Use of aromatase inhibitors in precocious puberty

During puberty, estrogen causes breast maturation and growth of the uterine lining in girls, and accelerates linear growth and bone maturation in both boys and girls. Decreasing the biosynthesis of estrogen can attenuate thes e processes. In 12 girls with the McCune-Albright syndrome (MAS), in which precocious puberty is due to production of estrogen from ovarian cysts, tes tolactone (40 mg/kg per day) decreased the volume of ovarian cysts, the fre quency of menses, and the rates of growth and bone maturation, for periods of 1-4 years. in a 6-month pilot study of 12 children (eight boys; four gir ls) with congenital adrenal hyperplasia, testolactone, in combination with an antiandrogen (flutamide), a mineralocorticoid (fludrocortisone acetate, Florinef), and a reduced glucocorticoid dose, improved the control of growt h and bone maturation compared with conventional therapy. In a 6-year study of 10 boys with familial male precocious puberty, testolactone, in combina tion with an antiandrogen (spironolactone), decreased rates of growth and b one maturation, and increased predicted adult height. All patients who deve loped evidence for gonadotropin-dependent puberty were also treated with a GnRH analog, Testolactone had no important adverse effects in any group of patients, although the need for a four-times-daily dosing schedule made com pliance difficult for many families. We conclude that suppressing of estrog en with testolactone was effective therapy, and that more potent and specif ic inhibitors of aromatase could further improve the treatment of these dis orders.