Treatment of Familial Male Precocious Puberty with Spironolactone and Testolactone

Because the pubertal growth spurt in boys appears to be mediated by both androgens and estrogens, we hypothesized that blockade of both androgen action and estrogen synthesis would normalize the growth of boys with familial male precocious puberty. To test this hypothesis, we studied nine boys (age range, 3.3 to 7.7 years) during treatment with an antiandrogen (spironolactone) or an inhibitor of androgen-to-estrogen conversion (testolactone), followed by treatment with both agents. After six months of observation without treatment, the first four boys received spironolactone for six months, followed by spironolactone and testolactone. The next five boys received testolactone for six months, followed by spironolactone and testolactone. Neither spironolactone nor testolactone, given alone, was satisfactory as a treatment for this condition. However, a combination of spironolactone and testolactone, given for at least six months, restored both the growth rate and the rate of bone maturation to normal prepubertal levels and controlled acne, spontaneous erections, and aggressive behavior. The combined therapy was associated with a significantly lower growth rate than testolactone alone (P<0.05) and a significantly lower rate of bone maturation than spironolactone alone (P<0.05). No important adverse effects were observed during combined treatment. Six of the nine boys continued to receive the combined therapy for an additional 12 months and maintained normal prepubertal rates of growth and bone maturation. The mean predicted height (±SEM) increased progressively during the combined treatment although the difference between the pretreatment and post-treatment predictions was not significant (169.5±2.8 at the end of treatment vs. 166.2±4.5 cm before treatment; P = 0.29). We conclude that blockade of both androgen action and estrogen synthesis with the combination of spironolactone and testolactone is an effective short-term treatment for familial male precocious puberty. Further study will be required, however, to assess the long-term outcome in boys who receive this treatment. FAMILIAL male precocious puberty is a form of isosexual precocious puberty, occurring in boys, that is independent of luteinizing hormone–releasing hormone (LHRH).^{1 2 3 4 5} The pattern of inheritance is autosomal dominant, although sporadic cases can occur. Signs of puberty usually appear by 2 to 3 years of age in boys with this disorder. Examination of testicular biopsy specimens shows hyperplasia of Leydig's cells.⁶ Rapid virilization and premature epiphyseal fusion result in short adult stature.^7,8 In familial male precocious puberty, in contrast to LHRH-dependent central precocious puberty, testicular activation occurs without the normal pubertal increase in gonadotropin secretion.^{1 2 3} Consequently, the long-acting LHRH agonists,…