Arch Gynecol Obstet

DOI 10.1007/s00404-016-4034-9

GYNECOLOGIC ENDOCRINOLOGY AND REPRODUCTIVE MEDICINE

Comparison of the symptomatic response in Indian menopausal

women with different estrogen preparations for the treatment
of menopausal symptoms: a randomized controlled trial
Sunita Malik1 • Deepika Pannu1 • Shashi Prateek1 • Renuka Sinha1 •

Harsha Gaikwad1

Received: 24 September 2015 / Accepted: 2 February 2016

 Springer-Verlag Berlin Heidelberg 2016

Abstract Conclusion Low doses of both CEE and E2V were

Purpose To compare symptomatic response in Indian equally effective for management of vasomotor/vaginal
women using different estrogen preparations for treatment symptoms when administered over 24 weeks. However, it
of menopausal symptoms. seems more reasonable to replenish with less costly and
Methodology A randomized, single blind, four arm, par- bio-identical hormone, i.e. micronized estradiol valerate
allel assignment study was conducted in VMMC and SJH, which is equally effective.
New Delhi, India. 200 Indian menopausal women were Trial registry The trial was registered under Clinical trial
recruited and assigned into four treatment groups viz., registry of India prospectively (number: CTRI/2012/04/
estradiol valerate (E2V), conjugated equine estrogen 002566).
(CEE), isoflavones and Placebo group. The statistical sig-
nificance of categorical variables was determined by Chi- Keywords Estrogen
Estradiol
Isoflavones
Post-
square, Fisher’s exact test. In case of quantitative variable menopausal
parametric test Student’s t test was used. In case of quan-
titative variables where data are not normally distributed,
Kruskal–wallis test and Wilcoxon Mann–Whitney test Introduction
were used. Symptomatic response in vasomotor/vaginal
symptoms was assessed in all groups. Menopause is the time in a woman’s life when the function
Results Both E2V and CEE groups were effective in of ovary ceases completely following a gradual decline and
reducing severity and frequency of hot flashes. 91.9 % they experience a number of menopausal symptoms which
decrease was observed in mean hot flash score in the E2V includes hot flushes, vaginal and urinary symptoms, mood
group after 24 weeks of treatment, 89.2 % in the CEE changes, psychological effects such as depression, anxiety,
group, 60.42 % decrease in the isoflavones group. While irritability, etc. [1, 2].
placebo led to 47.9 % decrease in mean hot flash score. Out of all vasomotor symptoms, the hot flushes and the
After 24 weeks of therapy there was significant increase in vaginal symptoms are the most closely associated with the
vaginal health index in the E2V and CEE and the iso- hormonal changes of the menopause most notably with
flavones group. No serious side effect was reported in any the deficiency of estrogen [3]. Change in thermoregula-
of the groups. tory mechanism is also attributed to the vasomotor
symptoms [1]. Vaginal atrophy is also due to the
hypoestrogenic state seen during menopause that results
in anatomical and physiological changes in the geni-
& Deepika Pannu tourinary tract [1].
[email protected] Estrogen alone or in combination with progesterone
1 has been traditionally the standard treatment for symp-
Department of Obstetrics and Gynecology, Vardhman
Mahavir Medical College and Safdarjung Hospital, tomatic relief for vasomotor symptoms and also the
New Delhi, India genitourinary symptoms. However, a drop in the use of

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hormonal replacement therapy (HRT) was noticed after • Menopausal women up to 70 years of age.
2002, when Women health initiative randomized control • Hysterectomized women with one or both ovaries
trial of estrogen along with progesterone was halted in preserved, considered only if serum FSH [40 IU/L and
v/o some serious side effects reported [4, 5]. There is serum estradiol \20 pg/ml.
resurgence in the prescription of HRT by clinicians after • Women with bilateral oophorectomy.
many studies documented the safety of HRT for the • Women with premature menopause due to premature
management of menopausal symptoms in women ovarian failure.
younger than 60 years [6–9]. Even reanalysis of WHI
trial in women younger than 70 years documented the
Exclusion criteria
fact [10].
Estrogens have always been the most frequently pre-
• Tobacco or alcohol abuser.
scribed HRT. However, different forms of estrogen should
• History of malignant disease.
be studied more extensively as there are different side
• Abnormal mammogram within 2 years of study entry.
effect profile and efficacy of different forms of estrogens.
• History of hormone-dependent tumours.
Recent studies have suggested that other low dose for-
• Women with chronic diseases such as uncontrolled
mulations like oral micronized estradiol, ethinyl estradiol
hypertension, diabetes, liver, kidney and thyroid
are as efficacious as conjugated equine estrogen (CEE)
dysfunction.
[11, 12]. Micronized estradiol valerate is a bio-identical
• Women on long term therapy such as antiepileptic
estrogen that is structurally similar to endogenous estro-
drugs or diuretics.
gen. It naturally replenishes the estrogen level and is
• Prior intake of hormonal medications within 3 months.
better accepted by physiological systems of the body. It is
• Women with history of thrombophlebitis, estrogen
micronized which enhances its dissolution and thereby
related thrombosis or thromboembolism, cerebrovascu-
absorption [13]. Also it is esterified which prevents the
lar accident, with known or suspected estrogen-depen-
first pass metabolism. Various natural products have also
dent tumour, undiagnosed vaginal bleeding, migraine,
been used like phytoestrogen, herbal supplements, etc.
uterine disorders, breast disorders, gall bladder disease,
However, data on the efficacy of these products are
arterial thrombosis and hypercholesterolemia.
lacking [14]. The most studied of them are the
• Obese women (BMI [ 36).
isoflavones.
• Known hypersensitivity to drugs used in the study.
However, additional data from RCTs are required to
compare the efficacy of various regimens. The aims of the
researchers were to compare the symptomatic response in Patient workup
Indian menopausal women using different estrogen
preparations for treatment of vasomotor symptoms and 200 Indian menopausal women were included in the study.
vaginal atrophy. Prior to recruiting women, some of the baseline investiga-
tions were done: serum follicle stimulating hormone (FSH)
and estradiol (E2) levels, serum thyroid stimulating hormone
Methodology (TSH) levels, lipid profile, liver function tests, pap smear,
mammography, ultrasound (USG) upper abdomen and pel-
Study design vis, transvaginal sonography. The eligible women meeting
the inclusion criteria and with no exclusion criteria were
Randomized, single blind, four arm, parallel assignment given adequate information about the nature and purpose of
study. Patients were blinded from the drug group they were the study and a written informed consent was obtained from
allocated. each participant who was willing to participate in the study.
To establish the baseline level of symptoms, women were
Study population allotted a screening period of 1 week followed by a total
treatment period of 24 weeks.
200 postmenopausal women. After completing the screening women were randomly
allocated to the four treatment groups. Computerized ran-
Inclusion criteria domization code was generated with a block size of four to
ensure equal distribution of treatment groups. On alloca-
Women presenting with symptoms of menopause (vaso- tion, women were assigned into to the lowest available
motor symptoms or vaginal/urinary symptoms) with any of randomization for each site. That is the group with lowest
the following characteristics were recruited: number of patients was allocated first and so on.

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Group A 50 women received placebo continuously for Women were asked to keep diaries in which they recorded
24 weeks. daily number and frequency of hot flushes. Hot flushes
Group B Women with intact uterus were given estradiol were graded into mild when there was sensation of heat
valerate tablets (0.5 mg) along with natural micronized without perspiration, moderate when there was sensation of
progesterone tablets (200 mg) as a continuous combined heat with perspiration and severe when there was sensation
regime daily for 24 weeks. of heat with sweating and women was not able to continue
Hysterectomized women received estradiol valerate her routine activities, scored 1, 2 and 3, respectively. Then
(Tablet Valest 0.5 mg) continuously for 24 weeks without the hot flush score was calculated by multiplying the
progesterone. average hot flush severity and daily frequency.
Women in whom symptoms were not relieved with Genitourinary symptoms included were vaginal dryness,
0.5 mg estradiol valerate, a higher dose of 1 mg was given. dyspareunia and urinary frequency.
Group C Women with intact uterus were given CEEs Vaginal health index (VHI) It consisted of eight
tablets (0.3 mg) along with natural micronized proges- parameters, each graded from 1 to 3 with total score
terone tablets (200 mg) as a continuous combined regimen ranging from 8 to 24. Vaginal pH was measured by keeping
daily for 24 weeks. a litmus paper in vagina for 1 min and observing the col-
Hysterectomized women received CEE (0.3 mg) con- our, moisture measured by putting the vaginal fluid on a
tinuously for 24 weeks. clean slide for visualization. Inspecting and then palpating
Women in whom symptoms were not relieved with the vaginal mucosa by index finger assessed rugosity and
0.3 mg of conjugated estrogen, a higher dose of 0.625 mg elasticity. Length of vagina was assessed by Ayer’s spatula.
was given. TVS was done to measure vaginal thickness. Epithelial
Group D 50 women (both hysterectomized and those integrity was assessed by the presence of petechiae on the
with intact uterus) were given phytoestrogens, 60 mg vaginal wall. Finally noticing the colour of the vagina
continuously for 24 weeks. assessed vascularity.
End point Patients were called for the interview at the
end of 4, 12 weeks and finally evaluated at the end of Secondary outcome measures
24 weeks. Subjects were also called once 1 month after
completion of their treatment schedule of 24 weeks. Hormone profile (FSH and E2 levels), TSH levels, lipid
profile, liver function tests, TVS, body mass index (BMI),
quality of menopausal life by Greene Climacteric Scale
Evaluation of subjects [17].
Compliance, adverse events use of any concomitant
Patients were separated symptom wise in each group and medications since last visit were assessed at each subse-
were analyzed for the following parameters at the end of 4, quent visit at 4, 12 and 24 weeks. History taken from the
12 and 24 weeks. women regarding the symptoms at the time of visit and
examination was done including breast examination. Hot
Primary outcome measures flush symptoms and genitourinary symptoms were assessed
at each visit and VHI was measured at the start and the end
1. Improvement in vasomotor symptoms (hot flushes). of the study. TVS, hormonal and blood profile was done at
the start and the end of the study.
• Frequency (number of hot flushes per day recorded
Compliance was assessed and considered satisfactory if
at 4, 12 and 24 weeks).
the patients completed the study and took medication as
• Severity of hot flushes (mild, moderate and severe)
prescribed that was validated at the end of the study.
by Mayo hot flushes diary [15].
P The protocol was approved by the institutional ethics
• Hot flash score (hot flush frequency 9 average
board and was implemented in accordance with the insti-
severity).
tutional guidelines.
2. Improvement in vaginal health. Women who were willing to continue with the therapy
were registered in the menopausal clinic and provided
• Symptom relief (genital and urinary symptoms).
further care.
• Vaginal health index (pre- and post-therapy).
Lower the score, greater the vaginal atrophy. It
Statistical analysis
consisted of eight parameters, each graded from
1 to 3 with total score ranging from 8 to 24
Number of subjects to be enrolled was calculated after
[16].
taking reference from effect of different type of estrogen on

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menopausal symptoms from literature. A sample size of 45 menopause in the E2V/NMP group than in other groups
subjects per group was required to detect a difference of with statistical significance (p value 0.006). The distribu-
hot flash score between an active treatment group and tion of BMI in all the four groups was comparable at
placebo with a statistical power of 80 % at a significance registration (p value 0.156). There was no significant
level of 0.05. The reduction in hot flash score and fre- change in the BMI after treatment for 24 weeks in all the
quency was assumed to be 80 % for the estrogen groups four groups (p value 0.104). There was no significant
and 58 % for the placebo. change in the endometrial thickness after treatment over
The data were presented in terms of descriptive 24 weeks in any of the groups.
statistics as range (minimum, maximum, mean ± standard
deviation)/median (inter quartile range) for quantitative Vasomotor symptoms
variable and frequency (percentage) for categorical vari-
ables. The difference in changes was taken from the Severity of hot flashes
baseline between active treatment groups and the placebo
group and at 4, 12 and 24 weeks of treatment. Baseline There was no significant difference in the distribution of
was taken as the average of readings in the screening symptoms of hot flash by severity between different groups
period. The statistical significance of categorical variables at registration (p value = 0.118).
(hot flash severity) was determined by Chi-square, Fish- Within group analysis Both CEE/NMP and E2V/NMP
er’s exact test. In case of quantitative variables parametric were found to have significant effect on the severity of hot
test Student’s t test was used. In case of quantitative flashes experienced by the women on treatment (p value
variables where data are not normally distributed Krus- 0.001 for both group B and C).
kal–Wallis test and Wilcoxon Mann–Whitney test were The effect of placebo on reducing severity of hot flash
used (hot flash frequency, hot flash score, Greene Cli- symptoms was statistically nonsignificant in group A
macteric Scale). We used analysis of variance to see the (p value 0.054). In the placebo group, 25 women were
effect of drugs on across various groups in case of con- experiencing moderate to severe symptoms at registration
tinuous variables (vaginal health index). First within while after 24 weeks of treatment 18 women were still
group analysis was done and the significance of the effect experiencing moderate and severe hot flash symptoms. In
of drugs in each individual group was analyzed. There- the E2V/NMP group 36 women had moderate and severe
after, the change in symptoms from the baseline at 4, 12 hot flash symptoms at registration while this number was
and 24 weeks was assessed pairwise comparing each decreased to 4 after treatment of 24 weeks. In the CEE/
active treatment group with placebo. NMP group the figures were 39 at registration and 2 at
p value B0.05 was considered statistically significant. 24 weeks while in isoflavones 29 at registration and 12
after 24 weeks of treatment.
Inter group analysis In group C CEE/NMP led to sta-
Results tistically significant reduction in severity of hot flashes as
compared to group A (p value 0.034) and group D (p value
Based on computer generated randomization the enrolled 0.032). However, both the groups B and C were compa-
women were divided into four study groups A, B, C, and D. rable for there therapeutic effect with respect to each other
Each group consisted of 50 patients at the start of the study. (p value 0.25). None of the other groups had statically
significant reductions in hot flash in comparison to each
Demographic data other.

47 women from placebo group (group A), 48 women from Frequency

estradiol valerate group (group B), 49 women from CEE
group (group C), and 45 women from isoflavones group The daily frequency of hot flashes experienced by the
(group D), completed the study. Rest 11 women were lost women in the study group ranged from absent to 25. Both
to follow up. E2V/NMP and CEE/NMP groups were effective in
Women in estradiol valerate/natural micronized pro- reducing the frequency of hot flash symptoms experienced
gesterone (E2V/NMP) were little younger than women in by the women per day (Fig. 1). Both the drugs were
the other groups but the values were not significant sta- comparable with respect to their effect on the frequency of
tistically. Out of all, ten enrolled women were more than hot flashes (p value 0.714). Isoflavones did reduce the
65 years of age (Table 1). 91 women with natural meno- frequency of hot flushes but there was 46.04 % reduction in
pause and 98 women with surgical menopause completed the average frequency as compared to E2V/NMP group in
the study. There were more women with surgical which there was 90.4 % reduction and CEE/NMP in which

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Table 1 Demographic
Demographic characteristics Placebo Valest Premarin Isoflav CR
characteristics of the study
groups Randomized (n) 50 50 50 50
Completed (n) 47 48 49 45
Mean age (years) 48.2 ± 8.9 45.8 ± 8.4 46.4 ± 9.2 48.9 ± 6.7
Type of menopause
Natural 24 13 27 27
Surgical 23 35 22 18
Body mass index (kg/m2) 25.5 ± 4 24.9 ± 4.9 24.1 ± 5 26.1 ± 4
Endometrial thickness (mm) 2.8 2.88 2.4 2.49
Mean serum TSH 3.03 ± 1.7 3.07 ± 1.43 3.73 ± 2.86 4.5 ± 4.64
Mean serum FSH 55.34 ± 37.2 55.17 ± 40.5 77.44 ± 49.4 62 ± 35
Mean estradiol (E2) levels 56 ± 67 57 ± 79 77.44 ± 49.4 57.2 ± 67.9
Lipid profile
Mean HDL levels 48.1 ± 4.62 49.2 ± 9 49.3 ± 9 47.96 ± 4.42
Mean LDL levels 112.8 ± 30.3 123.3 ± 31.8 114. ± 27.6 47.96 ± 4.42
Mean triglycerides levels 11.1 ± 44.2 10.6.8 ± 42.7 119.7 ± 40.72 130.9 ± 64.4
Mean total cholesterol 182.4 ± 27.3 195.7 ± 27.1 187.3 ± 28.7 195.4 ± 34.7

Fig. 1 Change in mean hot

flash frequency over 24 weeks
in different drug regimens

there was 88.9 % reduction. In the placebo group only mean hot flash score in group D that was statistically sig-
20.4 % reduction was noticed. nificant (Fig. 2).
In the groups B and C reductions in hot flash score were
Hot flash score 91.9 and 89.2 %, respectively, compared to 47.9 % with
placebo (p value 0.001 for both groups A and B vs. pla-
Hot flash score was calculated by multiplying hot flash cebo). There was no statistically significant difference
frequency with severity experienced by each woman. In all between B and C treatment groups (p value 0.913). Both
the four drug groups there was a significant decrease in hot the E2V/NMP and CEE/NMP groups had significant
flash score. However, the quantum of the decrease was reductions in hot flash score as compared to isoflavones
highest in the E2V/NMP and CEE/NMP group. The change group (p value 0.001 for both groups A and B vs.
in hot flash score was observed as early as 4 weeks. In isoflavones).
within group analysis, the reduction in hot flash score was
statistically significant in both groups B (p value 0.001) and Vaginal health index
C (p value 0.001). However, there was statistically non-
significant decrease in hot flash score in group A (p value The VHI of all the groups was statistically comparable to
0.212). Isoflavones also led to 60.42 % decrease in the each other pre-therapy (p value 0.178). After 24 weeks of

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Fig. 2 Figure showing change

in mean hot flash score over
24 weeks of treatment in
different drug regimens

therapy there was a significant increase in the vaginal Secondary outcome measures
health index in the E2V/NMP and CEE/NMP and the
isoflavones group. However, no significant change was Quality of menopausal life
observed in the vaginal health index of the placebo group
(Table 2). Quality of menopausal life of the woman was assessed by
The improvement of vaginal health index in group A the Greene Climacteric Scale. Higher the score more dis-
and D was comparable to each other statistically (p value tressed is the woman out of menopausal symptoms. Some
0.250). Also, there was no statistically significant differ- change in the quality of life was noted in women in all the
ence between improvement in VHI between groups B and four groups. However, the quantum of change of the
C (p value 0.422). Groups B and C both had significant Greene Climacteric Scale varied across the groups
change in VHI when compared to groups A (p value 0.006 (Table 3).
and 0.001, respectively) and D (p value 0.05 and 0.002, There was no change observed in the serum FSH and
respectively). serum estradiol levels in any of the four groups over
24 weeks of treatment. There was no difference in the
Genital and urinary symptoms hormonal level whether any effect on the symptoms was
observed or not. There was no relation with the level of
In placebo group only 14.3 % of women got cured of the hormones and the menopausal symptoms.
complaint of vaginal dryness after 24 weeks of treatment. Also the serum TSH levels in all of the drug regimens
E2V/NMP cured 45.45 % of women from vaginal dryness. did not change significantly over the 24 weeks period.
In CEE/NMP group 52.3 % women were relieved of their At registration all the groups were comparable with
complaint. In isoflavones group 35 % women were respect to the lipid profile levels. After 24 weeks of ther-
relieved of complaints. In placebo group 17.6 % women apy, no change was observed in the lipid profile levels in
were relieved of symptoms of dyspareunia, 21.4 % in E2V/ all the four groups. This means that treatment has no effect
NMP group, 30.7 % in the CEE/NMP group and 25 % in on the lipid profile of the patients and all the drugs were
the isoflavones group. 25 % women in the placebo group, safe.
63.6 % women in the E2V/NMP group, 64.3 % women in All the groups were comparable. There was a significant
the CEE/NMP group and 33.3 % women in the isoflavones drop in serum bilirubin levels in the study groups and the
were relieved of their symptoms of urinary frequency. control groups. No significant change was observed in the

Table 2 Effect of different

Drug regimen Registration 24 weeks Mean Percentage p value
drug regimens on mean vaginal
(mean ± SD) (mean ± SD) change change (%)
health index
Placebo 19.19 ± 2.45 20.36 ± 2.48 1.07 6.09 0.362
Valest 18.6 ± 2.71 21.73 ± 2.27 3.1 16.82 0.001
Premarin 18.29 ± 2.46 22.06 ± 1.74 3.78 20.61 0.001
Isoflavones 19.02 ± 2.04 20.89 ± 1.85 1.87 9.83 0.276

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Table 3 Effect of different

Drug Registration 24 weeks Mean change Percentage
drug regimens on quality of
regimen (mean ± SD) (mean ± SD) change (%)
menopausal life assessed by
Greene Climacteric Scale Placebo 6.51 ± 3.91 3.68 ± 3.163 2.83 43.47
Valest 9.33 ± 6.026 4.48 ± 4.85 4.86 51.98
Premarin 8.33 ± 5.26 3.29 ± 3.137 6.073 60.5
Isoflavones 8.3 ± 5.385 3.59 ± 3.02 5.05 57.1

values of the liver enzymes over 24 weeks of the treatment (OR 0.42; 95 % CI 0.28–0.62) and estrogen and proges-
in any of the four groups. terone arms (OR 0.38; 95 % CI 0.25–0.58) [18].
The main side effects reported were restlessness, vaginal Another randomized trial on 333 women randomized to
discharge and mild breast tenderness. No serious side effect 0.5 mg/day of oral estradiol and placebo demonstrated that
was reported. None of the women experienced abnormal oral estradiol in doses as low as 0 .5 mg/day is effective for
vaginal bleeding. Breast tenderness was observed in 4 % of the relief of menopausal symptoms [12]. Oral CEE in doses
women in group A (placebo). While it was observed in 6 % as low as 0.3 mg/day and transdermal estradiol in doses of
of women in group B and 8 % in group C. None of the 12.5 lg/day has demonstrated effect on the vaginal
women in group D observed breast symptoms. 4 % of symptoms [19, 20]. It has been shown that estradiol is
women in group A, 2 % in group B and none in group C effective in relieving vaginal symptoms in doses as low as
observed restlessness. 8 % women in group D observed 0.5 mg/day when administered over 8 weeks. FDA
restlessness. approves both systemic and local estrogen regimens for
treating vaginal menopausal symptoms. However, if sys-
temic hormonal therapy is given only for the relief of
Discussion vaginal symptoms local vaginal estrogen is preferred due to
less side effects [21].
In this study 200 patients were recruited, however 11 Although both drugs have been found to have significant
dropped out from the study in between. Out of 11, 8 therapeutic benefit on the menopausal symptoms, none of
women were from placebo and isoflavones group. Reasons the drug has established superiority over one another.
for dropout were various viz. lack of perceived effect of the And though, we do not have long-term safety profile
drug, family reasons, etc. None of the women dropped out associated with different oestrogen preparations, CEE is a
of the study due to adverse effects. This may be due to the mix of hormones derived from horse urine and do not
low dose estrogen formulations used in the study. Rest 189 represent a ‘‘replacement’’ of natural human estrogens such
women were analyzed into various groups. This study as 17-beta estradiol [22].
results confirmed the effectiveness of low-dose CEE and Equilin metabolites have toxic properties with carcino-
low-dose estradiol valerate in the relief of menopausal genic potential through the formation of quinones and
symptoms. Our findings demonstrated the superiority of semiquinone-adducts with DNA [23].
oral estrogen preparations viz. CEE and estradiol valerate Equine hormones also contain androgens and several sex
over isoflavones and placebo drug for the treatment of steroids of yet unknown vascular activity [24]. It cannot be
vasomotor and vaginal symptoms in the menopausal assumed that other HRT preparations like estradiol valerate
women. The higher mean hot flash score at registration in share the same potential for an increase in associated breast
the estradiol valerate group may be due to more number of cancer with long-term use [25]. Estradiol valerate is now
women with surgical menopause in this group leading to available in micronized form. When a tablet of crystalline
abrupt cessation of hormone levels. The decrease in the estradiol is administered orally, very low estradiol levels
number and severity of hot flashes was evident as early as appear in the systemic circulation. To improve its absorption,
4 weeks. All the four groups demonstrated an increase in the process of micronization was developed, in which crys-
the vaginal health index. However, the therapeutic effect of talline estradiol is broken down to minute particles. This
the estrogen preparations was far more superior to the other results in increased surface area and enhanced dissolution,
two treatment groups. thereby improving absorption, and hence bioavailability and
Cochrane review had earlier established the efficacy of clinical efficacy of estradiol valerate. Moreover, in a study by
oral estrogen on the severity and frequency of hot flashes. Smith et al. women using oral CEEs were found to have more
CEE was found to have significant therapeutic effect on the than twice the risk of venous thromboembolism observed in
hot flushes as compared to placebo in both estrogen alone women using oral estradiol.

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Isoflavones have demonstrated 60.4 % decrease in the with very minimal and non-serious side effects. Isoflavones
mean hot flash score in the present study. Cochrane meta though have some effect on the control of menopausal
analysis from 2010 on 30 placebo controlled trials on symptoms, the effect is not comparable to the other
phytoestrogens for the relief of vasomotor symptoms have estrogen preparations. At present nothing conclusive can be
not found any evidence of benefit [14]. According to the said for isoflavones for the management of menopausal
British Menopausal society the efficacy for vasomotor symptom as their side effect profile is not well known and
symptom relief is said to be lower than with traditional the effect is inferior to the available estrogens.
HRT (maximally 60 % symptom reduction compared to
90–100 % with traditional HRT) [26]. Acknowledgments The authors would like to acknowledge all the
women who participated in the study and the staff of Safdarjung
Present study has also demonstrated strong placebo Hospital for their support. Authors would also like to acknowledge
effect. There was 47.9 % reduction in the hot flash score Walter Bushnell Laboratories for their support.
and 4.53 % improvement in the vaginal health index.
Strong placebo effect has earlier been demonstrated [12, Compliance with ethical standards
27]. However, there was no difference in the hormonal
Conflict of interest None.
level in the estrogen group and the placebo group. Self
reported menopausal symptoms are highly subjective. Also Funding Funding was provided by Walter Bushnell Laboratories.
it has been quoted earlier by authors that women’s own
perceptions of symptom improvement are more useful than Ethics approval Institutional ethics committee approved the pro-
ject. No: 47-11/EC (5/81), dated 13/10/12.
monitoring serum hormone levels [12]. Further it has been
reported earlier that serum levels of estradiol are not a good
indicator of treatment response. Despite the strong placebo References
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