Transdermal Testosterone Application: Pharmacokinetics and Effects on Pubertal Status, Short-Term Growth, and Bone Turnover

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 2; pp. 681 - 687
• Main Authors: Mayo, A., Macintyre, H., Wallace, A. M., Ahmed, S. F.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.02.2004; Copyright by The Endocrine Society
• Subjects: Administration, Cutaneous; Adolescent; Alkaline Phosphatase - metabolism; Amino Acids - chemistry; Amino Acids - metabolism; Androgens - administration & dosage; Androgens - adverse effects; Androgens - pharmacokinetics; Biological and medical sciences; Biomarkers - analysis; Bone and Bones - enzymology; Bone Development - drug effects; Bone Remodeling - drug effects; Child; Cross-Over Studies; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Humans; Leg; Male; Medical sciences; Puberty - drug effects; Saliva - metabolism; Testosterone - administration & dosage; Testosterone - adverse effects; Testosterone - pharmacokinetics; Vertebrates: endocrinology; Short term; Transdermal system; Androgen; Growth; Percutaneous route; Osteoarticular system; Testosterone; Turnover; Testicular hormone; Bone; Sex steroid hormone; Pharmacokinetics; Endocrinology
• ISSN: 0021-972X; 1945-7197
• 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.