Extremes of Endogenous Testosterone Are Associated with Increased Risk of Incident Coronary Events in Older Women

Objective: Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. Design: Prospective cohort study with a 4.5-year follow-up period. Methods: From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. Results: At baseline, the study population was aged 57.96G14.37 years with a mean body mass index of 26.71G5.17 kg/m 2 . No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2-Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2-Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33-0.74; adjusted HR 0.62, 95% CI 0.42-0.939; CV events: Q2-Q5 versus Q1: crude HR 0.54, 95% CI 0.38-0.77; adjusted HR 0.68, 95% CI 0.48-0.97). Kaplan-Meier curves revealed similar data. Conclusions: Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

Section: Discussionsupporting

confidence: 79%

Section: Laboratory Variablesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients

Sievers

Klotsche²,

Pieper³

et al. 2010

“…The lowest and the highest bioavailable testosterone (BT) quintiles were associated with significantly increase age-adjusted risk of incident CHD, with a 79% (PZ0.046) increase risk for women with low BT and a 96% (PZ0.022) increased risk for those with high BT. This U-shaped association with incident CHD persisted after additional adjustment for adiposity and lifestyle characteristics (38).…”

Section: European Journal Of Endocrinologymentioning

confidence: 88%

Low testosterone levels are associated with endothelial dysfunction in oophorectomized early postmenopausal women

Rech

Clapauch

Souza

2016

Background: The actual consequences of low testosterone levels in women remain uncertain. Objective: To assess endogenous testosterone influence on body composition, vascular and metabolic function in recent postmenopausal women. Design: We studied 81 postmenopausal women under transdermal estradiol (E 2 ) replacement therapy, 36 with bilateral oophorectomy (group O), and 45 controls (group C) through venous occlusion plethysmography, bioimpedance, DEXA, biochemical, hormonal, and inflammatory profile. Results: Total testosterone level (TT) in group O was 11.0 (4.0-17.75) vs 23.0 (10.0-42.5) ng/dl in group C (PZ0.001). Forearm blood flow, in ml/min/100 ml tissue, was lower in group O compared to group C at baseline (1.57 (1.05-2.47) vs 2.19 (1.59-2.66) PZ0.036), following reactive hyperemia response (endothelium-dependent flow mediated dilatation, 3.44 (2.38-4.35) vs 4.3 (3.09-5.52), PZ0.031) and following nitroglycerin (endothelium-independent dilation, 1.39 (0.99-1.7) vs 1.76 (1.15-2.0), PZ0.025), with a positive correlation between TT and all parameters except for the reactive hyperemia response (rZ0.233-0.312, PZ0.036-0.004). The sVCAM1 levels were negatively correlated with TT (rZ-0.320, PZ0.005). E 2 and other hormone levels, biochemical parameters and body composition did not differ between groups. Multiple linear regressions showed that the levels of TT, compared with other confounding variables, may explain the variation observed on endothelial parameters, with low explanatory power. Conclusion: The absence of ovarian testosterone production in recent postmenopausal oophorectomized women was associated with deleterious effects on endothelial function.

“…Studies on postmenopausal, middle-aged, and elderly women have shown that there was a significantly increased age-adjusted risk for incident CHD and events for the highest quintiles of total, bioavailable, and free testosterone relative to the median and bottom quintiles (6,7). Although these studies did not distinguish between women with a history of irregular menses or PCOS, the above data have implications for the cardiometabolic role of hyperandrogenemia, which persists after menopause in PCOS women (8).…”

Section: Introductionmentioning

confidence: 93%

MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

Sathyapalan

Atkin²

2012

Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed.