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Comparison of Vitex Agnus Castus with Meloxicam and Placebo in Treatment of Patients with Cyclical Mastalgia

Authors:

Abstract

Background: Mastalgia is classified as cyclic and non-cyclic. Cyclical one constitutes approximately 60-70% of mastalgia. It is seen between 2 to 3 decades of age, and it usually responds to treatment. Objectives: To compare efficacy of vitex agnus castus (VAC) preparation with meloxicam and placebo in treatment of mastalgia. Methods: The study was designed as prospective and placebo-controlled clinical trial. Three groups were constituted. Before grouping, prolactin level was tested for every patient. The group1 enrolled the patients with cyclical mastalgia and high level prolactin. VAC was administered to patients from study group1. The second group enrolled the patients with cyclical mastalgia along with normal prolactin level, and to which meloxicam was given. Third group was placebo group, and placebo was applied. Before treatment, VAS (Visual analogue scale) scoring was applied to every patient. Prolactin level was tested for patients from group 1. After 3 months of study, VAS scoring was applied to every patient, but only prolactin levels were re- evaluated in patients from group1. Results: 95 patients were analyzed; enrolling women aged 19 to 54 years. Intensity of mastalgia diminished in VAC group 1, 2 more than in placebo group (p<0.0001). In addition to VAS scoring, prolactin level in group 1 after treatment was significantly reduced, comparing with before treatment (p<0.0001). In conclusion, we found that VAC preparation was effective in the treatment of mastalgia and hyperprolactinemia, with good tolerability.
Düzce Tıp Dergisi 2012; 14(1): 1-5 1
1İbrahim AYDIN
2Davut BALTACI
3Serdar TÜRKYILMAZ
3Mustafa ÖNCÜ
1Rize District Hospital,
General Surgery Clinic, Rize,
Turkey.
2Düzce University, Medical
Faculty, Department of
Family Medicine, Duzce,
Turkey
3Karadeniz Technical
University, Medical Faculty,
Department of General
Surgery, Trabzon, Turkey
Submitted/Başvuru tarihi:
14. 05. 2010
Accepted/Kabul tarihi:
15. 12. 2011
Registration/Kayıt no:
10 05 124
Corresponding Address
/Yazışma Adresi:
Davut BALTACI, MD
Duzce University, Medical
Faculty, Department of Family
Medicine,
Phone: (90) 541 7165619
(mobile)
Phone: (90) 380 5421390–
5820(work)
E-mail:
davutbaltaci@hotmail.com
ABSTRACT
Background: Mastalgia is classified as cyclic and non-cyclic. Cyclical one constitutes
approximately 60-70% of mastalgia. It is seen between 2 to 3 decades of age, and it usually
responds to treatment.
Objectives: To compare efficacy of vitex agnus castus (VAC) preparation with meloxicam and
placebo in treatment of mastalgia.
Methods: The study was designed as prospective and placebo-controlled clinical trial. Three
groups were constituted. Before grouping, prolactin level was tested for every patient. The
group1 enrolled the patients with cyclical mastalgia and high level prolactin. VAC was
administered to patients from study group1. The second group enrolled the patients with cyclical
mastalgia along with normal prolactin level, and to which meloxicam was given. Third group
was placebo group, and placebo was applied. Before treatment, VAS (Visual analogue scale)
scoring was applied to every patient. Prolactin level was tested for patients from group 1. After
3 months of study, VAS scoring was applied to every patient, but only prolactin levels were re-
evaluated in patients from group1.
Results: 95 patients were analyzed; enrolling women aged 19 to 54 years. Intensity of mastalgia
diminished in VAC group 1, 2 more than in placebo group (p<0.0001). In addition to VAS
scoring, prolactin level in group 1 after treatment was significantly reduced, comparing with
before treatment (p<0.0001). In conclusion, we found that VAC preparation was effective in the
treatment of mastalgia and hyperprolactinemia, with good tolerability.
Key Words: Mastalgia, vitex agnus castus, prolactin.
ÖZET
Giriş: Mastalji meme ağrısı olup klinik olarak siklik ve siklik olmayan şeklinde sınıflandırılır.
Siklik mastalji mastaljilerin yaklaşık %60’ını kapsar. Siklik mastaljiler en sık 20 ve 30 yaşlarda
görülür ve genellikle tedaviye iyi cevap verir.
Amaç: Vastus Agnus Castus preparasyonunun (VAC) mastalgi ve hiperprolaktinemi üzerine
olan etkinliğinin araştırılması amaçlandı.
Metot: Araştırma prospektif ve palsebo kontrollü klinik çalışma olarak yapıldı. Hastalar gruplara
ayrılmadan önce her hastadan prolaktin seviyesine bakıldı. Hastalar gruplara ayrıldıktan sonra
her hastaya tedavi öncesi VAS uygulandı. Grub 1 siklik mastaljisi ve hiperprolaktinemisi olan
hastalardan oluştu. Bu hastalara VAC (agnucaston) başlandı. Grup 2 siklik mastaljisi ve normal
prolaktin seviyesi olan ve meloksikam 15 mg/gün başlanan hastalardan oluşmuştur. Placebo
grubu mastaljisi olan ve prolaktin seviyesi normal olan hastalardan oluştu. 3 aylık tedavi sonrası
her hastaya VAS ve grup 1 için prolactin seviyesine bakıldı.
Sonuçlar: Toplam 19–54 yaş arası 95 hastanın analizi yapıldı. VAC alan grupta mastaljinin
yoğunluğu plasebo grubundan anlamlı ölçüde azaldığı zlendi (p<0,0001). VAS skoruna
ilaveten, prolaktin seviyesinde tedavi öncesine göre anlamlı azalma tespit edildi (p <0.0001).
Sonuç olarak, VAC preperasyonunun mastalji ve hiperprolaktinemi tedavisinde iyi tolerabilite
ile birlikte etkin olduğunu bulduk.
Anahtar Kelimeler: Mastalji, vitex agnus castus, prolaktin
INTRODUCTION
Mastalgia is a painful condition originated from breast tissue, and clinically is
classified into two types as cyclical and non-cyclical one. Cyclical one can be
Comparison of Vitex Agnus Castus with Meloxicam and Placebo
in Treatment of Patients with Cyclical Mastalgia
Siklik Mastaljili Hastaların Tedavisinde Vitex Agnus Castus
Preperatının Meloksikam Ve Plasebo İle Karşılaştırılması
2011 Düzce Medical Journal
e-ISSN 1307- 671X
www.tipdergi.duzce.edu.tr
duzcetipdergisi@duzce.edu.tr
DÜZCE TIP DERGİSİ
DUZCE MEDICAL JOURNAL
ORİJİNAL MAKALE / ORIGINAL ARTICLE
Düzce Tıp Dergisi 2012; 14(1): 1-5 2
described as middle to severe level breast pain lasting
approximately 5 days, or more. Cyclical mastalgia is
commonly seen between 20 to 30 years of age, but it
can be seen after menopause. It comprises 60-70 %
of mastalgia. Approximately 90% of cyclical
mastalgia respond to treatment. It occurs mainly
during menstrual period, so it is considered to be
associated with hormonal change. Non-cyclical
mastalgia comprises 20-30 % of cases, and is more
severe and resistant to treatment, comparing with
cyclical one (1, 2).
It is one of the most common symptoms of female
patients seeking health care at both primary health
clinics and breast referral centers. Its prevalence is not
exactly known, but is estimated to be seen as 66% in
community-based screening and 50% in outpatient
clinic (3). 50% to 80% of women are estimated to
have experienced with mastalgia at some point in their
life, but in only 1% of patients is mastalgia a symptom
of breast cancer (4,5).
Today’s, we have several options to treat mastalgia as
pharmacologic and non-pharmacologic, but these are
not standardized therapies. Firstly, it should be
evaluated carefully for its reasons. History taking,
physical examination and imaging methods such as
mammography and ultrasonography should be
performed before deciding treatment. Bromocriptine,
danazol, tamoxifen, LNRH analogues, gamma
linoleic asid, testesteron, gestrinon, gabergolin,
vitamins such as B6 and E, and analgesic agents
(6,7,8,9). However, hormonal therapies such as
bromocriptine, danazol, LNRH analogues have severe
side effects. Nevertheless, efficacy of any treatment
modality is not superior to each other.
VAC has been also used in the treatment of female
conditions such as premenstrual syndrome, corpus
luteum insufficiency, menstrual disorders,
hyperprolactinemia and menopause. Agnus castus is
thought to be effective in the management of
mastalgia because of its dopaminergic effects. It could
be helpful in the management of mastalgia may be
because of its effect on latent hyperprolactinemia,
estrogen receptors or other unknown mechanisms
(10).
The aim of study presented here was to compare
efficacy of Vitex agnus castus (VAC) preparations
with meloxicam and placebo in the treatment of
patients with cyclical mastalgia.
MATERIAL and METHODS
Study Population
The study was prospective, placebo-controlled
clinical trial, enrolling consecutive female patients
presenting with mastalgia to our clinic, general
surgery out-patient clinic, Karadeniz Technical
University, School of Medicine, and Trabzon, Turkey.
On admission, the patients suffering from mastalgia
were classified into cyclical and non-cyclical form.
Among them, 108 women were enrolled into study by
taking their informed consent. The study was
approved by ethical committee of our institution.
Study Protocol
For every patient, prolactin level was measured before
grouping. Visual Analogue Scale (VAS) for scoring
breast pain was performed for every patient before
arranging into groups. Group 1 consisted of subjects
with cyclical mastalgia and hyperprolactinemia, group
2 consisted of those with cyclical mastalgia and
normal prolactin (3.4 ng/mL-24.1 ng/mL,
radioimmunoassay method), and placebo group
consisted of those with cyclical mastalgia and normal
prolactin Mammography for patients over 35 years of
age and ultrasonography for those less than 35 years
of age were performed for every subject to rule out
malign conditions. Cyclical mastalgia during at least
5 days of menstrual cycle before grouping was the
strict inclusion criteria. The patients with non-cyclical
mastalgia, history of breast cancer and family history
of breast cancer, being male, medical conditions
requiring mammary biopsy, doubtful positive signs on
imaging, prolactin level over 120 ng/mL (high
probability sign for intracranial pathology), and the
patients who rejected to participate in study were
excluded. Other exclusion criteria are Granulomatous
infiltration of the hypothalamus, severe head trauma,
primary hypothyroidism, renal failure.
Visual Analogue Scale (VAS) was used for breast pain
scoring. The patients were asked to fill VAS scale.
VAS was degreed from one to ten degree according
to severity of pain. One degree referred very light
pain, and ten referred very severe pain on VAS. Very
light pain (VAS 1) indicated painful condition on
resting state and without working. Very severe pain
(VAS 10) indicated that it awaked the patient from
sleep, and interrupted her daily activities. Score of
middle pain indicated that interrupted her daily
activities but not awaked her.
Clinical and demographic features of patients,
including, age, marital and educational state, smoking
and alcohol drinking, co-morbid diseases, medicines,
and occupation were recorded by medical notes and
semi-structured interview with them. Vitex Agnus
Castus preparation (Agnucaston 40 mg a day in a
single dose, Biomeks) was administered to patients
from group 1. Meloxicam 15 mg/day (Mobic tablet in
a single dose, Boehringer Ingelheim) was given to
patients from group 2. For group 3, placebo (a day in
a single dose) was applied. The patients from 3 groups
AYDIN et al.
Düzce Tıp Dergisi 2012; 14(1): 1-5 3
have been followed for three menstrual cycles. They
were also recruiting to re-evaluate for tolerability and
efficacy of VAC preparation at the end of 1st and 3rd
month. VAS scoring was re-applied at the end of 3rd
month. Serum Prolactin level of patients from group
1 was measured at the end of third month of treatment.
Statistical Analysis
Data were analyzed using Statistical Package for
Social Science for Windows (SPSS) version 10.0. The
results are presented as mean ± standard deviation for
scale variables, and stated as median and range for
nominal variables and percentages for proportions.
For parametric two-dependent variables, paired
Student-t was used, but Wilcoxon Signed Ranks Test
test for non-parametric ones. Analysis for non-scale
variables was done using X2-test (Ficher’s exact test).
Comparisons of VAS scoring between groups are
computed by using one-way ANOVA with post-hoc
Bonferroni test.
RESULTS
The study was employed between April 2005 and
September 2005. Initially, 108 female patients were
enrolled, but data of 60 patients (n= 30 for group 1,
n= 30 for group 2, and 35 group placebo) were
analyzed. Out of 108 patients, 13 ones left the study.
Overall, the study sample consisted of 95 subjects
aged from 19 to 54 years, averaging 36.31±8.92 yrs.
Based on results, cyclical mastalgia was commonly
observed after 30 years of age. Average age for group
1, group 2 and group 3 (placebo) was 43.47±8.71,
35.38±9.05 and 37.38±7.77 respectively. In study,
were not any patients having consumed alcohol. Only
the patients with current smoker were recorded. Most
of them have had informal education. They were
mostly married and housewife. Before treatment,
there were not significant differences for age, VAS
scoring, marital status, education level, occupation,
mammographic and ultrasonografic findings, and
smoking situation between groups (Table 1).
In group 1, two patients for hypertension and one for
asthma had been using medicine. On the other hand,
4 patients from group2 had been using medicine for
hypertension. In placebo group, two patients for
hypertension had been using medicine.
Mammography was performed for 14 (46%), 12
(%40), and 15 (50%) patients from groups,
respectively. Ultrasonography was applied to 16
(53%), 18 (%60), and 12 (40%) patients of group 1,
2, and 3, respectively. Comparing findings on USG
and mammographic examination, there were similar
results between groups (p>0.05) (table 1).
Median of VAS scoring for groups 1 before initiating
treatment was 6. After treatment with Vitex Agnus
Castus, median of VAS scoring was 1.5. It was
statistically significant (p<0.0001). Median VAS
scoring before and after in group 2 treated with
meloxicam 15 mg7day was 6 and 2, respectively. It is
also significant. For placebo group, median VAS
scoring before and after treatment was almost similar
and not significant (VAS before: 7, VAS after: 6)
(p=0,052). 30% of patients treated with responded
completely to therapy, 56% of them were affirmative,
and remaining was unresponsive (Table 2). Average
prolactin level of patients from group 1 was
38.93±19.57 ng/mL at initial (min: 25.0 ng/mL, max:
113.0 ng/mL). After treatment, it was measured as
21.90± 10.76 ng/mL (p<0.0001) (Figure 1). moreover,
we did not observed any side effects due to vitex
agnus castus administration, but one patient from
group 2 specified gastrointestinal discomfort, but not
severe.
Comparing VAS scoring of group 1 with group 2 was
not significant, but it was significant with that of
placebo after third month of treatment administration
(p<0.0001). Median VAS scoring of group 2 after
treatment was significant with placebo, but not with
group 1.
İbrahim AYDIN et al.
Table 1. Basic features of subjects according to groups.
Table 2. Comparison of VAS scoring between groups before
and after treatment.
Düzce Tıp Dergisi 2012; 14(1): 1-5 4
DISCUSSION
Cyclical mastalgia is diffuse and transient or periodic,
non-localized and usually bilateral breast pain.
Cyclical mastalgia is seen commonly between second
and third decades. Careful evaluation of patients
presenting with mastalgia lights the way for efficacy
and harmony of treatment, because most patients
spontaneously improve without treatment after they
are ensured that it would be not due to cancer (11).
44% of Mastalgia can be continued until menopausal
period. Spontaneous regression can be seen in 22% of
patients (12).
Patients with cyclical and non-cyclical mastalgia
responded to anti-prolactin therapy in different results
(12). Gatalay and et al. (13) obtained 47% and 20%
respond in cyclical and non-cyclical mastalgia
respectively after anti-prolactin treatment in their
study. In another study, they also reported that the
patients responded as 54% in cyclical and 33% in
non-cyclical mastalgia after anti-prolactin therapy
(14). In our study, 30% of patients from group 1
completely responded, and 50% of them affirmatively
(decrease in VAS scoring as 50% and more)
responded after Vitex Agnus Castus administration. It
was statistically significant, comparing with placebo
results. Generally response ratio change between 20
and 40% in literatures (15, 16). For our patients,
response was obtained higher, comparing with
previous studies.
Although mastalgia improved in a few subjects from
our placebo group, intensity of mastalgia mostly
remained during 3 three menstrual cycles, and small
number of patients specified that intensity of their
mastalgia increased. When the patients are satisfied
that their mastalgia is due to benign conditions, after
complete assessment and work-up, intensity of
mastalgia improves in most cases, remains in a few
cases.
Results of the double-blind, placebo-controlled
clinical trial which conducted by Halaska et al. (17)
were almost consistent with our results. They included
97 patients were into their study (VACS: n = 48,
placebo: n = 49). They found that Intensity of breast
pain diminished quicker with VACS group, the
tolerability was satisfactory. They stated that VACS
was useful in the treatment of cyclical breast pain in
women. In other hands, we investigated change in
prolactin level in group 1. It was significantly
different from level before treatment administration.
Van Die et al. (28) concluded in their study that, while
evidence from rigorous randomized controlled trials
is lacking for the individual herb in this context,
emerging pharmacological evidence supports a role
for Vitex Agnus Castus in the alleviation of
menopausal symptoms. Vitex Agnus Castus extract is
considered to be dopaminergic effect. Efficacy of
VAC is between 70-90% in mastalgia. In recent
clinical trial, improvements in 53-67% of symptoms
have been reported (11, 19-21).
In several studies, spontaneous improvements in
mastalgia were reported after the patients was inspired
confidence about whose breast pain was not
commonly resulted from breast cancer and it would
be benign conditions. Although mastalgia improved
in a few subjects from our placebo group, intensity of
mastalgia mostly remained during 3 three menstrual
cycles, and small number of patients specified that
intensity of their mastalgia increased. When the
patients are satisfied that their mastalgia is due to
benign conditions, after complete assessment and
work-up, intensity of mastalgia improves in most
cases, remains in a few cases. We estimated that
improvement in mastalgia of our patients was
quenched about their medical problems related
mastalgia. This result was consistent with previous
reports (22, 23).
In conclusion, patients with mastalgia should be
carefully evaluated for breast cancer. On inquiring,
mastalgia should be classified into cyclic and non-
cyclic. If necessary, blood prolactin should be
obtained. Due to effectiveness, tolerability and
usefulness of Vitex Agnus Castus might be chosen as
first-line therapy for patients as well as non-steroidal
anti-inflammatory agents due to high its efficacy and
good tolerability. It is also used to reduce prolactin
level over normal.
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Figure 1. Serum prolactin level before and after treatment
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Düzce Tıp Dergisi 2012; 14(1): 1-5 5
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... The findings showed that the severity of the pain was lower in the herbal medicine group in comparison with the control group (p < 0.001). 2,9,10,[13][14][15][16]18,19,21,22,[24][25][26]28,30 Herbal Medicines versus Placebo ...
... Sensitivity analysis was conducted based on the type and severity of mastalgia. 2,9,10,[13][14][15]18,19,22,[24][25][26]28,30 The intensity of mastalgia was reported mild, therefore Sensitivity analysis was performed to exclude Saghafi et al. 15 The SMD and heterogeneity did not change after the removal of Saghafi study (SMD ¼ -0.58; 95%CI: -0.75--0.42; heterogeneity; p ¼ 0.03; I2 ¼ 44%; random effect model). ...
... 4). 2,10,[13][14][15][16]18,22,[24][25][26][27]33 The severity of pain was lower in the phytoestrogen group compared with in the control group (p < 0.001). ...
Article
Full-text available
Objective Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare providers are interested in herbal medicines. Therefore we aim to study the effectiveness of phytoestrogens on the severity of cyclic mastalgia. Methods To carry out the present study, English electronic resources such as the Cochrane Library, ISI Web of Science, Scopus, and PubMed were used systematically and with no time limitation up to February 10, 2020. Results In total, 20 studies were included in the present meta-analysis. The results of the meta-analysis showed that herbal medicines versus the control group (standard mean difference [SMD] = - 0.585; 95% confidence interval [CI]: - 0.728–- 0.44; heterogeneity; p = 0.02; I2 = 42%), herbal medicines versus the B group (SMD = - 0.59; 95%CI: - 0.75–- 0.44; heterogeneity; p = 0.03; I2 = 42%), and its subgroups, such as phytoestrogen (SMD = - 0.691; 95%CI: - 0.82–- 0.55; heterogeneity; p = 0.669; I2 = 0%), Vitex-agnus-castus (SMD = - 0.642; 95%CI: - 0.84–- 0.44; p < 0.001; p = 203; I2 = 32%), flaxseed (SMD = - 0.63; 95%CI: - 0.901–- 0.367; p = 0.871; I2 = 0%), and evening primrose (SMD= - 0.485; 95%CI:- 0.84–- 0.12; p = 0.008; heterogeneity; p = 0.06; I2 = 56%] may have effective and helpful effects on improving cyclic breast mastalgia. Also, chamomile, isoflavone, cinnamon, and nigella sativa significantly reduced mastalgia symptoms. Conclusion Herbal medicines and their subgroups may have effective and helpful effects on improving cyclic breast mastalgia. The findings of our meta-analysis must be done cautiously because low methodological quality in some evaluated studies of this systematic review.
... Cyclic mastalgia. Nine clinical trials [8][9][10][11][12][13][14][15][16] studied the effects of VAC in patients with CM (Table 1). The participants were mostly reproductive-age (18-45 years) gynecological patients with regular menstrual cycles who experienced CM and absence of any breast malignancies or other severe breast conditions or endocrinopathies. ...
... VAC versus placebo. Comparing the subjective pain intensity indicated by the patients on a linear visual analog scale (VAS), four studies 8,9,11,14 found VAC therapy to be more effective than placebo in relieving the breast pain intensity after 3 months of treatment. Pain intensity was shown by Halaska et al. 9 to drop significantly faster during the first 2 months of VAC treatment compared with that of placebo. ...
... VAC was compared with pharmaceutical interventions for CM in one open-label RCT 10 and three NRTs. [13][14][15] VAC was found to be as effective as dopamine agonists in Kilicdag et al. 10 (bromocriptine) and Malykhina 13 (bromocriptine and dostinex) as well as nonsteroidal anti-inflammatory drugs in Aydin et al. 14 (meloxicam) and Dinc and Coskun 15 (flurbiprofen). All these studies found no significant difference in the pain intensity reduction measures between VAC and its pharmaceutical comparators. ...
Article
Background. Cyclic mastalgia (CM) is premenstrual bilateral and diffuse breast pain that presents cyclically and affects women in their reproductive years. It may associate with latent hyperprolactinemia due to the insufficient inhibitory effect of dopamine on the pituitary gland. Vitex agnus-castus (VAC) is known for its dopaminergic activity and its possible actions on CM and latent hyperprolactinemia. However, the treatment effect of VAC on CM remains unclear.Materials and methods. To perform a systematic review and meta-analysis of clinical trials that report on the efficacy ofVAC treatment in CM patients, literature search was performed in major research databases.Results. This review includes 25 studies (17 randomized control trials plus eight nonrandomized trials). VAC was effective in relieving breast pain intensity and lowering the increased serum prolactin level in reproductive age CM patients (18-45 years) with or without premenstrual syndromes. Typical dosage was 20-40 mg/day with a treatment duration of 3 months. A conservative meta-analysis included only six studies (n = 718: VAC - 356, placebo - 362) and revealed a moderate effect size (SMD 0.67, 95% CI 0.5­0.85) favoring VAC over a placebo. Seven trials demonstrated VAC to be a noninferior alternative to pharmaceutical therapies for CM, including dopamine agonists, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors, and hormonal contraceptives. VAC was safe and associated with only mild and reversible adverse events. However, the risk of bias in most studies was unclear due to insufficient information.Conclusion. VAC is a safe and effective treatment option for CM. More high-qualityclinicaltrialsareneededto strengthentheevidencebase.
... Cyclic mastalgia. Nine clinical trials [8][9][10][11][12][13][14][15][16] studied the effects of VAC in patients with CM (Table 1). The participants were mostly reproductive-age (18-45 years) gynecological patients with regular menstrual cycles who experienced CM and absence of any breast malignancies or other severe breast conditions or endocrinopathies. ...
... VAC versus placebo. Comparing the subjective pain intensity indicated by the patients on a linear visual analog scale (VAS), four studies 8,9,11,14 found VAC therapy to be more effective than placebo in relieving the breast pain intensity after 3 months of treatment. Pain intensity was shown by Halaska et al. 9 to drop significantly faster during the first 2 months of VAC treatment compared with that of placebo. ...
... VAC was compared with pharmaceutical interventions for CM in one open-label RCT 10 and three NRTs. [13][14][15] VAC was found to be as effective as dopamine agonists in Kilicdag et al. 10 (bromocriptine) and Malykhina 13 (bromocriptine and dostinex) as well as nonsteroidal anti-inflammatory drugs in Aydin et al. 14 (meloxicam) and Dinc and Coskun 15 (flurbiprofen). All these studies found no significant difference in the pain intensity reduction measures between VAC and its pharmaceutical comparators. ...
Article
Background: Cyclic mastalgia (CM) is premenstrual bilateral and diffuse breast pain that presents cyclically and affects women in their reproductive years. It may associate with latent hyperprolactinemia due to the insufficient inhibitory effect of dopamine on the pituitary gland. Vitex agnus-castus (VAC) is known for its dopaminergic activity and its possible actions on CM and latent hyperprolactinemia. However, the treatment effect of VAC on CM remains unclear. Materials and Methods: To perform a systematic review and meta-analysis of clinical trials that report on the efficacy of VAC treatment in CM patients, literature search was performed in major research databases. Results: This review includes 25 studies (17 randomized control trials plus eight nonrandomized trials). VAC was effective in relieving breast pain intensity and lowering the increased serum prolactin level in reproductive age CM patients (18-45 years) with or without premenstrual syndromes. Typical dosage was 20-40 mg/day with a treatment duration of 3 months. A conservative meta-analysis included only six studies (n = 718, VAC = 356, placebo = 362) and revealed a moderate effect size (SMD: 0.67, 95% CI: 0.5-0.85) favoring VAC over a placebo. Seven trials demonstrated VAC to be a noninferior alternative to pharmaceutical therapies for CM, including dopamine agonists, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors, and hormonal contraceptives. VAC was safe and associated with only mild and reversible adverse events. However, the risk of bias in most studies was unclear due to insufficient information. Conclusions: VAC is a safe and effective treatment option for CM. More high-quality clinical trials are needed to strengthen the evidence base.
... Eighteen placebo-control studies were included in this systematic review [11,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. In 12 studies, herbal medicines were compared with other herbal medicines or vitamins or Open study and non-randomized (7) Other language (n=4) non-herbal medicines (Pyridoxine, Mefenamic acid, Diclofenac, Flubiprofen and Nonsteroidal anti-inflammatory) [44][45][46][47][48][49][50][51][52][53][54][55]. ...
... The results of the "risk of bias" evaluation for the included studies have been indicated in Figures 2 and 3. Four studies [27][28][29][30] were merely low-risk in terms of all the bias criteria and three other studies [31,32,44] were low-risk in terms of all the criteria except for reporting bias; in fact, their reporting bias was unclear. There was no information about randomization, blinding, and allocation concealment in three papers [33,34,45,46]. Eleven papers [11, 27-32, 35, 36, 44, 47] had done allocation concealment and in other papers, there was no information about allocation concealment. ...
Article
Cyclic mastalgia is one of the most prevalent problems in women of reproductive age and sometimes it is so severe that it influences their activities and requires treatment. The available drug treatments for mastalgia are not satisfactory and most patients have inclined towards complementary and alternative medicine including herbal medicines. Therefore, in order to evaluate the effectiveness and side effects of herbal medicines conducting systematic review studies and meta-analysis seems essential, thus this systematic review was conducted with the aim of determining the effect of herbal medicines on cyclic mastalgia and its probable side effects. The databases of Pubmed, Medline, Embase, ProQuest, Scopus, Web of science, Complementary Medicine Database, SID (Scientific information database), Magiran and Iranmedex were searched from 1997 to 2020 and limited only for English and Persian languages. The studies were appraised according to the Cochrane Collaboration’s tool. Meta-analysis was conducted using RevMan software. Standardized mean difference (SMD) was calculated to assess an overall estimate of effectiveness for the continuous data. Odds ratio (OR) was calculated for dichotomous data. Thirty papers were included in the study. Meta-analysis of data demonstrated that herbal medicine was an effective method in reducing the severity of mastalgia compared to the placebo (SMD: −3.26, 95% CI: −5.05 to −1.46, p=0.00004). Subanalysis of data showed no difference between the effectiveness of herbal medicine on the severity of mastalgia compared to the pharmacologic treatment. This research demonstrated efficacy of herbal medicines in alleviating cyclic mastalgia. Therefore, these herbal medicines can be regarded as an alternative treatment for women suffering from cyclic mastalgia. However, due to the limited number of studies in relation to each specific herbal treatment, conducting further studies in this area is recommended.
... bağımsız olup; postmenopozal kadınlarda daha sık görülmektedir. 3 Yapılan çalışmalara göre mastalji, 20-50 yaş arasındaki kadınlarda daha sık görülmekte ve prevalansı %50-80 arasında değişmekte olup; mastaljili kadınların %10-25'i şiddetli ağrı yaşamaktadır. [3][4][5][6][7][8][9][10] Bununla birlikte toplumda henüz tanı almamış birçok mastaljili kadının olduğu tahmin edilmektedir. 10 Mastalji, kadınların yaşam kalitesini büyük oranda düşürmekte, hatta günlük aktivitelerin yapılmasını dahi olumsuz yönde etkileyebilmektedir. 11 Bunlara ek olarak sık görülen mastalji atakları ile posttravmatik stres bozukluğu, depresyon ve panik bozukluğu, irritabl bağırsak sendromu, kronik pelvik ağrısı, fibromiyalji ve meme kanseri arasında bir ilişki olduğu ileri sürülmektedir. ...
Article
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Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.
Article
Vitex agnus-castus L. ist eine bewährte Arzneipflanze zur Behandlung zyklusabhängiger Beschwerden. Umfangreiche pharmakologische und klinische Daten untermauern den Stellenwert des Mönchspfeffers als evidenzbasierte Therapieoption. Extrakte aus den getrockneten Früchten zeigen dopaminerge Wirkungen und können damit eine Hyperprolaktinämie günstig beeinflussen, welche Zyklusbeschwerden in vielen Fällen zugrunde liegt. Mastodynien, prämenstruelle Beschwerden sowie Regeltempoanomalien können effektiv behandelt werden. Auch bei Corpus-luteum-Insuffizienz-bedingter Infertilität und Dysmenorrhö ist der Einsatz von Vitex agnus-castus sinnvoll. Summary Vitex agnus-castus: evidence-based treatment of menstrual cycle complaints Vitex agnus-castus L. is a proven medicinal herb for treating menstrual cycle-related complaints. Extensive pharmacological and clinical data support the significance of Vitex agnus-castus as evidence-based treatment option. Extracts from the dried fruits show dopaminergic effects and can therefore have a positive effect on hyperprolactinemia, in many cases the cause of menstrual cycle complaints. Breast tenderness, premenstrual symptoms and cycle irregularities can be effectively treated. In addition, the use of Vitex agnus-castus is reasonable for the treatment of corpus luteum insufficiency-related infertility and dysmenorrhea.
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The origin of the current practice of administering Vitex agnus-castus in menopause-related complaints is uncertain, but appears to be relatively recent. Here we review the evidence for this application of Vitex based on evidence from pharmacological studies and clinical research. The mechanisms of potential relevance in the context of menopause are explored with reference to the current understanding of the endocrinology and neuroendocrinology of menopause and associated symptoms. We conclude that, while evidence from rigorous randomized controlled trials is lacking for the individual herb in this context, emerging pharmacological evidence supports a role for V. agnus-castus in the alleviation of menopausal symptoms and suggests that further investigation may be appropriate.
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There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.
Article
Literature searches were conducted in six electronic databases, in references lists of all identified papers and in departmental files. Data from spontaneous reporting schemes of the WHO and national drug safety bodies were also included. Twelve manufacturers of VAC-containing preparations and five herbalist organisations were contacted for additional information. No language restrictions were imposed. Combination preparations including VAC or homeopathic preparations of VAC were excluded. Data extraction of key data from all articles reporting adverse events or interactions was performed independently by at least two reviewers, regardless of study design. Data from clinical trials, postmarketing surveillance studies, surveys, spontaneous reporting schemes, manufacturers and herbalist organisations indicate that the adverse events following VAC treatment are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash. No drug interactions were reported. Use of VAC should be avoided during pregnancy or lactation. Theoretically, VAC might also interfere with dopaminergic antagonists. Although further rigorous studies are needed to assess the safety of VAC, the data available seem to indicate that VAC is a safe herbal medicine.
Article
dular, but usually the symptoms are most distinct in the upper outer quadrant. The cyclical type occurs as a bilateral disorder in well over 50% of cases. In unilateral cases, left and right breasts are affected with equal frequency (23). In unilateral cases especially, radiation of pain to ipsilateral axilla and arm is often noted. Furthermore, the pain can shift from one breast to the other. In non-cyclical mastalgia, the pain is localized to a distinct part of the breast. The patient is almost always able to point to the exact site of the pain, and the tender site is also easily located by the physician. Furthermore, the localization of the pain is characteristically constant. Unilateral cases clearly predominate.
Article
Mild breast pain and nodularity are common and may be considered normal. Only when symptoms are severe enough to affect the patient's lifestyle should drug treatment be considered. Using danazol, bromocriptine or evening primrose oil a clinically useful improvement in pain can be anticipated in 77% of patients with cyclical mastalgia and 44% with non-cyclical mastalgia. Benign nodularity should not be biopsied surgically as it is unnecessary and makes subsequent assessment of the breast difficult.
Article
Management of the patient with mastalgia who fails to respond to first line therapy is a difficult problem and there is a group of patients who do not respond to any therapy. A group of 126 patients with mastalgia who failed to respond to first line therapy and completed further treatment options was studied. The response rate of those with cyclical mastalgia fell to 57 and 25 per cent for second and third line therapy respectively. Equivalent figures for non-cyclical mastalgia were 24 and 21 per cent. Danazol maintains a high response rate after the failure of other drugs, whereas the second line response to bromocriptine and evening primrose oil is poor. Unresponsive patients were matched to a group of patients who responded to first line therapy, and reproductive and historical factors were compared using the chi 2 test, but failed to identify which patients would respond to therapy.
Article
Severe breast pain or mastalgia is a common symptom, affecting up to 70% of the female population at some time in their lives. It accounts for approximately 50% of referrals to a specialised breast clinic, two-thirds of patients having cyclical and one-third experiencing noncyclical mastalgia, or pain arising from the chest wall deep to the breast. After exclusion of breast cancer and proper reassurance, 85% of patients can be discharged from the clinic without specific treatment. In only 15% of patients is the pain severe enough to affect their lifestyle and warrant drug therapy. Using EF-12 (gammalinolenic acid; gamolenic acid) as first-line therapy, with danazol and bromocriptine usually as second-line agents, a clinically useful improvement in pain can be anticipated in 92% of patients with cyclical and 64% with noncyclical mastalgia. Patients with severe recurrent or refractory mastalgia may require treatment with tamoxifen, goserelin or testosterone, but the short and long term adverse effects of these drugs preclude their use as first-line agents. Chest wall pain is usually self-limiting, but symptomatic relief can often be obtained using steroidal and local anaesthetic injections or nonsteroidal anti-inflammatory drugs.
Article
In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.