Document Type : Original article
Authors
1 M.D, Division of Female Pelvic Medicine and Surgery, Department of Obstetrics and Gynecology, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Physical Medicine and Rehabilitation, School of Medicine, Hamedan University of Medical Science, Hamedan, Iran
4 Division of Female Pelvic Medicine and Surgery, Department of Obstetrics and Gynecology, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Keywords
Main Subjects
Abstract
Background: Cardiovascular Diseases (CVD), mainly Hypertension (HTN), is the leading cause of death among women. Uterine Leiomyomas (UL) which have been associated with hypertension in multiple studies, may be a female-specific risk factor. Fibroids have become a primary reason for myomectomy and hysterectomy, nowadays. This study aims at the relationship between HTN and fibroids.
Methods: This case-control study was conducted on patients with symptomatic UL, scheduled for surgery. Patients were studied based on Blood Pressure (BP), the number and size of fibroids, past medical conditions, and gynecological history.
Results: Four hundred patients, divided into two groups of control and case, were studied. Menometrorrhagia was the most common reason for referral in both groups (328 patients in general). The use of Oral Contraceptives (OCP) (12 vs. 5%), anemia (57 vs. 38.5%), history of infertility (11.5 vs. 3.5%), and abortion (38.5 vs. 22%) was significantly higher in patients with fibroids. 24% of patients with fibroid suffered from hypertension; which was higher in comparison to the control group (9%). Patients with UL were 4.9 times in danger of having HTN.
Conclusion: UL is associated with hypertension. It is also concluded that anemia, rate of abortion, and infertility are higher in patients with UL.
Keywords: Cardiovascular disease, Fibroid, Hypertension, Uterine leiomyoma
Introduction
Uterine Leiomyomas or fibroids (UL) has become a public health concern and a prior indication for hysterectomy in female of reproductive age (1,2). Over 200,000 hysterectomies and a growing number of myomectomies are performed due to UL each year (3,4). UL is considered to be the most common female genital tract tumor (5). They are benign monoclonal tumors with smooth muscle origin (4,6). The etiology of this tumor is yet unknown, but they are mainly hormone-dependent, and Estrogen has an important role in fibroid growth (7-9). Although some clinical and biological studies suggest the impact of progesterone in UL development (10), age and African American ethnicity are considered to be major risk factors for UL (11). Studies have suggested that fibroids can be found in up to 70% of females but only 30% accompany by clinical features such as abdominal pain, pelvic pain, infertility, bladder or rectum obstruction, pregnancy complication, and abnormal uterine bleeding (4,7). Bimanual examination and transvaginal ultrasonography are the conventional diagnostic methods of UL (9).
As is known, Hypertension (HTN) is the most common cause of cardiovascular and kidney diseases (12,13) and the leading cause of mortality in cardiovascular diseases (1). UL and HTN can lead to smooth muscle cell alteration, linking these two diseases (14). Studies have brought up the coexistence of hypertension and fibroids. The relationship between these two is yet unknown (10). Therefore, this study aims to assess the relationship between fibroids and hypertension in a case-control study.
Materials and Methods
Study design and setting
This case-control study was conducted on patients with symptomatic UL, including menometrorrhagia, abdominal pain, and infertility, who were scheduled for surgery at the obstetrics and gynecology department of Yas Hospital, a referral center in Tehran, Iran. The study was approved by ethics committee of the Tehran University of Medical Sciences. The information about patients was collected, analyzed, and provided anonymously. The researchers adhered to the ethical principles of the Helsinki recommendations.
Participants
This study was conducted via patients admitted to Yas Hospital, scheduled for gynecological surgery during a three-year study period, from 2017 to 2020.
This study includes 18 to 60 years old females with a confirmed diagnosis of UL via clinical examination, ultrasonography, and pathology who were scheduled for myomectomy or total hysterectomy at this center, in case group. The control group includes 18 to 60-year-old females who were scheduled for a non-fibroid total hysterectomy surgery and admitted at the same center. We included patients who reported blood pressure unknown or not checked in the past 2 years and excluded women with a history of secondary hypertension, malignancy or receiving antihypertensive drug therapy. Using the reported values in previous studies (1,15), study power of 80%, the two-sided significance level of 5%, and using the sample size formula for proportional studies, the sample size for each group was calculated to be 200.
Data collection
Using a predesigned checklist, information was collected regarding demographics, Blood Pressure (BP), the number and size of fibroids, previous use of Oral Contraceptive Pills (OCP), history of infertility, diabetes, anemia, thyroid diseases, hyperlipidemia, number of abortions, number of pregnancies, and chief complaints when admitted. Blood pressure was measured twice at thirty-minute intervals in both groups. Hypertension (HTN) was defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg or a patient receiving anti-hypertensive medication (16).
Data analysis
All statistical analyses were conducted via the SPSS-25 (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp; 2017). Study findings were reported as frequency (%) or mean ± standard deviation (SD) for categorical and numerical variables. We reported “median and range” for data that were not normally distributed. Comparisons were performed using Chi-Square or Fisher’s exact test. The mean differences in numerical variables between the two groups were compared by independent t-test. For numerical variables, Pearson’s correlation and linear regression were utilized. A p-value lower than 0.05 was considered statically significant.
Table 1. The baseline characteristics (N=400)
|
Variables |
Patients with UL |
Control group |
p-value |
|
|
Chief compliant |
Menometrorrhagia |
156 (78%) |
172 (86%) |
0.892 |
|
Abdominal pain |
38 (19%) |
22 (11%) |
0.291 |
|
|
Infertility |
6 (3%) |
6 (3%) |
1.000 |
|
|
Age |
42.77±8.75 |
48±7.35 |
0.163 |
|
|
OCP use |
24 (12%) |
10 (5%) |
0.019 |
|
|
Anemia |
114 (57%) |
77 (38.5%) |
<0.001 |
|
|
Diabetes |
18 (9%) |
26 (13%) |
0.263 |
|
|
Hyperlipidemia |
25 (12.5%) |
25 (12.5%) |
1.000 |
|
|
Thyroid diseases |
29 (14.5%) |
18 (9%) |
0.120 |
|
|
Infertility |
23 (11.5%) |
7 (3.5%) |
0.004 |
|
|
Abortion |
77 (38.5%) |
44 (22%) |
<0.001 |
|
|
Pregnancy |
2.99±1.92 |
3.61±1.53 |
<0.001 |
|
UL (Uterine Leiomyoma).
Table 2. Associations of systolic and diastolic blood pressure in patients with UL according to their age
|
Variants |
Patients with UL |
Control group |
p-value |
|
SBP (mmHg) |
126.68±19.67 |
119.23±13.96 |
<0.001 |
|
SBP in ages below 40 (mmHg) |
124.23±21.2 |
113.9±11.45 |
0.049 |
|
SBP in ages above 40 (mmHg) |
128.21±1857 |
119.75±14.1 |
<0.001 |
|
DBP (mmHg) |
71.18±9.52 |
67.58±8.53 |
<0.001 |
|
DBP in ages below 40 (mmHg) |
70.83±7.7 |
62.56±15.72 |
0.002 |
|
DBP in ages above 40 (mmHg) |
71.4±10.5 |
68.08±7.35 |
0.001 |
|
HTN |
24% (48) |
9% (18) |
<0.001 |
|
HTN in ages above 40 |
27.6% (34) |
8.8% (16) |
<0.001 |
|
HTN in ages below 40 |
18.42% (14) |
10.52% (2) |
0.288 |
SBP (Systolic blood pressure); DBP (Diastolic blood pressure); HTN (Hypertension); UL (Uterine Leiomyoma).
Results
The baseline characteristics
Four hundred patients, divided into two groups, were studied. Group one contains 200 patients with UL with a mean age of 42.77 years scheduled for surgery. Group two was the control group, with a mean age of 48.31 years scheduled for non-fibroid gynecological surgery. The baseline characteristics of both groups are thoroughly mentioned in table 1.
Menometrorrhagia was the most common reason for referral in both groups. The use of OCP, anemia, history of infertility, and abortion were significantly higher in fibroid group.
The median number and range of myomas was 2 (1-5) and the median size range was 69.6 (13-200) mm in patients with UL.
Blood pressure and UL
Blood pressure was measured twice at thirty-minute intervals in both groups. We documented patients’ Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) separately in table 2. Hypertension was significantly higher in patients with UL (p-value< 0.001). Patients were divided into 2 groups: older than 40 years old and younger than 40 years old. The prevalence of HTN in patients with UL older than 40 years old was the highest. Considering age, patients with UL are 4.9 times in danger of having HTN.
Factors concerning HTN in patients with UL
In order to find effective factors in blood pressure, the relationship between systolic and diastolic blood pressure and other variables was measured using Pearson’s correlation test. Systolic blood pressure of patients was significantly related to age (r=0.258, p=0.026).
Anemia (r=0.194, p=0.006), hyperlipidemia (r=0.172, p=0.015), number of pregnancies (r=0.229, p=0.001), and chief complaint of abdominal pain and menometrorrhagia (r=-0.200, p=0.005) were significantly associated with higher SBP.
No significant relationship was found between blood pressure and other variables (myoma number, myoma size, OCP consumption, infertility, diabetes, thyroid diseases, and abortion) (p>0.05).
Finally, using linear regression test, the significance of the above findings (age, hyperlipidemia, anemia, number of pregnancies, reason for referral) in predicting systolic blood pressure of patients with uterine leiomyoma was measured. Only the coefficients of anemia (p=0.017) and reason for referral (chief complaint of abdominal pain and menometrorrhagia) (p=0.001) were significant in this model.
Anemia (p=0.017) and chief complaint of abdominal pain and menometrorrhagia (p=0.001) had a predicting value for higher systolic blood pressure.
Discussion
A total of 400 were studied in a case-control study to define the relationship between UL and hypertension. Studies showed that UL mostly presented in younger patients but there were no significant age differences between patients with UL and the control group.
Considering menometrorrhagia and abnormal uterine bleeding as the most common causes of referral for patients with UL, anemia can be expected as a result (17). As we can see, there was a relationship between anemia and UL in this study which was similar to previous studies (18,19). Some studies presented anemia mostly as a result of submucosal myoma (20,21). Promising theories were mentioned regarding the effect of UL on fertility. For instance, the effect of myomas on cavity distortion, the functional change of endometrium and myometrium that reduces uterine receptivity, as well as endocrine and paracrine molecular mechanisms. This can cause a hostile environment, impairing embryo implantation (22,23). In the event of pregnancy, spontaneous abortion, fetal malpresentation, preterm birth, and caesarian section are inevitable (24). In this study, pregnancy, infertility, and abortion were significantly affected by UL. Based on other studies, the location of the myomas, especially submucosal myomas, can have an important impact on this matter (10,23).
The use of OCP was significantly higher in patients with UL in our study. It is proven that OCP can be helpful in menstrual diseases in patients with UL (25). Younger age and higher infertility rate in patients with UL support the theory of sex hormone influence on UL occurrence (4,6,9,26).
Although the relationship between UL and diabetes and hyperlipidemia was not significant in this study, patients with UL displayed higher cardiovascular disease risk profiles in similar studies (2,27).
Our study proved the association between hypertension and UL as its main goal. Systolic and diastolic blood pressures were significantly higher and the frequency of hypertension was 4.9 times higher in patients with UL. The results were consistent with previous studies (1,2,8,11,14,28,29). A theory suggests the impact of hypertension on fibroid development and growth in uterine smooth similar to atherosclerotic changes in arterial smooth muscles (8). Patients referred with anemia or chief complaints of abnormal uterine bleeding and abdominal pain were accompanied by higher SBP, in this study. Patients were divided into two groups considering the importance of age in high blood pressure (30). Hypertension was mostly detected in patients diagnosed with UL older than 40 years. However, a previous study demonstrated that the incidence of UL was higher in patients affected by hypertension for at least 5 years and those diagnosed before 35 years old (10).
Limitations
The majority of researches on UL, including this study, are based on surgical cases. Therefore, selection bias and temporal bias are inevitable. Also, our control group contained no healthy individuals. African-American ethnicity is a major risk factor in patients with UL, however ethnicity was also a limitation based on the geographical location of the study. Data regarding Myomas’ location were another limitation.
Conclusion
It is confirmed that patients with UL are in danger of cardiovascular diseases mainly HTN. The prevalence of hypertension, anemia, abortion and infertility were higher in patients with UL. We recommend HTN screening in patients with UL, especially in patients with anemia, abdominal pain, and menometrorrhagia.
Acknowledgements
Ethical approval for this study was obtained from the ethics committee of the Tehran University of Medical Sciences (IR.TUMS.REC.1394.400).
We would like to express our commitment to obstetric and gynecological unit of Yas Hospital, Tehran University of Medical Sciences.
Conflict of Interest
The authors declare that there are no conflicts of interest.
Funding
This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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