1.
Pelvic organ prolapse: does hormone therapy use matter?
Wasenda, EJ, Kamisan Atan, I, Subramaniam, N, Dietz, HP
Menopause (New York, N.Y.). 2017;(10):1185-1189
Abstract
OBJECTIVE To determine the effect of hormone therapy (HT) use on pelvic organ support. METHODS A retrospective observational study involving postmenopausal women with pelvic floor dysfunction attending a tertiary urogynecology center between January 2012 and March 2015. All underwent a clinical examination including International Continence Society Pelvic Organ Prolapse Quantification and 4D translabial ultrasound imaging. Information on current or former use of systemic HT and current local estrogen use was collected. Main outcome measure was pelvic organ support. RESULTS One thousand four hundred forty-three women were seen during the study period. On univariate analysis, current HT was significantly associated with sonographically determined descent of the rectal ampulla (β [95% confidence interval] 3.4 mm [0.4-6.5], P = 0.03) and Gh + Pb (-0.45 mm [-0.8 to -0.1], P = 0.005). Past HT use, duration of HT use, or current vaginal estrogen use was not associated with pelvic organ support. On multivariate analysis controlling for age, parity, body mass index, history of forceps delivery, and avulsion, the association between current HT on the one hand and Gh + Pb as well as increased descent of the rectal ampulla on ultrasound, remained significant (P = 0.008 and P = 0.012, respectively). CONCLUSION HT may have a minor negative effect on pelvic organ support; however, the effect is likely too small to be clinically relevant.
2.
Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study.
Oh, H, Arem, H, Matthews, CE, Wentzensen, N, Reding, KW, Brinton, LA, Anderson, GL, Coburn, SB, Cauley, JA, Chen, C, et al
British journal of cancer. 2017;(7):1070-1078
-
-
Free full text
-
Abstract
BACKGROUND Prolonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels. METHODS Among 1804 postmenopausal women enrolled in the Women's Health Initiative Observational Study, 15 serum oestrogens/oestrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting were self-reported via questionnaire. Using baseline, cross-sectional data, geometric means (GM) of oestrogens/oestrogen metabolites (pmol l-1) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. RESULTS Longer time spent sitting (⩾10 vs ⩽5h per day) was associated with higher levels of unconjugated oestrone, independent of moderate- to vigorous-intensity physical activity and body mass index, among both never/former (GM=70.6 vs 57.7) and current MHT users (GM=242 vs 179) (P-trend ⩽0.03). Among never/former MHT users, sitting (⩾10 vs ⩽5h per day) was positively associated with 2-methoxyestradiol (GM=16.4 vs 14.4) and 4-methoxyestradiol (GM=2.36 vs 1.98) (P-trend ⩽0.04), independent of parent oestrogens. Inverse associations between moderate- to vigorous-intensity physical activity (⩾15 vs 0 metabolic equivalent task-hours per week) and parent oestrogens were found as expected. After adjustment for parent oestrogens, physical activity was not associated with oestrogen metabolites. CONCLUSIONS Our data suggest that prolonged sitting and lower moderate- to vigorous-intensity physical activity are associated with higher levels of postmenopausal oestrogens/oestrogen metabolites, the oestrogen metabolism patterns that have previously been associated with higher endometrial and breast cancer risk.
3.
Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women.
Boyne, DJ, Friedenreich, CM, McIntyre, JB, Stanczyk, FZ, Courneya, KS, King, WD
Cancer causes & control : CCC. 2017;(12):1369-1379
Abstract
PURPOSE Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women. METHODS We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2006). Study participants consisted of healthy postmenopausal women who had never been diagnosed with cancer (n = 289). Sex hormone exposures included serum concentrations of estradiol, estrone, testosterone, androstenedione, and sex hormone-binding globulin. We estimated the participants' lifetime number of menstrual cycles (LNMC) as a proxy for cumulative exposure to ovarian sex hormones. Buffy coat samples were assessed for DNA methylation. Linear regression was used to model the associations of interest and to control for confounding. RESULTS Both estradiol and estrone had a significant positive dose-response association with LINE-1 methylation. LNMC was associated with both LINE-1 and Alu methylation. Specifically, LNMC had a non-linear "U-shaped" association with LINE-1 methylation regardless of folate intake and a negative linear association with Alu methylation, but only amongst low folate consumers. Androgen exposure was not associated with either outcome. CONCLUSION Current and cumulative estrogen exposure was associated with repetitive element DNA methylation in a group of healthy postmenopausal women. LINE-1 and Alu methylation may be epigenetic mechanisms through which estrogen exposure impacts cancer risk.