Evidence of a Causal Effect of Estradiol on Fracture Risk in Men

The Journal of Clinical Endocrinology and Metabolism
Maria NethanderClaes Ohlsson

Abstract

Observational studies indicate that serum estradiol (E2) is more strongly associated with bone mineral density (BMD) than serum testosterone (T) is, whereas both E2 and T associate with fracture risk in men. To evaluate the possible causal effect of serum E2 and T on fracture risk in men. A Mendelian randomization (MR) approach was undertaken using individual-level data on genotypes, BMD as estimated by quantitative ultrasound of the heel (eBMD), fractures (n = 17,650), and relevant covariates of 175,583 unrelated men of European origin from the UK Biobank. The genetic instruments for serum E2 and T were taken from the most recent large-scale genome-wide association study meta-analyses on these hormones in men. MR analyses demonstrated a causal effect of serum E2 on eBMD and fracture risk. A 1 SD (or 9.6 pg/mL) genetically instrumented decrease in serum E2 levels was associated with a 0.38 SD decrease in eBMD (P value: 9.7 × 10-74) and an increased risk of any fracture (OR: 1.35; 95% CI: 1.18, 1.55), nonvertebral major osteoporotic fractures (OR: 1.75; 95% CI: 1.35, 2.27), and wrist fractures (OR: 2.27; 95% CI: 1.62, 3.16). These causal effects of serum E2 levels on fracture risk were robust in sensitivity analyses and remained...Continue Reading

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Citations

Apr 17, 2019·The Journal of Clinical Endocrinology and Metabolism·Sung Hun Won, Jae Heon Kim
Mar 11, 2020·The Journal of Clinical Endocrinology and Metabolism·Bu B YeapLeon Flicker
May 30, 2020·Andrology·Vincenzo Rochira
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Jun 25, 2019·Frontiers in Endocrinology·Fjorda KoromaniLing Oei
Dec 12, 2019·Frontiers in Endocrinology·Jie ZhengJonathan H Tobias
Feb 16, 2021·The Journal of Clinical Investigation·Shalender Bhasin
Mar 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Maria NethanderClaes Ohlsson
Jul 14, 2021·The Journal of Clinical Endocrinology and Metabolism·Daniel SchmitzÅsa Johansson
Aug 21, 2021·The Journal of Clinical Endocrinology and Metabolism·Maki Yokomoto-UmakoshiYoshihiro Ogawa
Aug 17, 2021·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Bruno LunenfeldAbraham Morgentaler

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