Associations between circulating sex steroid hormones and leukocyte telomere length in men in the National Health and Nutrition Examination Survey

Abstract

Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age-related conditions. Therefore, we conducted a cross-sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999-2002 surveys). Sample-weighted linear regression analyses were conducted to assess age-adjusted and multivariable-adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (β = -61, p = 0.04; free estradiol β = -67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol-induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.

Cross‐sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community‐based cohort of older men

“…These findings are in contrast to previous reports (see Table ) which reported neutral or inverse associations of E2 with LTL in men . In the study by Bekaert of 110 men with median age 75.0 years, circulating T and E2 were measured using immunoassay, bioavailable (non‐SHBG bound) T and E2 were calculated, and LTL was assayed using Southern blots.…”

“…Neither calculated bioavailable T nor E2 correlated with LTL . Coburn studied 499 men from NHANES 1992‐2002 surveys with median age 42.0 years, with circulating T and E2 concentrations assayed using immunoassays and LTL measured using PCR. In that study, circulating T was not associated with LTL, whereas circulating E2 was inversely associated with LTL in analyses adjusting for age, ethnicity, education, BMI and smoking status .…”

“…By contrast, an analysis of 980 predominantly middle‐aged men from the Busselton Health Study found that circulating concentrations of both bioactive metabolites of T, dihydrotestosterone (DHT) and E2, assayed using mass spectrometry, correlated with LTL . However a recent analysis of 499 adult men from the National Health and Nutrition Examination Survey (NHANES) was contradictory, reporting an inverse association of circulating E2 measured using immunoassay with LTL . A larger and more comprehensive analysis involving older men and using mass spectrometry for analysis of sex hormones would address this question.…”

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

“…Preliminary evidence suggests that sex steroid hormones could be involved in enhancing telomerase activity since serum dihydrotestosterone and estradiol are positively correlated with leukocyte TL independently of age (Yeap et al, 2016(Yeap et al, , 2020. However, other studies have demonstrated no association of short TL with sex hormones in healthy men and women (Coburn et al, 2018;Gu et al, 2020).…”

Investigação da associação de variantes polimórficas, sítios de metilação e tamanho de telômeros com resposta a longo prazo de lítio em transtorno bipolar

“…Esperava-se também uma relação negativa com qualquer situação estressora de vida, como já observado em diferentes estudos. O encurtamento do telômero tem sido mais acelerado em mulheres do que em homens e sua preservação não se associa a hormônios esteróides masculinos (Coburn et al, 2018).…”