Adenomyosis in Focus: Age-Related Trends and the Lack of Cardiovascular Risk Factor Correlation

Adenomyosis is a common benign gynecological pathology that is frequently associated with endometriosis. Although numerous studies have investigated cardiovascular risk factors in endometriosis, research on these risks in patients with adenomyosis remains scarce. This study aimed to evaluate cardiovascular risk factors in patients diagnosed with adenomyosis.

A total of 135 patients (65-study group, 70-control group) were included in the study. Age, known chronic comorbidities, smoking status, blood pressure, body mass index (BMI), and waist-to-hip ratio (WHR) were recorded preoperatively. Blood samples were obtained from patients who received pathology results within the first month after surgery. To evaluate cardiovascular risk factors, tests for total cholesterol, HDL, LDL, triglycerides, and CRP levels were performed.

The presence of chronic diseases and smoking status were compared between groups, and no significant differences were found. Additionally, comparisons of smoking, systolic and diastolic blood pressure, height, weight, BMI, WHR, total cholesterol, HDL, LDL, triglycerides, and CRP levels between the groups revealed no significant differences. However, a significant relationship was found between age and adenomyosis, with the mean age of the adenomyosis group being higher than that of the other groups (p < 0.05).

No significant relationship was found between adenomyosis and known chronic diseases, smoking (pack-years), systolic and diastolic blood pressure, BMI, WHR, total cholesterol, HDL, LDL, triglycerides, or CRP levels. However, the frequency of adenomyosis increases with age.

Adenomyosis is a gynecological disorder characterized by the presence of endometrial glands and stroma within the myometrium, resulting in uterine enlargement and myometrial thickening [1]. Although traditionally considered a disease of parous women in their late reproductive years, adenomyosis is increasingly being identified in younger populations; approximately 20% of patients are under the age of 40. While up to one-third of cases may be asymptomatic, the majority of affected individuals present with symptoms such as abnormal uterine bleeding, dysmenorrhea, and infertility. A definitive diagnosis typically requires histopathological confirmation, often obtained via surgical specimens from a hysterectomy or targeted biopsy. Microscopically, the condition is characterized by benign endometrial glands surrounded by stroma embedded within a hypertrophied myometrial context. However, the etiopathogenesis of adenomyosis remains unclear. Several hypotheses have been proposed, including invagination of the endometrial basalis into the myometrium, de novo metaplasia of Müllerian remnants, and mechanical injury from uterine peristalsis. Hormonal factors also play a pivotal role, and local hyperestrogenism in ectopic endometrial tissues may exacerbate proliferation and inflammation. Notably, these ectopic tissues are known to produce elevated levels of prostaglandins, contributing to increased uterine contractility and dysmenorrhea, a pathophysiological mechanism shared by endometriosis [1]. Endometriosis, a condition closely related to the presence of endometrial-like tissue outside the uterus, is increasingly linked to systemic comorbidities. Epidemiological studies have demonstrated associations between endometriosis and chronic diseases such as cardiovascular disease (CVD). Both conditions are characterized by systemic inflammation, oxidative stress, endothelial dysfunction, and pro-atherogenic lipid alterations [2]. CVD remains the leading cause of death among women in the United States, accounting for nearly one in three deaths. Although the potential relationship between endometriosis and CVD has received increasing research attention, the intersection between adenomyosis and cardiovascular risk factors remains poorly understood. This gap is particularly striking given the frequent coexistence of adenomyosis and endometriosis and their shared inflammatory and hormonal underpinnings. The present study aimed to investigate whether common cardiovascular risk factors are associated with the pathogenesis of adenomyosis. By evaluating these potential associations, we aimed to shed light on the possible coexistence and mutual reinforcement of these two conditions, contributing to a broader understanding of women’s cardiovascular and reproductive health.

This was an observational case-control study, conducted between January 2020 and June 2021 at the Health Sciences University Istanbul Training and Research Hospital Department of Gynecology and Obstetrics. A total of 135 patients who underwent hysterectomy for benign reasons and had negative smears and HPV test results were included in the study. The study group consisted of 65 patients who underwent hysterectomy and were diagnosed with adenomyosis by pathology. The control group included 70 patients whose hysterectomy results did not show adenomyosis or endometriosis. Patients with malignant pathology results and those who underwent postpartum hysterectomy were also excluded from the study. Each patient’s systolic and diastolic blood pressure (SBP, DBP; mm Hg), height (cm), weight (kg), waist circumference (cm), hip measurements (cm), age, known chronic comorbidities, and smoking status were obtained preoperatively through face-to-face interviews with patients, patient files, and the clinical database. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. On the same day, after surgery, the patient visited the clinic to learn about their pathology results, and a single tube of blood was collected from each participant following the current phlebotomy guidelines using one red-top tube containing a clot activator and a gel separator (Vacuette, Greiner bio-one, REF 455071). Total Cholesterol, HDL, LDL, Triglycerides, and CRP levels were investigated. After all data were collected, the parameters (BMI, WHR, Total Cholesterol, HDL, LDL, Triglyceride, CRP, SBP, DBP) were also classified into subgroups in accordance with the guidelines. The relationship between these parameters and adenomyosis was also evaluated in this study. All patients were provided with detailed information about the study before participation and given an informed consent form. Signatures were obtained from those who agreed to participate. Patients who had previously signed the consent form but later refused blood collection or changed their minds when receiving their pathology results were excluded from the study. This study protocol was reviewed and approved by the Clinical Research Ethics Committee of the Ministry of Health University, Istanbul Training and Research Hospital (approval number 2562; date: 30.10.2020). Statistical analyses were performed using SPSS version 17.0 program. The normality of the distribution of variables was examined using histogram charts and the Kolmogorov-Smirnov test. Descriptive analyses were performed using mean, standard deviation, and median values. Categorical variables were compared using Pearson’s chi-squared test. For non-normally distributed (non-parametric) groups, the Mann-Whitney U Test was used. Cases where the p-value was below 0.05 were considered statistically significant.

The study included 65 patients with adenomyosis and 70 with other pathological results. Of the 135 patients, 72 had chronic illnesses, including 10 with asthma, 13 with diabetes, 3 with epilepsy, 1 with hyperthyroidism, 24 with hypothyroidism, 42 with hypertension, 3 with coronary artery disease, 1 with chronic kidney failure, and 3 with chronic obstructive pulmonary disease. A total of 41 patients were smokers. The pathology results and the presence of diseases, various medical conditions, and smoking status were compared between the two groups, and no significant differences were found (p > 0.05) (See Table I). | Adenomyosis | Other pathology | p-value | ||| |---|---|---|---|---|---| | n | % | n | % | || | Chronic illness | 36 | 55.38 | 36 | 51.43 | 0.645 | | Asthma | 3 | 4.62 | 7 | 10.00 | 0.233 | | Diabetes | 4 | 6.15 | 9 | 12.86 | 0.187 | | Epilepsy | 1 | 1.54 | 2 | 2.86 | 0.604 | | Hyperthyroidism | 1 | 1.54 | 0 | 0 | 0.298 | | Hypothyroidism | 13 | 20.00 | 11 | 15.71 | 0.515 | | Hypertension | 21 | 32.31 | 21 | 30.00 | 0.772 | | Coronary artery disease | 2 | 3.08 | 1 | 1.43 | 0.516 | | Chronic kidney failure | 0 | 0 | 1 | 1.43 | 0.333 | | COPD | 2 | 3.08 | 1 | 1.43 | 10.516 | | Smoking | 19 | 29.23 | 22 | 31.43 | 0.781 | The two groups were compared in terms of BMI, waist-to-hip ratio, cholesterol, HDL, LDL, triglycerides, CRP, systolic, and diastolic values. Considering these as risk factors and negative prognostic indicators for CVD, the number of patients with BMI > 35, total cholesterol ≥ 200, HDL < 45, and LDL ≥ 160 were higher in the adenomyosis group. However, none of these differences were statistically significant (See Table II). | Pathology result | Adenomyosis | Other pathology | p-value | ||| |---|---|---|---|---|---|---| | n | % | n | % | ||| | BMI group | <18.5 | 0 | 0 | 1 | 1.43 | 0.243 | | 18.5–24.9 | 8 | 12.31 | 18 | 25.71 | || | 25–29.9 | 22 | 33.85 | 18 | 25.71 | || | 30–34.99 | 20 | 30.77 | 23 | 32.86 | || | 35–39.99 | 12 | 18.46 | 9 | 12.86 | || | ≥40 | 3 | 4.62 | 1 | 1.43 | || | WHR group | 0.85 | 30 | 46.15 | 31 | 44.29 | || | Cholesterol group | <200 (Normal) | 37 | 56.92 | 50 | 71.43 | 0.079 | | ≥200 (Abnormal) | 28 | 43.08 | 20 | 28.57 | || | HDL group | 65 (High) | 6 | 9.23 | 4 | 5.71 | || | LDL group | <130 (Normal) | 37 | 56.92 | 49 | 70.00 | 0.288 | | 130–159 (Borderline high) | 20 | 30.77 | 15 | 21.43 | || | ≥160 (High) | 8 | 12.31 | 6 | 8.57 | || | Triglyceride group | <150 (Normal) | 48 | 73.85 | 54 | 77.14 | 0.896 | | 150–199 (Borderline high) | 10 | 15.38 | 9 | 12.86 | || | ≥200 (High) | 7 | 10.77 | 7 | 10.00 | || | CRP group | <5 (Normal) | 43 | 66.15 | 41 | 58.57 | 0.364 | | ≥5 (Abnormal) | 22 | 33.85 | 29 | 41.43 | || | Systolic group | <120 (Normal) | 25 | 38.46 | 27 | 38.57 | 0.856 | | 120–139 (Prehypertension) | 23 | 35.38 | 21 | 30.00 | || | 140–159 (HTN Stage 1) | 14 | 21.54 | 17 | 24.29 | || | ≥160 (HTN Stage 2) | 3 | 4.62 | 5 | 7.14 | || | Diastolic group | <80 (Normal) | 32 | 49.23 | 31 | 44.29 | 0.452 | | 80–89 (Prehypertension) | 23 | 35.38 | 24 | 34.29 | || | 90–99 (HTN Stage 1) | 8 | 12.31 | 8 | 11.43 | || | ≥100 (HTN Stage 2) | 2 | 3.08 | 7 | 10.00 | The two groups were compared in terms of mean age, smoking (pack/years), height, weight, BMI, waist circumference, hip circumference, WHR, total cholesterol, HDL, LDL, triglycerides, CRP, SBP, and DBP values. The mean age of the adenomyosis group was significantly higher than that of the control group (51.06 and 47.60, respectively; p = 0.005). Although the number of smokers was similar in both groups (adenomyosis group n = 19, control group n = 22), the mean pack-years of smoking was higher in the adenomyosis group than in the other group (34.95 and 27.82, respectively). However, this difference was not statistically significant (p = 0.191) (See Table III). | Adenomyosis | Other | p-value | ||||| |---|---|---|---|---|---|---|---| | Mean | SD | Median | Mean | SD | Median | || | Age (Years) | 51.06 | ±6.99 | 50.00 | 47.60 | ±7.26 | 47.00 | 0.005 | | Smoking (Pack-years) | 34.95 | ±18.00 | 30.00 | 27.82 | ±12.80 | 25.00 | 0.191 | | Height (cm) | 159.80 | ±5.67 | 160.00 | 160.84 | ±5.51 | 160.00 | 0.237 | | Weight (kg) | 78.23 | ±12.14 | 78.00 | 75.66 | ±12.09 | 76.00 | 0.274 | | BMI (kg/m2) | 30.80 | ±5.14 | 30.11 | 29.35 | ±5.19 | 29.38 | 0.192 | | Waist (cm) | 101.66 | ±21.67 | 96.00 | 95.73 | ±17.88 | 93.00 | 0.152 | | Hip (cm) | 115.98 | ±19.19 | 116.00 | 112.26 | ±15.60 | 112.50 | 0.372 | | WHR | 0.87 | ±0.10 | 0.85 | 0.84 | ±0.07 | 0.85 | 0.359 | | Cholesterol | 194.74 | ±41.64 | 187.00 | 184.40 | ±39.72 | 178.50 | 0.174 | | HDL | 46.45 | ±12.61 | 44.00 | 47.24 | ±11.41 | 46.50 | 0.644 | | LDL | 122.28 | ±33.53 | 121.00 | 111.89 | ±31.97 | 109.00 | 0.098 | | Triglyceride | 128.51 | ±75.19 | 112.00 | 126.31 | ±66.17 | 107.50 | 0.909 | | CRP | 10.30 | ±21.58 | 2.40 | 9.01 | ±14.03 | 4.30 | 0.322 | | SBP (mm Hg) | 126.60 | ±18.14 | 125.00 | 126.84 | ±19.92 | 122.00 | 0.991 | | DBP (mm Hg) | 78.11 | ±10.58 | 80.00 | 79.66 | ±11.28 | 80.00 | 0.492 |

Our study sought to explore the potential association between uterine adenomyosis and cardiovascular disease (CVD) risk factors, a link that remains understudied despite the established relationship between endometriosis and cardiovascular pathology. Although statistical significance was not achieved for several measured parameters, important trends were observed that merit deeper exploration and may suggest shared pathogenic mechanisms between adenomyosis and CVD. Adenomyosis, similar to endometriosis, is increasingly being recognized as a systemic condition characterized by chronic inflammation and hormonal dysregulation [3], [4]. These features are central to the pathogenesis of atherosclerotic cardiovascular disease. The elevated, albeit non-significant, CRP levels in our adenomyosis group echo the prior findings that systemic inflammation, even at subclinical levels, may contribute to endothelial dysfunction, a key early event in atherogenesis. Ridker et al.’s seminal work on high-sensitivity CRP as a predictor of cardiovascular events underscores the potential value of inflammatory biomarkers for assessing cardiovascular risk in women [5]. The lack of statistical significance in our CRP measurements may be attributable to the small sample size and the use of standard rather than high-sensitivity CRP assays. Lipids also play crucial roles in atherogenesis. Our data indicated higher total cholesterol and lower HDL cholesterol levels in patients with adenomyosis, both indicative of a more atherogenic profile. Although the differences did not reach statistical significance (p = 0.079 and p = 0.06, respectively), the observed trends were consistent with those reported in previous epidemiological studies. Choi et al. [6] and Mu et al. [7] reported elevated rates of hyperlipidemia and hypertension in women with endometriosis, suggesting that shared endocrine and inflammatory mechanisms may extend to those with adenomyosis. Of particular interest is the evolving understanding of the vascular involvement in adenomyosis. The condition is histologically characterized by ectopic endometrial tissue within the myometrium, which may lead to localized hypervascularity and altered angiogenic signaling. These vascular changes may not be confined to the uterus. Emerging evidence suggests that chronic vascular activation and impaired endothelial repair mechanisms may contribute to systemic cardiovascular dysfunction in women with gynecological inflammatory disorders. However, the role of smoking in the pathogenesis of adenomyosis remains controversial. While early hypotheses suggested that smoking may reduce estrogen synthesis via aromatase inhibition [8], recent studies have indicated a positive association between long-term smoking and increased adenomyosis risk [9]. Our findings support the latter view, with smoking prevalence being higher in the adenomyosis group, albeit without statistical significance. Future studies employing stricter control group criteria, particularly in non-smokers without gynecological pathology, may help clarify this relationship. The relationship between adenomyosis and ischemic stroke is an underexplored, but potentially important, avenue. Although ischemic events have been sporadically reported in patients with adenomyosis, causality remains elusive. Overlap in risk factors (hypertension, dyslipidemia, inflammation, and coagulopathy) warrants further investigation, particularly through prospective cohort studies. Our preliminary findings raise the possibility that adenomyosis may be a marker or even a contributor to elevated cardiovascular risk in women. The observed trends, combined with the biological plausibility and supportive findings from related gynecological conditions, underscore the need for larger longitudinal studies with detailed cardiovascular phenotyping and hormonal profiling. Given that adenomyosis is often diagnosed in women during the perimenopausal period—a time of increasing cardiovascular vulnerability—this association may have important clinical implications for preventive care. This study was limited by its cross-sectional design and modest sample size, which reduced the statistical power to detect any significant associations. The lack of hs-CRP measurements and reliance on single-point lipid profiles are additional limitations. Moreover, potential confounders such as physical activity, diet, and hormonal therapy were not assessed. Despite these limitations, our findings contribute to a growing body of literature advocating the integration of gynecological history into cardiovascular risk assessment in women. In conclusion, our study highlights a potentially important but underrecognized intersection between adenomyosis and cardiovascular disease risk. Although our results did not reach statistical significance, the observed trends suggest that women with adenomyosis may have a more adverse cardiovascular risk profile. Further large-scale, prospective studies are warranted to elucidate this relationship and to inform integrated models of care that address both reproductive and cardiovascular health in women. We would like to sincerely thank Prof. Dr. Fatma Ferda Verit, our supervisor and Head of the Department of Obstetrics and Gynecology for her valuable guidance and continuous support throughout this study. Conflict of Interest Conflict of Interest: The authors have no conflicts of interest relevant to this article.

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