Polycystic ovary syndrome is associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women: a retrospective study in a tertiary teaching hospital

Endometrial polyps are localized overgrowths of endometrial tissue that form finger-like projections from the surface of the endometrium. They consist of stroma, glands, and blood vessels and can be single or multiple [1‐3]. According to previous studies, the prevalence of endometrial polyps in women of all age groups ranges from 10 to 40% [4, 5]. Endometrial polyps may be asymptomatic, and the most common symptoms include excessive leukorrhea, abnormal uterine bleeding, and infertility [2, 6]. Most endometrial polyps are benign lesions, but approximately 3–5% of endometrial polyps have been reported as premalignant or malignant [7‐9]. However, the factors associated with premalignant and malignant changes in endometrial polyps are not completely understood.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. It has been reported that 5% to 10% of women of reproductive age are diagnosed with PCOS worldwide, and the symptoms of PCOS include amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, and acne [10‐13]. PCOS is characterized by anovulation, insufficient progesterone, hyperandrogenism, and insulin resistance. These factors can disrupt the endometrium of PCOS patients and can lead to chronic low-grade inflammation in the endometrium, infertility, endometrial hyperplasia, or even endometrial cancer [13‐16]. The risk of endometrial cancer has been shown to be between 2–6 times higher in women with PCOS than in women without PCOS [13]. The pathogenesis of endometrial cancer in PCOS patients is thought to be related to the prolonged stimulation of the endometrium by unopposed oestrogen in the setting of anovulation and prevention of endometrial exfoliation [17]. Thus, it is imperative to determine whether PCOS patients diagnosed with endometrial polyps are at greater risk of developing cancer so that a more judicious indication regarding hysteroscopic polypectomy can be established.

The aim of the current study was to investigate the prevalence of premalignant and malignant endometrial polyps that were removed by hysteroscopy in premenopausal women and to further explore whether PCOS is associated with premalignant and malignant changes in endometrial polyps.

Our study revealed that the prevalence of premalignant and malignant endometrial polyps was 2.15%, comprising rates of 1.13% for hyperplasia with atypia and 1.02% for endometrial carcinoma, among the polyps removed by hysteroscopic polypectomy in premenopausal women (Table 2). Moreover, PCOS was found to be associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women after adjustment for potential confounding factors (Table 4). These findings may provide guidance for clinical practice in the management of endometrial polyps among premenopausal women with PCOS.

A meta-analysis study that included 35,345 premenopausal and postmenopausal women showed that the prevalence of premalignant and malignant endometrial polyps was 2.73% [8]. Another meta-analysis study involved recruitment of 21,057 patients and reported that 3.4% of patients presented with premalignant and malignant endometrial polyps [9]. However, our study revealed that the prevalence of premalignant endometrial polyps was 1.13%, and the prevalence of malignant endometrial polyps was 1.02% (Table 2). The discrepancies could be attributed to differences in the characteristics of the study populations; these other studies included premenopausal women as well as postmenopausal women. However, only premenopausal women were included in our study, which may explain the lower prevalence in our population compared to that in the populations of these other studies when considering menopause as a risk factor for malignant changes in endometrial polyps [4]. Definition of the standards of obesity may also be an important factor that contributes to the difference in the prevalence of premalignant and malignant polyps between our population and others. We used the Chinese criteria BMI ≥ 28.0 kg/m² to define obesity, while the other studies used the World Health Organization recommended criteria BMI ≥ 30.0 kg/m² to define obesity [20]. Another explanation for the discrepancies might be attributed to the different methods used for the removal of polyps. Some studies performed the removal of polyps by uterine curettage, which usually fails to extract the whole polyp and obtains only a mixed specimen of polyps and endometrial mucosae. This may result in inconsistency of histological diagnosis. Our study involved performing the removal of polyps by hysteroscopic polypectomy, which is a more reliable technique for removing the entire polyp and allowing a more complete histological examination.

In the univariate analysis, we found that age (≥ 40 years), obesity, nulliparity, diabetes mellitus, PCOS, and polyp number were significantly associated with the risk of premalignant and malignant polyps in premenopausal women. However, analysed by a multivariate logistic regression model, only PCOS was found to be significantly associated with the risk of premalignant and malignant polyps when potential confounding factors were controlled (Table 4). The prevalence of hyperplasia with atypia and endometrial carcinoma was 3.96 times and 3.58 times greater in women with PCOS than in those without PCOS (Table 5). This may be explained by the operation of a mechanism that involves endocrinologic and metabolic disorders in PCOS, specifically chronic anovulation, hyperandrogenism, and insulin resistance [17]. Chronic anovulation results in endometrial proliferation by long-term exposure to oestrogen without the opposing action of progesterone [23, 24]. Androgens can convert to oestrogens and indirectly stimulate endometrial proliferation [25]. Insulin resistance is accompanied by hyperinsulinism, which increases the levels of free androgen in the plasma by reducing the production of sex hormone-binding globulin, and high levels of androgen and insulin in the plasma can affect endometrial cell differentiation [26, 27].

In the present study, the prevalence of premalignant and malignant polyps was not associated with the presence of abnormal uterine bleeding. However, other studies have reported that abnormal uterine bleeding is associated with an increased risk of malignant polyps in postmenopausal women [28]. The discrepancy may be attributed to our study including only premenopausal women. It may also be explained by the fact that some small premalignant and malignant lesions existed on the surface or inside the polyps that were detected only by the pathological examinations and did not cause abnormal uterine bleeding. Therefore, when women are diagnosed with endometrial polyps, we propose that active management involving hysteroscopic polypectomy should be offered to premenopausal women with PCOS regardless of symptoms and to postmenopausal women with symptoms. Moreover, although screening for premalignant and malignant polyps with hysteroscopy is not recommended when considering the invasive nature of the procedure and the economic costs, we recommend routine pelvic ultrasonography for premenopausal women as well as for postmenopausal women regardless of symptoms. Evidence-based management of incidental ultrasound findings such as endometrial polyps has gained importance for modern gynaecologists. Therefore, it will be of great value to understand the significance of both symptomatic and asymptomatic endometrial polyps and their proposed management.

Our study has many strengths. First, this study included a large sample size, and polyp removal was performed by a standardized procedure. Second, potential confounding factors were controlled in our evaluation of the association between PCOS and the premalignant and malignant endometrial polyps. Third, this study focused on premenopausal women because a considerable proportion of endometrial polyps are asymptomatic and are found incidentally in premenopausal women. Nevertheless, this study also has limitations. First, this study was conducted by a retrospective review of patient data and is subject to potential selection bias. Second, although a variety of potential confounding factors were controlled when we evaluated the association between PCOS and the premalignant and malignant endometrial polyps in premenopausal women, we cannot rule out the effect of any residual confounding factors on the findings. Third, the number of PCOS cases may have been underestimated in this study because we did not routinely screen PCOS in all outpatients. Finally, since this is a single-centre study, further multicentre studies are needed to confirm our findings.

PCOS is associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women. Therefore, it is necessary to evaluate the endometrium in PCOS patients with ultrasonography or hysteroscopy, and active management involving hysteroscopic polypectomy should be offered to PCOS patients diagnosed with endometrial polyps regardless of symptoms.