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

Abstract

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. 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. 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±11.91g/m2 in G1 and 55.12±8.29g/m2 in G2 (p=0.244) after 30 days of treatment, and 61.13± 11.69g/m2 in G1 and 62.84±35.99g/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±7.18mmHg) in the group who receive testosterone (G1) compared with controls (77.5±6.69mmHg) (p=0.010). After 90 days, SBP levels returned to basal levels in G1 (82.35± 5.62mmHg) and in G2 (81.38±4.79mmHg) (p=0.588). 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.