Epidemiological and mendelian randomization studies of dihydrotestosterone and estradiol and leukocyte telomere length in men

Abstract

Context: Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is metabolized to DHT by 5α-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro. Objective: The objective of the study was to establish whether circulating T or its metabolites, DHT or E2, and single-nucleotide polymorphisms in SRD5A2 or CYP19A1 associate with leucocyte telomere length (LTL) in men. Participants and Methods: Early-morning serum T, DHT, and E2 were assayed using mass spectrometry, and SRD5A2 and CYP19A1 single-nucleotide polymorphisms and LTL analyzed by PCR in 980 men from the Western Australian Busselton Health Survey who participated in the study. LTL was expressed as the T/S ratio. Results: Men were aged (mean α SD) 53.7 α 15.6 years. LTL decreased linearly with age, from the T/S ratio of 1.89 α 0.41 at younger than 30 years to 1.50 α 0.49 at 70 to younger than 80 years (r =-0.225, P