家族性男性性早熟的病因与治疗研究进展

Advances on the pathogenesis and therapeutics of familial male-limited precocious puberty

家族性男性性早熟(FMPP)的病因主要由编码黄体生成素/人绒毛膜促性腺激素受体基因激活突变引起,已鉴定出多种突变,但是其基因型与表型的关系尚不完全明确。FMPP的主要治疗目的是抑制第二性征过早发育以及降低体内过高的性激素水平,延缓骨骺过早闭合,从而改善成年身高。目前临床用药主要有抑制性腺类固醇生成药物、抗雄激素药物、P450酶抑制剂、芳香化酶抑制剂等几大类。由于该病属罕见病,临床虽有上述药物单独和联合应用,以及药物不良反应的相关报道,但均较少,目前仍缺乏多中心、大样本的系统研究。

Familial male-limited precocious puberty(FMPP)is mainly caused by activating mutations of luteinizing hormone/choriogonadotropin receptor(LHCGR)gene.Many mutations have been identified,but the relationship between genotypes and phenotypes is not completely clear.The main therapeutic purpose of FMPP is to inhibit pubertal development,decrease the excessively high level of sexual hormone and delay the early closure of epiphysis in order to improve the adult height.There are several major categories of clinical drugs for FMPP,including gonadal steroidogenesis inhibitors,antiestrogen,cytochrome P450 inhibitors,and aromatase inhibitors.FMPP is a rare disease.Although there are some reports on single or combined clinical applications of the above drugs and their adverse reactions,multi-centered and large-sample systematic studies are still in need.