From the Department of Epidemiology, Graduate School of Public Health,
University of Pittsburgh (Pa) (C.M.Z.-J., H.C.L., K.S.-T., L.H.K.), and the
Department of Nursing and Allied Health Professions, College of Health and
Human Services, Indiana University of Pennsylvania (J.L.H.), Indiana, Pa.
Correspondence to Charnita M. Zeigler-Johnson, Department of Epidemiology, 127 Parran Hall, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, Pittsburgh, PA 15261. E-mail CMZST2{at}cis.vms.pitt.edu
Methods—Women aged 34 to 58 years were recruited from the
Pittsburgh, Pa, area. Postmenopausal status was defined as a serum
follicle-stimulating hormone level of >30 mIU/mL. Carotid duplex scans
were performed to assess the degree of focal plaque.
Results—Among premenopausal women, focal plaque was present
in 20% of nonhysterectomized versus 49% of hysterectomized-only women
(P=.004). Among postmenopausal women, plaque was
present in 69% of nonhysterectomized women, 86% of women with
hysterectomy only, and 48% of women with oophorectomy and hysterectomy
(P=.056). Among postmenopausal women, hormone
replacement therapy was used by 23% of women who had undergone natural
menopause, 0% of women with hysterectomy only, and 36% of women with
oophorectomy and hysterectomy. The prevalence of plaque was 33% among
hormone replacement therapy users versus 73% among nonusers
(P=.014). In multivariate
analysis, independent associations with the presence of at
least 1 plaque were postmenopausal status and hysterectomy only.
Conclusions—These data suggest that black women who undergo
hysterectomy without oophorectomy may be at higher risk of subclinical
carotid atherosclerosis than black women who undergo
natural menopause or hysterectomy plus oophorectomy.
Removal of the uterus alone or in combination with oophorectomy is
believed to result in an increased risk of
cardiovascular events.16 17 18 19 It
has been suggested that the rates of hysterectomy are higher for black
women than for white women,20 21 although the
data are inconsistent.15 22 23 In
Pittsburgh, Pa, the prevalence rate for hysterectomy in black women
(47%) is almost twice that in white women
(24%).20 21 Data from 16 states indicate that
overall rates for hysterectomy are approximately 23% for white women
and 22% for black women. The prevalence rates of leiomyomas
necessitating hysterectomy are consistently higher in black
women.15 20 24
Variation in hysterectomy rates among black and white women may be
related to access to health care and health insurance and the
prevalence of disease associated with need for hysterectomy. There is
substantial variation in hysterectomy rates by
state.22
The high prevalence rate of hysterectomy related to uterine fibroids in
black women younger than 60 years potentially may be associated with an
increased risk of cardiovascular disease. Few studies
have examined the risk of cardiovascular disease after
hysterectomy, especially among black women. Subclinical
cardiovascular disease can be identified by ultrasound
techniques used to determine subclinical carotid artery
disease.25 The carotid arteries have been used in
research, because they are easily accessible through noninvasive
ultrasound techniques. The purpose of this study was to assess
cardiovascular disease risk through evaluation of
subclinical carotid atherosclerosis in 138 black women
aged 34 to 58 years and living in Pittsburgh, Pa. We compared the
prevalence of subclinical disease between women who underwent
hysterectomy with or without oophorectomy and those who experienced
natural menopause.
All participants were evaluated between 1992 and 1994 at the University
of Pittsburgh. This evaluation included anthropometric measures and
blood analysis for determination of lipid, glucose, and
follicle-stimulating hormone (FSH) levels. Postmenopausal status was
defined as a serum FSH level of >30
mIU/mL.26
From 1995 to 1996, HOPE participants were invited by letter and
telephone contact to undergo a carotid ultrasound evaluation. Of 287
eligible women, 49 (17%) were lost to follow-up and 87 (30%) refused,
leaving 151 women who were studied successfully. Three of the women in
the final sample were excluded because their menopausal status could
not be confirmed by the FSH assay, and 5 oophorectomized women were
excluded because their FSH levels were below those defined as
postmenopausal. Four women were excluded because of missing data and 1
because she was unilaterally oophorectomized. The final sample (n=138)
consisted of 54 control subjects, 59 women with hysterectomy only, and
25 women with hysterectomy and bilateral oophorectomy. All participants
signed informed consent forms approved by the Institutional Review
Board of the University of Pittsburgh.
Duplex scanning was performed at the University of Pittsburgh
Ultrasound Research Laboratory with a Toshiba SSA-270A scanner (Toshiba
American Medical Systems). The participant was placed in a supine
position, with the head tilted at a 45° angle. The probe was first
positioned to obtain a cross-sectional overview of the carotid artery.
More detailed longitudinal pictures were then obtained of the distal
common carotid, the carotid bulb, and the internal carotid arteries for
evaluation of each area from a number of projections.
Video images were evaluated for the number and size of focal plaques.
Plaque was defined as a focal protrusion into the lumen vessel or an
echogenic focal area seen on any wall of the artery. The carotid system
was divided into five segments. For each segment, the degree of plaque
was graded from 0 (no observable plaque) to 3 (plaque covering 50% of
the vessel diameter). The presence of carotid artery plaque was
determined from these grades.27 Sonographers and
readers were masked to the hysterectomy status of participants.
Statistical Analysis
The distribution of risk factors by hysterectomy and menopausal status
is shown in Tables 1
At least 1 focal plaque was present in 46% of all participants.
The prevalence of plaque was clearly associated with hysterectomy
status for both premenopausal and postmenopausal women (Fig 1
A number of other baseline variables were associated with focal
plaque. Women with at least 1 plaque were significantly older and had
significantly higher total cholesterol, LDL, apo A-2, and
triglyceride levels. However, after adjusting for age,
these relationships were no longer significant (Table 3
HRT use was evaluated among postmenopausal women. Thirty-three percent
of HRT users had plaque compared with 72.5% of HRT nonusers
(P=.014). This was despite the fact that the mean age of HRT
users (50.3 years) was similar to that of nonusers (52.8
years). HRT was used by 3 of 13 nonhysterectomized women, 0
hysterectomized women, and 9 of 25 oophorectomized/hysterectomized
women. Within each group, a lower percentage of HRT users than
nonusers were likely to have plaque. However, because of the
small numbers represented in these groups, this did not
reach statistical significance.
Multivariate analyses were performed for
the total HOPE sample as well as separately for premenopausal and
postmenopausal women (Table 4
If lower levels of endogenous estrogens were the primary
factor linking hysterectomy with increased
atherosclerosis, one would expect the highest risk
group to be the hysterectomized/oophorectomized group. Surprisingly,
this was not the case. Among the postmenopausal women, those who had a
combined hysterectomy/oophorectomy actually had the lowest levels of
plaque. One limitation of the current study is that there were only 25
women in the hysterectomy/oophorectomy group. Thus, the low levels of
carotid plaque found in these women may not be
representative of all women in this category. Another
possibility is that the primary indication for surgery differed for
those with hysterectomy/oophorectomy versus hysterectomy alone. A final
possibility may relate to higher endogenous and exogenous
hormone levels in women with oophorectomy. Women with oophorectomy were
much more likely to be HRT users, and although not significant, they
also had a higher body mass index than those with hysterectomy alone.
Higher levels of body fat have been associated with higher levels of
circulating estrogens.33 34
Higher circulating estrogen resulting from obesity may in part account
for the relatively low HRT use among black women. In the present
study, 33% of women with oophorectomy were HRT users compared
with 0% of the hysterectomy-only group. HRT therapy
consistently has been associated with a better lipid profile as
well as a reduction in cardiovascular events. In the
ARIC Study,35 postmenopausal women who were
current users of estrogen replacement therapy had significantly higher
levels of HDL, HDL2, HDL3,
and apo A-1 than did postmenopausal nonusers. They also had
significantly lower levels of glucose, LDL, apo B, and lipoprotein(a)
than nonusers. The Nurses' Study36
showed a significantly decreased risk of myocardial infarction for
bilaterally oophorectomized women who used HRT compared with
bilaterally oophorectomized nonusers. In the current study, HRT
nonuse was associated with higher levels of carotid plaque. It is
possible that HRT should be recommended for surgical as well as natural
menopause, after individual assessment.
Although the results of this study are compelling, there are
limitations to the interpretation. Weaknesses of this study include the
observational design, which inhibits our ability to make conclusions
regarding causality; a small sample size, which results in lack of
statistical power and perhaps a unique sample of women; and possible
biases. One such bias might be a compliance bias, whereby women who
comply with HRT use may be more health conscious than nonusers.
There also may be confounding by socioeconomic status or other risk
factors that were not measured. Last, because this is a sample of black
women from a distinct geographical area, the generalizability of these
results to the general population is limited.
The results of this study demonstrate that there is an
increased risk of subclinical carotid atherosclerosis
among postmenopausal women and in premenopausal women with a history of
hysterectomy. Such women have a high prevalence rate of plaque. The
exact mechanism that places hysterectomized women at increased risk of
atherosclerosis is not completely understood. Given the
known high prevalence rate of hysterectomy among black women,
especially at younger ages, the need to identify and treat these women
is a public health priority if we are to reduce the increased
cardiovascular morbidity and mortality within the black
community.
Received September 24, 1997;
revision received December 9, 1997;
accepted December 23, 1997.
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© 1998 American Heart Association, Inc.
Original Contributions
Subclinical Atherosclerosis in Relation to Hysterectomy Status in Black Women
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—This study
was designed to investigate whether black women who underwent
hysterectomy only (n=59) or hysterectomy plus bilateral oophorectomy
(n=25) were at increased risk of subclinical carotid
atherosclerosis compared with black women who underwent
natural menopause (n=54). The effects of both surgery and menopausal
status were evaluated.
Key Words: atherosclerosis • blacks • carotid arteries • hormones • ultrasonography, Doppler
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Heart disease and
stroke are among the leading causes of morbidity and mortality for
women who live in industrialized nations.1 In the
United States, morbidity and mortality rates for myocardial infarction
and stroke in women younger than 60 years are significantly greater for
black women than for white women.2 3 4 5 Black women
also have an increased prevalence of hypertension, diabetes, and
obesity, common cardiovascular risk
factors.6 7 8 9 10 11 12 13 14 These same factors have been found
to be independently associated with leiomyomas (uterine
fibroids),9 14 the primary reason for
hysterectomy in black women.15
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The Heart, Osteoporosis, Postmenopausal Estrogen (HOPE) Study
was designed to determine the risk factors related to hysterectomy in
black women. Hysterectomized women were patients at Magee Women's
Hospital (Pittsburgh, Pa) who had been hysterectomized with or without
bilateral oophorectomy. Patients were excluded from the study if
hysterectomy occurred after age 45 or if there was a personal history
of gynecological cancer. Nonhysterectomized women were randomly
selected (via block sampling) from a list of 1000 females on the voter
registration list for Allegheny County, Pennsylvania. Initial screening
was done via a telephone interview with each participant.
Descriptive statistics were computed for all variables.
Comparisons between groups were performed by the t test (or
the Mann-Whitney test for variables not normally distributed) and
ANOVA. Age adjustment was achieved by ANCOVA. The Pearson
2 statistic was used to investigate the
association between plaque and categorical variables such as
hormone replacement therapy (HRT) use, smoking status, hysterectomy
status, and menopausal status. Logistic regres-sion was used to
determine which risk factors were related independently to the presence
or absence of any carotid plaque.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In the HOPE sample, there were 54 nonhysterectomized women, of
whom 41 were premenopausal and 13 were postmenopausal. There were 59
hysterectomized-only women, of whom 45 were premenopausal and 14 were
postmenopausal. All 25 oophorectomized/hysterectomized women were
postmenopausal. The average age in the sample population was 49.0
years, and 25% were current smokers. 
and 2. Levels of apolipoprotein (apo) A-1
differed by hysterectomy status for both premenopausal and
postmenopausal women. In postmenopausal women, use of HRT also varied
dramatically across the groups: 23.1% for postmenopausal controls, 0%
for postmenopausal hysterectomized-only women, and 36% for
oophorectomized/hysterectomized women.
View this table:
[in a new window]
Table 1. Comparisons of Means Across Hysterectomy Groups for
Premenopausal Women
View this table:
[in a new window]
Table 2. Comparisons of Means Across Hysterectomy Groups for
Postmenopausal Women ). Among premenopausal women, 19.5% of
nonhysterectomized women had plaque compared with 48.9% of
hysterectomized-only women (P=.004). Among postmenopausal
women, plaque was present in 69.2% of nonhysterectomized women,
85.7% of hysterectomized-only women, and 48% of
oophorectomized/hysterectomized women (P=.056).
View larger version (24K):
[in a new window]
Figure 1. Graph showing by group the percentage of women with at least
1 plaque (n=138). Premen indicates premenopausal; Postmen,
postmenopausal; Non-Hyst, nonhysterectomy; Hyst, hysterectomy without
oophorectomy; and Ooph-Hyst, oophorectomy with hysterectomy. ). Current smoking was reported for 30%
of women with plaque and 21% of women without plaque
(P=.345).
View this table:
[in a new window]
Table 3. Age-Adjusted Comparisons of Means for HOPE
Participants With and Without Plaque (n=138) ). Age or
menopausal status, systolic blood pressure, LDL level, smoking
status, and hysterectomy status were included in the model, with HRT
added to the postmenopausal model only. For the entire group, each of
these variables was positively related to the presence of plaque.
Results reached statistical significance for menopausal status and
hysterectomy without oophorectomy. (Age also reached statistical
significance, but because of the strong relationship between age and
menopausal status, only one or the other could be placed in the
models.) The odds of carotid plaque presence were 3.7 times greater for
postmenopausal than premenopausal women. In women with hysterectomy
only, the odds were 4.5 times greater than those for nonhysterectomized
women. These odds were similar for both premenopausal and
postmenopausal women. Among postmenopausal women, HRT nonusers
appeared to have a greater prevalence of plaque than HRT users.
However, because of the small numbers in the group, this did not reach
statistical significance.
View this table:
[in a new window]
Table 4. Factors Associated With Prevalence of Plaque in HOPE
Sample: Multivariate Models
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The study results indicate an increase in carotid
atherosclerosis among women who have undergone
hysterectomy without an oophorectomy. This was especially true for
premenopausal women. These findings are consistent with those
in the literature reporting that hysterectomy alone is associated with
an increase in cardiovascular disease risk
factors.16 18 28 It has been hypothesized that
the uterus may serve a hormonal or other secretory function (such as
prostaglandin secretion, which may act on blood pressure or
blood vessel contraction) that prevents cardiovascular
disease in premenopausal women.28 It is also
possible that removal of the uterus decreases blood flow to the
ovaries, thus affecting their function.29 Another
hypothesis is that the loss of iron during menstruation reduces
oxidized LDL and subsequently impedes the progression of
atherosclerosis.30 31 However, it
is more likely that women who undergo hysterectomy are a select group
with higher levels of cardiovascular risk factors.
Uterine fibroids, the leading cause of hysterectomy in black
women,15 are known to be associated with obesity
and hypertension.9 14 Factors associated with
susceptibility to fibroid development may also predispose women to
plaque development.32 Another possibility is that
the irregular menstrual cycles associated with obesity and fibroids may
result in lower peripheral estrogen levels during the
reproductive years and therefore increase the risk of
atherosclerosis.
Acknowledgments
This project was funded by an Office of Research in
Women's Health supplement to grant HL50439. Research was done under
the tenure of an Established Investigatorship from the American Heart
Association (Dr Sutton-Tyrrell) and a National Heart, Lung, and Blood
Institute minority investigator research award (Dr Holmes).
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Kannel WB, Wilson PWF. Risk factors that attenuate
the female coronary disease advantage. Arch Intern
Med. 1995;155:57–61.
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