PCOS is a common reproductive endocrine disease, and the majority of PCOS patients have different degrees of insulin resistance, chronic inflammation, T2DM, lipids dysfunction [1,2], all of which are exacerbated with the presence of obesity. As a specific manifestation of ovarian dysfunction, the recovery of the menstrual cycle is the main goal of PCOS management in clinical, and also the main appeal of PCOS patients with obesity. Multiple observational studies have reported that LSG could improve hormone profile and fertility outcome in patients with PCOS [21,22]. However, limited studies were available on the prognostic of the menstrual status in PCOS patients with obesity after LSG. Our study is the first to explore the predictive factors for regular menstruation in PCOS women with obesity after LSG.
In our study, although the mean age and BMI were comparable in the PCOS group and the control group, the PCOS group had higher WC, WHR, and VAT mass. The findings were generally in line with previous studies that PCOS patients tend to be more centrally obese than non-PCOS patients [23,24]. In addition, we found that PCOS patients with obesity had higher UA, severer insulin resistance and lipids dysfunction than regular menstruation patients with obesity at baseline, which is consistent with previous studies that PCOS patients with obesity demonstrate more severe metabolic abnormalities [25,26,27]. However, there were no differences in the levels of IL-6 and SOD between the PCOS group and the control group. Conversely, some studies reported that IL-6 levels and SOD activity increased in the patients with PCOS [28,29]. The discrepancy might be explained by different populations of studies (age, ethnicity, body weight, and duration of PCOS). Meanwhile, we also found that PCOS women with obesity exhibited increased levels of TT and cFT than the control groups, which is in lined with previous population-based studies [30,31]. In addition, other sex hormones of PCOS patients with obesity, including LH, FSH and SHBG were not statistically significant different compared with the control group in our study, which is inconsistent with other studies [32,33]. However, this result needs to be validated in studies with a larger sample size.
To our knowledge, regular menstruation is determined by a dynamic reproductive endocrine system, including ovarian events, hypothalamic-pituitary interactions, and changes in the endometrium and myometrium [34]. Therefore, menstrual recovery is an easily ascertainable external parameter for the improvement of ovarian function. Moreover, the regularity of menstruation is the main demand of PCOS patients with obesity. Thus, it is important to explore the menstrual status in PCOS women with obesity after LSG.
In the present study, we followed-up the menstrual status in the PCOS group via telephone interview, and the median follow-up time was 3.07 years. Our data showed that 75.86% of PCOS patients with obesity could recover regular menstrual cycles within 6 months after LSG. In line with our study, a meta-analysis found that patients with PCOS after surgery had a significantly high incidence of having normal menstruation [35]. Damhof et al. has reported that there was significant, nearly 2-fold, reduction of oral contraceptives in women after bariatric surgery [36]. Consistent with this research, our data showed that the use of oral contraceptives in PCOS women after LSG was significantly decreased after the operation, which supported the fact of menstrual recovery in these patients. It was interesting to note that 24.66% of patients in the PCOS group started their first menstruation after LSG within 7 days. However, the underlying mechanism of this phenomenon was unclear, which might be attributed to the changes in gastrointestinal hormones, insulin resistance, and hypothalamic-pituitary-adrenal axis right after LSG [37]. Further studies are needed to address this issue.
Our further analyses were performed to explore the factors that may predict the regularity of menstrual cycles in PCOS patients after LSG. Our results showed duration of PCOS (≤4.5 years), number of preoperative menstruations per year (>4.0 times/years) levels of HOMA-IR (≤7.3), and TT (≤1.5 nmol/L) were useful predictors for the regularity of menstrual cycles in PCOS patients with obesity within 6 months after LSG. The findings suggested that the resumption of menses in PCOS women with obesity after LSG was closely associated with the duration of PCOS and previous menstrual status. Moreover, growing evidence has demonstrated that the menstrual cycle abnormality appeared to be associated with more pronounced insulin resistance and hyperandrogenemia in PCOS [38, 39], as insulin resistance can induce oligo- or anovulation and cause menstrual cycle irregularity by exacerbating hyperandrogenemia and disrupting follicular growth [2, 40]. In addition, previous studies showed that hyperandrogenemia was significantly associated with long and irregular menstruation in women with PCOS [41]. Ovarian hyperandrogenism can inhibit folliculogenesis and lead to poly-follicular morphology, which can disrupt the menstrual cycle. Overall, it is suggested that serum TT and HOMA-IR levels may be used as predictors for the recovery of the menstrual cycle after LSG.
Consistent with our research, Ran Y et al. have reported that the components of blood lipids were not statistically significant between the menstrual regularity group and the menstrual disorder group [42], as a result, changes in lipid metabolism might not be the main cause of the improvement of menstruation in PCOS patients with obesity after LSG. Besides, there was no correlation between other clinical features (especially BMI, HbA1c, UA, and body fat composition) and the recovery of the menstrual cycles in PCOS patients with obesity after LSG in our study, although some studies have reported that the recovery degree of metabolic syndrome after bariatric surgery can also be used as one of the evaluation criteria for the improvement of clinical efficacy of PCOS patients with obesity [43,44]. Among sex hormones, the regular menstruation within 6 months after surgery in women with PCOS was not correlated with levels of LH, FSH and SHBG at baseline. Therefore, those clinical indicators may have a limited effect on the recovery of menstruation after LSG.
Furthermore, we formed a combined model with the four clinical indices at baseline (including duration of PCOS, number of preoperative menstruations per year, HOMA-IR and TT) to predict the recovery of menstruation after LSG, and the area under the ROC curve of the combined model is 0.837 [95%CI: 0.735-0.939]. Additionally, we further categorized patients into low probability and high probability groups according to the optimal cut-off point. Compared with the low probability group, those in the high probability group had 2.5-fold increases in the odds of the resumption of menses within 6 months after LSG. Thus, the combined model is fairly accurate in predicting the regular menstruation in PCOS women with obesity within 6 months after LSG.
The limitations in this study were listed as follows: first, our study was a retrospective study and menstrual status was self-reported by patients, which might result in recall bias; second, telephone follow-up to assess menstrual recovery may lack of accuracy than gynecological ultrasound. Third, the prediction model has not been verified in other populations and future studies need to involve a larger population of PCOS women with obesity to confirm the accuracy of this prediction model.