Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform... Show morePelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes—epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function—that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments. Show less
STUDY QUESTION: Do sexual functioning, sexual esteem, genital self-image and psychological and relational functioning in women with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome differ from a... Show moreSTUDY QUESTION: Do sexual functioning, sexual esteem, genital self-image and psychological and relational functioning in women with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome differ from a comparison group of women without the condition?SUMMARY ANSWER: In comparison to controls, women with MRKH with a non-surgically or surgically created neovagina did not differ in psychological and relational functioning but reported lower sexual esteem and more negative genital self-image, intercourse-related pain, clinically relevant sexual distress and sexual dysfunction, with sexual esteem levels strongly associated with sexual distress and sexual dysfunction.WHAT IS KNOWN ALREADY: Studies on sexual functioning measured with standardized questionnaires in women with MRKH syndrome compared with women without the condition have yielded contradictory results. Factors associated with sexual functioning in this patient population have rarely been investigated.STUDY DESIGN, SIZE, DURATION: Between November 2015 and May 2017, 54 women with MRKH syndrome with a neovagina and 79 age-matched healthy women without the condition were enrolled in this case-control study.PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had to be at least 18-years old and had to live in a steady heterosexual relationship. Women with MRKH syndrome were asked to participate by their (former) gynecologists at three university hospitals and by MRKH peer support group. Controls were recruited via advertisement in local newspapers and social media. Standardized questionnaires were administered to assess sexual functioning, sexual esteem, genital self-image and psychological and relational functioning.MAIN RESULTS AND THE ROLE OF CHANCE: Women with MRKH syndrome with a surgically or non-surgically created neovagina reported significantly more pain during intercourse (P< 0.05, d= 0.5), but did not differ in overall sexual functioning fromcontrol women. More women with MRKH syndrome reported clinically relevant sexuality-related distress (P< 0.05, odds ratio (OR): 2.756, 95% CI 1.219-6.232) and suffered a sexual dysfunction (P< 0.05, OR: 2.654, 95% CI: 1.088-6.471) in comparison with controls. MRKH women scored significantly lower on the sexual esteem scale (SES) (P< 0.01, d= 0.5) and the female genital self-image scale (FGSIS) (P< 0.01, d= 0.6) than controls. No significant differences were found between the two groups regarding psychological distress, anxiety and depression, global self-esteem and relational dissatisfaction. Sexual esteem was significantly associated with the presence of clinically relevant sexual distress (beta= 0.455, P= 0.001) and suffering a sexual dysfunction (beta= 0.554, P= 0.001) and explained, respectively, 40% and 28% of the variance.LIMITATIONS, REASONS FOR CAUTION: Given the nature of the study focusing on sexual functioning, a potential selection bias cannot be excluded. It is possible that those women with the most severe sexual and/or psychological disturbances did or did not choose to participate in our study.WIDER IMPLICATIONS OF THE FINDINGS: The study results add new data to the very limited knowledge about psychosexual functioning of women with MRKH syndrome and are of importance for more adequate counseling and treatment of these women. Show less
Dongen, H. van; Vaart, H. van der; Kluivers, K.B.; Elzevier, H.; Roovers, J.P.; Milani, A.L. 2019
