Association between uterine fibroids and hypertension among women of reproductive age in Eastern Sudan: a matched case–control study

Abstract

The association between uterine fibroids and hypertension is not yet settled. Thus, this study aimed to investigate the association between fibroids and hypertension in women of reproductive age in Sudan. A matched case–control study (107 in each arm) was conducted at New Halfa Hospital, Eastern Sudan. The cases were nonpregnant women of reproductive age diagnosed with uterine fibroids confirmed by ultrasound, while the controls were nonpregnant women without uterine fibroids. The women’s sociodemographic characteristics and clinical data were assessed via a questionnaire. Conditional logistic regression analysis was performed. There was no significant difference between the two groups regarding age, parity, body mass index (BMI), and hemoglobin. However, compared with the controls, a significantly higher number of women with uterine fibroids had hypertension, [46 (43.0%) versus 22 (20.6%), P = 0.001]. Multivariable logistic regression showed that women with hypertension (adjusted odds ratio [AOR] = 2.26, 95% confidence interval [CI] 1.14–4.48) were positively associated with uterine fibroids. BMI, education level, occupational status, and marital status were not associated with uterine fibroids. Our study revealed that uterine fibroids are significantly positively associated with hypertension among women of reproductive age in Sudan. This supports the literature calling for further analysis of the shared risk factors and underlying mechanisms of such an interconnected association between hypertension and uterine fibroids.

Introduction

Uterine fibroids, also known as uterine leiomyomata, are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide^1,2. Clinically significant uterine fibroids are reported in about 25% of women during their reproductive years; they affect an even larger proportion of women, with over 70% developing fibroids by menopause³. Uterine fibroids have been associated with several morbidities^4,5, including hypertensive disorders of pregnancy and hysterectomy^4,5. The burden of uterine fibroids is much higher among women who live in resource-limited settings, such as Sub-Saharan Africa, or are of African ancestry^6,7. Several factors, such as age, education, occupation, marital status, obesity, and anemia, have been reported as risk factors for uterine fibroids^2,3,5,7,8. Recently, more attention has been paid to the role of hypertension in the development of uterine fibroids^5,6,9–12. According to the World Health Organization (WHO), hypertension is a condition in which the blood vessels have persistently raised pressure; it is the major cause of premature death worldwide, with upwards of 1 in 4 men and 1 in 5 women, over a billion people, having hypertension, especially in resource-limited settings¹³.

Most studies show a significant association between hypertension and uterine fibroids^3,6,9–12. Although Henry et al. reported that uterine fibroids share a substantial genetic basis with traits related to blood pressure and obesity, no causal effect on blood pressure was found⁵. Vitamin D plays a role in many diseases¹⁴. It is thought that vitamin D plays an important role in fibroid development¹⁵. In addition, reviews reported an association between vitamin D deficiency and risk of hypertension, atherosclerosis, and heart failure¹⁶. Few studies have been conducted in Sub-Saharan Africa regarding the association between uterine fibroids and hypertension, where both high prevalence of uterine fibroids and hypertension exist⁷. For example, Sudan shows a high prevalence of both uterine fibroids¹⁷ and hypertension among Sudanese women^18,19. However, the association between uterine fibroids and hypertension has not been assessed in Sudan. Thus, this study aimed to investigate the association between uterine fibroids and hypertension among women of reproductive age at New Halfa Maternity Hospital, Eastern Sudan.

Methods

Study area

Kassala state is one of the 18 states of Sudan²⁰ It has 11 localities (the lowest administrative unit in Sudan), including New Halfa, where the New Halfa Maternity Hospital is located.

Case and control definition

In this study, the authors followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines²¹. The study population consisted of women of reproductive age who attended New Halfa Maternity Hospital during the study period (March to November 2024). The cases were nonpregnant women of reproductive age who were diagnosed with uterine fibroids based on clinical examination and confirmed by ultrasound at the new Halfa Maternity Hospital during the study period. The controls were nonpregnant women without uterine fibroids who attended the same hospital during the same study period and were matched for age and parity. Controls were recruited from women who visited the hospital for routine check-ups, family planning services, or another gynecological complaint unrelated to uterine fibroids. The matching criteria were as follows: For each case identified, one control was selected and matched for age and parity.

Study population and design

This matched (age and parity) case–control study was conducted from March to November 2024 at New Halfa Maternity Hospital, New Halfa locality, Kassala state, Eastern Sudan. This government-run hospital provided gynecological and obstetric services to all women, regardless of residency.

All women of reproductive age who attended the hospital were approached to participate in the study after being informed of the study’s objectives and relevant ethical issues. After signing an informed consent form, all the nonpregnant women of reproductive age (18 to 49 years) were enrolled. Participants aged below 18 years, pregnant women, patients with poor cognitive functions, and severely ill patients were excluded from this study. Based on clinical examination and gynecological ultrasound findings (i.e., the presence or absence of uterine fibroids), a woman was categorized as a case or a control, respectively. The desired sample size was achieved over the eight-month study period.

Data collection

Experienced gynecologists performed the gynecological ultrasound. The investigators trained a female medical officer in data-collection methods to standardize procedures and maintain data quality. The questionnaire was developed based on previous similar studies^6,7,9–11. It aimed to gather data on sociodemographic characteristics, including age, employment status (employed/housewife), marital status (married/unmarried), and education level (< secondary or ≥secondary). Additionally, anthropometrics, blood pressure measurements, and blood samples were collected as detailed below.

Procedures

The woman’s weight was measured in kilograms (kg) using well-calibrated scales adjusted to zero before each measurement, according to standard procedures. The woman stood with minimal movement, her hands at her sides. Shoes and excess clothing were removed. Her height was measured in centimeters (cm) and later converted into meters (m) after she stood straight with her back against the wall and her feet together. The body mass index (BMI) was computed as the weight in kg divided by the square of the height in meters (kg/m²)²².

Blood pressure was measured using an appropriately sized cuff with a calibrated sphygmomanometer after the woman had rested for at least 10 min in a sitting position with her arm at heart level. With an appropriately-sized cuff, the mean of two (at an interval of 1–2 min) blood pressure readings was calculated. If the difference between the two readings exceeded 5 mmHg, the measurement was repeated until the readings stabilized. A woman was diagnosed as hypertensive with an average blood pressure of ≥ 140/90 mmHg, or if she had reported the use of anti-hypertensive medication for high blood pressure²³.

Under a septic condition, each woman was requested to give 3 ml of blood for hemoglobin analysis. These samples were used as part of a complete blood count. An automated hematology analyzer (Sysmex KX-21, Japan) was used to measure hemoglobin levels, as previously detailed in our published work²⁴.

Sample size calculation

A sample size of 107 women in each study group (107 with uterine fibroids vs. 107 without uterine fibroids) in a ratio of 1:1 was computed, assuming a prevalence of hypertension of 24% and 9% among women with and without fibroids, respectively. This assumption was based on the reports of hypertension in Iran (24% among women with fibroid vs. 9.0% among those without fibroid)⁸. This sample size of 107 participants in each group was determined to detect a 5% difference at α = 0.05 with 80% power.

Statistical analysis

The IBM Statistical Package for the Social Sciences (SPSS) for Windows, version 22.0 (SPSS Inc., New York, United States), was used to analyze the data, which were double-entered and cross–checked for accuracy before analysis. The proportions were expressed as frequencies (%) and were compared between the groups using the chi-square test. The continuous data were evaluated for normality using the Shapiro–Wilk test and were found to be non-normally distributed. Non-normally distributed data, such as age, parity, BMI, and hemoglobin, were reported as median (interquartile range [IQR]). Univariate binary analysis was performed with uterine fibroids as the dependent variable, and sociodemographic variables (age, BMI, educational level, occupation, marital status, and family history of hypertension) and clinical variables (parity, hemoglobin, and having hypertension) were used as the independent variables. Variables with a p-value of ≤ 0.20 in the univariate binary analysis were selected to construct multivariable models that considered crude associations between uterine fibroids and the variables. Backward elimination (conditional logistic regression) was performed to adjust the model for covariates. Adjusted odds ratios (AORs), 95% confidence intervals (CIs), were calculated as they were applied to assess the strength and direction of the association. A two-sided p-value of < 0.05 was considered statistically significant.

Ethical approval

This study was conducted per the Declaration of Helsinki. Ethical approval was obtained from New Halfa Maternity Hospital, Eastern Sudan. The reference number is # 9, 2024. Written informed consent was obtained from all the enrolled women in accordance with the Human Rights Declaration of Helsinki.

Results

In this study, 107 participants were enrolled in each arm (uterine fibroids and controls). Among the cases (107), the uterine fibroids were detected most commonly in the posterior wall (66.3%) and in the fundus (26.2%). Intramural (58.9%) and subserosal fibroids (33.6%) are the most common. The median (IRQ) of the uterine fibroids size was 4.8 (2.4‒6.1) cm.

The cases and controls were matched, and there was no significant difference between the two groups regarding age, parity, BMI, and hemoglobin. However, compared with the controls, women with uterine fibroids were more educated: 62 (57.9%) women with uterine fibroids and 33 (30.8%) women in the control group had a high educational level of ≥ secondary, P < 0.001/There were also other differences: 16 (15.0%) women with uterine fibroids and 3 (2.8%) women in the control group were employed, P = 0.001; 14 (13.1%) women with uterine fibroids and 2 (1.9%) women in the control group were unmarried, P = 0.001. Compared with the controls, a significantly higher number of women with uterine fibroids had hypertension, [46 (43.0%) versus 22 (20.6%), P = 0.001], (Table 1).

Table 1.

Univariate analysis of the factors associated with uterine fibroids among women attending New Halfa Hospital, Eastern Sudan, 2024.

Variable	Women with uterine fibroids (number = 107)	Women without uterine fibroids (number = 107)	Univariate analysis
	Median (Interquartile range)		Odds ratio (95% confidence interval)	P value
Age, years	30.5(29.0‒34.0)	29.6(27.0‒33.0)	1.03(0.97‒1.09)	0.270
Parity	1.4(0.0‒3.3)	1.5(0.0‒3.0)	1.05(0.91‒1.21)	0.468
Body mass index, kg/m2	21.0(19.6‒23.5)	19.4(17.3‒22.5)	1.06(0.99‒1.14)	0.058

	Frequency (Percentage)
Education level
< Secondary	45(42.1)	74(69.2)	Reference
≥ Secondary	62(57.9)	33(30.8)	3.10(1.76‒5.42)	< 0.001
Occupational status
Housewife	91(85.0)	104(97.2)	Reference
Employed	16(15.0)	3(2.8)	6.09(1.72‒21.59)	0.005
Marital status
Married	93(86.9)	105(98.1)	Reference
Unmarried	14(13.1)	2(1.9)	7.90(1.75‒36.69)	0.007
Hypertension
No	61(57.0)	85(79.4)	Reference
Yes	46(43.0)	22(20.6)	2.91(1.59‒5.33)	0.001

Univariate binary logistic regression analysis showed that education, occupation, marital status, and hypertension were significantly associated with uterine fibroids (p < 0.05). However, age, parity, BMI, and hemoglobin were not associated with it (p value > 0.05) (Table 1).

The multivariable logistic regression (backward conditional) results showed that women having hypertension (AOR = 2.26, 95% CI 1.14–4.48) were significantly positively associated with uterine fibroids. BMI, education level, occupational status, and marital status were not associated with uterine fibroids (Table 2).

Table 2.

Multivariate analysis of the factors associated with uterine fibroids among women attending New Halfa Hospital, eastern Sudan, 2024.

Variable	Adjusted odds ratio	95% confidence interval	P value
Body mass index, kg/m2	1.03	0.96‒1.11	0.350
Education level
< Secondary	Reference
≥ Secondary	1.43	0.73‒2.79	0.293
Occupational status
Housewife	Reference
Employed	3.18	0.77‒13.03	0.108
Marital status
Married	Reference
Unmarried	3.74	0.72‒19.36	0.115
Hypertension
No	Reference
Yes	2.26	1.14‒4.48	0.019

Discussion

This matched (for age and parity) case–control study investigated the association between uterine fibroids and hypertension among women of reproductive age at New Halfa Maternity Hospital in Eastern Sudan. Our findings showed a significant association between uterine fibroids and hypertension. This study’s reported association between uterine fibroids and hypertension aligns with the growing body of evidence suggesting an interconnected association between these two conditions in various countries, including those in Africa^6,7,9–11. In the north of Benin, a recent cross-sectional study included 744 women, revealing that 10.1% were diagnosed with uterine fibroids; age and hypertension were significantly associated with the presence of uterine fibroids⁷. In the United States, a multicenter prospective study included 2570 women without a history of diagnosed fibroids, which revealed that women with untreated and new-onset hypertension had an increased risk of newly diagnosed uterine fibroids of 19%, compared to those on antihypertensive treatment, who had a 20% lower risk¹⁰. Although the exact mechanisms by which blood pressure influences uterine fibroids, and vice versa, are not fully understood, researchers have proposed several explanations for their interrelationship. Chronic high blood pressure can cause damage and inflammation to the smooth muscle cells and blood vessels within the uterine wall¹². This vascular injury may create a suitable environment for abnormal smooth muscle cell proliferation, a key process in uterine fibroid development. Second, hypertension is often associated with an imbalance in various growth factors and cytokines, such as angiotensin II, which plays a role in blood pressure regulation and tissue growth^12,25. Increased levels of these factors in hypertensive women may stimulate the growth and development of uterine fibroid tissue. Third, some studies suggest that hypertension might affect hormonal balance (estrogen and progesterone) and oxidative stress, which are known to influence fibroid growth^26–28. Fourth, both uterine fibroids and hypertension may share similar risk factors, such as food additive consumption^3,29. While the exact interplay is complex, hypertension-related vascular changes could potentially alter local hormone delivery and metabolism within the uterus, creating a hormonal milieu that favors fibroid formation. Taking into consideration the potential for limited access to healthcare, especially during the ongoing war and higher rates of undiagnosed and untreated hypertension in the study setting of Eastern Sudan among both genders^18,19. These mechanisms could be particularly relevant in understanding the prevalence and association between uterine fibroids and hypertension in this population. It is essential to mention that the majority of the studied women were newly diagnosed with hypertension. Further research is recommended to elucidate these pathways and their significance in this context.

It is important to mention that the objectively measured association between the women’s hypertension status and uterine fibroids warrants greater emphasis in this study. Consequently, the findings related to the women’s hypertension status provide a more reliable and robust assessment of the association between these two conditions (uterine fibroids and hypertension) in this study population.

The present study assessed the association between uterine fibroids and hypertension. As mentioned above, several factors, such as age, education, occupation, marital status, obesity, and anemia, have been reported as risk factors for uterine fibroids and are associated with uterine fibroids^2,5,8. In this study, in addition to the matched factors (age and parity), marital status, education, and occupation were found to be as confounding factors as shown in the regression analysis, as these factors were associated with uterine fibroids in the univariate analysis only, and BMI was not associated in all regressions. Likewise, Mitro et al. in their sizable study reported that anthropometric factors, such as BMI, were not associated with the risk of uterine fibroids¹⁰. Moreover, most fibroids are intramural or subserosal (with a few submucosal), which may explain the absence of a difference in hemoglobin levels between cases and controls.

Strengths and implications of the study

This study has several strengths and implications. As a strength, this study addressed a research gap in a specific population. No prior research has investigated the association between uterine fibroids and hypertension in Sudan. This gives the study the novelty of contributing valuable context-specific data to the existing global literature^2,3,5–12. Studying this association in a specific population, such as women of reproductive age in Eastern Sudan, can reveal patterns that may be influenced by local genetic, environmental, dietary, or lifestyle factors. This study employed a robust case–control design, a robust methodological approach for investigating the association between uterine fibroids and hypertension. The study identified a significant positive association between having hypertension and the presence of uterine fibroids after adjusting for other factors in a multivariable logistic regression. Such a strong odds ratio suggests a substantial association between these two conditions in the studied population. In addition to these strengths, the study identified specific implications for improving women’s health in the study region and similar contexts. It addressed the need for integrated screening and management for uterine fibroids and hypertension, which could lead to earlier detection and potentially better management of uterine fibroids, reducing their incidence and the associated morbidities. Likewise, women who are diagnosed with uterine fibroids might benefit from routine blood pressure monitoring and assessment of their family history of hypertension. This study calls for further mechanistic research to investigate the underlying mechanisms linking uterine fibroids and hypertension, as well as the reciprocal relationship between them. Although this study provides epidemiological evidence, understanding the biological pathways involved (as discussed in the previous response about potential genetic, vascular, and hormonal links) is crucial for developing targeted prevention and treatment strategies. Future research could focus on genetic studies within the Sudanese population, investigating specific biomarkers and exploring the molecular interplay of these conditions. Also, this study’s findings can inform public health strategies and resource allocation. Identifying these significant associations has implications for public health planning in Sudan. Understanding the prevalence and risk factors for uterine fibroids can help in allocating healthcare resources more effectively for screening, diagnosis, and treatment. For example, public health campaigns could also raise awareness about the potential association between uterine fibroids and hypertension, encouraging women with a family history of hypertension or known hypertension to seek timely gynecological care.

Limitations

Despite the aforementioned strengths of this study, it has limitations that should be acknowledged to inform future similar designs. First, this study was a single-centre study that included a single maternity hospital, which limits the generalizability of its findings to the broader population of women of reproductive age in Sudan or other regions because the prevalence of uterine fibroids and hypertension, as well as their associated factors, might vary geographically and across different healthcare settings. Second, although the study design was a matched case–control study, in a cross-sectional study, the assessment of hypertension, including both known and newly diagnosed cases, was likely conducted at enrollment. This makes it challenging to establish the temporal relationship between hypertension and the development of uterine fibroids. It is unclear whether hypertension preceded the development of fibroids or vice versa¹⁰. Third, recall bias is a potential concern; for example, the study relied on the questionnaire to assess family history of hypertension. Participants’ recall of their family’s medical history may be inaccurate or incomplete, leading to misclassification of exposure. Finally, there is a limited assessment of confounding factors. Although the study adjusted for BMI, education level, occupational status, and marital status in the multivariate analysis and matched for age and parity, there may still be unmeasured or inadequately assessed confounding factors that could influence the association between uterine fibroids and hypertension. Based on previous studies, these factors may include dietary habits, physical activity levels, socioeconomic status beyond education and occupation, and other medical conditions (11, 27). Therefore, a prospective longitudinal study with multicentre involvement and a variety of potential associated factors is recommended to overcome these limitations.

Conclusion

In this matched case–control study in Eastern Sudan, a positive family history of hypertension and the presence of hypertension were significantly associated with increased odds of having uterine fibroids among women of reproductive age. This study supports the existing literature calling for further investigation into the shared risk factors and underlying mechanisms of the association between uterine fibroids and hypertension.

Author contributions

A.A.A., O.A.H., and I.A. contributed to the study’s design and supervised the data collection. O.A.H., N.A., and I.A. contributed to the data analysis. All authors contributed to the preparation of the manuscript, this version of which they have read and agreed to.

Funding

None.

Data availability

The data supporting the current study’s findings are available from the corresponding author upon reasonable request.

Competing interests

The other authors have nothing to declare.