Laue L, Kenigsberg D, Pescovitz O H, Hench K D, Barnes K M, Loriaux D L, Cutler G B
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda 20892.
N Engl J Med. 1989 Feb 23;320(8):496-502. doi: 10.1056/NEJM198902233200805.
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 less than 0.05) and a significantly lower rate of bone maturation than spironolactone alone (P less than 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.
由于男孩青春期生长突增似乎是由雄激素和雌激素共同介导的，我们推测阻断雄激素作用和雌激素合成可使患有家族性男性性早熟的男孩生长恢复正常。为验证这一假设，我们研究了9名男孩（年龄范围为3.3至7.7岁），他们先接受抗雄激素药物（螺内酯）或雄激素向雌激素转化抑制剂（睾酮内酯）治疗，随后接受两种药物联合治疗。在未经治疗观察6个月后，前4名男孩接受螺内酯治疗6个月，之后接受螺内酯和睾酮内酯联合治疗。接下来的5名男孩接受睾酮内酯治疗6个月，之后接受螺内酯和睾酮内酯联合治疗。单独使用螺内酯或睾酮内酯作为这种病症的治疗方法均不理想。然而，螺内酯和睾酮内酯联合使用至少6个月，可使生长速率和骨成熟速率恢复到青春期前的正常水平，并控制痤疮、自发性勃起和攻击性行为。联合治疗与单独使用睾酮内酯相比生长速率显著降低（P<0.05），与单独使用螺内酯相比骨成熟速率显著降低（P<0.05）。联合治疗期间未观察到重要不良反应。9名男孩中有6名继续接受联合治疗12个月，并维持青春期前正常的生长速率和骨成熟速率。联合治疗期间平均预测身高（±SEM）逐渐增加，尽管治疗前和治疗后预测值之间的差异不显著（治疗结束时为169.5±2.8 cm，治疗前为166.2±4.5 cm；P = 0.29）。我们得出结论，螺内酯和睾酮内酯联合阻断雄激素作用和雌激素合成是家族性男性性早熟的一种有效的短期治疗方法。然而，需要进一步研究以评估接受这种治疗的男孩的长期结局。
