INFLUENCE OF PROBIOTIC SUPPLEMENTATION ON CLIMACTERIC SYMPTOMS IN
MENOPAUSAL WOMEN-A MINI REVIEW
BHAGAVATHI SUNDARAM SIVAMARUTHI, PERIYANAINA KESIKA, CHAIYAVAT CHAIYASUT
Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200,
Received: 21 Feb 2018, Revised and Accepted: 04 Sep 2018
Menopause (MP) is a natural physiological event of woman’s life and is defined as the absence of menstrual periods for at least twelve months and
loss of function of ovarian. The common symptoms of MP are irregular vaginal bleeding, hot flushes especially in head and chest, night sweats,
insomnia, vaginal and urinary symptoms, cognitive dysfunction, increased cancer risk, osteopenia, high blood pressure, diabetes, and cardiovascular
diseases. Microbiome has been associated with several health benefits. Probiotic supplementation helps to enhance the quality of microbiome
thereby confers the health benefits to the host system. The microbiome, hormone (estrogen) changes, and probiotic intervention are related to the
health status of the female reproductive system. The vaginal microbiome (VM) play a critical role in female reproductive health and MP, which can
be greatly influenced by probiotics, and other medicine especially antibiotics and hormone therapy. The role of VM in supporting vaginal health is
not clear and debatable. Understanding the role of vaginal Lactobacillus could expose the pathogenesis of vaginal dysbiosis, which helps to improve
diagnostic and therapeutic strategies for several dysbiosis associated health issues and menopause-related symptoms. Recent studies suggested
that the intervention of probiotic preparation with or without nutraceutical formulation (mostly with isoflavones) improve the health status of
menopausal women. The mechanism of probiotics mediated health improvement in menopausal women is not yet described clearly. Several
controversies are there on the link between probiotic, gut microbiota, vaginal microbiota, and estrogen deficit. The present review summarizes the
influence of probiotic supplementation on climacteric symptoms in menopausal women. The literature search was made in Scopus, Google Scholar,
PubMed using the keywords “probiotics” and “menopause”. The documents were carefully checked for the relevance to the current manuscript, and
the selection was made without any restriction in the year of publication.
Keywords: Probiotics, Estrogen, Menopause, Vaginal microbiome, Climacteric symptoms
© 2018 The Authors. Published by I nnovare Academic Sciences Pvt Ltd. This is an open ac cess article u nder the CC BY license (http://creativecommons.org/licenses/by/4. 0/)
DOI: http://dx.doi.org/10.22 159/ijap.2018v10i6.29156
Menopause (MP) is a natural physiological event of woman’s life and
is defined as the absence of menstrual periods for at least twelve
months and loss of function of ovarian. MP is not a rapid biological
event but is a relatively slow biological process. The age of MP varies
(46-52 y) among the people, which greatly depends on the
socioeconomic status, personal health care, and food habits. There is
no unswerving test to predict the onset of MP. Moreover, MP can’t be
predictable with the time of initial mensural period. The symptoms
and the experience of the perimenopausal transition period differ
for each woman [1, 2].
The common symptoms of MP are irregular vaginal bleeding, hot
flushes especially in head and chest (about 85% of woman
experiencing the hot flushes), night sweats, insomnia, vaginal
symptoms (dryness, irritation, dyspareunia, and infections), urinary
symptoms (frequent urination, urinary incontinence), cognitive
dysfunction, physical changes, restlessness, muscle and joint pain,
and MP also associated with increased cancer risk, osteopenia, high
blood pressure, diabetes, and cardiovascular diseases. The
symptoms are not common to all woman. Some people do not feel
any or some of the symptoms during their MP [3-5].
The hormone changes or deficiency is the main cause of MP. Thus,
hormone replacement therapy (HRT) is the primary treatment
method to nullify or reduce the MP symptoms and to prevent the
development of heart diseases and osteoporosis. The mode of
administration, dose, and combination of the hormone are the key
factors that affect the efficiency of the treatment and help to reduce
the adverse side effects. Oral administration therapy was less
effective compared to transdermal estrogen therapy .
Though HRT has beneficial effects, some of the controversial side
effects were reported. The contentious HRT increased the risk of
cancer development, thromboembolism, and cardiovascular
consequences. There was no general treatment procedure, and HRT
should be customized for each woman [6-8]. Moreover, many
women seek alternative treatments other than HRT, when there are
several health risks and uncertainty on reported benefits of HRT .
The serotonin-norepinephrine reuptake inhibitor and selective
serotonin reuptake inhibitor were used to treat the hot flushes. These
inhibitors help to improve vasomotor symptoms and sleep quality .
The phytoestrogens (PE) are phenolic compounds present in plants with
mammalian estrogenic activity. PE binds to estrogen receptors and
endorses either agonist or antagonist functions .
Probiotics are living microbes when administered in an adequate
amount, confers beneficial effects in the host health. Commonly,
lactic acid bacteria (LAB) are considered as probiotics, and
beneficial impact of the probiotics is highly associated with an
individual’s health status, age, and lifestyle . Probiotic strains
were reported for several health aids and applications [11-23].
Changes in the gut microbiome influence the several physiological
and biological process. The microbiome changes during estrogen
deficiency, characteristics of MP, critically affects the MP symptoms
and facilitates the development of illness like inflammatory diseases.
The supplementation of probiotics significantly influences the gut
microbiome of an individual .
Since the alternative therapies for MP with phytoestrogen and herbal
products have been detailed previously by Borrelli and Ernst . The
current review narrates the probiotic based alternative treatment for MP
and its impact on climacteric symptoms of menopausal women. The
literature search was made in Scopus, Google Scholar, PubMed using the
keywords “probiotics” and “menopause”. The documents were carefully
checked for the relevance to the current review, and the selection was
made without any restriction in the year of publication.
Microbiome of women
The microbiome is unique for every individual to some extent. The
gut microbiome plays an essential role in almost all biological events
ISSN- 0975-7058 Vol 10, Issue 6, 2018
Chaiyas ut et al.
Int J App Pharm, Vol 10, Issue 6, 2018, 43-46
and cognitive functions. Subsequently, microbiome might possibly
have a role in making healthy offspring moreover in persuading the
general health status of an individual. The microbiome of a woman
differs from man. The vaginal microbiome (VM) is influenced by
several factors like menses, vaginal discharge, and sperm. VM
greatly influences the health status of offspring. Lactobacillus spp.
(especially Lactobacillus crispatus, L. gasseri, L. iners, and L. jensenii)
are the dominant bacterial species present in VM of healthy women,
and any alteration in the composition of VM leads to several adverse
conditions like preterm birth, infertility, inflammatory and high risk
of sexually transmitted diseases. Finally, it affects the quality of life
[26-28]. Atopobium, Prevotella, Peptoniphilus, Dialister, Megasphaera,
Gardnerella are some of the leading non-Lactobacillus microbial
community residing in the urogenital tract of women .
The role of VM in sustaining vaginal health is not clear and
controversial. Understanding the role of vaginal Lactobacillus could
uncover the pathogenesis of vaginal dysbiosis, which helps to refine
diagnostic and therapeutic strategies for several dysbiosis
associated health issues and to diminish or manage the menopause-
related symptoms .
The VM composition differs in post-menopausal women when
compared with premenopausal women, particularity the Lactobacillus
content. The VM is extremely affected by the HRT [30-32]. Menopause
decreases a load of Lactobacillus in VM, and also affects the diversity of
microbes. Age, menstruation, hormone levels, intercourse, other lifestyle
habits like smoking, hygiene have an impact on the bacterial community
of a woman [33, 34]. The description of the VM in different stages in a
woman’s life is multifaceted .
The dramatic change in VM could be noted at the time of puberty
when hormone (estrogen) and glycogen levels increase . The
increased level of estrogen and glycogen facilitates or promote the
growth of Lactobacillus, and it is known that the high level of
glycogen is maintained during the fertile period of a woman and
further decline in its level during menopause. Lactobacillus protects
the vaginal area from pathogenic colonization by creating the acidic
microenvironment, but an overgrowth of microaerophilic bacteria
cause distress, itching, and foul-smelling discharge [37, 38]. Several
studies suggested that diversity of Lactobacillus spp. and its richness
has been decreased during or after menopause .
Probiotics and menopause
The postmenopausal women with the significantly high Nugent
score (between 4 to 6) were screened and selected for the study.
The Nugent scoring is an unbiased, semi-quantitative evaluation
(microbial content) of vaginal secretion. The subjects were
randomly divided into two groups and supplemented with either
probiotic (lyophilized L. reuteri RC-14 and L. rhamnosus GR-1 along
with sodium alginate; 2.5 × 109
About 2044 women (40-65 y) were supplemented with a mixture of
soybean extract (contains genistein and daidzein; 30 mg each), L.
sporogenes (500 million spores), 5 µg of vitamin D and 141 mg of
calcium for six months and the changes in climacteric symptoms
were assessed by questionnaire. The changes were noted by
gynecologists and self-assessment. The results suggested that the
soybean extract with probiotic supplementation significantly
improved the climacteric symptoms and sexuality .
CFU each) or placebo (lactose) for
fourteen days. After the intervention, vaginal swabs were collected
and further subjected to Nugent scoring. The results showed that
about 60% of women who received probiotic supplement had a
reduction in their Nugent score from the baseline when compared to
that of the placebo group. About three grade reduction was observed
among the probiotic group, which indicates the significant
improvement in the host health. The results suggested that the oral
supplementation of probiotics help to restore the normal flora of the
A double-blind, randomized, placebo-controlled study was conducted
with postmenopausal women with vaginal atrophy symptoms to know
the impact of supplementation of Gynoflor® vaginal tablets (a blend of L.
acidophilus KS400 and estriol 0.03 mg). The supplement was provided
for 12 d for initial treatment and 2 tablets per week for 12 w to maintain
the effects. Vaginal maturation index (VMI) was changed positively in the
treatment group (35.2%) when compared to placebo (9.9%). The study
proved that Gynoflor® is effective in reducing vaginal atrophy
symptoms and improved the VMI .
The ovariectomized mouse was supplemented with L. reuteri ATCC
PTA 6475 via oral gavage (1×109 CFU/ml trice per day) and through
drinking water (1.5×108 CFU/ml) for four weeks. The probiotic
supplementation significantly reduced the bone resorption and
osteoclastogenesis. The increase in CD4+
Postmenopausal breast cancer patients receiving chemotherapy (with
vaginal atrophy and altered microbiota) were treated with probiotics (a
mixture of 1 × 10
T-lymphocytes has been
reduced and thereby L. reuteri directly repressed osteoclastogenesis,
and probiotic intervention altered the gut microbiome of the
experimental mouse, especially Clostridiales was increased in the
treated mouse. The results suggested that supplementation of L.
reuteri suppress the post-menopausal bone loss .
Symptomatic postmenopausal women were treated with probiotic
(B. breve B3 ATCC 15700; 1 trillion CFU) and nutraceutical formula
(80 mg of soy isoflavones, 50 mg of Angelica sinensis extract, 200 mg
of Morus alba leaf extract, and 56.25 mg of magnesium) for 4 w or
probiotic and placebo or vice versa. The menopause rating scale
(MRS) score was reduced, and a significant reduction in
triglycerides, LDL, and increase in HDL was observed in the
probiotic-treated group. The intervention of probiotic and
nutraceutical formula improved the MRS score and risk of
cardiovascular diseases . Peri-menopausal women subjects were
supplemented with isoflavones and probiotics (34 mg/d isoflavones;
probiotic combinations and dosage were not revealed in the study)
for 12 w. The hot flush frequency (HFF), hot flush intensity, self-
reported HFF, and hot flush severity, plasma lipids and blood
pressure were measured. The results suggested that moderate
intervention of red clover isoflavone and probiotics significantly
reduced the self-reported vasomotor symptoms .
9 CFU of L. crispatus LbV 88, 1 × 109CFU of L. rhamnosus
LbV 96, 0.2 × 109 CFU of L. ensenii LbV 116 and 0.3 × 109
CFU of L. gasseri
LbV 150N) twice daily for two weeks. After treatment, changes in the
vaginal microbiota and Nugent score were reexamined and compared
with baseline. The results suggested that probiotic intervention
significantly reduced the Nugent score in the probiotic-treated group
when compared to that of the placebo. The vaginal microbiota also
altered positively in probiotic-treated women. The study proved that
probiotic supplementation helps to regain the normal vaginal flora in
women receiving chemotherapy for cancer .
Table 1: The influence of probiotic supplementation on the consequences of menopause
L. rhamnosus GR-1 and L.
2.5 × 109
Nugent score was reduced, and
health status improved
Women (2044 subjects)
Soy extract (genistein and
daidzein; 30 mg each),
mg) and vitamin D (5 µg).
Improved the climacteric
symptoms and sexuality
with vaginal atrophy
L. acidophilus KS400 and
estriol 0.03 mg (Gynoflor®)
Single tablet for
12 d followed by
Gynoflor ® improved VMI after
the 12-day initial therapy, and
Chaiyas ut et al.
Int J App Pharm, Vol 10, Issue 6, 2018, 43-46
2 tablets per
week for 12 w
two tablets weekly was
appropriate to prevent the
L. reuteri ATCC PTA 6475
CFU/ml via oral
1.5 × 10
Trice per day for
Significantly protected mice from
bone resorption and loss.
Suppressed the CD4+T-
B. breve B3 ATCC 15700,
1 trillion CFU
Menopause rating scale score
was reduced. Reduced the risk of
women (62 subjects)
A mixture of probiotic LAB
Suppressed the self-reported
L. crispatus LbV 88, L.
LbV 116 and
2.5 × 109
Reduction in Nugent score,
Improved the vaginal microbiota
Generally, probiotic supplementation improved the health status of
gastrointestinal (GI) system, and it has been proved by several
clinical and human studies. Recently, the health benefits of probiotic
were beyond the GI and its associated system such as anti-aging,
anti-inflammation, improved the cognitive decline, anti-
hypertension, anti-hypercholesterolemia, etc. The role of probiotic
to manage the postmenopausal disorders and to control the
climacteric symptoms is the recent subject of interest for several
researchers . The well-planned, placebo-controlled clinical
studies on the health benefits of probiotics in menopausal women
are very limited (table 1). The reports clearly suggested that the
intervention of optimum level of probiotic supplementation along
with some nutraceuticals improved the climacteric symptoms and
vaginal health status by altering the microbiota. Several studies
recommend the isoflavones supplementation to treat symptoms of
menopause. The combination of an enzyme producing probiotics
such as β-glucosidase producing probiotics with soy extract help to
improve the symptoms of menopause via producing bioactive
isoflavone aglycones . A study reported that the fermentation of
soy milk with L. acidophilus does not significantly increase the
absorption of Ca in osteopenic post-menopausal women . Some
controversial reports stated that the supplementation of soy-
isoflavone does not influence the microbiota of menopausal women
. The mechanism of probiotics mediated health improvement in
menopausal women is not yet explained clearly. The connection
between probiotic, gut microbiota, vaginal microbiota, and hormone
(estrogen) deficit are the subject of several controversies. Further
detailed well-planned intensive studies are required to explore the
mysteries between the probiotics and menopause.
BSS and PK gratefully acknowledge the CMU Post-Doctoral
Fellowship, and Faculty of Pharmacy, Chiang Mai University for the
support. All the authors wish to thank CMU research grant for the
BSS and PK contributed to conception and design, acquisition,
manuscript preparation, and critical revision of the manuscript. CC
involved in the review and finalization of the manuscript. All the
authors agree with the content of the manuscript.
CONFLICT OF INTERESTS
The authors declare that there is no conflict of interests
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