Leschek Ellen Werber, Flor Armando C, Bryant Joy C, Jones Janet V, Barnes Kevin M, Cutler Gordon B
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
MedImmune, Gaithersburg, MD.
J Pediatr. 2017 Nov;190:229-235. doi: 10.1016/j.jpeds.2017.07.047.
Antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog (GnRHa) treatment normalizes growth rate and bone maturation and increases predicted adult height (AH) in boys with familial male-limited precocious puberty (FMPP). To evaluate the effect of long-term antiandrogen, aromatase inhibitor, and GnRHa on AH, boys with FMPP who were treated were followed to AH.
Twenty-eight boys with FMPP, referred to the National Institutes of Health, were started on antiandrogen and aromatase inhibitor at 4.9 ± 1.5 years of age; GnRHa was added at 6.9 ± 1.5 years of age. Treatment was discontinued at 12.2 ± 0.5 years of age (bone age, 14.4 ± 1.3). AH was assessed at 16.4 ± 1.3 years of age (bone age, 18.5 ± 0.6).
AH (mean ± SD) for all treated subjects was 173.6 ± 6.8 cm (-0.4 ± 1.0 SD relative to adult US males). For 25 subjects with pretreatment predicted AH, AH significantly exceeded predicted AH at treatment onset (173.8 ± 6.9 vs 164.9 ± 10.7 cm; P < .001), but fell short of predicted AH at treatment discontinuation (177.3 ± 9.0 cm; P < .001). For 11 subjects with maternal or sporadic inheritance, the mean AH was 3.1 cm (0.4 SD score) below sex-adjusted midparental height (175.4 ± 5.8 vs 178.5 ± 3.1 cm [midparental height]; P = .10). For 16 subjects with affected and untreated fathers, AH was significantly greater than fathers' AH (172.8 ± 7.4 vs 168.8 ± 7.2 cm; P < .05).
Long-term treatment with antiandrogen, aromatase inhibitor, and GnRHa in boys with FMPP results in AH modestly below sex-adjusted midparental height and within the range for adult males in the general population.
抗雄激素、芳香化酶抑制剂和促性腺激素释放激素类似物(GnRHa)治疗可使家族性男性性早熟(FMPP)男孩的生长速率和骨骼成熟正常化,并增加预测成年身高(AH)。为评估长期使用抗雄激素、芳香化酶抑制剂和GnRHa对AH的影响,对接受治疗的FMPP男孩进行随访直至成年身高。
28名转诊至美国国立卫生研究院的FMPP男孩在4.9±1.5岁时开始使用抗雄激素和芳香化酶抑制剂治疗;6.9±1.5岁时加用GnRHa。治疗在12.2±0.5岁(骨龄14.4±1.3)时停止。在16.4±1.3岁(骨龄18.5±0.6)时评估AH。
所有接受治疗的受试者的AH(均值±标准差)为173.6±6.8cm(相对于美国成年男性,标准差为-0.4±1.0)。对于25名有治疗前预测AH的受试者,AH在治疗开始时显著超过预测AH(173.8±6.9 vs 164.9±10.7cm;P<.001),但在治疗停止时低于预测AH(177.3±9.0cm;P<.001)。对于11名有母系或散发性遗传的受试者,平均AH比按性别调整的父母平均身高低3.1cm(标准差分数为0.4)(175.4±5.8 vs 178.5±3.1cm[父母平均身高];P=.10)。对于16名父亲患病且未接受治疗的受试者,AH显著高于父亲的AH(172.8±7.4 vs 168.8±7.2cm;P<.05)。
FMPP男孩长期使用抗雄激素、芳香化酶抑制剂和GnRHa治疗后,AH略低于按性别调整的父母平均身高,处于一般人群成年男性的范围内。