Endogenous sex hormones and risk of venous thromboembolism in women and men

Abstract

To cite this article: Holmegard HN, Nordestgaard BG, Schnohr P, Tybjaerg-Hansen A, Benn M. Endogenous sex hormones and risk of venous thromboembolism in women and men. J Thromb Haemost 2014; 12: 297-305.Summary. Background: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown. Objective: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population. Methods: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the [1981][1982][1983] Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias. Results: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre-and postmenopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE. Conclusion: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.

Testosterone Treatment and Cardiovascular and Venous Thromboembolism Risk: What is ‘New’?

“…Similar results were reported by Holmegard et al 52 in the Copenhagen City Heart Study, including 4673 men representative for the adult Danish population. In line with these data, Mumoli et al 53 were unable to detect any difference in T and oestradiol levels between 63 patients with unprovoked deep venous thrombosis (DVT) and matched controls (table 3).…”

“…Two large population-based studies failed to find an association between endogenous T and VTE (table 3). 51 52…”

Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy

“…However, there is also evidence that testosterone therapy may have protective endothelial actions. [8][9][10][11] Two large population-based studies 12,13 reported that endogenous testosterone levels were not associated with VTE. To date, no comparative studies examining an association between testosterone therapy and VTE have been reported.…”

Adverse effects of testosterone replacement therapy: an update on the evidence and controversy

“…The Copenhagen City Heart Study, a prospective study of 4673 men, found no associations with extreme levels of endogenous T (defined as > 95th percentile) and elevated risk of deep venous thrombosis, pulmonary embolism, or recurrent VTE [Holmegard et al 2014]. Similarly, a prospective, population-based study of 1350 men aged 50-84 years yielded only 4.5 VTE events per 1000 person-years over 10.4 years of follow up with an insignificant HR of 1.06 (95% CI 0.83-1.35) [Svartberg et al 2009].…”