a placebo

(n = 84) during 3 consecutive menstrual cycles. Diagnosis was made

according to the Diagnostic and Statistical Manual for Mental Disorders

(DSM-III). The main efficacy variable was change from baseline to

endpoint (end of cycle 3) in the patient's self assessment (PSA) of 6

PMS symptoms (irritability, mood alteration, anger, headache, breast

fullness, and other symptoms including bloating). A secondary efficacy

variable was change in Clinical Global Impressions (CGI) score for

factors: severity of condition, global improvement, and risk/benefit.

Mean improvement in PSA was significantly greater in the treatment group

compared to placebo (P <0.001). CGI scores for each of the 3 factors

also revealed significant superiority of the treatment relative to

placebo (P< 0.001). Responder rates (> 50% reduction in symptoms were

52% and 24% for treatment and placebo, respectively. Adverse events

reported included active: treatment, n = 4: acne, multiple abscesses,

inter-menstrual bleeding, urticaria; placebo, n = 3 acne, early

menstrual period, gastric upset).

 

A randomized, double-blind, placebo-controlled trial involving 217 women

with self-diagnosed PMS according to a modified version of the Menstrual

Distress Questionnaire (MDQ, a rating scale covering most of the

important symptoms) assessed the efficacy of the fruit for the

management of PMS symptoms (Turner and Mills 1993). Subjects were

treated with either a powder of the dried fruit (300 mg tablets; 2

tablets 3 times daily; n = 105) or a soy-based placebo (n = 112) for a

period of 3 months, after which they all completed the modified MMDQ

again. Other than a statistically significant difference in effect

between the active powder and the soy placebo for the symptom of " feel

jittery and restless " (P = 0.05), no other statistically significant

results were reported. Unfortunately, soy was a poor choice as a

placebo, as it is not considered to be biologically inert.

 

A multi-center, randomized, double-blind, controlled clinical trial

compared the activity of a dried ethanol extract of the fruit with that

of pyridoxine (vitamin B6) treatment of women with PMS (Lauritzen et al

1997). The intent-to-treat population included 127 women: 61 women were

given one capsule of extract plus one placebo capsule daily for 3

cycles, while 66 were given one capsule of placebo twice daily on days

1-15 of their cycle, followed by one capsule (100 mg) of pyridoxine

twice daily on days 16-35. Therapeutic response was assessed using the

Premenstrual Tension Syndrome (PMTS) scale, the Clinical Global

Impressions scale, and by recording 6 characteristic symptoms of PMS

(breast tenderness, edema, inner tension, headache, constipation, and

depression). Therapeutic efficacy was assessed by both patients and

physicians, at the end of the trial. Initial mean PMTS scores were

higher in the chaste tree group (15.2) compared to the pyridoxine group

(11.9). By the end of therapy, the mean absolute change in PMTS score in

each group was 5.1, representing a reduction of 10.1 and 6.8,

respectively, for the chaste tree and pyridoxine groups (P < 0.038, both

groups, 95% CI -6.4261 to - 0.1670). Therefore no difference could be

found between the two treatment groups. The CGI scale showed a 77.1%

(chaste berry) and 60.6% (pyridoxine) of patients showed improvement.

Adverse events were rare, but included gastrointestinal complaints, skin

reactions and transient headache.

 

One randomized, double-blind controlled trial examined the effect of the

fruit in lactating women (Mohr 1954). Women were treated with the fruit

extract (15 drops three times daily) or Vitamin B1 (no dose stated) or

control (not stated). Lactation in all groups increased up to day 10

postpartum, from days 10 through 20 a decrease in lactation was observed

in the control and Vitamin B1 groups. Lactation in the group treated

with the fruit extract increased or was maintained up to day 20.

Lactating women with poor milk production treated with a fruit extract

were able to effectively increase production. No statistical analyses

were performed.

 

 

Dose

 

 

The standard dose of vitex is 20 mg (capsule or tablet) or 40 drops of

the tincture with some liquid in the morning for at least 3 cycles. It

is recommended that treatment be continued for several weeks after

relief of symptoms is observed. It is important to note that Vitex

treatments for cases of anovulatory cycles and infertility, may be as

long as 5-7 months before conception occurs. 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 medications. Adverse events are limited to

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,

thus women with heavy menstrual flow should be warned about this

possibility.

 

 

References

 

 

* Abel G, Goez C, Wolf H. 1994 Vitex. In: Hänsel R, Keller K,

Rimpler H, Schneider G editors. Hagers Handbuch der Pharmazeutischen

Praxis. Volume 6 (P-Z). Berlin: Springer. P 1183-96.

 

 

* AHP = Upton R, ed. Chaste tree fruit, American herbal

pharmacopoeia and therapeutic compendium, Santa Cruz, CA, American

Herbal Pharmacopoeia, 2001.

 

 

* Amann W. Acne vulgaris and Agnus castus (Agnolyt®). Zeitschrift

für Allgemeinmedizin, 1975, 51:1645-1648.

 

 

* Amann W. Amenorrhoe-Günstige Wirkung von Agnus castus (Agnolyt®)

auf Amenorrhoe. Zeitschrift für Allgemeinmedizin, 1982, 58:228-231.

 

 

* Anon. Monograph Agni casti fructus (Chaste tree fruits).

Bundesanzeiger No. 90, May 15,1985. Agni cast fructus (chaste tree

fruits). Commission E Monograph, December 2, 1992.

 

 

* Berger D. Vitex agnus-castus: Safety and efficacy in the

treatment of the premenstrual syndrome, principles and mechanisms of

action of a newly developed extract [thesis]. Basel, Switzerland:

University of Basel, 1998. Available from: College of Philosophy and

Natural Sciences, University of Basel.

 

 

* Berger D et al. Efficacy of Vitex agnus-castus L. extract Ze 440

in patients with premenstrual syndrome (PMS). Archive of Gynecology and

Obstetrics, 2000, 264:150-153.

 

 

* Bleier W. Phytotherapy in irregular menstrual cycles or bleeding

periods and other gynecoloigical disorders of endocrine origin.

Zentralblatt für Gynäkologie, 1959, 81(18):701-9.

 

 

* Blumenthal M et al. The Complete German Commission E Monographs:

Therapeutic Guide to Herbal Medicines, Austin, TX, American Botanical

Council, 1998.

 

 

* Brugisser R, Burkard W, Simmen U, Schaffner W. 1999.

Untersuchungen an Opioid-Rezeptoren mit Vitex agnus-castus L.

Zeitschrift für Phytotherapie, 1999, 20:154.

 

 

* Burdette J et al. Estrogenic activity of Vitex agnus-castus and

Linoleic Acid. Phytomedicine, 2003 (in press).

 

 

* Christie S, Walker AF. Vitex agnus-castus L.: (1) A review of

its traditional and modern therapeutic use: (2) Current use from a

survey of practitioners. European Journal of Herbal Medicine, 1997,

3(3):29-45.

 

 

* Christoffel V et al. Prolactin inhibiting dopaminergic activity

of diterpenes from Vitex agnus-castus. In: Loew D, Blume H, Dingermann

TH eds. Phytopharmaka V, Forschung und klinische Anwendung. Darmstadt:

Steinkopff. 1999.

 

 

* Chuong CJ, Coulam CB. 1988. Current views and the beta-endorphin

hypothesis. In: Gise LH, Kase NG, Berkowith RL editors. The premenstrual

syndrome. New York: Churchill Livingstone. P 75-95.

 

 

* Chuong CJ, Coulam CB, Kao, PC. Neuropeptide levels in

premenstrual syndrome. Fertility and Sterility, 1985, 44:760-764.

 

 

* Coeugniet E, Elek E, Kühnast R. Das prämenstruelle Syndrom (PMS)

und seine Behandlung. Ärztezeitdchrift für Naturaheilverf 1986,

27:619-22.

 

 

* Dittmar FW, Böhnert KJ, Peeters M, Albrecht M, Lamentz M,

Schmidt U. 1992. Prämenstruelles Syndrom: Behandlung mit einem

Phytopharmakon. TW Gynäkologie 5:60-68.

 

 

* Eagon CL, Elm MS, Teepe AG, Eagon PK. 1997. Medicinal

botanicals: estrogenicity in rat uterus and liver. Proceedings of the

American Association of Cancer Research, 1997, 38:193.

 

 

* Farnsworth NR, ed. NAPRALERT database. Chicago, University of

Illinois at Chicago, IL, November 30, 2002 production (an online

database available directly through the University of Illinois at

Chicago or through the Scientific and Technical Network [sTN] of

Chemical Abstracts Services).

 

 

* Feldman HU et al. Therapie bei Gelbkörperschwäche bzw.

Prämenstruellem Syndrom mit Vitex-agnus-castus-Tinktur. Gyne 1990,

11:421-5.

 

 

* Fersizoglou NE. Hormonale und thermographische Veränderungen

unter konserativer Therapie der Mastophathie. Vergleich von Danazol,

Tamoxifen, Lisurid, Lynestrenol und einem Phytopharmakon [dissertation].

Heidelberg: Universitäts-Frauenklinik Heidelberg, 1989. Available from:

Universtiy of Fraunklinik Heidelberg.

 

 

* Fikentscher H. Ätiologie, Diagnose und Therapie der Mastopathie

und Mastodynie. Erfahungren bei der Behandlung mit Mastodynon®.

Medizinische Klinik, 1977, 72:1327-1330.

 

 

* Fournier D, Grumbrecht C. 1987. Behandlung der Mastopathie,

Mastodynie und des prämenstruellen Syndroms. Verleich medikamentöser

Behandlung zu unbehandelten Kontrollen. Therapiewoche 37(5):430-4.

 

 

* Gerhard I, Patek A, Monga B, Blank A, Gorkow C. Mastodynon bei

weiblicher Sterilität: Randomisierte plazebokontrollierte klinische

Doppelblindstudie. Forschritte Komplemen, 1998, 20:272-278.

 

 

* Giss G, Rothenberg W. Phytotherapeutische Behandlung der Akne.

Zeitschrift für Haut Geschl Krankheiten 1968, 43:645-647.

 

 

* Gregl A. Klinik und Therapie der Mastodynie. Die Medizinische

Welt 1985, 36:242-6

 

 

* Halaska M, Beles P, Gorkow C, Sieder C. 1999. Treatment of

cyclical mastalgia with a solution containing an extract of Vitex

agnus-castus: recent results of a placebo-controlled double-blind study.

Breast 8:175-81.

 

 

* Hoberg E, Meier B, Sticher O. Quantitative high performance

liquid chromatography analysis of casticin in the fruits of Vitex

agnus-castus. Pharmaceutical Biology, 2001, 39:57-61.

 

 

* Hoberg E et al. Diterpenoids from the fruits of Vitex

agnus-castus. Phytochemistry, 1999, 52(8):1555-1558.

 

 

* Jarry H et al. In vitro prolactin but not LH and FSH release is

inhibited by compounds in extracts of Angus castus: direct evidence for

a dopaminergic principle by the dopamine receptor assay. Experimental

and Clinical Endocrinolology, 1994, 102: 448-454.

 

 

* Jarry H et al. Diterpenes isolated from Vitex agnus castus BNO

1095 inhibit prolactin secretion via specific interaction with dopamine

D2 receptors in the pituitary [abstract]. 10. Jahrestagung der

Gesellschaft für Phytotherapie; 1999 Nov 11-13; Münster, Verl Sci Data

Supp. P 3-4, 1999.

 

 

* Jarry H et al. Erste Hinweise Für Estrogen-wirkende Inhaltstoffe

im Vitex agnus-castus: Effeckte auf die in-vitro Steroidsekretion von

humanen Granulosa-und porcinen Luteal-Zellen. J Menopause 2000, 4:12-13

(abstract).

 

 

* Jarry H et al. Agnus castus als dopaminerges Wirkprinzip in

Mastodynon. Zeitschrift für Phytotherapie, 1991, 12:77-82.

 

 

* Kase NG, Weingold, eds., Principles and Practice of Clinical

Gynecology. John Wiley & Sons, New York, 1983.

 

 

* Krapfl E. Prospektiv randomisierte klinische Therapiestudie zum

Wirksamkeitsvergleich von Orgametril®, einem 19 Nor-Testosteron-Derivat,

versus Mastodynon®, einem Agnus Castus-Haltigen alkoholischen

Pflanzenextrakt, bei schmerzhafter Mastopathie [dissertation].

Heidelberg: Universitäts-Frauenklinik Heidelberg. 150 p, 1988. Available

from: University Frauenklinik Heidelberg.

 

 

* Kress D, Thanner E. Behandlund der mastopathie: möglichst

risikoarm. Medizinische Klinik, 1981, 76:566-567.

 

 

* Kubista E, Müller G, Spona J. Behandlung der Mastopathie mit

zyklischer Mastodynie: Klinische Ergebnisse und Hormonprofile.

Gynäkologie Rund 1986, 26:65-79.

 

 

* Lauritzen C et al. Treatment of premenstrual tension syndrome

with Vitex agnus-castus; contolled double-blind study versus pyridoxine.

Phytomedicine, 1997, 4:183-189.

 

 

* Li SH. Studies on the chemical and biological constituents of

three Taxaceae plants, Vitex agnus-castus and Isodon xerophilus. Ph.D.

Dissertation, Kuming, PRC, Kuming Institute of Botany, Chinese Academy

of Science, 2001, pp 122-143. (in Chinese)

 

 

* Li SH, et al. Vitexlactam A, a novel labdane diterpenes lactam

from the fruits of Vitex agnus castus. Tetrahedron Letters, 2002,

43:5131-5134.

 

 

* Liebl A. Behandlung des prämenstruellen Syndroms:

Agnus-castus-haltiges Kombinationsarzneimittel im Test. TW Gynäkologie,

1992, 5:147-154.

 

 

* Liu J et al. Evaluation of estrogenic activity of plant extracts

for the potential treatment of menopausal symptoms. Journal of

Agricultural and Food Chemistry, 2001, 49: 2472-2479, 2001.

 

 

* Loch EG et al. Die Behandlung von Blutungsstörungen mit

Vitex-agnus-castus-Tinktur. Der Frauen 1991, 32:867-870.

 

 

* Loch EG, Kaiser E. Diagnostik und Therapie dyshormonaler

Blutungen in der Praxis. Gynäkologie Praxis, 1990, 14:489-495.

 

 

* Loch EG, Selle H, Bobbitz N. Treatment of premenstrual syndrome

with a phytopharmaceutical formulation containing Vitex ag nus-castus.

Journal of Women's Health and Gender Based Medicine 2000, 9:315-20.

 

 

* Meier B et al. Pharmacological activities of Vitex agnus-castus

extracts in vitro. Phytomedicine, 2000, 7:373-81.

 

 

* Meier B, Hoberg E. Agni-casti fructus. New Findings on quality

and effectiveness. Zeitschrift für Phytotherpie 1999, 20(3):140-58.

 

 

* Mergner R. Zyklusstörungen: Therapie mit einem Vitex

-agnus-castus-haltigen Kombinationsarzneimittel. Der Kassenarzt 1992,

7:51-60.

 

 

* Merz PG, Gorkow C, Schroedter A, Rietborch S, Sieder C, Loew D,

Dericks-Tan JSE, Taubert HD. 1996. The effects of a special agnus castus

extract (BP1095E1) on prolactin secretion in healthy male subjects.

Experimental Clinical Endocrinology Diab 1996, 104:447-53.

 

 

* Meyl C. Therapie des prämenstruellen Syndroms. Vergleich einer

kombinierten Behandlung von Mastodynon und Vitamin E mit der Vitamin

E-Monotherapie. Therapeutikon 1991, 5:518-525.

 

 

* Milewicz A et al. Vitex agnus-castus Extrakt zur Behandlung von

Regeltempoanomalien infolge latenter Hyperprolaktinämie: Ergebnisse

einer randomisierten Plazebo-kontrollierten Doppelblindstudie.

Arzneimittel-Forschung, 1993, 43:752-756.

 

 

* Mohr H. Clinical investigations of means to increase lactation.

Deutsche Medizin Wochenschrift 1954, 79:1513-1516.

 

 

* Neumann-Kuhnelt B et al. Investigations of possible effects of

the phytotherapeutic agent agnus-castus on the follicular and corpus

luteum phases. Human Reproduction, 1993, 8(Suppl 1):110.

 

 

* Opitz G, Liebl A. Zur konservativen Behandlung der Mastopathie

mit Mastodynon. Ther Gegen 1980, 119(7):804-9.

 

 

* Peters-Welte C, Albrecht M. Regeltempostörungen und PMS: Vitex

agnus-castus in einer Anwendungsbeobachtung. TW Gynäkologie, 1994, 7:49.

 

 

* Probst V, Roth O. A vegetable extract with hormone-like effect.

Deutsche Medizin Wochenschrift 1954, 79:1271-4.

 

 

* Propping D, Katzorke T. 1987. Behandlung der Gelbkörperschwäche

in der Praxis. Therapiewoche 38:2992-3001.

 

 

* Schellenberg R, Kunze G, Pfaff ER, Massing A, Wältner H,

Kirschbaum M, Boedecker RH, Dudeck J. Pre-menstrual syndrome treatment

with agnus castus extract: a randomised, placebo-controlled study.

British Medical Journal, 2001, 322:134-7.

 

 

* Schwalbe E. Ein Geitrag zur Behandlung der Mastodynie.

Zeitschrift für Allgemeinmedizin, 1979, 55(22):1239-42.

 

 

* Sliutz G, Speiser P, Schultz A, Spona J, Zeillinger R. Agnus

castus extracts inhibit prolactin secretion of rat pituitary cells.

Hormorne Metabolism Research, 1993, 25:253-5.

 

 

* Turner S, Mills S. A double-blind clinical trial on a herbal

remedy for premenstrual syndrome: a case study. Complementary Therapy in

Medicine, 1993 1:73-7.

 

 

* Tyler VE, Herbs of choice. Binghampton, NY, Pharmaceutical

Products Press, The Haworth Press, Inc, 1994, pp137.

 

 

* Winterhoff H, Münster C, Gorkow C. Die Hemmung der Laktation bei

Ratten als indirekter Beweis für die Senkung von Prolaktin durch Agnus

castus. Zeitschrift für Phytotherapie, 1991, 12:175-179.

 

 

* Wuttke W, Gorkow C, Jarry H. 1995. Dopaminergic compounds in

Vitex agnus castus. In: Lowe D, Rietbrock N editors. Phytopharmaka in

Forschung und klinischer Anwendung. Darmstadt: Steinkopff. p S81-91.

 

 

* Wuttke W, Solitt G, Gorkow C, Sieder C. 1997. Behandlung

zyklusabhängiger Brustschmerzen mit einem Agnus-castus-haltigen

Anzneimittel. Ergebnisse einer randomisierten plazebokontrollierten

Doppelblindstudie. Geb Frauenh 57(10):569-74.