title: Gonadal steroid-dependent effects on bone turnover and bone mineral density in men.
abstract: BACKGROUND
  Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.
  
  
  METHODS
  One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.
  
  
  RESULTS
  As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.
  
  
  CONCLUSIONS
  Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT00114114.
  
  
  BACKGROUND
  AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Finkelstein
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Benjamin Z
authors.initials: BZ
authors.lastname: Leder
authors.forename: Sherri-Ann M
authors.initials: SA
authors.lastname: Burnett-Bowie
authors.forename: David W
authors.initials: DW
authors.lastname: Goldstein
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Hahn
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Hirsch
authors.forename: Alex
authors.initials: A
authors.lastname: Linker
authors.forename: Nicholas
authors.initials: N
authors.lastname: Perros
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Servais
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Taylor
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Webb
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Youngner
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Yu
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling; D004958:Estradiol / Q000097:blood; D005058:Eunuchism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013739:Testosterone; D004958:Estradiol