Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis

Abstract

Uterine fibroids (UFs) are the most common benign gynecological tumor and greatly affect reproductive health in women of reproductive age. Some studies have indicated an association between UFs and several cardiovascular disease (CVD) risk factors. To determine whether UFs are associated with increased blood pressure, we performed a cross-sectional study and meta-analysis. In the cross-sectional study, 8401 participants who underwent a physical examination at the First Affiliated Hospital of Shantou University Medical College from June 2011 to June 2013 were divided into a uterine fibroid group (1617 cases) and a control group (6784 cases) to assess the relationship between UFs and blood pressure. Then, we conducted a systematic review to confirm the results. The cross-sectional study showed that UFs were associated with an increased rate of elevated blood pressure [OR = 1.35, 95% confidence interval (CI): 1.016–1.792]. The meta-analysis revealed a significant association between UFs and the prevalence of hypertension [pooled OR = 1.44, 95% CI: 1.17–1.75, P = 0.0004; I2 = 68%]. Thus, UFs may be associated with the prevalence of hypertension. Women with uterine fibroids should be closely monitored for hypertension. Uterine fibroids may increase the prevalence of hypertension.

Full text

Hypertension Research (2022) 45:715–721
https://doi.org/10.1038/s41440-022-00856-w
ARTICLE
Association of uterine fibroids with increased blood pressure: a
cross-sectional study and meta-analysis
Yequn Chen1,2,3,4 ●Nianling Xiong5●Jiaxin Xiao1●Xiru Huang1,6 ●Rongbing Chen1,6 ●Shu Ye1,6,7 ●Xuerui Tan1,2,3,4,6,7
Received: 12 July 2021 / Revised: 1 January 2022 / Accepted: 4 January 2022 / Published online: 15 February 2022
© The Author(s), under exclusive licence to The Japanese Society of Hypertension 2022
Abstract
Uterine fibroids (UFs) are the most common benign gynecological tumor and greatly affect reproductive health in women of
reproductive age. Some studies have indicated an association between UFs and several cardiovascular disease (CVD) risk
factors. To determine whether UFs are associated with increased blood pressure, we performed a cross-sectional study and
meta-analysis. In the cross-sectional study, 8401 participants who underwent a physical examination at the First Affiliated
Hospital of Shantou University Medical College from June 2011 to June 2013 were divided into a uterine fibroid group
(1617 cases) and a control group (6784 cases) to assess the relationship between UFs and blood pressure. Then, we
conducted a systematic review to confirm the results. The cross-sectional study showed that UFs were associated with an
increased rate of elevated blood pressure [OR =1.35, 95% confidence interval (CI): 1.016–1.792]. The meta-analysis
revealed a significant association between UFs and the prevalence of hypertension [pooled OR =1.44, 95% CI: 1.17–1.75,
P=0.0004; I2=68%]. Thus, UFs may be associated with the prevalence of hypertension. Women with uterine fibroids
should be closely monitored for hypertension.
Keywords Hypertension; ●Blood pressure; ●Uterine fibroids
Background
Uterine fibroids (UFs) are the most common gynecological
benign tumor and greatly affect reproductive health in women
of reproductive age [1]. These tumors, which cause a variety
of symptoms, including menorrhagia, dyspareunia, secondary
anemia, pain, urinary urgency, and frequent urination, are a
major indication for hysterectomy in premenopausal women
and result in a very large medical burden. Hypertension is
characterized by persistently elevated arterial blood pressure,
which is the main risk factor for cardiovascular and cere-
brovascular diseases [2]. Persistently elevated blood pressure
can lead to heart failure, renal function damage and other
target organ damage, leading to serious disability, and
mortality.
In recent years, epidemiological studies have suggested a
correlation between UFs and hypertension [3–15], but the
conclusions have been inconsistent regarding the relationship
of hypertension with UFs. In the cohort study of the Nurses’
Health Study II [8], an increased risk of hypertension was
found in patients with UFs. However, the Northern Finland
Birth Cohort [10] study showed no correlation between UFs
and hypertension. which may be a result of differences in
sample size and inclusion criteria. Thus, we performed this
These authors contributed equally: Yequn Chen, Nianling Xiong,
Jiaxin Xiao
*Shu Ye
sy127@leicester.au.uk
*Xuerui Tan
doctortxr@126.com
1The First Affiliated Hospital of Shantou University Medical
College, Shantou, Guangdong, China
2Clinical Research Center, The First Affiliated Hospital of Shantou
University Medical College (SUMC), Shantou, China
3Institute of Clinical Electrocardiology, The First Affiliated
Hospital of Shantou University Medical College (SUMC),
Shantou, China
4Institute of Cardiac Engineering, The First Affiliated Hospital of
Shantou University Medical College (SUMC), Shantou, China
5Nanchang University Second Affiliated Hospital,
Nanchang, Jiangxi, China
6Shantou University Medical College, Shantou, Guangdong, China
7Department of Cardiovascular Sciences and NIHR Leicester
Biomedical Research Centre, University of Leicester,
Leicester, UK
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study to determine whether women with fibroids have a
greater risk of increased blood pressure independent of
common risk factors by collecting and analyzing the data of
females who underwent a physical examination. Additionally,
a meta-analysis was conducted to confirm the results.
Methods and design
Cross-sectional study
This study included women who underwent a physical exam-
ination at the First Affiliated Hospital of Shantou University
Medical College from June 2011 to June 2013 and excluded
those who had undergone hysterectomy or previously had
adenomyosis or endometrial cancer. Laboratory information,
including serum total cholesterol (TC), low-density lipoprotein
(LDL-C), high-density lipoprotein (HDL-C), serum creatinine
(Scr), age, systolic blood pressure (SBP), and diastolic blood
pressure (DBP), was collected at baseline from the Health
Management Center of the First Affiliated Hospital of Shantou
University Medical College.
Clinical and laboratory assessment
Blood pressure was measured by trained medical staff using an
Omron electronic sphygmomanometer (hem-7052, Omron
Healthcare Ltd., Dalian, China) according to the blood pressure
measurement standard recommended by the American Heart
Association [16]. Hypertension is defined as (SBP) >140
mmHg, (DBP) >90 mmHg or the use of antihypertensive
medication [17]. UFs were diagnosed by an ultrasound spe-
cialist based on ultrasound data retrieved from the electronic
system of the Ultrasound Department of the First Affiliated
Hospital of Shantou University Medical College. UFs were
classified based on their location: subserosal (projecting outside
the uterus), intramural (within the myometrium), and sub-
mucosal (projecting into the uterine cavity).
This study utilized anonymized data for analyses and was
approved by the Research Ethics Committee of the First
Affiliated Hospital of Shantou University Medical College.
Meta-analysis
The meta-analysis followed the Systematic Reviews and
Meta-Analysis statement [18]. Ethical approval was not
necessary because the meta-analysis was based on data from
previously published studies.
Search strategy
Literature searches were performed in PubMed, Embase,
and the Cochrane Library up to May 2020 by using various
combinations of keywords including “Leiomyoma”,
“Leiomyomas”,“Fibroid Tumor”,“Fibroid Tumors”,
“Tumor, Fibroid”,“Tumors, Fibroid”,“Fibromyoma”,
“Fibromyomas”,“Fibroid”,“Fibroids”,“Fibroid Uterus”,
“Uterus, Fibroid”,“Fibroma, Uterine”,“Fibromas, Uterine”,
“Uterine Fibroma”,“Uterine Fibromas”,“Fibroids, Uter-
ine”,“Fibroid, Uterine”,“Uterine Fibroid”,“Uterine
Fibroids”,“Leiomyoma, Uterine”,“Hypertension”,“Blood
Pressure, High”,“Blood Pressures, High”,“High Blood
Pressure”, and “High Blood Pressures”. In addition, we
manually searched the references of the retrieved literature
to avoid missing potential eligible studies.
Eligibility criteria
The retrieval period was from the establishment of the data-
bases to May 2020. The outcome for this analysis was
hypertension prevalence. Articles were included if they: (1)
were published in English, (2) compared the prevalence of
hypertension among patients with and without UFs, and (3)
reported relative risks with 95% CIs or the data to calculate
them. Studies where only abstracts were available were
excluded.
716 Y. Chen et al.
Graphical Abstract
Uterine fibroids may increase the prevalence of hypertension.
Uterine fibroids Hypertension
We conducted a
cross-sectional study of 8,401
participants who was divided
into a uterine fibroid group
Association of
Uterine Fibroids
and increased blood
pressure: a
cross-sectional
study and

Data extraction
After study selection, two reviewers extracted the following
characteristics: name of first author, year of publication, age
of participants, the group to which the subjects belonged,
sample size, OR (adjusted OR if provided) and 95% CI.
Statistical analysis
For the cross-sectional study, normally distributed measure-
ment data are expressed as the meanthe cross deviation. The
data that were not normally distributed, such as glucose and
TG, were log10 converted and were then normally distributed.
Then, the differences between the hysteromyoma group and the
nonhysteromyoma group were compared by the two indepen-
dent sample ttest. Count data are expressed as frequencies
(percentages), and the differences between the two groups were
compared using the chi-square test. Logistic regression was
performed to determine whether UFs were associated with the
odds of hypertension. The multivariable model controlled for
age, glucose, TC, LDL-c, and TGs. Univariate and multivariate
odds ratios (ORs) of the individual risk factors were calculated.
The analysis was performed using SPSS 19 (SPSS Inc., Chi-
cago, IL), and statistical significance was indicated by a Pvalue
<0.05.
In the meta-analysis, the Newcastlealysisds ratios (ORs) of
theindividualriskfaedtoassessthequalityoftheincluded
studies [19]. The I2statistic was applied to quantify the degree
of heterogeneity. A fixed effects model was used if I2≤50%;
otherwise, a random effects model was used. In addition, a
sensitivity analysis was performed using a one-study-removed
analysis. All analyses were performed with Review Manager
software (Version 5.3. Copenhagen: The Nordic Cochrane
Center, The Cochrane Collaboration, 2014).
Results
Cross-sectional study
A total of 8401 participants who underwent physical exam-
ination at the First Affiliated Hospital of Shantou University
Medical College from June 2011 to June 2013 were enrolled in
this study. They were divided into a uterine fibroid group (1617
cases) and a control group (6784 cases). Initially, we compared
the baseline characteristics of women in the UF and control
groups and found that the age, SBP and DBP of the UF group
were significantly higher than those of the control group (SBP:
122.07 ± 18.57 vs. 120.31 ± 17.48, P< 0.001 and DBP: 75.70
± 11.51 vs. 74.11 ± 10.74, P< 0.001). The incidence of
hypertension in the UF group was significantly higher than that
in the control group (0.18 vs. 0.13, P<0.001, Table 1). After
adjusting for age, TC, glucose, LDL-c, and TGs, the rate was
still significantly higher (P< 0.001, OR =1.35, 95% CI
1.016–1.792, Table 2).
Meta-analysis
Figure 1shows the search strategy. According to the
inclusion criteria, ten studies involving 8361 patients were
Table 1 Clinical characteristics of individuals in the case–control
study
Control group
n=6784
UF group
n=1617
P
Age (Y) 41.90 ± 13.10 42.40 ± 13.41 <0.001
BMI 22.28 ± 3.15 22.45 ± 3.19 0.062
SBP (mmHg) 120.31 ± 17.48 122.07 ± 18.57 <0.001
DBP (mmHg) 74.11 ± 10.74 75.70 ± 11.51 <0.001
TC (mmol/L) 5.07 ± 1.07 5.23 ± 0.96 <0.001
HDL-C (mmol/L) 1.38 ± 0.35 1.39 ± 0.33 0.346
LDL-C (mmol/L) 3.23 ± 0.91 3.34 ± 0.83 <0.001
TG (mmol/L) 1.07 ± 0.79 1.17 ± 0.88 <0.001
Glucose(mmol/L) 5.10 ± 1.30 5.22 ± 1.38 <0.001
Hypertension(%) 919 (0.13) 296 (0.18) <0.001
Measurement data were expressed as meanurement d deviation, the
difference between the two groups was compared by the two
independent sample ttest. Counting data were expressed by frequency
(percentage), the difference between the two groups was compared
using the chi-square test
Table 2 Odds ratio (95% CI) for uterine fibroids by hypertension
Crude OR (95%) ModelaOR (95%)
Hypertension 1.43 (1.238–1.615) 1.35 (1.016–1.792)
aModel with the Age, TC, Glucose, LDL-c, TG in the regression
equation
Fig. 1 Flowchart of study selection for the meta-analysis
Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis 717

Table 4 Newcastle-Ottawa scale of the meta-analysis
Author, ref. Selection Comparability Exposure
Adequate
definition of cases
Representativeness of cases Selection of
controls
Definition of
controls
Control for important
factors
Ascertainment of
exposure
Same method to
ascertain for cases and
controls
Nonresponse rate Scores
Faerstein et al. [26]* * * * * * 6
Luoto et al. [6]* * * * * * 6
Parazzini et al. [24]* * * * * * 6
Takeda et al. [8]* * * * * * * 7
Spies et al. [23]* ** *4
Lambertino et al.
[22]
** *3
Sivri et al. [5]* * * * * 5
Aksoy et al. [12]* * * * * * 6
Haan et al. [10]* * * * * * 6
Tak et al. [4]* * * ** * * * 8
Haan et al. [29]* ** **5
Table 3 Characteristics of included studies for meta-analysis
Year Continent Age Total Uterine fibroids Hypertension No-hypertension No-uterine fibroids Hypertension No-hypertension OR 95% CI
2001 America Premenopause 712 318 70 248 394 31 363 1.7 1.0–2.8
2001 Europe 41–89 543 365 152 213 178 65 113 1.7 1.1–2.7
2004 Europe 21–54 2400 843 53 790 1557 121 1436 0.9 0.7–1.3
2010 America 35–50 375 274 47 227 101 7 94
2011 America 31–82 577 122 43 79 455 113 342
2012 Asia Not mentioned 378 189 80 109 189 53 136 2.02 1.25–3.27
2014 Asia 40–50 389 204 78 126 185 76 109
2015 Europe 18–60 657 272 114 158 385 106 279 1.77 1.03–3.05
2016 Asia 40–47 1230 615 126 489 615 110 505 1.09 0.89–1.34
2018 America 18–70 728 104 67 37 624 216 408 1.84 1.09–3.10
718 Y. Chen et al.

eventually enrolled [4,5,8,12,20–26], with a total of
16,762 participants ultimatelybeingincludedinthemeta-
analysis after including the participants of the present
study. Table 3describes the main features of the selected
studies. Most of the studies were given more than five
stars according to the Newcastleontrol study. II. Athero-
genic risk factorstem, indicating good quality (Table 4).
The datasets were heterogeneous (I2=68%). Therefore,
random effects models were used for analyses. The meta-
analysis of the included studies and our study revealed a
significant association between UFs and hypertension
[pooled OR =1.44, 95% CI: 1.17–1.75, P=0.0004; I2=
68%] (Fig. 2)(Table5). When we excluded one study at a
time in the sensitivity analysis, none of the individual
studies substantially influenced the results, confirming the
stability of our results. A funnel plot showed asymmetry
(Fig. 3), which might be because studies with negative
results have remained unpublished because the authors
failed to write manuscripts and submit them to journals
[27].
Discussion
UFs are the most common benign gynecological tumor that
occurs in women between 30 and 50 years old, and with
increasing age, the prevalence before menopause can be as
high as 70–80% [28]. The prevalence of hypertension is
increasing rapidly in China, with more than 200 million people
acquiring the disease each year, resulting in a very large
medical burden. Since investigators have been reporting the
phenomenon of UFs combined with hypertension since the
1930s, many epidemiological studies have demonstrated a
correlation between UFs and hypertension [3–15]. However,
there are still controversies. For example, the Nurses’Health
Study II [9] found a correlation between hypertension and UFs.
However, the Northern Finland Birth Cohort [11] showed no
correlation between UFs and hypertension during the follow-up
period from birth to 46 years of age.
To clarify the correlation between the two diseases, we
performed this cross-sectional study. We found that blood
pressure was significantly higher in patients with UFs; the
prevalence of hypertension remained significantly higher in
patients with UFs even after adjusting for age, similar to the
findings of previous studies [5,6,10,12,20,22,23,26,29].
The data presented in our study indicate that hypertension risk
is 1.35 times higher in patients with UFs than in those
without UFs.
To validate the results of our cross-sectional study, we
performed a meta-analysis. The meta-analysis of the included
studies and our study indicated that hypertension risk was
1.44 times higher in women with UFs than in those without
UFs, which was also similar to the finding of our study, and
the association remained statistically significant in the sensi-
tivity analysis. We only included studies published in English,
and this language restriction could mean that some relevant
studies in particular ethnic groups might have been missed if
they were not published in English.
Fig. 2 Forest plot of the association of hypertension with uterine fibroids
Fig. 3 Funnel plot of the association of hypertension with uterine
fibroids
Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis 719

The strength of our study is that we presented well-
controlled and adjusted data, included different populations,
blood pressure was measured by trained staff rather than
obtaining data through self-report, and UFs were confirmed by
ultrasound rather than self-report.
As the present study is cross-sectional, the results do not
inform causal inferences. Whether there is a difference in the
prevalence of UFs in women with and without hypertension
remains unclear. In future studies, we will compare the pre-
valence of UFs between hypertensive women and non-
hypertensive women, which could help elucidate whether UF
causes increased blood pressure or high blood pressure pre-
disposes individuals to UFs.
The pathomechanism between UFs and hypertension has
not been clarified. Studies suggest that UFs, through several
growth factors and vasoactive peptides, increase the risk of
hypertension, such as in circulating endothelin-1 secreted by
UFs [10,30]. More studies are needed to clarify the molecular
mechanism of the induction of hypertension by UFs.
Conclusion
Our cross-sectional study and meta-analysis indicate that
blood pressure is higher in patients with UFs than in those
without UFs. Women with UFs should be offered screening
for hypertension.
Acknowledgements We would like to thank the participants involved in
this study for their critical contributions. We would like to thank Dr.
Stanley Li Lin, Department of Cell Biology and Genetics, Shantou Uni-
versity Medical College, for his helpful comments and English language
editing. The corresponding author attests that all listed authors meet
authorship criteria and that no others meeting the criteria have been
omitted.
Funding 1. Grant for Key Disciplinary Project of Clinical Medicine under
the High-level University Development Program, Guangdong, China
(2020); 2. Innovation Team Project of Guangdong Universities, China
(Natural, No. 2019KCXTD003); 3. Supported by 2020 Li Ka Shing
Foundation Cross-Disciplinary Research Grant (2020LKSFG19B); 4.
Funding for Guangdong Medical Leading Talent, the First Affiliated
Hospital, SUMC, China (2019–2022); 5. Supported by the National
Natural Science Foundation of China (No. 82073659).
Compliance with ethical standards
Conflict of interest The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
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