Background

Physical activity and macronutrient intake, important contributors to energy balance, may be independently associated with female urinary incontinence (UI).

Methods

We evaluated the association of baseline self-reported physical activity and macronutrient intake, via food frequency questionnaire, with incident UI subtypes after 3 years among 19 741 postmenopausal women in the Women's Health Initiative Observational Study. Odds ratios (ORs) for incident urgency, stress, and mixed UI were calculated using multivariable logistic regression.

Results

Women who reported total physical activity (metabolic equivalent task [MET]-hours/week) ≥30 versus <0.1 were 16% less likely to develop urgency UI (OR = 0.84; 95% CI 0.70, 1.00) and 34% less likely for mixed UI (OR = 0.66; 95% CI 0.46, 0.95), although linear trends were no longer statistically significant after adjusting for baseline weight and weight change (p trend = .15 and .16, respectively). The association between physical activity and incident stress UI was less consistent. Higher uncalibrated protein intake was associated with increased odds of incident urgency UI (≥19.4% vs <14.1% of energy intake OR = 1.14; 95% CI 0.99, 1.30; p trend = .02), while CIs were wide and included 1.0 for calibrated protein intake. Other macronutrients were not associated with urgency UI and macronutrient intake was not associated with incident stress or mixed UI (p trend > .05 for all).

Conclusions

Among postmenopausal women, higher physical activity was associated with lower risk of incident urgency and mixed UI, but not stress UI, independent of baseline weight and weight change. Higher protein intake was associated with increased risk of urgency UI, but no associations were observed between other macronutrient and UI subtypes.

Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women's Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1-3) or moderate/severe POP (grades 2-3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relation to POP (grade 0 vs 1-3; grade 0 vs 2-3) adjusting for age at diagnosis, body mass index, parity, and genetic ancestry. There were 1274 controls and 1427 cases of any POP and 317 cases of moderate/severe POP. Although none of the analyses reached genome-wide significance (p<5x10-8), we noted variants in several loci that met p<10-6. In race-specific analysis of grade 0 vs 2-3, intronic SNPs in the CPE gene (rs28573326, OR:2.14; 95% CI 1.62-2.83; p = 1.0x10-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96-4.48, p = 2.6x10-7) were associated with POP in HPs. Inverse variance fixed-effect meta-analysis of the race-specific results showed suggestive signals for SNPs in the DPP6 gene (rs11243354, OR:1.36; p = 4.2x10-7) in the grade 0 vs 1-3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6x10-7) and SHC3 (rs2209875, OR:0.60; p = 9.3x10-7) in the grade 0 vs 2-3 analyses. While we did not identify genome-wide significant findings, we document several SNPs reaching suggestive statistical significance. Further interrogation of POP in larger minority samples is warranted.

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.