title: A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol.
abstract: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa.
  
  
  
  To compare BMD change in men receiving either LHRHa or oestradiol patches (OP).
  
  
  
  Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006-2011; 1:1, thereafter) were recruited into a BMD study (2006-2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr.
  
  
  
  LHRHa as per local practice, OP (FemSeven 100μg/24h patches).
  
  
  
  The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance.
  
  
  
  A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was -0.021g/cm(3) for patients randomised to the LHRHa arm (mean percentage change -1.4%) and +0.069g/cm(3) for the OP arm (+6.0%; p<0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa -3.0% and OP +7.9% (p<0.001).
  
  
  
  Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial.
  
  
  
  This study found that prostate cancer patients treated with transdermal oestradiol for hormonal therapy did not experience the loss in bone mineral density seen with luteinising hormone-releasing hormone agonists. Other clinical outcomes for this treatment approach are being evaluated in the ongoing PATCH trial.
  
  
  
  ISRCTN70406718, PATCH trial (ClinicalTrials.gov NCT00303784).
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK. Electronic address: ruth.langley@ucl.ac.uk.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Langley
authors.affiliation: Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Howard G
authors.initials: HG
authors.lastname: Kynaston
authors.affiliation: The Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Abdulla A
authors.initials: AA
authors.lastname: Alhasso
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Trinh
authors.initials: T
authors.lastname: Duong
authors.affiliation: Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Paez
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Gordana
authors.initials: G
authors.lastname: Jovic
authors.affiliation: Ipswich Hospital NHS Trust, Ipswich, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Scrase
authors.affiliation: Scarborough General Hospital, Scarborough, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Robertson
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Fay
authors.initials: F
authors.lastname: Cafferty
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Welland
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Carpenter
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Honeyfield
authors.affiliation: Imperial College London, London, UK.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Abel
authors.affiliation: Cardiff University, Bone Research Unit, Penarth, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Stone
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK; Imperial College London, London, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Abel
mesh_terms: D015502:Absorptiometry, Photon; D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005270:Femur Head / Q000000981:diagnostic imaging; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013739:Testosterone / Q000097:blood; D057968:Transdermal Patch
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol
keywords: Androgen-deprivation therapy; Bone mineral density; Prostate cancer; Transdermal oestradiol