title: Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects.
abstract: OBJECTIVE
  Testosterone therapy for osteoporosis has not been studied extensively in women because of its potential to cause virilization. Female-to-male transsexuals are genetic females who suffer from gender dysphoria and thus take supra-physiologic doses of testosterone to change from the female to male phenotype. The aim of this study is to examine the effects of testosterone treatment on the genetic female skeleton.
  
  
  METHODS
  A group of 15 female-to-male transsexuals was prospectively enrolled for observation over a 2-year period. The subjects had a mean age of 37.0 +/- 3.0 years. All of the subjects self-administered testosterone esters intramuscularly at a mean dose of 70.7 +/- 4.5 mg weekly.
  
  
  METHODS
  The subjects had measurements of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) of the femoral neck and spine (L2-L4) at 12-month intervals. They had determinations of serum oestradiol, testosterone, soluble RANKL (sRANKL), osteoprotegerin (OPG) and urine N-telopeptide (NTX) at the date of enrolment and at the end of 2 years. results There was a significant positive increase in mean BMD of 7.8% at the femoral neck and a nonsignificant increase in mean BMD of 3.1% at the spine over 2 years. The levels of testosterone reached the upper normal range for males and the levels of oestradiol declined to near the postmenopausal range. sRANKL levels decreased significantly in female-to-male transsexuals who newly initiated testosterone therapy. There was no significant change in urine NTX or serum OPG during the study.
  
  
  CONCLUSIONS
  We conclude that supra-physiologic testosterone therapy increases BMD at the hip while maintaining BMD at the spine in female-to-male transsexuals. The effects of testosterone may be the result of testosterone hormone directly acting on the bone or indirectly through aromatization to oestradiol. Lower RANKL levels coupled with unchanged OPG levels results in an increased OPG/RANKL ratio, which may be beneficial to the bone by inhibiting osteoclastogenesis.
authors.affiliation: Boston University School of Medicine, Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston, Massachusetts, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Turner
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
authors.forename: Tom W
authors.initials: TW
authors.lastname: Barber
authors.forename: Alan O
authors.initials: AO
authors.lastname: Malabanan
authors.forename: Michael F
authors.initials: MF
authors.lastname: Holick
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D002352:Carrier Proteins / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013131:Spine / Q000503:physiopathology; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use*; D014189:Transsexualism / Q000097:blood / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D013739:Testosterone; D004958:Estradiol