Duration of estrogen exposure during reproductive years, age at menarche and age at menopause, and risk of cardiovascular disease events, all-cause and cardiovascular mortality: a systematic review and meta-analysis.

BACKGROUND: Little is known about the estrogen exposure measurement and mutual effect of age at menarche and age at menopause in the risk of cardiovascular disease (CVD) events. OBJECTIVES: To evaluate estrogen exposure measurement and describe mutual effect of age at menarche and age at menopause in the risk of CVD events. SEARCH STRATEGY: Systematic review of literature in PubMed, Embase and Web of Science for studies published up to 28 June 2020. SELECTION CRITERIA: Observational studies related to estrogen exposure measurement, including mutual effect of age at menarche and age at menopause and risk of CVD events. DATA COLLECTION AND ANALYSIS: Synthesis of evidence was conducted by reviewing individual estimates, followed by meta-analysis. The study received no external funding. MAIN RESULTS: A total of 75 studies were included in synthesis of evidence, of which 17 studies were included in meta-analysis. Reproductive lifespan (age at menopause - age at menarche), endogenous estrogen exposure and total estrogen exposure were used for estrogen exposure measurement. Reproductive lifespan was by far the most commonly used method for estrogen exposure measurement. A shorter reproductive lifespan was associated with a higher risk of CVD events; the pooled relative risk (95% CI) was 1.31 (1.25-1.36) for stroke events. Robust epidemiological studies with measurement of estrogen exposure and associated health risk would strengthen the evidence. CONCLUSIONS: Reproductive lifespan was the most commonly used method for estrogen exposure measurement in epidemiological studies. A shorter reproductive lifespan was associated with a higher risk of CVD events, particularly stroke. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that women with a shorter reproductive lifespan have a higher risk of stroke events.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Effect of nitroblue tetrazolium concentration on the fructosamine assay for quantifying glycated protein.

Experiments with nitroblue tetrazolium (NBT) at 0.25, 0.50, and 0.75 mmol/L confirmed that reactivity of 1-deoxy-1-morpholino-D-fructose, the standard, was more sensitive to reagent concentration than was protein ketoamine and demonstrated why an increase in NBT or a decrease in sample volume yields lower values for serum fructosamine. Analyses of clinical samples from diabetic and nondiabetic patients and from healthy subjects indicated that, with NBT at 0.25 mmol/L, discrimination between diabetics and other subjects was improved by changing the sample:reagent volume ratio from the usual 1:10 to 1:25 (9- to 12-min reading time). Discrimination improved further with NBT at 0.75 mmol/L and a 1:25 ratio but a later reading time (18-21 min); these conditions may minimize the effects of some but not all interferents.