Nelson Vergel
Founder, ExcelMale.com
Epidemiological and Mendelian Randomisation Studies of Dihydrotestosterone and Estradiol, and Leucocyte Telomere Length in Men
Context: - Advancing age is accompanied by accumulation of ill-health and shortening of chromosomal telomeres signifying biological ageing. Testosterone (T) is metabolised to dihydrotestosterone (DHT) by 5|ga-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro.
Objectives: - To establish whether circulating T or its metabolites DHT or E2, and single nucleotide polymorphisms (SNPS) 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 snps and LTL analysed by PCR in 980 men from the Western Australian Busselton Health Survey. LTL was expressed as the T/S ratio.
Results: - Men were aged (mean±SD) 53.7±15.6 years. LTL decreased linearly with age, from T/S ratio 1.89±0.41 at <30 years to 1.50±0.49 at 70 to <80 years (r=-0.225, p<0.0001).
After adjustment for age, DHT and E2 were positively correlated with LTL (DHT r=0.069, p=0.030; E2 r=0.068, p=0.034).
The SRD5A2 rs9282858 polymorphism was associated with serum DHT but not with LTL. Three dominant alleles of CYP19A1 were each associated with lower serum E2 and shorter LTL: rs2899470 T (E2 59.3 vs 68.6 pmol/L, p<0.0001; T/S ratio 1.54 vs 1.62, p=0.045), rs10046 C (60.5 vs 68.1 pmol/L, p=0.0005, 1.54 vs 1.62, p=0.035) and rs700518 A (59.9 vs 68.9 pmol/L, p<0.0001, 1.54 vs 1.63, p=0.020).
A single copy haplotype C/T/I/A/T rs10046/rs2899470/rs11575899/rs700518/rs17703883 (52% prevalence) was associated with both lower E2 and shorter LTL.
Conclusions: - In men, serum DHT and E2 correlate with LTL independently of age. Aromatase gene polymorphisms include 3 dominant alleles which are associated with both lower serum E2 and shorter LTL. E2 influences telomere length in vivo thus warranting further studies to examine whether hormonal interventions might slow biological ageing in men.
Yeap BB, Knuiman MW, Divitini ML, et al. Epidemiological and Mendelian randomisation studies of dihydrotestosterone and estradiol, and leucocyte telomere length in men. The Journal of Clinical Endocrinology & Metabolism.
Context: - Advancing age is accompanied by accumulation of ill-health and shortening of chromosomal telomeres signifying biological ageing. Testosterone (T) is metabolised to dihydrotestosterone (DHT) by 5|ga-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro.
Objectives: - To establish whether circulating T or its metabolites DHT or E2, and single nucleotide polymorphisms (SNPS) 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 snps and LTL analysed by PCR in 980 men from the Western Australian Busselton Health Survey. LTL was expressed as the T/S ratio.
Results: - Men were aged (mean±SD) 53.7±15.6 years. LTL decreased linearly with age, from T/S ratio 1.89±0.41 at <30 years to 1.50±0.49 at 70 to <80 years (r=-0.225, p<0.0001).
After adjustment for age, DHT and E2 were positively correlated with LTL (DHT r=0.069, p=0.030; E2 r=0.068, p=0.034).
The SRD5A2 rs9282858 polymorphism was associated with serum DHT but not with LTL. Three dominant alleles of CYP19A1 were each associated with lower serum E2 and shorter LTL: rs2899470 T (E2 59.3 vs 68.6 pmol/L, p<0.0001; T/S ratio 1.54 vs 1.62, p=0.045), rs10046 C (60.5 vs 68.1 pmol/L, p=0.0005, 1.54 vs 1.62, p=0.035) and rs700518 A (59.9 vs 68.9 pmol/L, p<0.0001, 1.54 vs 1.63, p=0.020).
A single copy haplotype C/T/I/A/T rs10046/rs2899470/rs11575899/rs700518/rs17703883 (52% prevalence) was associated with both lower E2 and shorter LTL.
Conclusions: - In men, serum DHT and E2 correlate with LTL independently of age. Aromatase gene polymorphisms include 3 dominant alleles which are associated with both lower serum E2 and shorter LTL. E2 influences telomere length in vivo thus warranting further studies to examine whether hormonal interventions might slow biological ageing in men.
Yeap BB, Knuiman MW, Divitini ML, et al. Epidemiological and Mendelian randomisation studies of dihydrotestosterone and estradiol, and leucocyte telomere length in men. The Journal of Clinical Endocrinology & Metabolism.
