Transdermal testosterone gel for induction and continuation of puberty in adolescent boys with hepatic dysfunction.

Treatment to induce puberty in boys is indicated in those who do not undergo spontaneous development at a normal age. Stimulating development of the secondary sex characteristics is possible using gradually increasing doses of testosterone esters (TEs) via intramuscular (IM) administration, which is the most widely used method of testosterone (T) supplementation. When TEs are administered as monthly injection, serum T levels exhibit large fluctuations with supraphysiologic levels seen immediately after the injection followed by a decrease into the low range. Transdermal T (TT) has also been used for replacement therapy in adult males with hypogonadism and this provides steadier serum T levels. We report three adolescent boys with delayed puberty who were treated with TT gel for pubertal induction/continuation. This route was chosen as an alternative therapy due to their hepatic dysfunction, as is known that TT avoids the hepatic first-pass metabolism.

Salivary Testosterone during the Minipuberty of Infancy
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BACKGROUND: The hypothalamic-pituitary-gonadal axis is transiently activated during the postnatal months in boys, a phenomenon termed "minipuberty" of infancy, when serum testosterone (T) increases to pubertal levels. Despite high circulating T there are no signs of virilization. We hypothesize that free T as measured in saliva is low, which would explain the absence of virilization. METHODS: We measured serum total T and free T in saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 30 infant boys, aged 1-6 months, and in 12 adolescents, aged 11-17 years. RESULTS: Total serum T in all infants was, as expected, high (172 ± 78 ng/dL) while salivary T was low (7.7 ± 4 pg/mL or 0.45 ± 0.20%). In contrast, salivary T in the adolescents was much higher (41 ± 18 pg/mL or 1.3 ± 0.36%) in relation to their total serum T (323 ± 117 ng/dL). We provide for the first time reference data for salivary T in infants. CONCLUSION: Measurement of salivary T by LC-MS/MS is a promising noninvasive technique to reflect free T in infants. The low free T explains the absence of virilization. The minipuberty of infancy is more likely of intragonadal than peripheral significance.
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Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

Exogenous pubertal induction by oral versus transdermal estrogen therapy.

Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction.

Letrozole significantly improves growth potential in a pubertal boy with growth hormone deficiency.

Clinical experience with using an aromatase inhibitor to suppress estrogen production during puberty for improvement of growth potential in adolescents with short stature is limited. This report documents treatment of such a patient with a combination of growth hormone and letrozole, a third-generation aromatase inhibitor. Our case demonstrates a favorable outcome on a short-term basis.