Genetic epidemiology of pelvic organ prolapse: a systematic review

Ward, Renée M; Edwards, Digna R. Velez; Edwards, Todd L.; Giri, Ayush; Jerome, Rebecca N; Wu, Jennifer M.

doi:10.1016/j.ajog.2014.04.006

Cited by 71 publications

(63 citation statements)

References 40 publications

(154 reference statements)

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“…Given how common both childbirth and surgery for pelvic floor disorders are, it is surprising how very little data are present about how the dose and timing of physical activity during these potentially vulnerable times impact the pelvic floor and subsequent pelvic floor disorders. It is also crucial to understand the role physical activity, a potentially modifiable risk factor, plays in women at potentially high genetic risk 82 , women with risk factors for levator ani muscle injury 83 , or, importantly, the substantial minority of women with asymptomatic pelvic organ prolapse. 84–86 …”

Section: Future Researchmentioning

confidence: 99%

Physical activity and the pelvic floor

Nygaard

Shaw

2016

American Journal of Obstetrics and Gynecology

148

124

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Pelvic floor disorders (PFDs) are common, with one in four U.S. women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review is to summarize studies reporting the association between physical activity and PFDs. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include: Urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this exam finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods.

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Section: Future Researchmentioning

confidence: 99%

Physical activity and the pelvic floor

Nygaard

Shaw

2016

American Journal of Obstetrics and Gynecology

148

124

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“…23 Although specific genetic predisposition has not been identified, a systematic review of genetic studies found that collagen type 3 alpha 1 was associated with POP (OR 4.79). 24 …”

Section: Phase I: Predisposing Factors For Pelvic Floor Disordersmentioning

confidence: 99%

The Epidemiology of Pelvic Floor Disorders and Childbirth

Hallock

Handa²

2016

Obstetrics and Gynecology Clinics of North America

156

122

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SYNOPSIS Using a life span model, this article presents new scientific findings regarding risk factors for pelvic floor disorders (PFDs), with a focus on the role of childbirth in the development of single or multiple co-existing PFDs. Phase I of the life span model includes predisposing factors such as genetic predisposition and race. Phase II of the model includes inciting factors such as obstetric events. Prolapse, urinary incontinence (UI) and fecal incontinence (FI) are more common among vaginally parous women, although the impact of vaginal delivery on risk of FI is less dramatic than for prolapse and UI. Finally, Phase III includes intervening factors such as age and obesity. Both age and obesity are associated with prevalence of PFDs. The prevention and treatment of obesity is an important component to PFD prevention.

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“…[43] In the first GWAS for POP, Allen-Brady and colleagues identified six loci (4q21, 8q24, 9q22, 15q11, 20p13, and 21q22) with genome-wide statistical significance in a population of EA women [42]. The second GWAS, undertaken in AA and Hispanic women from the WHI-HT [15], reported several loci with suggestive statistical significance but found no evidence of association for previously reported loci.…”

Section: Discussionmentioning

confidence: 99%

Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial

et al. 2017

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Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women’s Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.

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Genetic epidemiology of pelvic organ prolapse: a systematic review

Cited by 71 publications

References 40 publications

Physical activity and the pelvic floor

Physical activity and the pelvic floor

The Epidemiology of Pelvic Floor Disorders and Childbirth

Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial

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