Original Article

The Impact of Soy Isoflavone Supplementation on the Menopausal

Symptoms in Perimenopausal and Postmenopausal Women
Shrutika Khapre, Ujjwala Deshmukh1, Sheela Jain

Department of Obstetrics and Introduction: Approximately one‑third of a woman’s life is spent in the

Abstract
Gynaecology, NKP Salve
Institute of Medical Sciences
menopausal phase. The unpleasant menopausal symptoms are unacceptable as a
and Lata Mangeshkar part of routine life. Indications of menopausal hormone therapy (MHT) are for
Hospital and Research alleviation of vasomotor symptoms, prevention of osteoporosis, and genitourinary
Centre, 1Dr. Deshmukh symptoms associated with menopause. MHT is associated with an increased
Shree Clinic Nursing Home, risk of breast cancer, cerebrovascular accidents, and coronary heart disease. Soy
Nagpur, Maharashtra, India isoflavones have been extensively used as an alternative treatment in patients
who cannot take MHT. The evidence of the efficacy of isoflavones in the
literature is equivocal. Aim: The aim of the study was to evaluate the efficacy
of soy isoflavone supplementation on menopausal symptoms in perimenopausal
and postmenopausal women and to evaluate the effect on blood pressure (BP)
and body mass index (BMI). Materials and Methods: A questionnaire‑based
prospective observational study was undertaken involving 39 perimenopausal
and 61 postmenopausal women, who were prescribed 40 mg soy isoflavone
supplements twice daily for 12 weeks. Menopause Rating Scale questionnaire
was given to the patients before starting soy isoflavone therapy and at the end of
the treatment; BP and BMI were also noted. Results: The total score of both the
groups was comparable at baseline. Among perimenopausal and postmenopausal
women, the highest score was noted in symptoms of somatic domain. At the
completion of our study, the total scores improved significantly by 38.6%
and 33.3% in perimenopausal and postmenopausal women, respectively. The
greatest improvement was seen in somatic subscale (42.5%) and psychological
subscale (42.5%) and the least in urogenital subscale (16.1%) for perimenopausal
women. For postmenopausal women, the greatest improvement was seen in
psychological subscale (40.0%) and the least in urogenital subscale (14.2%).
Conclusion: Soy isoflavone supplementation is beneficial in both perimenopausal
and postmenopausal women, more so in perimenopausal women. There is no
beneficial effect of soy isoflavone supplementation on lowering systolic BP and
BMI.
Submitted: 24‑Oct‑2021
Revised: 24‑Mar‑2022
Keywords: Blood pressure, body mass index, menopausal hormone therapy,
Accepted: 30‑Jun‑2022
menopause, Menopause Rating Scale questionnaire, selective estrogen receptor
Published: 16-Sep-2022 modulator, soy isoflavones

Introduction

M
Address for correspondence: Dr. Ujjwala Deshmukh,
enopause, i.e., cessation of menses, is an important 16, Dindayal Nagar, Friends Layout 2, Swavalambi
event in the life of a woman. It is a transition phase Nagar Square, Nagpur ‑ 440 022, Maharashtra, India.
from the reproductive to the nonreproductive phase. E‑mail: drujwaladeshmukh59@gmail.com
Menopause is retrospectively diagnosed by a history This is an open access journal, and articles are distributed under the terms of the Creative
of amenorrhea for 1 year. FSH level >40 IU/L, done at Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is
Access this article online given and the new creations are licensed under the identical terms.
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Website: www.jmidlifehealth.org For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

How to cite this article: Khapre S, Deshmukh U, Jain S. The impact

of soy isoflavone supplementation on the menopausal symptoms
DOI: 10.4103/jmh.jmh_190_21 in perimenopausal and postmenopausal women. J Mid-life Health
2022;13:175-84.

© 2022 Journal of Mid-life Health | Published by Wolters Kluwer - Medknow 175

 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

least 4 weeks apart, is a reliable marker for menopause There has been a dramatic rise in the academic and
or impending menopause.[1] The estimated mean age of clinical interests in isoflavones as an alternative to
perimenopause and menopause is 44.69 and 46.2 years, conventional MHT for menopause. Previous studies
respectively, in India according to a Pan India survey by have shown high heterogeneity, making it difficult to
IMS.[2] Thus, approximately one‑third of a woman’s life conclude. Questions such as which active component
is spent in the menopausal phase. Hormonal fluctuations of isoflavones provides estrogen‑like benefits, which
culminating in the final menstrual period begin at least substances in soy, apart from isoflavones, exert
a decade earlier and continue for much longer and are beneficial effects, and whether synthetic isoflavones
characterized by reduced fertility, irregular menstrual are superior to soy isoflavones remain unanswered.
cycles, vasomotor symptoms (VMS), sleep disturbances, No study has suggested an upper limit of dose of
emotional changes, osteoporosis, reduced metabolism, isoflavone supplements. Although soy isoflavones are
and vaginal dryness, which can have a large impact extensively used, scientific evidence for their efficacy
on a woman’s psychological health and well‑being.[3] in the management of menopausal symptoms among
The menopausal symptoms vary with the phase of the Indian women is mixed. We planned this study to
menopausal transition, region, and ethnicity and show a evaluate the impact of soy isoflavone supplementation
greater interindividual variation.[4] on the Menopause Rating Scale (MRS) scores among
Isoflavone is a phytoestrogen and a nonsteroidal perimenopausal and postmenopausal Indian women.
compound. Isoflavones are abundant in soybeans, beans, Aims and objectives
pulses, lentils, red clover, and alfalfa. The major dietary Primary objective
source of isoflavones in the most populations is soy. The primary objective of this study was to study
Soybeans are nutritious and healthy. It is an important the effect of soy isoflavone supplementation on the
source of proteins; contains polyunsaturated fats, fiber, menopausal symptoms (somatic, psychological,
and vitamins; and does not contain starch, saturated fats, and urogenital symptoms) in perimenopausal and
and cholesterol. Soy extract products have been widely
postmenopausal women.
used as an alternative treatment, targeting menopausal
symptoms in patients who cannot or have concerns Secondary objective
related to and are unwilling to take menopausal hormone The secondary objective of this study was to study the
therapy (MHT). Isoflavone is a selective estrogen effect of soy isoflavone supplementation on:
receptor (ER) modulator, with main constituents of 1. Blood pressure (BP)
genistein, daidzein, and glycitein.[5] The studies of 2. Body mass index (BMI).
isoflavone intake in Western countries indicate an
average daily isoflavone intake of approximately <3 mg, Materials and Methods
and Asian populations consuming a high soy diet or Study design
people consuming soy supplements have a daily intake This was a prospective observational study
of approximately 40 mg/day.[6] (questionnaire‑based).
There are two types of ERs: ERα, which is present in Study setting
the breast, uterus, and vagina, and ERβ, which is present The study was conducted at the Outpatient
in the bone, urogenital tract (bladder, urethra, vaginal Department (OPD), Dr. Deshmukh Shree Clinic Nursing
mucosa, and levator ani), cardiovascular system, and Home, Nagpur.
brain. Conventional estrogens bind to both ERα and
ERβ with the same affinity. Isoflavones bind weakly to Study population
ERα, but the affinity to ERβ is stronger (83‑fold).[7] The All perimenopausal and postmenopausal women who
preferential binding of isoflavones to ER‑β receptors gave informed consent to participate in the study and
is responsible for the beneficial effects, and a higher who attended the OPD of Dr. Deshmukh Shree Clinic
concentration of isoflavones required for cellular growth Nursing Home, Nagpur, were enrolled in the study
explains a fewer chances of adverse effects such as according to the inclusion and exclusion criteria.
breast cancer.[8] Before menopause, when there are higher Study duration
circulating levels of endogenous estrogen, isoflavones act
The study duration was 4 months (from June 1, 2021, to
as an estrogen antagonist.[9] Whereas, after menopause,
September 30, 2021).
when there is a low estrogen environment, isoflavones
act as an estrogen agonist and thus effectively balance Sampling technique
the estrogen metabolism in the body. Convenience sampling technique was used.

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 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

Sample size Menopause Rating Scale questionnaire

One hundred perimenopausal and postmenopausal It is an internationally accepted tool for the evaluation
women were included in the study. of menopausal symptoms. It is also validated as a tool to
evaluate the response to therapy. The MRS questionnaire
Sample size calculation
consists of 11 common menopausal symptoms which
Prior data indicated that the difference in the response of
are further grouped into three subscales: somatic,
matched pairs was normally distributed with a standard
psychological, and urogenital. Each of the symptoms is
deviation of 0.8. If the true difference in the mean
scored from 0 (none) to 4 (very severe).[11,12]
response of matched pairs was 2.50 (total MRS score),
we required 100 cases to be studied to be able to reject MRS questionnaire was administered to the patients by
the null hypothesis that this response difference was a face‑to‑face interview in the local language, before
zero with probability (power) of 1.000. The Type I error starting soy isoflavone therapy and at the end of the
probability was kept at 0.05. treatment. Baseline investigations were repeated at
the end of the treatment. The total score and somatic,
Inclusion criteria
psychological, and urogenital subscale scores of both the
Perimenopausal and postmenopausal women with: groups were compared at baseline. Improvement in the
1. BMI 20–40 kg/m2 mean total score and the mean somatic, psychological,
2. Irregular cycles (variable cycle length of >7 days and urogenital subscale scores of both the groups was
different from normal) in case of perimenopausal women noted at the end of the treatment, and a percentage
3. Newly diagnosed patients willing to participate in the reduction was calculated.
study
4. Patients refusing MHT and patients not taking MHT. The effect of soy isoflavone supplementation on various
symptoms was observed and it was ascertained, which
Exclusion criteria subset of symptoms showed maximum improvement.
1. Perimenopausal and postmenopausal women who had It was also seen whether it was more beneficial in
previous treatment with MHT or soy supplements in perimenopausal or postmenopausal women.
the past 12 months
2. Women with a history of a cardiovascular event like During the study, the patients were advised to take a
myocardial infarction within the past 6 months balanced diet and maintain a normal level of physical
3. Allergic to soy products activity. They were given a list of soy‑based foods to
4. Hepatic impairment and renal impairment. be avoided during the therapy. They were advised to
avoid smoking, alcohol consumption, and refrain from
Methodology taking vitamin or mineral supplementation. They were
Perimenopausal and postmenopausal women attending prescribed 40 mg soy isoflavone supplements twice
the OPD were enrolled in the study as per the formulated daily, to be taken between meals for 12 weeks. They
inclusion and exclusion criteria, after counseling and were observed for any untoward side effect or other
detailed written informed consent. complaints.
Sociodemographic data such as age, marital status, The study visits were scheduled at baseline, 6 weeks,
education, and occupation were noted. All the participants and the end of the treatment, and the participants
were subjected to general physical examination, and BMI were contacted telephonically to ensure compliance.
was calculated. Detailed menstrual history and obstetric Compliance was analyzed by checking empty wrappers.
history were elicited. Lifestyle history was elicited. Soy isoflavones were well tolerated and no serious
A history of intake of any medication and previous adverse events were noted during the study.
surgery was noted. Detailed history and family history Statistical analysis
were noted, and baseline investigations were done.
The data were compiled using MS Excel and were
The menstrual status of the patient was evaluated analyzed using using IBM SPSS software version 20.
according to the Stages of Reproduction Aging IBM corp. Armonk New York. Categorical variables
Workshop (STRAW)+10 criteria.[10] were expressed as frequency and proportions, whereas
1. Postmenopausal: No menstrual bleeding for the past continuous variables were expressed as mean and
12 months standard deviation. Chi‑square test was used to assess
2. Late perimenopausal: Amenorrhea for ≥60 days the severity of symptoms in perimenopausal and
3. Early perimenopausal: Irregular periods without postmenopausal women, whereas paired t‑test was used
skipping cycles and >7‑day difference in length of to assess the improvement in symptoms. P < 0.05 was
consecutive cycles. considered statistically significant.

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 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

Results 16. 
2 (5.13%) perimenopausal and 4 (6.56%)
According to the STRAW+10 criteria, of the postmenopausal women were suffering from
100 women enrolled, 39 were perimenopausal and rheumatoid arthritis and 6 (9.84%) postmenopausal
61 were postmenopausal. women were suffering from osteoarthritis
1. The mean age of the perimenopausal group was 17. 
1 (2.56%) perimenopausal and 5 (8.20%)
45.23 years (standard deviation: 3.460 years) and postmenopausal women had suffered a fragility
that of the postmenopausal group was 56.25 years fracture
(standard deviation [SD]: 8.258 years) 18. 
Among perimenopausal women, various problems
2. The mean age of attaining menopause in the such as abnormal uterine bleeding (3 patients),
postmenopausal group was 45.72 years (SD: fibroid (2), adenomyosis (2), cervicitis (4),
4.817 years). The average time since menopause was vaginitis (4), and urinary tract infections (1) were
10.57 years (SD: 8.64 years) seen
3. The women participating in our study had varied 19. 
Among postmenopausal women, various problems
educational qualifications and occupations such as stroke (1 patient), myocardial infarction (2),
4. The mean BMI of perimenopausal women in the atrophic vaginitis (1), and cataract (6) were seen.
study was 25.59 kg/m2 and that of postmenopausal We documented no statistically significant difference
women was 25.74 kg/m2. The distribution of mean in symptomatology between perimenopausal and
BMI did not differ significantly between the two postmenopausal women, except for sleep problems and
study groups (P > 0.05) irritability being more prevalent among perimenopausal
5. The mean systolic BP of perimenopausal women in the women [Table 1].
study was 120.28 mmHg and that of postmenopausal
women was 126.61 mmHg. The distribution of mean In our study, there was no statistically significant
systolic BP did not differ significantly between the difference in the mean total score, somatic, psychological,
two study groups (P > 0.05) and urogenital subscale score between perimenopausal
6. 6 (15.38%) perimenopausal women and 10 (16.39%) and postmenopausal women. In perimenopausal and
postmenopausal women had high caffeine consumption postmenopausal women, the highest score was observed
7. 16 (41.03%) perimenopausal women exercised in the somatic subscale and the lowest score was
daily and 11 (28.21%) women practiced yoga. observed in the urogenital subscale [Table 2].
24 (39.34%) postmenopausal women exercised daily
The reduction in the mean total score, somatic
and 17 (27.87%) women practiced yoga
subscale score, and psychological subscale score in
8. 10 (25.64%) perimenopausal women and 21 (34.43%)
perimenopausal women was statistically significant after
postmenopausal women took calcium supplements daily
12 weeks of soy isoflavone supplementation [Table 3].
9. 5 (12.82%) perimenopausal women and 14 (22.95%)
postmenopausal women took Vitamin D supplements The reduction in the mean total score, somatic
regularly subscale score, and psychological subscale score in
10. None of the participants had a history of intake of postmenopausal women was statistically significant after
soy supplements 12 weeks of soy isoflavone supplementation [Table 4].
11. 1 (2.56%) perimenopausal women and 3 (4.92%)
The reduction in systolic BP, after 12 weeks of soy
postmenopausal women reported a history of intake
isoflavone supplementation, in perimenopausal and
of MHT in the past (>12 months before the start of
postmenopausal women was not statistically significant.
the study)
Of particular note, all the patients reported a reduction
12. 12 (19.67%) women had attained surgical
in systolic BP [Table 5].
menopause. Oophorectomy was done in 4 (6.56%)
of them The reduction in BMI, after 12 weeks of soy isoflavone
13. 9 (23.08%) perimenopausal and 23 (37.70%) supplementation, in perimenopausal and postmenopausal
postmenopausal women were suffering from was not statistically significant. Of particular note, all
hypertension the patients reported a reduction in BMI [Table 6].
14. 4 (10.26%) perimenopausal and 9 (14.75%)
None of the hypothyroid patients reported worsening of
postmenopausal women were suffering from
thyroid function necessitating an increase in thyroxine
diabetes mellitus
supplementation.
15. 3 (7.69%) perimenopausal and 5 (8.20%)
postmenopausal women were suffering from thyroid Thus, soy isoflavone supplementation was beneficial in
disorders both perimenopausal (38.6% reduction in symptoms)

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 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

Table 1: Analysis of individual symptoms in perimenopausal and postmenopausal women as per Menopause Rating
Scale
Symptoms Group None, n (%) Mild, n (%) Moderate, Severe, Very severe, Total, n (%) P
n (%) n (%) n (%)
Hot flashes, sweating Perimenopausal 12 (30.8) 13 (33.3) 3 (7.7) 9 (23.1) 2 (5.1) 39 (100.0) 0.234NS
Postmenopausal 26 (42.6) 23 (37.7) 4 (6.6) 8 (13.1) 0 61 (100.0)
Heart discomfort Perimenopausal 25 (64.1) 8 (20.5) 4 (10.3) 2 (5.1) 0 39 (100.0) 0.792NS
Postmenopausal 33 (54.1) 17 (27.9) 7 (11.5) 4 (6.6) 0 61 (100.0)
Sleep problems Perimenopausal 20 (51.3) 16 (41.0) 1 (2.6) 2 (5.6) 0 39 (100.0) 0.024*
Postmenopausal 33 (54.1) 13 (21.3) 13 (21.3) 2 (3.3) 0 61 (100.0)
Depressive mood Perimenopausal 17 (43.6) 20 (51.3) 2 (5.1) 0 0 39 (100.0) 0.477NS
Postmenopausal 26 (42.6) 27 (44.3) 5 (8.2) 3 (4.9) 0 61 (100.0)
Irritability Perimenopausal 18 (46.2) 19 (48.7) 2 (5.1) 0 0 39 (100.0) 0.050*
Postmenopausal 39 (63.9) 14 (23.0) 7 (11.5) 1 (1.6) 0 61 (100.0)
Anxiety Perimenopausal 21 (53.8) 16 (41.0) 2 (5.1) 0 0 39 (100.0) 0.691NS
Postmenopausal 35 (57.4) 20 (32.8) 5 (8.2) 1 (1.6) 0 61 (100.0)
Physical and mental Perimenopausal 21 (53.8) 12 (30.8) 4 (10.3) 2 (5.1) 0 39 (100.0) 0.604NS
exhaustion Postmenopausal 25 (41.0) 25 (41.0) 6 (9.8) 5 (8.2) 0 61 (100.0)
Sexual problems Perimenopausal 36 (92.3) 2 (5.1) 1 (2.6) 0 0 39 (100.0) 0.143NS
Postmenopausal 60 (98.4) 0 0 0 1 (1.6) 61 (100.0)
Bladder problems Perimenopausal 33 (84.6) 4 (10.3) 1 (2.6) 1 (2.6) 0 39 (100.0) 0.373NS
Postmenopausal 43 (70.5) 9 (14.8) 6 (9.8) 3 (4.9) 0 61 (100.0)
Dryness of vagina Perimenopausal 30 (76.9) 7 (17.9) 2 (5.1) 0 0 39 (100.0) 0.174NS
Postmenopausal 52 (85.2) 5 (8.2) 1 (1.6) 3 (4.9) 0 61 (100.0)
Joint and muscular Perimenopausal 16 (41.0) 14 (35.9) 6 (15.4) 2 (5.1) 1 (2.6) 39 (100.0) 0.381NS
discomfort Postmenopausal 25 (41.0) 21 (34.4) 6 (9.8) 9 (14.8) 0 61 (100.0)
*P<0.05. P by Chi-square test. P<0.05 is considered to be statistically significant. NS: Statistically nonsignificant

Table 2: Menopause Rating Scale score at baseline of psychological subscales. There was no statistically
perimenopausal and postmenopausal women significant effect on systolic BP and BMI in both
MRS domain Perimenopausal Postmenopausal P perimenopausal and postmenopausal women.
Mean SD Mean SD
MRS mean total score 6.51 4.74 7.03 4.86 0.586NS Discussion
Somatic subscale 3.49 2.95 3.44 2.43 0.927NS In the present study, the highest score and the greatest
Psychological subscale 2.38 2.15 2.75 2.40 0.436NS
improvement in perimenopausal women were noted in
Urogenital subscale 0.62 1.09 0.85 1.76 0.467NS
symptoms of somatic subscale, whereas the lowest score
MRS: Menopause Rating Scale, NS: Statistically nonsignificant, SD:
Standard deviation and the lowest improvement were noted in urogenital
subscale. The results of our study are in accordance
Table 3: Mean Menopause Rating Scale scores in the with the study by Ahsan and Mallick,[13] wherein the
perimenopausal group at baseline and after 12 weeks of greatest improvement was seen in symptoms of somatic
therapy (n=39) subscale (27.7%) and psychological subscale (26.32%)
MRS domain Score Score Absolute Percentage Significance and the least improvement was in urogenital
before after change change (P) subscale (1.19%) in perimenopausal women.
MRS mean total 6.51 4.01 2.51 38.6 0.001***
score Among postmenopausal women, the highest score and
Somatic subscale 3.49 2.03 1.48 42.5 0.001*** the lowest score were noted in symptoms of somatic
Psychological 2.38 1.41 1.01 42.5 0.001*** subscale and urogenital subscale, respectively. However,
subscale the greatest improvement was observed in psychological
Urogenital 0.62 0.51 0.10 16.1 0.349NS subscale (40.0%) and the least improvement was in
subscale
the urogenital subscale (14.2%). The results of our
NS: Statistically nonsignificant, MRS: Menopause Rating Scale,
*** highly significant study are in accordance with the study by Ahsan and
Mallick,[13] wherein the greatest improvement was
and postmenopausal women (33.3% reduction), more seen in symptoms of psychological subscale (26.79%)
so in perimenopausal women. Furthermore, it is more and the least improvement was in urogenital
beneficial with regard to symptoms of the somatic and subscale (1.11%) in postmenopausal women. In a study
Journal of Mid-life Health ¦ Volume 13 ¦ Issue 2 ¦ April-June 2022 179
 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

conducted by Tranche et al.,[14] the total scores on the results are in synchrony with the study by Ahsan and
MRS questionnaire decreased by 18.1%, after regular Mallick,[13] wherein a 40% reduction was seen in VMS.
consumption of ViveSoy® soy drink for 12 weeks. In a study conducted by Tranche et al.,[14] a statistically
significant reduction of VMS by 20.4% was observed
In 2002, the Women’s Health Initiative (WHI) study
after regular consumption of ViveSoy® soy drink for
showed that MHT increased the risk of breast cancer,
12 weeks.
cerebrovascular accidents, and coronary heart disease in
healthy postmenopausal women.[15] Of particular note, the Lambert et al.,[16] documented a statistically significant
results of WHI were prematurely released and were not decrease in physiological hot flash frequency and hot
completely analyzed. The results of the WHI showed that flash intensity, and selfreported hot flash frequency after
many of the adverse effects of MHT were due to initiating 3 months as compared to baseline in red clover extract
MHT at a late age (mean, 63 years). As MHT is associated (phytoestrogens) treatment group but not in placebo
with many side effects, even gynecologists are reluctant group. In this study, the change in total, vasomotor,
in prescribing MHT postWHI. These adverse effects somatic, and psychological parameters of the Greene
diverted the attention to complementary and alternative Climacteric Scale showed no significant difference
medicine therapies, the majority of which are based on soy between the treatment and placebo groups. Moreover,
isoflavones (phytoestrogens), presuming them to be safe. there was no significant difference in change in systolic
Furthermore, soy isoflavones can be used in all the stages and diastolic BP and plasma lipids (low‑density
of menopause without any serious adverse effect. lipoprotein [LDL], high‑density lipoprotein [HDL], or
Up to 80% of perimenopausal and postmenopausal triglycerides [TC]) between the treatment and placebo
women experience VMS such as hot flashes and groups.
sweating. In our study, 69.23% of perimenopausal women Hot flashes are the most immediate and troublesome
experienced hot flashes, and 57.38% of postmenopausal consequence of menopause. The median total duration
women experienced hot flashes. We documented a of VMS is 7.4 years. VMS causes physical and mental
42.5% reduction in VMS in perimenopausal women discomfort, sleep disturbance, and has a negative impact
and a 33.1% reduction in postmenopausal women. Our on the quality of life. It is one of the main reasons why
menopausal women seek medical help. In our study,
48.72% of perimenopausal women experienced sleep
Table 4: Mean Menopause Rating Scale scores in the disturbances, and 45.90% of postmenopausal women
postmenopausal group at baseline and after 12 weeks of
experienced sleep disturbances. Overall, we documented
therapy (n=61)
a 45% reduction in sleep disturbances in perimenopausal
MRS domain Score Score Absolute Percentage Significance
before after change change (P) women and a 30.1% reduction in postmenopausal women.
MRS mean total 7.03 4.69 2.34 33.3 0.001*** VMS is a consequence of natural endogenous
score
estrogen decline and dysregulation during peri‑ and
Somatic subscale 3.44 2.32 1.14 33.1 0.001***
postmenopause. A relative decrease in circulating
Psychological 2.75 1.68 1.10 40.0 0.001***
subscale
estrogen levels alters the norepinephrine and serotonin
Urogenital 0.85 0.74 0.12 14.2 0.405NS levels, thus causing dysfunction of the thermoregulatory
subscale nucleus.[17] A hot flash is characterized by a small
NS: Statistically nonsignificant, MRS: Menopause Rating Scale, increase in the core body temperature and subsequent
*** highly significant sweat response.

Table 5: Mean systolic blood pressure at baseline and after 12 weeks of therapy
Group Systolic BP Systolic BP Absolute Percentage Significance
before (mmHg) after (mmHg) change change (P)
Perimenopausal 120.28 120.22 0.058 0.05 0.630NS
Postmenopausal 126.61 125.21 1.421 1.11 0.251NS
NS: Statistically nonsignificant, BP: Blood pressure

Table 6: Mean body mass index at baseline and after 12 weeks of therapy
Group BMI before (kg/m2) BMI after (kg/m2) Absolute change Percentage change Significance (P)
Perimenopausal 26.61 25.71 0.89 3.35 0.396NS
Postmenopausal 25.74 25.39 0.37 1.43 0.512NS
NS: Statistically nonsignificant, BMI: Body mass index

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 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

The postmenopausal Asian women have a significantly causing osteoporosis predisposing to fractures. The
lower incidence (10%–25%) of hot flashes compared annual rates and cumulative amounts of BMD loss
to postmenopausal women in Western countries are greater 1 year before the onset of menopause and
(60%–90%) due to high levels of isoflavones in the through 2 years after menopause than those occurring
diet.[18] between 2 and 5 years after menopause.[24] Maximal
bone loss occurs in the first 2 years after menopause.
The frequency and severity of hot flash are
The rapid bone loss during early postmenopausal years
individualized. It is difficult to quantify VMS. Symptoms
is associated with a marked increase in biochemical
often subside over time even without any treatment.
markers of bone resorption, and due to the coupling
There is no evidence that lifestyle modifications like
of bone resorption and bone formation, the bone
lowering the room temperature, exercising, or avoiding
formation also increases over time.[24] In a study by
triggers such as alcohol and spicy foods can ameliorate
Sathyapalan et al.,[25] there was a significant reduction
VMS.[19] of the mean βCTX (type I collagen cross‑linked
Indications of MHT are for the relief of VMS, the beta C‑telopeptide) – a marker of bone resorption
prevention of osteoporosis, and vulvovaginal atrophy and P1NP (type I procollagen‑N‑propeptide) – a
associated with menopause. marker of bone formation, with soy protein isoflavone
supplementation for 6 months.
Estrogen remains the most intuitive therapy to combat
hot flashes and is currently the gold standard treatment The spine is the most sensitive to isoflavones due to the
for VMS and is approved by the U. S. Food and Drug higher content of trabecular bone compared to cortical
Administration. The IMS and Revised Global Consensus bone, higher expression of ERβ, and a larger surface
Guidelines recommend that the lowest effective dose area for receptor binding.[26] The hip contains a higher
of MHT should be given for the shortest duration of percentage of cortical bone and undergoes slower
time, and the duration of treatment should be limited remodeling than the spine.[27] Isoflavone intake can
to 5 years. The risk of cancer increases with a longer lead to a significant reduction in joint pain. Soy protein
duration of use and is affected by time from the start of may alleviate osteoarthritis symptoms and biochemical
menopause to initiation of MHT treatment. The standard markers of osteoarthritis.[20] A meta‑analysis showed
now is to initiate MHT within 1–5 years of onset of a significant attenuation of spinal bone loss (lumbar
menopause. The patients undertaking MHT should have spine) after 6 months of 90 mg/day of isoflavone
annual monitoring. MHTs are unsuitable for use in the supplement.[28]
breast cancer‑operated patients suffering from VMS.[20‑22] The incidence of cardiovascular events in women
Although isoflavones cannot entirely replace the role of increases after menopause due to estrogen deficiency,
traditional MHT in relieving menopausal symptoms, they which leads to a rise in LDL cholesterol, endothelial
have a good safety profile. The rule of thumb is to use dysfunction, and reduced carotid arterial pulsatility.[29]
conventional MHT for the relief of acute vasomotor and Genistein and daidzein cause arterial relaxation through
psychosomatic symptoms for a short time due to greater the release of nitric oxide.[30] Isoflavones improve
efficacy, and isoflavones have been recommended for systemic arterial compliance, reduce systolic BP,
long‑term prevention, as these products are usually slow improve endothelial function, and slow the progression
acting and are safe for prolonged use. of atherosclerosis in the early menopause. Isoflavones
cause no change in diastolic BP or lipoprotein
Isoflavones significantly lower the frequency and/or levels (total cholesterol, LDL, HDL, and TC).[31]
severity of hot flashes in menopausal women. Splitting
In our study, a 0.05% reduction in systolic BP was
the dose of soy supplement to twice daily decreased the
observed in perimenopausal women and a 1.11%
severity of hot flashes more than giving the total amount
reduction was observed in postmenopausal women. The
in one dose, suggesting consistent circulating levels of
reduction in systolic BP in both the groups was not
phytoestrogens to be more effective.[23] In our study, soy
statistically significant. This is in contrast to a study
isoflavone supplementation was given twice daily.
conducted by Sathyapalan et al.,[25] wherein there was
In our study, approximately 60% of perimenopausal a significant reduction in systolic BP with 6 months
and postmenopausal women experienced joint and of soy protein isoflavone supplementation. In the
muscular discomfort, and a reduction in the same was abovementioned study, there were no significant changes
noted in 40% of perimenopausal women and 36.1% of observed in lipid parameters and diastolic BP. Similar
postmenopausal women. The postmenopausal decline in findings were seen in a study by Tranche et al.,[14]
estrogen leads to loss of bone mineral density (BMD), wherein regular consumption of ViveSoy® soy drink

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 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

for 12 weeks did not cause any statistically significant the improvement was not statistically and clinically
change in lipid parameters. significant.
The safest and most effective treatment window for Isoflavone supplementation has a favorable effect on
cardiovascular disease would be early menopause, cognitive function, particularly verbal memory,[39] and
before critical atherosclerotic changes set in. may induce a feeling of well‑being and reduce risks for
cognitive impairment. The North American Menopause
The slowing of metabolism after menopause leads
Society in their study concluded the beneficial effect
to obesity, which is an important risk factor for
of soy in women younger than 65, but not older.
cardiovascular diseases. Isoflavones promote weight
Isoflavones suppress denervation‑induced apoptosis and
loss and coupled with exercise lead to a reduction of
could prevent denervation‑mediated muscle atrophy.
fat mass.[32] Isoflavones inhibit the mechanisms involved
in adipose tissue growth and regulate adipogenesis.[33] Soy isoflavones also have an antifatigue action. In our
In our study, a 3.35% reduction in BMI was observed study, 46.15% of perimenopausal women and 59.02%
in perimenopausal women and a 1.43% reduction was of postmenopausal women experienced physical and
observed in postmenopausal women. The reduction in mental exhaustion. In our study, a 47.5% reduction in
BMI in both the groups was not statistically significant. symptoms of fatigue was observed in perimenopausal
women. Our results are in synchrony with the study by
Isoflavones improve glycemic control. Genistein,
Ahsan and Mallick,[13] wherein 29.81% reduction was
daidzein, and equol, components of isoflavones
seen in symptoms of fatigue.
show higher binding affinity to peroxisome
proliferatoractivated receptor (PPAR)γ, a drug target Depression during the perimenopausal period has been
for type 2 diabetes.[33] Isoflavones lead to a significant influenced by the previous episodes of premenstrual
improvement in glucose metabolism through inhibition syndrome, hot flashes, postpartum depression, insomnia,
of glucose uptake at the intestinal brush border through nocturnal sweating, socioeconomic strata, and ethnicity,
an α‑glucosidase inhibitor action, tyrosine kinase and such depression is more resistant to conventional
inhibitory action, changes in insulin receptor numbers antidepressants. Soy isoflavones can be used as an
and affinity, intracellular phosphorylation, and alterations add‑on therapy to treat depression associated with
in glucose transport.[34] Soy has been shown to inhibit menopause. In our study, 56.41% of perimenopausal
insulin secretion from pancreatic β cells.[35] women experienced depressive symptoms, and 57.38%
of postmenopausal women experienced depressive
Isoflavones, by binding to ERβ, suppress ERα‑induced
symptoms. We documented a 37.5% reduction in
cancer cell proliferation and are, thus, cancer
symptoms of depression in perimenopausal and 40% in
protective.[36] Soy isoflavones do not seem to stimulate
postmenopausal women.
endometrial proliferation during short‑term treatment.[37]
In 2011, the North American Menopause Society
Urogenital tissues such as bladder, urethra, levator ani,
suggested a trial‑and‑error approach to prescribe
and vaginal mucosa possess Erα and Erβ receptors
isoflavones for menopausal symptoms – initial treatment
which have a great affinity for genistein and daidzein.
with high‑dose isoflavones (50 mg/day or higher) for
Isoflavone intake does not prevent stress incontinence or
12 weeks when monitoring for possible side effects,
urge incontinence.[38] Isoflavones exert a favorable effect
but stop if there is no response to treatment after
on sexual function and quality of life. Sexual problems
12 weeks.[37] The total amount of isoflavones required
were noted in 7.69% of perimenopausal women and
for symptom relief in humans is approximately
1.64% of postmenopausal women, and it was very
40–50 mg/day, and twice‑daily doses are more effective.
severe due to severe vaginal dryness. In our study, sexual
dysfunction improved by 16.1% in perimenopausal The potential side effects of isoflavones are nausea,
and by 14.2% in postmenopausal women, and the bloating, abdominal discomfort, diarrhea, constipation,
improvement was not statistically significant. This was malaise, fatigue, headache, dizziness, insomnia,
in contrast to the study by Ahsan and Mallick,[13] wherein irritability, depressed mood, rash, weight gain, breast
the complaints of severe sexual dysfunction improved cancer, and vaginal bleeding.
significantly among perimenopausal and postmenopausal
women. In a study conducted by Tranche et al.,[14] the Conclusion
regular consumption of ViveSoy® soy drink for 12 weeks Soy isoflavone supplementation is beneficial in both
caused a statistically significant (21.3%) reduction in perimenopausal and postmenopausal women, more so
urogenital symptoms. Whereas, in our study, a 15% in perimenopausal women. Soy isoflavones are the most
reduction in urogenital symptoms was observed, and effective on the somatic and psychological symptoms,

182 Journal of Mid-life Health ¦ Volume 13 ¦ Issue 2 ¦ April-June 2022

 Khapre, et al.: Impact of soy isoflavone supplementation on the menopausal symptoms

and therefore, their use is more beneficial during 3. Edmond DK, editor. Menopause and the postmenopausal woman.
perimenopause. Soy isoflavones are the least effective In: Dewhurst’s Textbook of Obstetrics and Gynaecology. 7th ed.
Oxford. UK Blackwell Publishing; 2007. p. 492.
on the urogenital symptoms. There is no beneficial effect 4. Ahsan M, Mallick AK, Singh R, Prasad RR. Assessment of
of soy isoflavone supplementation on lowering systolic menopausal symptoms during perimenopause and postmenopause
BP and BMI. in tertiary care hospital. J Basic Clin Reprod Sci 2015;4:14‑9.
5. Setchell KD, Brown NM, Desai P, Zimmer‑Nechemias L,
Furthermore, isoflavones: Wolfe BE, Brashear WT, et al. Bioavailability of pure isoflavones
1. Attenuate lumbar spine BMD loss in healthy humans and analysis of commercial soy isoflavone
2. Improve glycemic control in vitro supplements. J Nutr 2001;131:1362S‑75S.
3. Lower total blood cholesterol concentrations, LDL, 6. Jacobsen BK, Jaceldo‑Siegl K, Knutsen SF, Fan J, Oda K,
Fraser GE. Soy isoflavone intake and the likelihood of ever
and TC
becoming a mother: The Adventist Health Study‑2. Int J Womens
4. Reduce risk of coronary heart disease, breast cancer, Health 2014;6:377‑84.
the incidence of breast cancer recurrence, endometrial 7. Speroff L, Fritz M. Clinical Gynecologic Endocrinology. 8th ed.
cancer, ovarian cancer, colorectal cancer, and bladder Philadelphia. Lippincott Williams and Wilkins; 2011. p. 7849.
cancer 8. Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T,
et al. Interaction of phytoestrogens with estrogen receptors alpha
5. There are currently no conclusive benefits on
and beta. Biol Pharm Bull 2001;24:351‑6.
urogenital symptoms, stress incontinence, urge 9. Russell L, Hicks GS, Low AK, Shepherd JM, Brown CA.
incontinence, and cognition Phytoestrogens: A viable option? Am J Med Sci 2002;324:185‑8.
6. Isoflavones have a good safety profile and cause 10. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW,
benefits to overall health. et al. Executive summary of the Stages of Reproductive Aging
Workshop+10: Addressing the unfinished agenda of staging
Limitations reproductive aging. Fertil Steril 2012;97:843‑51.
Our study was nonrandomized; it was not placebo 11. Heinemann LA, Potthoff P, Schneider HP. International versions
controlled; and there was no comparison arm. of the Menopause Rating Scale (MRS). Health Qual Life
Outcomes 2003;1:28.
Furthermore, there was no blinding. There would
12. Heinemann K, Ruebig A, Potthoff P, Schneider HP, Strelow F,
have been a bias, because the MRS questionnaire was Heinemann LA, et al. The Menopause Rating Scale (MRS) scale:
administered by a face‑to‑face interview. Subjective A methodological review. Health Qual Life Outcomes 2004;2:45.
symptom assessment methods were used, which may be 13. Ahsan M, Mallick AK. The effect of soy isoflavones on
plagued with bias. There was a variable interval since the menopause rating scale scoring in perimenopausal and
postmenopausal women: A pilot study. J Clin Diagn Res
the onset of menopause, which was the biggest setback 2017;11:FC13‑6.
of the study. 14. Tranche S, Brotons C, Pascual de la Pisa B, Macías R, Hevia E,
Marzo‑Castillejo M. Impact of a soy drink on climacteric
Author contributions
symptoms: An open‑label, crossover, randomized clinical trial.
All authors have substantially contributed to the Gynecol Endocrinol 2016;32:477‑82.
conception and design of the work and the acquisition, 15. Krebs EE, Ensrud KE, MacDonald R, Wilt TJ. Phytoestrogens
analysis, and interpretation of data for the work. All for treatment of menopausal symptoms: A systematic review.
authors have contributed to drafting the work and Obstet Gynecol 2004;104:824‑36.
16. Lambert MN, Thorup AC, Hansen ES, Jeppesen PB. Combined
revising it critically for important intellectual content red clover isoflavones and probiotics potently reduce menopausal
and final approval of the version to be published. All vasomotor symptoms. PLoS One 2017;12:e0176590.
authors agree to be accountable for all aspects of the 17. Morrow PK, Mattair DN, Hortobagyi GN. Hot flashes: A review
work in ensuring that questions related to the accuracy of pathophysiology and treatment modalities. Oncologist
and integrity of any part of the work are appropriately 2011;16:1658‑64.
18. Reed SD, Lampe JW, Qu C, Gundersen G, Fuller S,
investigated and resolved.
Copeland WK, et al. Self‑reported menopausal symptoms in a
Financial support and sponsorship racially diverse population and soy food consumption. Maturitas
2013;75:152‑8.
Nil.
19. Hill DA, Crider M, Hill SR. Hormone therapy and other
Conflicts of interest treatments for symptoms of menopause. Am Fam Physician
2016;94:884‑9.
There are no conflicts of interest.
20. Baber RJ, Panay N, Fenton A, IMS Writing Group. 2016 IMS
Recommendations on women’s midlife health and menopause
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