Contributing factors related to abnormal uterine bleeding in perimenopausal women: a case–control study

Excessive menstrual bleeding, known as menorrhagia, has emerged as a prevalent manifestation of AUB in perimenopausal women. Alongside vaginal bleeding, other symptoms such as pallor, pelvic discomfort, and fatigue are frequently encountered. The duration of bleeding and the volume of blood loss prior to hospital admission are notably higher in perimenopausal individuals compared with their postmenopausal counterparts. Factors including age, menstrual characteristics, and diabetes heighten the susceptibility to endometrial cancer in women experiencing postmenopausal bleeding [18].

The results of this study indicated that the incidence of benign endometrial changes, cancer, or precancerous changes in women in the case group was notably higher than that in the control group. This suggests that benign endometrial changes or carcinogenesis are the primary causes of AUB. Moreover, due to dysfunction of the hypothalamic-pituitary-ovarian axis in perimenopausal women, the timing, amount, and ratio of oestrogen and progesterone production affecting the endometrium become imbalanced, leading to endometrial simple or complex hyperplasia [19]. Consequently, clinical practice should pay attention to physiological changes during the menopausal transition in women, and appropriate oestrogen supplementation to maintain certain physiological functions of the genital tract is beneficial in preventing infection.

In this study, colour Doppler ultrasound was employed to measure endometrial thickness and endometrial echogenicity. This technique allows for the visual detection of uterine size, intrauterine structure, the relationship of the endometrial lining, and blood flow distribution, offering the advantages of being non-invasive, allowing dynamic monitoring, and being repeatable [20]. The uterine artery Doppler indices, including resistance index, pulsatility index, and peak systolic velocity, exhibited substantially lower values in the malignant group than in the benign group. Endometrial thickness was found to be a reliable indicator for the diagnosis of endometrial cancer, achieving an area under the curve value of 0.89. For women with postmenopausal bleeding, a threshold value of 12.5 mm provided the highest levels of sensitivity and specificity [21]. The study also found that the proportion of women with endometrial thickness of > 10 mm was notably higher in the case group than in the control group, and the proportion of heterogeneous endometrial echogenicity was also higher. The potential reasons for this include the tendency of the endometrium in patients with AUB to show infiltrative growth, with benign changes or precancerous changes being more likely. Consequently, when lesions appear, they invade the endometrial myometrium and serosa, resulting in uneven endometrial echoes and unclear demarcation between the endometrium and myometrium [22]. It is suggested that colour Doppler ultrasonography can serve as a simple and effective tool for screening high-risk AUB groups in clinical practice by measuring endometrial thickness and echogenicity in the early evaluation of patients with AUB, offering substantial clinical application value.

The results of this study demonstrated that benign endometrial lesions, endometrial thickness ≥ 10 mm, age ≥ 50 years, BMI ≥ 25 kg/m2, and IUD placement are independent risk factors for AUB in perimenopausal women. These findings align with those reported by Xiao et al. [23], who identified IUD placement and obesity as risk factors for AUB in this demographic. A potential explanation for these results is that endometrial fibrinolytic activity increases following IUD placement, particularly in the early stages, when fibrinolytic activity is at its peak, leading to enhanced menstrual flow. Affected by IUDs, the endometrium augments prostaglandin production through its secretory effect, thereby increasing capillary permeability and fragility, resulting in a greater volume of menstrual blood [24]. Additionally, prolonged retention of the upper contraceptive ring in the uterine cavity may lead to inflammatory reactions and other forms of bleeding. Thus, it is advisable for perimenopausal women to remove the contraceptive device promptly to prevent postmenopausal bleeding and infection.

AUB may be an expression of hormonal milieu, or it could be the clinical presentation of benign or malignant lesions of female genital tract in perimenopausal woman. This study suggested that benign endometrial lesions was related to the risk for AUB in perimenopausal women. In line with our finding, Talukdar et al. [25] found that histopathology of endometrium in patients with AUB was predominantly simple typical type and that the majority of cases were diagnosed as fibroid uterus. Moreover, another study [26] demonstrated that structural causes of AUB were identified in 81.3% of cases, with adenomyosis (33.65%), concomitant adenomyosis and leiomyoma (31.5%), and leiomyoma (14.8%) being the most common. The present study also evinced that endometrial thickness ≥ 10 mm was an independent risk factor for AUB in perimenopausal women. Indeed, consistent with this result, a previous study [27] has showed that majority of women with AUB in aerimenopausal age had endometrial thickness of 10–12 mm (35.7%) followed by 7–9 mm (27.1%). Getpook et al. [28] concluded that endometrial thickness of 8 mm or less was less likely to be associated with malignant pathologies in premenopausal uterine bleeding. These findings indicated the significance of ultrasonography in measuring endometrial thickness and identifying organic causes in order to screen perimenopausal women at high risk for AUB.

Moreover, compared with women in other age groups, perimenopausal women tend to have a more stable lifestyle, better dietary conditions, lower activity levels, and more rest time. These factors, among others, contribute to the prevalence of menopausal transition obesity [29]. In this study, the proportion of obese women in the case group was considerably higher than in the control group, indicating that obesity is a risk factor for AUB. This condition may be attributed to the conversion of excessive androgens in the adipose tissue of obese women into estrone via aromatisation, leading to endometrial hyperplasia [30]. Therefore, managing body weight in perimenopausal women is crucial. Furthermore, this study underscores the importance of addressing obesity in clinical practice, as it facilitates the early detection and diagnosis of AUB in perimenopausal women.

Identifying and understanding the primary risk factors for AUB is crucial for the prevention and early detection of AUB in perimenopausal women. Investigating these influencing factors can assist healthcare professionals in identifying potential risks for AUB at an early stage. This facilitates the implementation of appropriate monitoring, examination, and intervention measures, thereby aiding in early intervention. Such steps enhance treatment success rates, reduce disease progression, and mitigate adverse outcomes. Consequently, the findings of this study are pivotal for improving the health of women in the perimenopausal period and providing essential guidance for clinical practice.

This study has several limitations. First, the study was conducted as a single-centre study in one hospital, which might limit the generalisability of the findings to a broader population. Second, the relatively short timeframe of the study, spanning between April 2021 and June 2022, may have influenced the comprehensiveness of the results. Furthermore, the study might not have accounted for all potential confounding variables that could affect the relationship between risk factors and AUB, and there may be additional clinical influences yet to be identified. It is also important to note that haemoglobin levels and uterine size are crucial indicators in assessing the nature of AUB. A related study observed a higher incidence of moderate to severe anaemia in perimenopausal women compared with that in postmenopausal women, and substantial differences in uterine size were noted between benign and malignant groups [31]. However, due to logistical constraints, collecting relevant data was not feasible in the current study. Future multicentre, large-sample studies that incorporate a wider range of potential influencing factors for AUB may help overcome these limitations.

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