Association between diabetes, diabetes treatment and risk of developing endometrial cancer.

BackgroundA growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).MethodsA total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.ResultsOver a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.ConclusionsOur results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains

Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities

Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dILA, and dILB subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dILB cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKC{gamma}-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities

Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women’s Health Initiative clinical trial and observational study

Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women’s Health Initiative (WHI) estrogen plus progestin randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and Methods: Postmenopausal women aged 50-79 at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were post-hysterectomy from the observational study and clinical trial respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53 to 1.20) for estrogen and 1.15 (0.74 to 1.79) for estrogen plus progestin, with respectively 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7-8 years of treatment and follow-up

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women

Background/Objectives Adherence to the Mediterranean Diet (MD) high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean Diet Score (aMED), anthropometry and measured adiposity by dual energy x-ray absorptiometry. Subjects/Methods This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-hr dietary recalls over 1–2 menstrual cycles (>97% had ≥7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake. Results: Participants had an average (SD) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist to hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% CI:−0.09,−0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI:−0.550,−0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI:0.002,0.117). Conclusions: Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD

Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in the US and Europe

Objectives To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design Individual patient data analysis using pooled data from randomised trials. Data sources Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. AA acknowledges personal funding from the UK Medical Research Council and Chief Scientist Office of the Scottish Government Health Directorates

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142052/1/jper0257.pd

The Impact of Dietary Folate Intake on Reproductive Function in Premenopausal Women: A Prospective Cohort Study

Background: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. Methodology/Principal Findings: The BioCycle study (2005–2007) prospectively followed 259 healthy women aged 18–44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration ≤5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3rd tertile of synthetic folate intake had, on average, 16.0% (95% CI, 0.5–33.8%) higher luteal progesterone levels compared to women in the 1st tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3rd tertile had a 64% (95% CI, 8–86%) decreased odds of anovulation compared to the women in the 1st tertile (P trend 0.03). Conclusions/Significance: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted

Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study

Objective To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women