Echocardiographic evaluation of left ventricular mass index in children with hypospadias after hormonal stimulation with topical testosterone: A randomized controlled trial.

INTRODUCTION: Testosterone is often used in the preoperative period of hypospadias surgery. Previous studies have demonstrated the presence of androgen receptors in cardiac myocytes that can modulate the phenotype. The use of supraphysiological doses of androgens can lead to toxicity on the heart muscle and, in some cases, to left ventricular hypertrophy. This randomized double blind controlled clinical trial aims to evaluate the effect of topical testosterone on left ventricular mass index in boys with hypospadias. MATERIALS AND METHODS: Boys with hypospadias aged 6 months to 9 years were included. Children were divided into two groups: G1 - boys who received testosterone propionate 1% ointment twice a day for 30 days, and G2 - boys receiving placebo ointment in the same regimen. All children were submitted to bi-dimensional echocardiographic evaluation to compare the left ventricular mass index, blood pressure, and body mass index before and after treatment (30 and 90 days). Levels of serum testosterone, LH, and FSH were measured. RESULTS: Thirty-five children were analyzed: 17 in G1 and 18 in G2. No differences were found in left ventricular mass index (left ventricular mass indexed by body surface area) prior to treatment. Left ventricular mass index was 59.21 ± 11.91 g/m2 in G1 and 55.12 ± 8.29 g/m2 in G2 (p = 0.244) after 30 days of treatment, and 61.13 ± 11.69 g/m2 in G1 and 62.84 ± 35.99 g/m2 in G2 (p = 0.852) after 90 days. Serum testosterone levels were 12 (7-80) ng/dL in G1 and 5 (5-7) ng/dL in G2 (p = 0.018) after 30 days of treatment, and 10 (5-11) ng/dL in G1 and 5 (4-5) ng/dL in G2 (p = 0.155), after 90 days (Figure). There was a small increase in systolic blood pressure (SBP) after 30 days (83.82 ± 7.18 mmHg) in the group who receive testosterone (G1) compared with controls (77.5 ± 6.69 mmHg) (p = 0.010). After 90 days, SBP levels returned to basal levels in G1 (82.35 ± 5.62 mmHg) and in G2 (81.38 ± 4.79 mmHg) (p = 0.588). CONCLUSION: Topical testosterone can be considered safe in the preoperative period of children with hypospadias with no risk of left ventricular hypertrophy. An increase in systolic blood pressure occurs while using testosterone but it is transitory, returning to normal levels after 90 days.

Biometry of the hypospadic penis after hormone therapy (testosterone and estrogen): A randomized, double-blind controlled trial.

INTRODUCTION: The use of preoperative hormonal stimulation before hypospadias surgery aims to increase penile size and achieve better surgical results; however, the rules are not clear in the literature. We evaluated the effects of topical testosterone and estrogen in the hypospadic penis regarding biometric measures, side effects, and serum hormonal levels. To our knowledge, this is the first study using estradiol prior to hypospadias surgery. PATIENTS AND METHODS: Sixty-nine children with hypospadias were randomly divided into three study groups: a control group (CG) of 17 children given placebo cream; a testosterone group (TG) of 28 children who used 1% testosterone propionate; and an estradiol group (EG) of 24 children using 0.01% estradiol. All subjects applied the topical ointment on the entire penis, twice daily for 30 days before surgical correction. Biometric evaluation of the penis included penile length and diameter, glans diameter, distance from the urethral meatus to the tip, and the width of the urethral plate. These measurements as well as serum hormone level, and side effects were evaluated prior to hormone use, and 30 and 90 days after. RESULTS: After 30 days an increase in penile diameter and length and diameter of the glans were observed in TG (p < 0.05). The width of the urethral plate and distance from meatus to the tip increased in TG, although not significantly. The most frequent side effects were appearance of pubic hair and darkening of the genital skin, mainly in TG, but these were transient and disappeared after 90 days of treatment. No significant variations were seen in serum hormonal levels (Table). CONCLUSION: As in previous studies, an increase in penile length and diameter, and glans diameter was observed with the use of testosterone. Proximal urethral plate width and distance from the meatus to the tip of the penis had a tendency to increase also in TG. Estradiol did not change biometric measure of the penis. Few side effects occurred after both hormones, and any that did improved after 90 days follow-up and did not change hormone serum levels. CONCLUSION: Preoperative use of topical testosterone increases penile size, diameter of the penis and glans. The use of estradiol does not change penile biometry. Side effects occur mainly with the use of testosterone and are transient. No significant and persistent hormonal changes were observed.