Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover

J Clin Endocrinol Metab. 2004 Feb;89(2):681-7. doi: 10.1210/jc.2003-031086.


The aim of the study was to assess the effect of transdermal testosterone on free testosterone concentrations in saliva and on short-term growth and bone turnover in boys with growth or pubertal delay. A prospective, randomized, crossover study was conducted over 26 wk with 4 wk of run-in, 8 wk of treatment I (8 or 12 h), 4 wk of washout, 8 wk of treatment II (8 or 12 h), and 4 wk of final washout. The main outcome measures were salivary testosterone profiles during the different study periods; weekly change in lower leg length (LLL) as measured by knemometry, i.e. LLL velocity; absolute and percentage change in bone alkaline phosphatase (bALP) levels; and deoxypyridinoline cross-links measured in urine. Eight boys who took part in the study had a median age of 13.5 yr (range, 12.4-14.9 yr), testicular volume of 3 ml (range, 2-6 ml), height SD score of -2.4 (range, -1.44 to -3.35), and bone age delay of 2 yr (range, 1-3.2 yr). Median salivary testosterone during 8- and 12-h treatments [179 pg/ml (range, 7-3579 pg/ml) and 150 pg/ml (range, 12-3472 pg/ml) (not significant)] was significantly higher than during the run-in and washout blocks (P < 0.0001) [9 pg/ml (range, <7 to 122 pg/ml) and 13 pg/ml (range, <7 to 285 pg/ml) (not significant)]. LLL velocity in the treatment blocks (median, 0.64 mm/wk; range, 0.1-1.08 mm/wk) was significantly higher than during the run-in and washout periods (median, 0.48 mm/wk; range, -0.06 to 0.92 mm/wk) (P < 0.001). The main rise in bALP occurred during the first treatment block with a median percentage change in bALP of 44.2% (range, -4 to 87%) and a smaller percentage change in bALP at the end of the second treatment block of 9.8% (range, -4 to 55%). The increases in bALP were not significantly different between the 8- and 12-h treatment periods, and there was no significant decline during the washout periods. Overnight transdermal testosterone application, as Virormone (5 mg), may be a potentially acceptable method of induction of puberty and stimulates short-term growth and bone turnover.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Alkaline Phosphatase / metabolism
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Androgens / administration & dosage*
  • Androgens / adverse effects
  • Androgens / pharmacokinetics*
  • Biomarkers / analysis
  • Bone Development / drug effects*
  • Bone Remodeling / drug effects*
  • Bone and Bones / enzymology
  • Child
  • Cross-Over Studies
  • Humans
  • Leg
  • Male
  • Puberty / drug effects*
  • Saliva / metabolism
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Testosterone / pharmacokinetics*


  • Amino Acids
  • Androgens
  • Biomarkers
  • Testosterone
  • deoxypyridinoline
  • Alkaline Phosphatase