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Concept: Menopause

491

Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.Design Umbrella review of systematic reviews and meta-analyses.Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m(2) increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.

Concepts: BRCA2, Breast cancer, Hereditary nonpolyposis colorectal cancer, Obesity, Menopause, Estrogen, Colorectal cancer, Cancer

347

Are parity and the timing of menarche associated with premature and early natural menopause?

Concepts: Menstrual cycle, Menopause, Menarche

204

Seventy percent of postmenopausal women experience vasomotor symptoms, which can be highly disruptive and persist for years. Hormone therapy and other treatments have variable efficacy and/or side effects. Neurokinin B signaling increases in response to estrogen deficiency and has been implicated in hot flash (HF) etiology. We recently reported that a neurokinin 3 receptor (NK3R) antagonist reduces HF in postmenopausal women after 4 weeks of treatment. In this article we report novel data from that study, which shows the detailed time course of this effect.

Concepts: Effectiveness, Receptor antagonist, Menopause, Receptor

200

Women have elevated rates of thyroid disease compared to men. Environmental toxicants have been implicated as contributors to this dimorphism, including polybrominated diphenyl ethers (PBDEs), flame retardant chemicals that disrupt thyroid hormone action. PBDEs have also been implicated in the disruption of estrogenic activity, and estrogen levels regulate thyroid hormones. Post-menopausal women may therefore be particularly vulnerable to PBDE induced thyroid effects, given low estrogen reserves. The objective of this study was to test for an association between serum PBDE concentrations and thyroid disease in women from the United States (U.S.), stratified by menopause status.

Concepts: Luteinizing hormone, Flame retardants, Flame retardant, Hormone replacement therapy, Menopause, Thyroid hormone, Hormone, Estrogen

195

The effect of menopausal hormone therapy (MHT)-previously known as hormone replacement therapy-on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort.

Concepts: Hormone replacement therapy, Menopause, Circulatory system, Cardiovascular disease, Medicine, Blood, Epidemiology, Heart

191

Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women.

Concepts: Decision making, Luteinizing hormone, Cognition, Hormone, Osteoporosis, Hormone replacement therapy, Estrogen, Menopause

188

Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.

Concepts: BRCA1, Breast cancer, Menopause, BRCA2, Metastasis, Estrogen, Epidemiology, Cancer

183

 To conduct a nationwide study of associations between removal of all ovarian tissue versus conservation of at least one ovary at the time of hysterectomy and important health outcomes (ischaemic heart disease, cancer, and all cause mortality).

Concepts: Hysterectomy, Ovary, Menopause

178

The reproductive-cell cycle theory of aging posits that reproductive hormone changes associated with menopause and andropause drive senescence via altered cell cycle signaling. Using data from the Wisconsin Longitudinal Study (n = 5,034), we analyzed the relationship between longevity and menopause, including other factors that impact “ovarian lifespan” such as births, oophorectomy, and hormone replacement therapy. We found that later onset of menopause was associated with lower mortality, with and without adjusting for additional factors (years of education, smoking status, body mass index, and marital status). Each year of delayed menopause resulted in a 2.9% reduction in mortality; after including a number of additional controls, the effect was attenuated modestly but remained statistically significant (2.6% reduction in mortality). We also found that no other reproductive parameters assessed added to the prediction of longevity, suggesting that reproductive factors shown to affect longevity elsewhere may be mediated by age of menopause. Thus, surgical and natural menopause at age 40, for example, resulted in identical survival probabilities. These results support the maintenance of the hypothalamic-pituitary-gonadal axis in homeostasis in prolonging human longevity, which provides a coherent framework for understanding the relationship between reproduction and longevity.

Concepts: Oophorectomy, Life expectancy, Gerontology, Organism, Hormone, Senescence, Ageing, Menopause

177

Soyfoods have long been recognized as sources of high-quality protein and healthful fat, but over the past 25 years these foods have been rigorously investigated for their role in chronic disease prevention and treatment. There is evidence, for example, that they reduce risk of coronary heart disease and breast and prostate cancer. In addition, soy alleviates hot flashes and may favorably affect renal function, alleviate depressive symptoms and improve skin health. Much of the focus on soyfoods is because they are uniquely-rich sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor modulators. Despite the many proposed benefits, the presence of isoflavones has led to concerns that soy may exert untoward effects in some individuals. However, these concerns are based primarily on animal studies, whereas the human research supports the safety and benefits of soyfoods. In support of safety is the recent conclusion of the European Food Safety Authority that isoflavones do not adversely affect the breast, thyroid or uterus of postmenopausal women. This review covers each of the major research areas involving soy focusing primarily on the clinical and epidemiologic research. Background information on Asian soy intake, isoflavones, and nutrient content is also provided.

Concepts: Medicine, Nutrition, Breast cancer, Osteoporosis, Menopause, Cancer, Epidemiology, Estrogen