LONGITUDINAL ASSESSMENT OF MENOPAUSAL SYMPTOMS AMONG SEVERELY
OBESE WOMEN UNDERGOING BARIATRIC SURGERY
by
Sharon Lorraine Goughnour
MS, Duquesne University, Pittsburgh, 1999
BS, University of Pittsburgh at Pittsburgh, 1980
Submitted to the Graduate Faculty of
Epidemiology
Graduate School of Public Health in partial fulfillment
of the requirements for the degree of
Master of Public Health
University of Pittsburgh
2014
UNIVERSITY OF PITTSBURGH
GRADUATE SCHOOL OF PUBLIC HEALTH
This essay is submitted
by
Sharon Lorraine Goughnour
on
August 5, 2014
and approved by
Essay Advisor:
Joyce T. Bromberger, PhD
Professor
Department of Epidemiology
and Psychiatry
Graduate School of Public Health
University of Pittsburgh
______________________________________
Essay Reader:
Faina Linkov, PhD, MPH
______________________________________
Associate Professor
Department of Epidemiology
Graduate School of Public Health
Department of Ob/Gyn and Reproductive Sciences
School of Medicine
University of Pittsburgh
(If you have an extra reader, add their info; you can adjust the spacing on this page to fit it.)
ii
Copyright © by Sharon Lorraine Goughnour
2014
iii
Joyce T. Bromberger, PhD
LONGITUDINAL ASSESSMENT OF MENOPAUSAL SYMPTOMS AMONG
SEVERELY OBESE WOMEN UNDERGOING BARIATRIC SURGERY
Sharon Lorraine Goughnour, MPH
University of Pittsburgh, 2014
ABSTRACT
Introduction: Studies suggest that severely obese women (BMI > 35) suffer more frequent
severe menopausal symptoms than their non-obese counterparts. For some women, the severity
of symptoms, coupled with obesity, has been strongly correlated with negative quality of life,
severe enough that women often seek medical treatment.
Few studies have been done to
evaluate the effect of bariatric surgery, a major weight loss procedure, on relief of menopausal
symptoms. The purpose of this study was to compare the severity of hot flashes and vaginal
dryness in severely obese women pre- and post-bariatric surgery to determine if the severity and
prevalence of the symptoms decreased after significant weight loss.
Methods: This study focuses on women participating in the Barimark Study who filled out
reproductive history forms, which included questions about menopausal symptoms, at the
baseline and first follow-up visits. Participants rated symptom severity on a scale of 1 (not
bothersome) to 5 (extremely bothersome). Anthropometric measurements were obtained preand post-operatively at Magee-Womens Hospital. Participants were divided into two age groups
(< 35 years and >35 years) for the purpose of statistical analysis. Presence of symptoms and
symptom severity at pre- and post-surgery were compared using McNemar’s test and Wilcoxon
signed-rank test.
iv
Results: Ninety-two women (age 22 – 72 years) participated in this study. Women < 35 years
reported no hot flashes and there was no change in the prevalence of hot flashes in either age
group. There was a significant reduction in severity of hot flashes in women aged >35 years
(p<0.01). There were significant reductions in both prevalence (p=0.03) and severity of vaginal
dryness (p=0.02) in women aged <35 years. While we did not have sufficient numbers to
explore relationships between hormone use, hysterectomy, hysterectomy plus oophorectomy, and
change in weight to the change in symptom severity, preliminary data suggested that there is no
statistically significant relationship between the change in symptom severity and the above
covariates.
Conclusion: The severity of hot flashes and vaginal dryness appears to decrease after bariatric
surgery, and its associated weight loss, suggesting that bariatric surgery may be an effective
means to improve quality of life in severely obese women. These findings have important
implications for public health and open new avenues of research in the area of weight loss as a
means to control menopausal symptoms. As obesity rates continue to increase, the burden on
public health resources will continue to increase as well.
v
TABLE OF CONTENTS
1.0
INTRODUCTION ........................................................................................................ 1
1.1
HOT FLASHES ................................................................................................... 1
1.2
VAGINAL DRYNESS ......................................................................................... 2
1.3
OBESITY.............................................................................................................. 3
2.0
MATERIALS AND METHODS ................................................................................ 5
2.1
STUDY PARTICIPANTS ................................................................................... 5
2.2
MEASURES ......................................................................................................... 6
2.3
STATISTICAL METHODS……………………………………………………7
3.0
RESULTS…………………………………………………………………………….7
4.0
DISCUSSION………………………………………………………………………...9
APPENDIX: TABLES.................................................................................................................12
BIBLIOGRAPHY ....................................................................................................................... 16
vi
LIST OF TABLES
Table 1. Baseline Characteristics .................................................................................................. 12
Table 2. Prevalence of symptoms ................................................................................................. 14
Table 3. Prevalence of the severity of symptoms………………………………………………. 15
vii
INTRODUCTION
1.1
HOT FLASHES
Menopausal symptoms, specifically hot flashes and vaginal dryness, are experienced by
50-80% of menopausal women.1,2 Approximately 29% of women report persistent hot flashes
and 33% vaginal dryness.1,3
For many women, these symptoms can be severe enough to
interfere with daily life.4 Among obese women (body mass index (BMI > 30), recent studies
suggest that menopausal symptoms are more severe and occur more frequently compared to
normal weight (BMI 18-25) women.5
Vasomotor symptoms, specifically hot flashes, can
become so severe that the negative impact on quality of life6 causes many women to seek
medical treatment.1 Additionally, recent studies demonstrate that a high adiposity and BMI are
associated with an increase in reported hot flashes.2,7-9 The underlying mechanisms of hot
flashes are not completely understood, but likely involve both thermoregulatory models and
endocrine factors. One thermoregulatory model is based on the hypothesis that obese women
experience decreased heat tolerance. Excess adipose tissue acts as insulating material, reducing
heat dissipation10, and resulting in the increased frequency of hot flashes to dissipate excess
heat.11
Another thermoregulatory model explains increased hot flashes based on a narrowed
thermoneutral zone in obese women. The thermoneutral zone is the temperature set points
between sweating and shivering. The body tries to maintain the core temperature within a
1
comfortable thermoneutral zone. When the core temperature rises above the upper threshold of
this zone, sweating occurs; when the core temperature falls below the lower threshold of this
zone, shivering occurs.12 Women with a wider thermoneutral zone would experience a greater
range in core temperatures before sweating or shivering occurs; women with a narrower
thermoneutral zone would experience a smaller range in core temperatures before sweating or
shivering occurs. Due to mechanisms that are not clearly understood, this zone becomes very
narrow in obese women, which causes an increase in sweating via hot flashes.13
Endocrine factors are also implicated in hot flashes in obese women. Literature suggests that
premenopausal and perimenopausal obese women have lower estrogen levels14-16 than their
normal weight counterparts, which may lead to the increase in hot flashes. 8,17 Specifically, both
estradiol and estrone levels are lower in obese women.18
1.2
VAGINAL DRYNESS
Generally, vaginal dryness is linked to low concentrations of estrogens and androgens.
Vaginal dryness has been linked to vulvovaginal atrophy resulting from estrogen deficiency and
affecting a large number of postmenopausal women.19 The vaginal response to these lowered
concentrations include: reduced secretions, tissue changes, and pH changes from acidic to
neutral fluids.1 In normal premenopausal women, glycogen-derived glucose is metabolized into
lactic acid which helps maintain a vaginal pH of 3.5 to 4.5. As estrogen-dependent glycogen
levels decrease during peri- and post-menopausal phases, exfoliation of the vaginal epithelium
decreases, resulting in reduced normal lactobacilli flora, and vaginal pH increases.20
The
increase in vaginal pH and thinning of the vaginal epithelium leads to vulvovaginal symptoms,
2
of which vaginal dryness/itching are the most common.20,21
Vaginal symptoms are also
associated with medications (i.e. anitdepressants), medical conditions (i.e. obesity, diabetes), and
behavioral factors (i.e. smoking). Literature indicates that obesity is correlated with circulating
levels of sex hormones, independent of age.22 Research has indicated that obese, premenopausal
women not only have lower levels of estrogens, but also have decreased levels of sex-hormone
binding globulin (SHBG).23,24 One hypothesis explaining vaginal dryness in premenopausal
women is based on decreased levels of SHBG, which is directly linked to lower levels of
circulating estrogens22; therefore, leading to lower levels of glycogen, and changes in vaginal pH
and epithelial density. Conversely, in obese, post-menopausal women, levels of estrogens are
actually higher.24
This can be attributed to the conversions of androgens into estrogens,
specifically estrone, via aromatase found in adipose tissue. Therefore, increased estrogen levels
may correlate with increased glycogen levels, leading to an acidic vaginal pH, which results in a
decrease of vaginal symptoms.
1.3
OBESITY
Obesity has been rapidly increasing in the United States22, and as of 2012, 34.9% of
adults were classified as obese (BMI > 30).25,26 In 2008, the United States spent $147 billion on
obesity related medical conditions.25 Obesity has been strongly associated with increased risk
for cardiovascular disease, hypertension, diabetes, sleep apnea, cancer, and premature death.
Among women, obesity is strongly linked to endometrial cancer (EC), the most common
gynecologic malignancy, where the risk of EC is two to four times that observed in non-obese
3
women.27 The National Cancer Institute predicts that the continued rates of obesity will result in
500,000 new cases of cancer by 2030 in the United States.27
As established above, obesity plays a major role in the development of menopausal
symptoms. Therefore, the debilitating effects of obesity, combined with severe menopausal
symptoms have the potential to negatively impact the daily lives of women to the extent that they
seek medical treatment. Numerous studies have shown that weight loss improves health, lowers
the risk for many chronic diseases, and improves quality of life.4,28,29 Research has been done
on the treatments for obesity, but no clear agreement has emerged on a particular method.
Treatments range from behavioral modifications (diet and exercise) to surgical interventions
(bariatric surgery).29 The RENEW Study evaluated the efficacy of diet and exercise on the
adverse health effects of severe obesity,30 with the key finding that behavioral modification was
successful resulting in clinically significant weight loss.31
Linkov et al, reported that this
significant weight loss in RENEW participants resulted in decreased levels of cancer-associated
biomarkers.30
For those individuals that do not respond to behavioral modifications, bariatric surgery
has emerged as the primary treatment for morbid obesity.32 In 2006, there were 113,000 bariatric
surgeries performed in the United States, costing the health care economy $1.5 billion.33 Recent
studies have shown that patients achieve effective weight loss34, and improvement or complete
resolution of chronic conditions, such as diabetes, sleep apnea, and cardiovascular disease.32
Adams et al, have reported that bariatric surgery is associated with a reduction in early
mortality.35 For morbidly obese women at high risk of endometrial neoplasia, Argenta and
Linkov et al, found that hormone receptor profiles tended to normalize in selected bariatric
surgery patients, especially those with early pathological changes of the endometrium, such as
4
hyperplasia.36
However, there have been few studies done to evaluate the effect of bariatric
surgery on the severity of menopausal symptoms. The purpose of this study was to compare the
severity of hot flashes and/or vaginal dryness in morbidly obese women (BMI > 35) pre- and
post-bariatric surgery to determine if the severity of the symptoms changed after significant
weight loss.
2.0
MATERIALS AND METHODS
2.1
STUDY PARTICIPANTS
Ninety-two female bariatric surgery candidates from the bariatric surgery clinic of
Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC) aged 22 to 72
were included in this preliminary analysis if they met the following inclusion criteria: women
approved for and scheduled for bariatric surgery (Roux-en-Y gastric bypass, laparoscopic
adjustable gastric banding, or sleeve gastrectomy), and completed health surveys at baseline and
six month post-operative follow-up visits. Self-reported data were obtained from reproductive
and general health questionnaires administered at both visits.
Exclusion criteria included:
refusal to sign informed consent, refusal or inability to complete anthropometric measurements
and paper based questionnaires, and inability to attend baseline and follow-up visits. Study
procedures were overseen by professional research staff in the Clinical and Translational
Research Center (CTRC) at Magee-Womens Hospital of UPMC.
5
2.2
MEASURES
The presence of hot flashes and /or vaginal dryness, along with severity of symptoms,
was obtained from the Reproductive Health Baseline (RHB) and the Screening Questionnaire for
General Health History (SQHH). The RHB has been used in the multi-center Longitudinal
Assessment of Bariatric Surgery-2 Study (LABS) to determine the reproductive health of women
undergoing bariatric surgery.37 The SQHH has been previously used in both the PREFER and
SMART studies testing behavioral weight management modifications.38,39 Symptom severity
was rated on a scale of 1 (not bothersome) to 5 (extremely bothersome).
Additionally,
reproductive history, menstrual history, and hormone use history (hormone replacement therapy,
birth control, and/or fertility medications) was obtained from the RHB.
measurements were obtained by a clinical nurse at the CTRC.
Anthropometric
Height was measured in
centimeters using a wall-mounted stadiometer. Weight (kilometers) and BMI (kg/m2) were
obtained from the Tanita body composition analyzer (Model TBF-310, Tanita Corporation of
America). The Tanita analyzer calculates BMI from measured height (meters) and weight (kg).
Height and weight measurements were taken in the absence of footwear and wearing light
clothing.
6
2.3
STATISTICAL METHODS
For description of the study population, continuous variables are reported as median
(range); categorical variables are reported as n (%). Women were first classified into two age
categories: < 35 years and >35 years; then the statistical comparisons of symptom presence and
severity between baseline and first follow-up visits were performed using McNemar’s test.
McNemar’s test is used to compare differences in paired data. Mean symptom severity at preand post-surgery was also computed as a continuous average of the scale rating systems from 1
(not bothersome) to 5 (extremely bothersome) and both Wilcoxon signed-rank test and paired ttest was used to compare the scores. Statisical analysis was conducted using
STATA 13.0. α level was set at 0.05 and was two sided.
3.0
RESULTS
Table 1 lists the baseline characteristics of study participants. The median age was 45.5
years (range: 22 -72), the median weight was 121.5 kg (range: 87.5 – 175.7), and the median
BMI was 45.1 kg/m2 (range: 35.0 – 61.1). The median weight loss was 31.9 kg (range: 0.5355.9) and the median post-operative BMI was 34.3 (range: 24.0 – 50.9). In women age <35
years, 39.1% reported hormone use (includes HT, birth control, fertility drugs), 5.6% reported
7
hysterectomy alone, 5.6 % reported hysterectomy/oophorectomy, none reported hot flashes, and
47.8% reported vaginal dryness. In the women aged >35 years, 27.7% reported hormone use,
6.4% reported hysterectomy alone, 26.2% reported hysterectomy/oophorectomy, 38.5% reported
hot flashes, and 41.3% reported vaginal dryness.
Table 2 compares the reporting of hot flashes and vaginal dryness between the baseline
and first-follow-up visit. There were no changes in those reporting hot flashes in either age
group; no women reported hot flashes at either time point in the <35 years group. In the >35 age
group, the same 25 women reported hot flashes at the baseline and at the follow-up visit. There
were significant changes in vaginal dryness, however. In the <35 age group, 7 women that had
reported vaginal dryness at the baseline visit did not do so at the follow-up visit, while only 1 did
the opposite, indicative of a significant group-wide decrease in vaginal dryness (p=0.03). A
similar pattern was observed in the >35 age group, with 7 women that had reported vaginal
dryness at the baseline visit no longer doing so a the follow-up visit, while only 2 did the
opposite; however, this did not reach conventional statistical significance p<0.05 (p=0.09).
Table 3 compares the severity of symptoms on a scale of 1 to 5 (none/not bothersome to
extremely bothersome), and the mean severity of symptoms between baseline and first follow-up
visits by age group. There was a significant decrease in severity of hot flashes after bariatric
surgery in the >35 age group using both the Wilcoxon test (p<0.01) and the paired t-test
(p<0.01).
The decrease in vaginal dryness severity in the <35 age group was also significant
(p=0.02 for Wilcoxon test and p=0.01 for paired t-test); however, there was no significant change
in the >35 age group (p>0.05 for both Wilcoxon and paired t-test). We do not have sufficient
numbers of participants to assess the relationships of hormone use, hysterectomy, hysterectomy
plus oophorectomy, and change in weight to the change in severity of symptoms before and after
8
bariatric surgery. The preliminary data indicates there are no significant associations between
these covariates and the change in symptom severity.
4.0
DISCUSSION
Among a cohort of 92 women that underwent bariatric surgery who had baseline and six
month post-operative visits, hot flash and vaginal dryness severity decreased six months after
bariatric surgery. Specifically, though we showed no reduction in the prevalence of hot flashes,
we did find that hot flash severity decreased in women age >35 years. We also found both
prevalence and severity of vaginal dryness decreased in women age <35 years.
For the
preliminary data, we did not find significant associations between hormone use, hysterectomy,
hysterectomy plus oophorectomy, change in weight, and reported change in symptom severity.
As obesity continues to be an increasing public health concern, it is vital to determine the
underlying comorbidities that are aggravated by obesity. Bariatric surgery significantly reduced
hot flash and vaginal dryness severity, which, for many women, are associated with a negative
impact on daily life, such as low self-esteem, depression, low physical activity.28 To the best of
our knowledge, no other studies have specifically looked at the change in menopausal symptoms
before and after bariatric surgery; therefore, our study is the first to focus on morbidly obese
women undergoing bariatric surgery, and look at the change in symptom severity pre- and postoperatively.
9
The major strength of this study is the prospective assessment of symptom severity and
prevalence change in obese females undergoing a procedure to reduce weight, bariatric surgery,
over time in a prospective study. The study is important because it provides empirical data
supporting the hypothesized relationship between weight and menopausal symptoms and the
association between weight loss and attenuation of severe hot flashes and vaginal dryness.
Future studies will require larger samples and a longer follow-up period to determine the extent
to which decreases in symptom severity, such as those reported here, are associated with longterm weight loss.
However, the study findings should be considered in the context of several key
limitations. First, this population is very specific: morbidly obese women undergoing bariatric
surgery, and is not representative of the general population. Second, symptom severity was selfreported and measured on a subjective scale of 1 to 5 (1 not bothersome to 5 extremely
bothersome). What may be not bothersome to one woman may be interpreted as extremely
bothersome to another woman. However, this classification has been used in several large,
multi-site trials with success.37
While hot flashes and vaginal dryness are not diagnosable diseases, these symptoms
cause major discomfort and have negative effects on quality of life. Future directions for
research include understanding of the underlying mechanisms of hot flashes and how these
symptoms are aggravated by obesity. Severe hot flashes are frequently reported as a result of
chemotherapy, and severity is strongly associated with increased BMI;40,41 therefore, this may
have implications for cancer research. Weight loss may be a valid treatment to reduce severity
of hot flashes. In addition, recognition and treatment of these symptoms in obese women should
10
be considered as vital components of their health and guidelines for treatment need to be
developed.
These findings have important implications for public health and open new avenues of
research in the area of weight loss as a means to control menopausal symptoms. As obesity rates
continue to increase, the burden on the health care economy will continue to increase as well.
Obesity is strongly associated with other comorbidities, which in turn lead to an additional drain
on public and medical resources. Severe hot flashes and vaginal dryness interfere with the daily
lives of women, often severe enough to require medical treatment. Our study has shown that the
severity of hot flashes and vaginal dryness decrease after bariatric surgery and its associated
weight loss. Weight loss is also associated with risk reduction for many cancers, cardiovascular
disease, and diabetes, among others. Decreasing the rates of these diseases greatly reduces the
burdens on public health.
11
APPENDIX: TABLES
Table 1: Baseline Characteristics
n = 92
Characteristics
Baseline
Age (years) median (range)
45.5 (22 – 72)
< 35 years n (%)
> 35 years
BMI (kg/m2) median (range)
23 (25.0)
69 (75.0)
45.1 (35.0 – 61.1)
Weight (kilograms) median (range)
121.5 (87.5 – 175.7)
Self-reported menopausal status by age
category n (%)
< 35 years
Pre-menopausal
Perimenopausal
Post-menopausal (natural)
Post-menopausal (surg/med)
>35 years
Pre-menopausal
Perimenopausal
Post-menopausal (natural)
Post-menopausal (surg/med)
Any Hormone Use by Age Category n (%)
< 35 years
Yes
No
No Response
>35 years
Yes
No
No Response
Hysterectomy (alone) n (%)
< 35 years
Yes
No
No response
>35 years
Yes
No
No Response
21 (95.5)
0
0
1 (4.6)
23
12
17
14
(33.9)
(18.5)
(26.2)
(21.5)
9 (39.1)
14 (60.9)
0
18 (26.1)
47 (68.1)
4 (5.8)
1 (4.3)
17 (73.9)
5 (21.7)
4 (5.8)
59 (85.5)
6 (8.7)
12
Table 1 continued
Characteristics
Hysterectomy/Oophorectomy n (%)
< 35 years
Yes
No
No Response
>35 years
Yes
No
No Response
Hot Flashes n (%)
< 35 years
Yes
No
No Response
>35 years
Yes
No
No Response
Vaginal Dryness n (%)
< 35 years
Yes
No
No Response
>35 years
Yes
No
No Response
Baseline
1 (4.3)
17 (73.9)
5 (21.7)
17 (24.6)
48 (69.6)
4 (5.8)
0
21 (91.3)
2 (8.7)
25 (36.2)
40 (58.0)
4 (5.8)
11 (47.8)
12 (52.2)
0
26 (37.7)
37 (53.6)
6 (8.7)
13
Table 2: Prevalence of symptoms with change in BMI
Hot Flashes
Baseline
Baseline
<35 years
Yes
No
Total
>35 years
Yes
No
Total
First follow-upa
Yes
No
0
0
0
21
0
21
Yes
25
0
25
No
0
39
39
p-valueb
Total
0
21
21
Total
25
39
64
NS
NS
Vaginal Dryness
Baseline
Baseline
<35 years
Yes
No
Total
>35 years
Yes
No
Total
First follow-upa
Yes
No
4
7
1
11
5
18
Yes
19
2
21
No
7
33
40
a
p-valueb
Total
11
12
23
Total
26
35
61
0.03
0.09
six month post-operative visit
p-values from McNemar’s test: no p-values reported for hot flashes because there were no
changes reported in either group (p-value=1)
b
14
Table 3: Prevalence of the severity of symptoms
n = 92
Symptom severity n (%)
Baseline
First
follow-upa
p-valueb
Hot Flashes
<35 years
0
0
NA
>35 years
1 None/Not Bothersome
2 Somewhat Bothersome
3 Moderately Bothersome
4 Severely Bothersome
5 Extremely Bothersome
Vaginal Dryness
<35 years
1 None/Not Bothersome
2 Somewhat Bothersome
3 Moderately Bothersome
4 Severely Bothersome
5 Extremely Bothersome
>35 years
1 None/Not Bothersome
2 Somewhat Bothersome
3 Moderately Bothersome
4 Severely Bothersome
5 Extremely Bothersome
3
(12.0)
11 (42.3)
9 (36.0) 11 (42.3)
5 (20.0)
2 (7.7)
5 (20.0)
1 (3.9)
3 (12.0)
1 (3.9)
2
4
2
3
0
(18.2)
(36.4)
(18.2)
(27.3)
4 (15.4)
12 46.2)
5 (19.2)
4 (15.4)
1 (3.9)
2 (40.0)
2 (40.0)
1 (20.0)
0
0
6
5
8
1
1
15
p-valuee
0
p<0.01
1.73 (1.43-2.03)
1.33 (1.14-1.53)
p<0.01
0.02
1.73(1.27–2.21)
1.17(0.96–1.37)
0.01
0.37
1.62(1.37–1.88)
1.45(1.23–1.69)
0.29
six month post-operative visit
p-values from Wilcoxon signed-rank test
c
Mean severity at baseline visit: mean (95% CI)
d
Mean severity at first follow-up visit: mean (95% CI)
e
p-values from paired t-test
b
First follow-upd
0
(28.6)
(23.8)
(38.1)
(4.8)
(4.8)
a
Baselinec
NA
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