Metabolomics study of serum and urine samples reveals metabolic pathways and biomarkers associated with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common medical condition among women and involves complicated diagnostics and controversial surgical management. The exact molecular mechanism underlying POP is poorly understood, especially at the metabolism level. To explore the metabolic mechanism underlying POP and discover potential biomarkers for POP diagnosis, we applied a non-targeted metabolomics approach using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Metabolomics study of serum samples from patients with POP (n = 24) and controls (n = 22) revealed a total of 59 metabolites that are significantly different (VIP ≥ 1 and p ≤ 0.05) between the two groups. Between urine samples from POP patients (n = 45) and controls (n = 59), 33 metabolites differed significantly (VIP ≥ 1 and p ≤ 0.05). Metabolic pathways affected by these differentially expressed metabolites were analyzed. In both serum and urine samples, three pathways including arginine biosynthesis and purine metabolism were found to be significantly related to POP. Six metabolites including GPC, 1-methyladenosine, maleic acid, L-pyroglutamic acid, inosine, and citrate are significantly changed (VIP ≥ 1 and p ≤ 0.05) in both serum and urine samples from patients with POP. Receiver operating characteristics (ROC) curve analysis showed that using these six metabolites as a biomarker could distinguish patients with POP from controls with good accuracy in both serum (AUC = 1) and urine samples (AUC = 0.854). Collectively, these results further extended our understanding of key regulatory metabolic pathways involved in the pathophysiology of POP, as well as provided some promising biomarkers for effective POP diagnosis.

Association of endogenous circulating sex steroids and condition-specific quality of life domains in postmenopausal women with pelvic floor disorders.

OBJECTIVE: To examine the relationship between endogenous sex steroids and various condition-specific quality of life domains in postmenopausal women with pelvic floor disorders. We hypothesized that woman with lowest androgen and estradiol concentrations would report worse scores of quality of life domains. METHODS: Forty-six women with pelvic organ prolapse (POP) and 47 cases with stress urinary incontinence (SUI) answered the validated pelvic floor questionnaire and underwent serum sex steroid measurement. A multivariate logistic regression model was used to determine the association between subjective outcome parameters and serum hormonal levels after adjusting for confounders. RESULTS: Univariate analysis revealed a strong inverse correlation between serum estradiol level (E2) and prolapse domain score (correlation coefficient = 0.005) as well as a significant positive correlation between SHBG level and prolapse domain score (correlation coefficient = 0.019) in cases with POP. Furthermore, the sex domain score showed a significant negative correlation with the androstendion (correlation coefficient = 0.020), DHEAS (correlation coefficient = 0.046) and testosterone level (correlation coefficient = 0.032) in the POP group. In the multivariate model, high serum SHBG (CI: 0.007-0.046) remained independently associated with worse scores in the prolapse domain and low serum DHEAS (CI: - 0.989 to 1.320) persisted as a significant predictor for a worse score in the sex domain. Regarding SUI cases, no association was noted between serum hormonal levels and quality of life related pelvic floor domains (correlation coefficient > 0.05). CONCLUSION: Our results suggest that pelvic floor related quality of life might also be affected by endogenous sex steroids in POP, but not in SUI cases.

Pelvic organ prolapse and endogenous circulating sex steroids in postmenopausal women: A case control-study.

OBJECTIVE: We compared sex steroid levels of postmenopausal patients with symptomatic pelvic organ prolapse (POP) with postmenopausal matched patients without any sign of POP. Furthermore, we evaluated a possible relationship between sex steroid levels and various urogynecologic parameters in cases with POP. Main outcome of interest were differences in circulating estradiol levels between the two groups. STUDY DESIGN: We conducted a case-control study and 46 postmenopausal women with symptomatic POP≥stage 2 were matched 1:1 with 46 urogynecologic healthy women. Blood samples were drawn from all patients for assessment for estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), testosterone (T), androstendion (AEON), dehydroepiandrosterone sulphate (DHEAS) and sex hormone binding globulin (SHBG) with an Electrochemiluminescence immunoassay. RESULTS: Our study failed to show any statistically significant differences in sex steroid levels between women with and without POP (p>0.05). However, serum concentration of E2 (p<0,0001), free testosterone (p=0,034) and DHEAS (p=0,024) was statistically significant lower in patients with severe prolapse stage. Serum levels of E2 were statistically significant higher in cases with moderate-strong Oxford Grading Scale (p<0,0001). Low circulating E2 (p=0,019) as well as menopausal age (p=0,022) remained independent risk factors for POP in multiple logistic regression analysis. CONCLUSION: The significant low hormonal levels in cases with high POP-Q stage as well as the significant higher estradiol levels in patients with strong Oxford Grading Scale may indicate that endogenous circulating sex steroids might have a potential role in the severity and progression of POP.

Systemic markers of collagen metabolism and vitamin C in smokers and non-smokers with pelvic organ prolapse.

OBJECTIVE: To evaluate systemic markers of collagen metabolism and vitamin C in female smokers with pelvic organ prolapse (POP). Secondary aims were to compare these levels in women based on prolapse or smoking history alone. STUDY DESIGN: This was a cross-sectional study with four groups: smokers with POP, non-smokers with POP, smokers without POP and non-smokers without POP. Subjects were age-matched based on smoking history and presence of POP. All underwent a fasting blood panel, including plasma procollagen 1-N propeptide (P1NP), matrix metalloproteinase 9 (MMP-9), and vitamin C. RESULTS: Ninety-six subjects were enrolled. There were no differences for any demographics other than stage of prolapse, which was highest in non-smokers with POP. Significant variations in the levels of vitamin C and MMP-9 were noted among the four groups. Smokers with POP had lower levels of vitamin C and higher levels of MMP-9, compared to non-smokers with POP, but this relationship was not statistically significant. However, when contrasting smokers without POP to non-smokers without POP, significant differences in both vitamin C and MMP-9 were documented, confirming an impact of smoking on these markers. Notwithstanding, when evaluated independent of smoking status, vitamin C and MMP-9 levels in women with POP were similar to those of women without POP. CONCLUSION: Lower vitamin C and higher MMP-9 among smokers confirms the usefulness of such markers in documenting the smoking's impact on collagen. However, the lack of a difference based on POP suggests these are poor measures for understanding the pathophysiology of this disorder.