THE
STANDARD
(none)
Volume 4, No. 2
Female Cycle Difficulties
Non-invasive Diagnosis and Natural Luteal phase
Thomas G. Guilliams Ph.D.
The menstrual cycle is one of the most exquisite displays of biological
rhythm. It is a fascinating combination of positive and negative feedback
controls involving the hypothalamus, pituitary, thyroid, adrenals, ovaries and
uterus. Unfortunately, for various reasons, the rhythm is often disrupted and
difficulties arise. This review will look at some of the more common
disruptions and difficulties with the menstrual cycle such as amenorrhea,
anovulation, luteal phase deficiencies, abnormal uterine bleeding and PMS. This
review focuses on several trends and diagnostic techniques used to distinguish
if the patient can be treated with natural remedies, what those remedies are,
and the research supporting those remedies. It will be clear that with the
proper diagnosis and treatment, natural medicine is well suited to set the
rhythm back in motion.
The normal menstrual cycle is a cascade of hormonal events. Signals received
and sent by both the brain and the uterus orchestrate the presentation of a
fully functional egg and the preparation of the endometrial lining of the
uterus to implant the egg, if and when it is fertilized. The cycle is typically
broken into three phases: the follicular, the ovulatory, and the luteal phase.
Let us briefly look at what occurs at each of these phases (Fig 1).
Click on image
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Fig 1 The Three Phases of the Menstral Cycle: Follicular, Ovulatory, and Luteal Phase
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The follicular phase begins with the first day of menses when estradiol and
progesterone levels are very low. The reduced levels of ovarian hormones stimulate
the pituitary secretion of follicle stimulating hormone (FSH), while at the same
time allow for menstruation. FSH levels then stimulate a cohort of follicles in one
of the ovaries to develop, leading to the maturation of one follicle containing a
mature egg. The maturing follicle begins to secrete estradiol, stimulating the
growth of the endometrium. As estradiol levels rise, FSH levels begin to drop
preparing for the ovulatory spikes in the next phase. In a typical 28-30 day cycle,
the follicular phase is 12-14 days (menstruation occurring on the first 4-7 days of
this phase)
Ovulation occurs 24-48 hours after a sudden release of leutinizing hormone (LH),
FSH from the pituitary gland, triggered by rising estradiol levels. This is often
called the pre-ovulatory spike. The result is the rupture of the mature follicle
and the release of the mature egg into the reproductive tract. LH, FSH and
estradiol level decrease rapidly after the ovulation phase, typically 2-4 days.
The egg-less follicle is now called the corpus luteum (yellow body) and begins to
secrete increasing levels of progesterone in response to pituitary LH secretion.
This progesterone continues to stimulate and prepare the endometrial lining for the
implantation of the fertilized egg. Estrogen levels also begin to rise, although
the luteal phase is dominated by progesterone secretion. If fertilization and
implantation do not occur, the corpus luteum ceases to produce progesterone and
estradiol. The resulting drop in these hormones at the end of the luteal phase will
initiate the rise in FSH levels, which will begin a new cycle. At the same time,
the decreased levels of estradiol and progesterone will no longer support the
endometrium and these tissues are shed gradually resulting in menstruation. The
luteal phase typically lasts 14 or more days depending on the length of the cycle.
Luteal phase deficiencies often result in infertility, difficult menstruation,
irregular cycle lengths, PMS and other cyclical disturbances.
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Diagnosing Irregularities
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The key to treating any aspect of menstrual irregularities or difficulties is
proper diagnosis. This is especially true because the root cause may stem from
areas not typically associated with the female reproductive organs. Specifically,
two endocrine systems that must always be kept in mind are the adrenal and thyroid
axis. Like the ovaries, each of these has positive and negative regulatory loops
with the hypothalamus and pituitary. Each of these is defined as an axis, the
hypothalamic-pituitary adrenal axis (HPA), HPO (ovarian), HPT thyroid. These axis
not only overlap in their regulation within the hypothalamus and pituitary; but
adrenal, thyroid and ovarian hormones have receptors on the other respective organ
systems that directly influences their function. We will discuss some of these
where they are applicable.
In the diagnoses of menstrual irregularities, the more information, the better.
Historical patterns of the menstrual cycle, sleep patterns, stress, STDs, and any
other information (some which may seem trivial and unrelated) are important clues
to find the root cause or trigger for the irregularity. Mapping a women's cycle
using basal body temperature charts (BBT) and cyclical salivary test for estradiol
and progesterone are non-invasive and inexpensive tools that are helpful to
determine ovulation and the abundance and timing of ovarian hormones. For instance,
if progesterone levels are low or do not rise within 48-72 hours of ovulation,
implantation of a fertilized egg is not likely. A spot check of hormone levels in
the luteal phase is unlikely to reveal this, while a cycle map of 10-15 samples is
very likely to reveal these types of timing issues. Measuring adrenal function,
thyroid function and serum levels of the pituitary hormone prolactin would also be
considered basic diagnostic tools in assessing irregularities of the menstrual
cycle. With these clues in hand, various patterns usually emerge, pointing to one
or more areas of weakness; leading either to further confirming tests, natural
treatments, or advanced diagnostic protocols beyond the scope of this review.
The lack of menstruation can be divided into primary (no menses by the normal age
of menstruation) or secondary amenorrhea (cease in menstruation for several months
following regular cycles or 6 months following irregular cycles). Primary
amenorrhea is due to a physical or end organ dysfunction 40% of the time; most
other causes are related to hormone dysregulation similar to those causing
secondary amenorrhea. Again, diagnosis is the key to treatment since amenorrhea is
a symptom, not a diagnosis.
The two most common causes of secondary amenorrhea are
pregnancy and menopause. These should be ruled out before proceeding further. Women
who are extremely underweight (i.e. anorexia nervosa) or overweight have an
increased risk of becoming amenorrheic. A complete history should evaluate the
level of stress, weight-loss/dieting and strenuous exercise as all of these can
lead to disturbances to the menstrual cycle through hypothalamic-pituitary adrenal
stress (1,2,3). One study reported that women with hypothalamic
amenorrhea had
higher cortisol levels than normal menstruating women, but they had a blunted
response from the hypothalamus (CRH). This led the authors to conclude that the
hypothalamus was impaired in both the adrenal stress response as well as the
gonadotropin hormone secretion in these women (4). Measuring salivary cortisol
rhythm is highly recommended to help determine the status of the HPA. Challenge
tests with dexamethasone, CRH or ACTH may also be helpful to distinguish the extent
and nature of HPA insufficiencies. For a review on how stress affects the HPA and
natural treatments for adrenal insufficiencies see The Standard volume 3 number 1.
Thyroid function should also be monitored, as there is increasing evidence in both
experimental and clinical studies linking the thyroid and ovarian axis. The effects
of both hyperthyroidism and hypothyroidism can lead to menstrual irregularities,
anovulation, amenorrhea, and infertility (5,6).
One of the most common endocrine
disorders of the hypothalamus-pituitary is hyperprolactinemia, the over production
of prolactin by the pituitary. The incidence in an unselected adult population is
less than 0.5%, but is as high as 17% in women with reproductive disorders
especially amenorrhea and infertility (8). The pituitary secretion of prolactin is
controlled by a number of factors, most notably stimulated by thyrotropin releasing
hormone (TRH) and inhibited by dopamine. Hypothyroidism, which increases TRH; or
stress, which decrease dopamine, are therefore directly related to the increase in
prolactin levels and therefore, menstrual irregularities. While pituitary adenomas
may be responsible for increased prolactin levels, other factors may be addressed
to decrease prolactin and improve menstrual regulation. Serum prolactin levels can
easily be measured and compared to reference ranges to address this concern.
Treatment for secondary amenorrhea should initiate with diet and lifestyle changes.
Normal body mass index (BMI), a healthy balanced diet, proper amounts of sleep and
stress management may have a dramatic affect on hypothalamic-related amenorrhea.
Increasing protein and healthy fatty acid (flax, fish, evening primrose) intake
while decreasing carbohydrate intake will help with glycemic balance allowing
proper endocrine function. Once diet and lifestyle factors have been addressed,
hormone level assessments and treatments can commence. To ensure that estrogen
levels are adequate to establish the endometrium, salivary estradiol levels can be
checked. If a progesterone challenge (400 mg of oral micronized progesterone for 10
days) is not followed by some amount of menstruation (even spotting), this points
to an end-organ dysfunction or a hypothalamus deficiency. These can be
distinguished by the use of estrogens followed by an estrogen/progesterone
challenges. Often times, estrogen levels will be adequate, while progesterone
levels will be low. This is typical of a luteal phase deficiency problem.
The most direct therapeutic approach would be to augment natural oral micronized
progesterone (or equivalent sublingual dose) through the luteal-phase (for
instance: gradually increasing from 50mg to 200 mg from day16-24, then decreasing
back to 50 mg on day 30). While this will bring about a cyclicity, and may lead to
ovulation; it will also help reduce long-term estrogen imbalance, which could lead
to increased risk of breast and uterine cancer. The use of chaste tree extract
(Vitex agnus castus L.) for amenorrhea, and other menstrual irregularities, has
been established as the herb of choice in Europe where phytomedicine is common
among physicians. See the related article on Vitex within this issue for a
discussion of its mechanisms and clinical research. Other, phytoestrogenic herbs
such as black cohosh, alfalfa, flax, licorice or red clover have been used to
support the reproductive cycle in hypo-estrogenic cases. These would also be used
in cases of menopause or premature ovarian failure (see The Standard Vol. 4 no. 1).
The use of two roots, peony (Paeonia lactiflora) and licorice (Glycyrrhiza glabra),
have been used in combination for a number of female conditions. Studies, mostly in
Japanese, have shown this combination to increase DHEA-S levels (51), decrease
prostaglandin production (52), lower prolactin levels (50), and helpful for the
treatment of polycystic ovarian disease (53).
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Irregular or Abnormal Uterine Bleeding
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This review will only discuss benign dysfunctions treatable with natural remedies.
Malignant conditions or extremely heavy bleeding should be handled by those
specializing in such conditions. Practitioners who are unsure how to rule out
fibroids, endometriosis, pre-cancerous conditions or non-gynecological blood
disorders, should refer patients to someone who can make these determinations
before proceeding with further diagnosis. That said, there are many conditions that
can be treated with natural ingredients with excellent results.
Irregular uterine bleeding can be categorized as menorrhagia (heavy or prolonged menses), polymenorrhea (frequent menses),
oligomenorrhea (light or infrequent menses) and even metrorrhagia (irregular and intermenstrual bleeding). Menorrhagia is
often the
result of anovulation, which may have its root cause in excessive estrogen
production, low or no midcycle LH surge, hypothyroidism, hyperprolactemia or
polycystic ovarian disease. The goal is to slow down the rate of the bleeding while
also addressing the root cause.
Beside hormone augmentation (which may be warranted
if other options are not successful) several astringent herbs may be quite helpful
in easing the flow of menstruation. Herbalist in both the U.S. and Europe recommend
herbs such as yarrow (Achillea millifolium), lady's mantle (Alchemilla vulgaris),
shepherd's purse (Capsella bursa-pastoris) and motherwort (Leonorus cardiaca).
Shepherd's purse, however, is the only approved herbal monograph for menorrhagia
listed in the German Commission E (7). The use of the Chinese herb sanchi (Panax
notoginseng) is also used to correct bleeding disorders and has been used for
menorrhagia. Chaste berry (Vitex agnus castus) is often used to help regulate the
underlying causes (see Chaste berry mini-monograph).
There is an interesting
relationship between menstrual blood loss and prostaglandin production. Not only
are various prostaglandins related to increased blood loss, women suffering from
menorrhagia have increased levels of arachidonic acid in uterine tissues (49).
Reducing dietary animal fats and replacing them with fish oils (containing EPA) and
GLA-rich oils like borage and evening primrose should lower the amount of type 2
prostaglandins that are formed from arachidonic acid. As with all health concerns,
diet and lifestyle factors should be always be addressed. Vitamin and mineral
intake should be assessed to insure that levels of iron, magnesium, Vitamin C, B12,
B6, and all essential fatty acids are adequate. Therapeutic levels of vitamin C
with additional bioflavonoids are often recommended to help maintain vascular
integrity.
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Premenstrual Syndrome (PMS)
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While there are nearly 150 symptoms that have been related to PMS, it is the regular cyclical
pattern that is most characteristic. These symptoms begin in the mid-to-late luteal phase and
almost disappear after the first day of menstruation. A typical list of symptoms would include
mood swings, depression/sadness, anger/short temper, crying spells, swelling of extremities,
breast pain/tenderness, abdominal bloating, lower abdominal cramping, low backache, headache,
fatigue, craving for sweets or salt and insomnia. Depending on which symptoms and their relative
severity, PMS may range from hardly noticeable to dramatically life-altering. It is reported
that up to 80% of women experience some PMS symptoms, less than half of who describe these
symptoms as contributing to "difficulties". In a recent study, 42% of women suffering from PMS
regularly took medication, of which 80% was over-the-counter (9). This shows the high level of
awareness, self-diagnosis and self-medication in this population. Many of the issues described
for luteal phase deficiency, apply to PMS sufferers. Very often, adrenal stress, thyroid
dysregulation, hyperprolactinemia and estrogen/progesterone imbalance will be found. One
interesting finding was that the HPA axis in PMS sufferers is under-active (lower cortisol
levels), similar to the findings in patients with seasonal affective disorder (SAD). This
differs from typical depressive disorders, characterized by an overactive HPA axis (10). A
direct correlation with hypothyroidism and PMS has not been established, but several reports
define a subset of patients whose PMS may be related to thyroid dysregulation (11,12).
From a
chiropractic perspective, a group of 54 women diagnosed with PMS were compared with 30 women
with no diagnosable PMS symptoms and found that the PMS sufferers had a higher incidence of
spinal dysfunction. Most significant were positive cervical, thoracic, and low back tenderness,
low back orthopedic testing, low back muscle weakness and neck stability index (13).
One of the factors thought to contribute to PMS symptoms is a sudden drop in progesterone levels
in the late luteal phase (not necessarily the absolute amount of progesterone made in the luteal
phase). This dramatic decline results in late luteal estrogen dominance and imbalances that lead
to PMS symptoms, it is speculated. While it would seem logical that progesterone therapy
throughout the month or specifically during the late luteal phase would benefit PMS sufferers,
clinical trials focused on this have yet to show conclusive positive results when vaginal
suppositories or oral doses were given (14,15,16). It is probably
best to measure progesterone
and estradiol throughout the cycle (salivary test) in order to determine if this approach may
have potential benefits before temporary augmentation of hormones are used.
Diet and nutrition play a major role in the treatment of PMS. One report listed PMS patients as
consuming 62% more refined carbohydrates, 275% more refined sugar, 79% more dairy products, 78%
more sodium, 53% less iron, 77% less manganese and 52% less zinc than women not suffering from
PMS (17). The role of dairy products and animal fat may contribute to increased arachidonic acid
levels, which subsequently are converted into prostaglandin PgE2. This prostaglandin is thought
to increase in the luteal phase of PMS sufferers and those with frequent menstrual cramps.
Consuming both omega-3 rich oils like flaxseed oil and fish oils, as well as GLA-containing oils
like evening primrose or borage oil will help balance the prostaglandin levels (See The
Standard
Vol 3 no 2). Last year, researchers at Georgetown University tested the role of a low-fat,
vegetarian diet on PMS and dysmenorrhea (painful menstruation/cramps), postulating a role for
sex-hormone binding globulin (SHBG) and estrogen levels (18). They found a significant increase
in SHBG and a significant decrease in body weight, dysmenorrhea symptoms and PMS symptoms during
months of low-fat and vegetarian diets compared to months on a control diet. While it is
difficult to assess all the ramifications diet plays in PMS, it is clear that increasing fresh
fruits and vegetables and decreasing processed foods, dairy, and animal fats would be
beneficial.
The role of nutritional supplements supplying vitamins, minerals and herbs has long been postulated to benefit women
suffering from PMS. Laboratory tests have shown that women suffering from PMS have nutritional deficiencies, most
significantly vitamin B6 and magnesium (19). There have been at least 25 different clinical trials in
which vitamin B6 has been used for the treatment of PMS. Of these, 9 of the best-controlled trials were used to conduct a
meta-analysis (20). This study pointed out the need for a large, properly controlled clinical trial,
but reported that there does seem to be a therapeutic benefit to using vitamin B6 for the treatment of PMS. While many of
these trials used 100mg or even 200mg per day without noticeable side effects, the authors believe that 50mg per day is
likely to be beneficial in the treatment of PMS. Consider all the sources of B6 (multivitamin, B-complex, PMS products
etc) prior to adding additional B6 to the regimen.
Not only is magnesium one of the minerals most often ingested in sub-optimal amount in women consuming a typical Western
diet, intracellular magnesium is the most consistent physiological abnormality found among PMS sufferers compared with
normal controls. Few clinical trials have been performed using magnesium for the treatment of PMS. A small trial, in
which data was collected from 38 women, compared placebo to 200 mg of magnesium per day as magnesium oxide (21). They found that the magnesium group had significantly reduced fluid retention when compared with the placebo
group but only after the second month of magnesium supplementation. The same group also reported a study where PMS
sufferers were given 200 mg of magnesium (MgO), 50 mg of vitamin B6, both, or placebo (22). Even though
this study had some major flaws, they still report a slight synergistic effect by combining magnesium and B6 in the
treatment of PMS. In their conclusion they state that magnesium oxide was so poorly absorbed that several months would be
required to see the full benefits of using this form and suggested the use of longer periods or other magnesium forms. The
use of magnesium as an amino acid chelate, citrate, aspartate, or ascorbate would all be of superior therapeutic benefit
when compared to MgO, frequently used for its high magnesium content and low cost. Hopefully, a better clinical trial will
be done to assess the role of magnesium as a therapeutic agent for PMS, for now it seems more than reasonable to increase
intake of magnesium for all individuals especially those being managed for menstrual irregularities and PMS.
Recent evidence has postulated a role for calcium regulation disturbances in symptoms associated
with PMS. From that, calcium supplementation is postulated to have a positive therapeutic
benefit for PMS sufferers. In order to investigate this possibility, 466 women were randomized
to receive either 1200 mg of elemental calcium (as calcium carbonate) or placebo for 3 menstrual
cycles (23). While the results showed an extremely high reduction in PMS scores for the placebo
group (30%), there was a significant drop in PMS scores in women taking calcium (48%). Since no
dose-response information has reported, and most other studies use 1000-1350 mg of calcium per
day with variable results, it is difficult to assess whether this represents a deficiency
correction or a therapeutic effect. It should be noted also that this study, like others, was
supported by a large manufacturer of commercial calcium carbonate products. They did not measure
calcium absorption in this study.
By far the most beneficial herb for treatment of luteal phase deficiencies and PMS is Vitex
agnus castus (Chaste tree extracts). See the vitex monograph in this volume for more details on
the benefits of using this herb. Other botanicals used are St. John's wort, Ginkgo, licorice,
evening primrose, wild yam, dong quai, black cohosh and many more. A pilot study of St. John's
wort extract (900 mg/day standardized extract) for treating PMS was recently published (24).
After two complete cycles they reported a significant reduction in all outcomes measured with a
51% improvement in overall PMS scores between baseline and the end of the trial. This was an
open, uncontrolled trial; and considered preliminary. It should be noted that while safety of
St. John's wort is excellent, it is speculated to cause oral contraceptives to be less effective
due to its stimulation of the p450 enzyme system.
One study, published in French, reported that
extracts of Ginkgo (dose unavailable) were capable of reducing congestive symptoms (primarily
breast fullness and tenderness) compared with placebo (25). Numerous studies have been published
using various Chinese herbs within the traditional Chinese medicine (TCM) model of diagnosis and
treatment, their effectiveness is difficult to assess especially with the different diagnostic
and social concepts that separate Western medicine from TCM.
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Other Alternative Approaches
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Menstrual cycle irregularities have engendered a myriad of treatment options. We have discussed
those that involve natural medicinal supplements, but in the field of complementary and
alternative medicine there are other treatments addressing female cycle management; some of
which have been published as clinical trials. The largest field in this category would be
traditional Chinese medicine (TCM). Not only numerous papers on Chinese herbal remedies for the
treatment of irregularities of the luteal phase (26), but also the use of acupuncture and
electro-acupuncture to stimulate ovulation, particularly in the case of polycystic ovarian
syndrome (27). Chiropractic manipulation was evaluated in a placebo-controlled trial as a
therapy for PMS. The findings showed that high-velocity, low amplitude spinal manipulation with
soft tissue therapy 2 to 3 times in the week prior to menses statistically reduced PMS symptoms
scores over placebo (spring-loaded adjusting instrument wound down for minimum force)(28). The
crossover design of the study led to some confusion in data interpretation, and more studies
need to be conducted to investigate the role of chiropractic adjustments in the treatment of PMS
or other cycle irregularities.
Additionally, reflexology of the ear, hand, and foot (29);
relaxation and guided imagery (30); and circadian/light therapy work (31) are among
a number of
therapies with published reports in the literature.
With the growing desire for natural remedies, particularly among women 30-50, understanding the
role of medicinal supplements for female cycle irregularities is vital to serving these
patients. And, while they may feel that their symptoms point to a self-diagnosable condition,
many have been disappointed with over-the-counter remedies or prescription medication. It is
evident from this review that, with a logical and less-invasive diagnostic protocol, a natural
treatment regimen can be selected that will be safe and highly effective.
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Vitex monograph - Female cycle emphasis
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Name and History
Vitex agnus castus L. is also known as chasteberry, chaste tree, vitex or monk's pepper. The names are derived from the
fact that in medieval times monks used it as a cooking spice for its taste and, it is said, for its abilities to suppress
libido. It has a long recorded history of medicinal use, being mentioned by Hippocrates in the 4th century BC and both
Pliny and Dioscorides in the 1st century A.D.
Vitex the medicine
The portion used for medicinal purposes is the dried ripe fruits
(peppers) of the plant. Foremost among its constituents are flavonoid components like vitexin, orientin, and the abundant
casticin; terpene compounds like the often measured agnuside and aucubin; and volatile oils. Tinctures, powders and dried
extracts are most often how vitex is delivered.
Endocrine Function
In the 1950's it was discovered that extracts of vitex were able to increase the size of the corpus luteum in animal
models, although not as a result of direct hormone-like activity (32). Years later, two major endocrine
modulations have been confirmed with extracts of vitex: 1) a decrease in prolactin levels and 2) an increase in
luteinizing hormone (LH). The decrease in prolactin secretion has been confirmed in animal models (33)
and was postulated to work by stimulating dopamine receptors on the pituitary. These findings were confirmed when in vitro
experiments concluded that vitex extracts contained active principals that bind directly to dopamine D2 receptors, which
mediate the inhibition of prolactin secretion from the pituitary (34,35).
Clinical Use of Vitex
The clinical use of vitex includes the same list of conditions that can be attributed to hyperprolactemia: cyclic
mastagia, PMS, abnormal cyclic ovarian function, amenorrhea, luteal phase deficiency, and infertility.
In a randomized, double-blind, placebo controlled study; women with latent hyperprolactinemia received either a vitex
extract or placebo for 3 months. These women were characterized before the study as having shortened luteal phases, low
luteal progesterone levels, and high levels of clinically stimulated prolactin (used to define latent hyperprolactinemia).
After the three-month study, the vitex group had significantly reduced prolactin compared to placebo, normalized mid-
luteal progesterone levels and their luteal phase lengthened by 5 days. In addition, women in the vitex group with
previous PMS symptoms showed a significant reduction in those symptoms (36). A similar but smaller
study of 13 women with hyperprolactinemia and cyclic disorders were treated with vitex. In every patient, prolactin levels
were reduced, some to normal ranges, and the menstrual cycle normalized (37).
Infertility
While pregnancy may be recorded as an outcome of other clinical trials using vitex, several studies have looked directly
at using vitex to treat infertility. In 1987, an open non-controlled study was done with a group of 18 infertile women of
childbearing age with normal prolactin levels and normal thyroid function (38). All had abnormally low
levels of progesterone in the mid-luteal phase (day 20). After only 3 months, progesterone levels rose in 11 of 18
patients, 7 of which returned to normal. All but 4 women had their basal body temperature phase shift normalize (a sign of
normalizing ovulatory function) and 2 became pregnant within 3 months. A randomized, placebo controlled trial with 96
infertile women was carried out for 3 months in which the measured outcome was pregnancy, spontaneous menstruation in
amenorrheic women, or improved luteal phase hormone profile. The vitex group had significantly more improvements in all
outcomes measured against placebo. In women with luteal phase deficiencies or amenorrhea, pregnancy occurred more than
twice as often in the vitex group than in the placebo group (39).
Cyclical mastalgia
As increased luteal-phase prolactin levels are thought to mediate much of the breast pain and tenderness experienced in
the premenstrual phase, the use of vitex has been used clinically to treat such conditions (40). Two
recent double-blind controlled studies were reported, one with 100 patients (41) and one with 120
patients (42). Each showed that the vitex group had significantly less pain and shortened duration of
pain. The second study showed a drop in PMS symptoms, prolactin levels, and estradiol levels in the vitex group compared
to placebo. Each of these studies lasted 3 months.
Menstrual irregularities
There are numerous clinical trials on a variety of menstrual irregularities and the treatment with extracts of vitex.
Perhaps the largest of these reported trials was a collection of cases from physicians (Germany) reporting the use of
vitex in their practice. 2,447 women with various menstrual complaints (1,016-PMS, 734-corpus luteal insufficiencies, 320-
uterine myomas, 167-menopausal symptoms) who were given vitex as treatment were included in the report. After an average 5
months of vitex treatment, the efficacy was rated at 90% with 31% of women reporting complete absence of symptoms. Of
these, nearly 3% became pregnant while on vitex and only 2.3% reported side effects (1% drop-out rate due to
side-effects) (43).
A similar report of an open trial with 1,592 women (average age 32) with corpus luteum insufficiency presenting as
menorrhagia (484), polymenorrhea (359), amenorrhea (202), dysmenorrhea (painful menstruation 186), anovulation (175), and
infertility (145) was reported. Patients were assessed after an average of 6 months of treatment (44). The doctors
reported a similar 90% satisfactory response with 33% of patients reporting completely free of symptoms after 6 months. Of
the 145 women expressing the desire to become pregnant, 56 (39%) became pregnant during treatment.
PMS
Much of the recent therapeutic focus for vitex extracts is for the treatment of PMS. In 1997, a study was conducted to
compare the use of vitex extracts with pyridoxine (B6) in the treatment of 175 women diagnosed with premenstrual tension
syndrome (PMTS). Since there had been several studies demonstrating the effectiveness of pyridoxine in the treatment of
PMTS, the authors felt it unnecessary and unethical to use a placebo arm for this three-month study (45). The results showed that, though both treatments were capable of reducing PMTS symptoms (breast
tenderness, edema, inner tension, headache, constipation and headache), the vitex treatment was rated as excellent by
twice as many physicians. In the patient assessment, 50% more said their symptoms were completely absent in the vitex
group (36%) than the pyridoxine group (21%).
PMS symptom relief was also the outcome of a study reporting the results of an open-label multi-center trial (46). Forty-three patients were monitored for 8 months; 2 pre-treatment baseline months, 3 treatment months, and
3 post-treatment months. Using several questionnaires, including a menstrual distress questionnaire and both a visual
analog scale and global impression scale for secondary assessment, they reported a 43% drop in PMS symptoms between the 3
treatment months versus baseline. Additionally, they found that at the end of the post-treatment months (month 8) a 20%
reduction of symptoms remained, when compared with the baseline months. In this study, women who were concurrently taking
oral contraceptives had similar results compared to women not taking oral contraceptives.
A large multicenter open trial conducted to monitor the effectiveness and safety of using vitex extracts for PMS was
recently published (47). Of the 1634 patients monitored after 3 months of treatment, 81% rated their
status as very much or much better. Physicians rated the treatment good or very good with 85% of their patients. A full
94% rated the tolerability of the treatment as good or very good and only 1.2% experienced adverse events (none rated
serious). Because this was not an intervention or controlled study, these numbers prove only to support the safe and
general effectiveness of vitex on a wide variety of patients.
The most recent study, published early this year in The British Medical Journal, discovered similar finding using a
randomized, placebo-controlled study. They reported twice as many responders (52% vs. 24%) in the active vitex group
compared with placebo. Responders included those with 50% or greater drop in symptoms including irritability, mood
alteration, anger, headache, breast tenderness, bloating etc. The researchers conclude that the dry extract of vitex (used
in this study) was an effective, safe, and well tolerated treatment for the relief of symptoms of premenstrual syndrome (
48).
Dose
Almost all of the initial clinical trials performed with extract of Vitex agnus castus were using a liquid preparation.
The dosage range was between 40-60 drops and given for at least 3 months. These dilute (1:5) extracts were also dried and
used to make powders that were dosed at 175 mg per day.
More potent extracts are now being used and reported in the most recent clinical trials. These powdered extracts range
from 9:1-12:1 in strength and are dosed either at 3-5 mg (equivalent to 175 mg of the 1:5 extract) (45,
47) or 20mg per day (46,48). Both dosing regimens performed
positively in the clinical trials tested, although the low dose regimen studies were designed poorly and had somewhat
vague outcome measurements.
At this time, several extracts are being marketed which are standardized to agnuside, aucubin or casticin. While these are
excellent marker constituents and likely represent some of the active components, it is unclear from a clinical
perspective exactly what standardization marker or method best characterizes the therapeutic activity. Further studies
into the active components may lead us to the extract of choice. Ideally, an extract of approximately 10:1, which
maintains as much of the potential active components (agnuside, aucubin and active flavonoids like casticin), dosed at 20
mg per day should have characteristically effective and safe outcomes for the conditions listed above.
Contraindications/Adverse Effects
The safety profile of vitex and its extracts is excellent. No severe side effect or allergic reaction has ever been
attributed to vitex use. Mild adverse reactions may include stomach upset, nausea, itching and headache. Use of vitex with
birth control pills or other hormone therapies is not recommended, although no known interactions have been reported and
one study reported that no differences were seen between patients on or off oral contraceptives when treated with vitex
for PMS (46). Use of vitex concomitant with dopamine-antagonist is not recommended because of the
dopaminergic actions of vitex constituents.
As there is no indication during pregnancy, vitex is not recommended during pregnancy. However, as it is often used during
infertility treatment, it should be noted that no known harm has been reported during any stage of pregnancy. Although
historical reports of vitex as a lactagogue (breast milk
stimulant) are widely circulated, this affect may only be possible at very dilute concentration when vitex may act as a
dopamine antagonist rather than a dopamine agonist. Unless recommended by someone experienced in the use of vitex as a
lactagogue, other remedies should be sought to stimulate milk production. One possible negative side effect of using vitex
as a postpartum lactagogue is the possibility of premature return of menses, as lactational amenorrhea is often considered
as one of the beneficial side effects of breast-feeding.
GENERAL REFERENCES:
Ferin M, Jewelewicz R, Warren M. The Menstrual Cycle- Physiology, Reproductive Disorders, and Infertility. 1993; Oxford
University Press.
Hudson T. Women's Encyclopedia of Natural Medicine..1999 Keats Publishing Los Angelos, CA.
Trickey R. Women, Hormones & the Menstrual Cycle- Herbal and Medical Solutions from Adolescence to Menopause.. 1998 Allen
& Unwin St. Leanards NSW, Australia.
The following three monographs were extremely helpful in compiling the information about the use of Vitex agnus
castus and the preparation of the mini-monograph in this review. A * beside the number in a cited reference signifies that
the information from these references was translated and interpreted in one or more of these excellent monographs and
subsequently reported here.
Brown DJ. Vitex agnus castus monograph. Quarterly Review of Natural Medicine, Summer 1994: 111-121.
Gardiner P. Chasteberry (Vitex agnus castus) The Longwood Herbal Task Force www.mcp.edu/herbal/default.htm
Institute for Natural Products Research (INPR) monographs-Vitex, found at www.naturalproducts.org
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