Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Effects of estradiol on bone density and fat mass in men undergoing androgen deprivation therapy for prostate cancer: a randomised placebo-controlled trial (#140)

Nicholas Russell 1 , Rudolf Hoermann 2 , Ali Ghasem-Zadeh 2 , Ada Cheung 2 , Jeffrey Zajac 2 , David Handelsman 3 , Mathis Grossmann 2
  1. Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
  2. Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC, Australia
  3. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia

Objective: Indirect evidence suggests that the effects of testosterone on bone and fat in men are dependent on aromatisation to estradiol (E2). No controlled study has examined this hypothesis in the absence of testosterone.

 

Design: 6-month randomised, placebo-controlled trial. We hypothesised that E2 would increase distal tibia total volumetric bone mineral density (vBMD) and reduce fat mass.

 

Methods: 78 participants receiving androgen deprivation therapy (ADT) for prostate cancer were randomised to 0.9mg topical E2 per day, or placebo. High-resolution peripheral quantitative CT was performed at baseline and study end. Body composition and areal bone mineral density (aBMD) were measured by dual energy x-ray absorptiometry at baseline, month 3 and month 6. At each visit sex steroids were measured by liquid chromatography tandem mass spectrometry, and serum beta carboxyl-terminal type 1 collagen telopeptide (CTX) and pro-collagen type 1 amino-terminal propeptide (P1NP) were measured by electrochemiluminescence.

 

Results: Serum E2 increased in the E2 group over 6 months compared to placebo, mean adjusted difference (MAD) 207pmol/L (95%CI 123–292), p<0.001. We observed no effect on distal tibia total vBMD, MAD 2.0mgHA/cm3 (95%CI -0.8–4.8), p=0.17. E2 increased distal radius cortical vBMD, MAD 14.8mgHg/cm3 (95%CI 4.5-25.0), p=0.005, and aBMD of lumbar spine, MAD 0.02g/cm2 (95%CI 0.01-0.03), p=0.01, and ultradistal radius, MAD 0.01g/cm2 (95%CI 0.00–0.02), p=0.01. E2 reduced CTX, MAD -224ng/L (95% CI -305 to -143), p<0.0001, and P1NP, MAD -13mcg/L (95% CI -22 to -5), p=0.005. E2 increased total fat mass, MAD 1007g (95%CI 124-1891), but not significantly, p=0.09. Android fat increased, MAD 164g (95%CI 41-286), p=0.04.

 

Conclusion: E2 did not change distal tibia vBMD in men undergoing ADT, despite decreasing bone remodelling and increasing regional aBMD and cortical vBMD. Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men.