Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover.
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.
Mayo
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Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, Scotland, United Kingdom.
Macintyre
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Wallace
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AM
Ahmed
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SF
D000279:Administration, Cutaneous; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000728:Androgens / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000032:analysis; D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000201:enzymology; D002648:Child; D018592:Cross-Over Studies; D006801:Humans; D007866:Leg; D008297:Male; D011627:Puberty / Q000187:drug effects*; D012463:Saliva / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000596:Amino Acids; D000728:Androgens; D015415:Biomarkers; D013739:Testosterone; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase