scholarly journals Metabolomic profiles associated with all-cause mortality in the Women’s Health Initiative

2019 ◽  
Vol 49 (1) ◽  
pp. 289-300 ◽  
Author(s):  
Raji Balasubramanian ◽  
Nina P Paynter ◽  
Franco Giulianini ◽  
JoAnn E Manson ◽  
Yibai Zhao ◽  
...  
Keyword(s):  
Women’S Health ◽  
Women's Health ◽  
Postmenopausal Women ◽  
Median Time ◽  
Time To Death ◽  
Women's Health Initiative ◽  
Women’S Health Initiative ◽  
Health Initiative ◽  
All Cause Mortality ◽  
The Women’S Health Initiative

Abstract Background Metabolomics profiling has shown promise in elucidating the biological pathways underpinning mortality, but there are limited data in female populations. Methods We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to EDTA-plasma to measure 470 metabolites at baseline in a discovery set of 943 postmenopausal women (including 417 incident deaths, median time to death of 10.6 years) with validation in an independent set of 1355 postmenopausal women (including 685 deaths, median time to death of 9.1 years) in the Women’s Health Initiative. Results Eight new metabolites were discovered to be associated with all-cause mortality. Findings included protective effects of increased levels of three amino acids (asparagine, homoarginine and tryptophan) and docosatrienoic acid; and detrimental effects of increased levels of C4-OH-carnitine, hexadecanedioate and two purine/pyrimidines (N2, N2-dimethylguanosine and N4-acetylcytidine). In addition, a set of nine previously published metabolite associations were replicated. A metabolite score comprising 17 metabolites was associated with mortality (P < 10–8) after adjustment for risk factors, with a hazard ratio of 1.95 (95% CI: 1.46–2.62) for women in the highest quartile compared with the lowest quartile of metabolite score. The score was robust among younger women and older women, for both cardiovascular and non-cardiovascular mortality, and associated with both early deaths (within the first 10 years of baseline) and later deaths. Conclusions Our study fills a gap in the literature by identifying eight novel metabolite associations with all-cause mortality in women, using a robust study design involving independent discovery and validation datasets.

scholarly journals Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women’s Health Initiative

2019 ◽  
Vol 112 (2) ◽  
pp. 170-178 ◽  
Author(s):  
Kathy Pan ◽  
Rebecca A Nelson ◽  
Jean Wactawski-Wende ◽  
Delphine J Lee ◽  
JoAnn E Manson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Women’S Health ◽  
Women's Health ◽  
Postmenopausal Women ◽  
Medical Record ◽  
Women's Health Initiative ◽  
Women’S Health Initiative ◽  
Health Initiative ◽  
All Cause Mortality ◽  
The Women’S Health Initiative

Abstract Background Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women’s Health Initiative (WHI). Methods Eligible were a subsample of 22 837 WHI participants aged 50–79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. Results During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). Conclusions High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.

scholarly journals Minireview: Effects of Different HT Formulations on Cognition

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3564-3570 ◽  
Author(s):  
Pauline M. Maki
Keyword(s):  
Women’S Health ◽  
Women's Health ◽  
Postmenopausal Women ◽  
Verbal Memory ◽  
Observational Studies ◽  
Negative Impact ◽  
Women's Health Initiative ◽  
Women’S Health Initiative ◽  
Health Initiative ◽  
The Women’S Health Initiative

Evidence from preclinical studies, randomized clinical trials (RCT), and observational studies underscores the importance of distinguishing among the different forms of estrogen and progestogens when evaluating the cognitive effects of hormone therapy (HT) in women. Despite this evidence, there is a lack of direct comparisons of different HT regimens. To provide insights into the effects of different HT formulations on cognition, this minireview focuses on RCT of verbal memory because evidence indicates that HT affects this cognitive domain more than others and because declines in verbal memory predict later development of Alzheimer's disease. Some observational studies indicate that estradiol confers benefits to verbal memory, whereas conjugated equine estrogens (CEE) confer risks. RCT to date show no negative impact of CEE on verbal memory, including the Women's Health Initiative Study of Cognitive Aging. Similarly, the Women's Health Initiative Memory Study showed no negative impact of CEE on dementia. Transdermal estradiol in younger postmenopausal women improved verbal memory in one small RCT but had no effect in another RCT. RCT of oral estradiol in younger and older postmenopausal women had neutral effects on cognitive function. In contrast, RCT show a negative impact of CEE plus medroxyprogesterone acetate on verbal memory in younger and older postmenopausal women. Small RCT show neutral or beneficial effects of other progestins on memory. Overall, RCT indicate that type of progestogen is a more important determinant of the effects of HT on memory than type of estrogen.

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