An Ambispective Cohort Study On The Etiology,Diagnosis And Treatment Of Girls With Breast Development Between Age 7-8 Years

Research BackgroundPrecocious puberty(PP)is traditionally defined as puberty that starts before 8 years in girls and 9 years in boys.However,a continuous down trend toward an early onset of puberty has been reported worldwide during the last 30 years.The Lawson Wilkins Pediatric Endocrine Society(LWPES)recommended in 1999 a new guideline that if girls with either breast development or pubic hair before 7 years old in white girls and before 6 years old in African-American girls,they should be evaluated for precocious puberty.However,most pediatric endocrinologists question the validity of these recommendations.The new guideline cannot be made due to the single cross-sectional epidemiologic study at present and normal time of the onset of pubertal development cannot exclude pathological conditions.The defined age of PP for girls is still 8 years old in China.However,girls in urban areas of China are also one of the populations with early breast development.Investigations on the development of secondary sexual characteristics of girls in nine major cities in China indicate the median age of onset of breast development were 9.20 years and 19.57%of girls had breast development before 8 years old.If the defined age used to evaluate PP in white girls is used to evaluate PP in Chinese urban girls,more than 10%of girls will be overdiagnosed.ObjectiveTo investigate the etiology,progression and treatment of precocious puberty in 7-to 8-year-old girls with breast development in Shenzhen.Additionally,we evaluate the value of diagnostic tests in differentiating rapidly progressive precocious puberty(RP-PP)and slowly progressive precocious puberty(SP-PP)in these girls.MethodsWe adopted an ambispective cohort study and retrospectively included girls with breast development between age 7-8 years during July 2016 to July 2018 in Pediatric Endocrinology Department of Baoan Hospital of Shenzhen,and prospectively followed up the growth data of these girls(≥2 years).They were divided into rapidly progression precocious puberty(RP-PP)and slowly progression precocious puberty(SP-PP)groups based on the speed of progression of puberty.We collected the medical records of these girls,and investigated the etiology of early breast development in 7-to 8-year-old girls,and the proportion of RP-PP and the proportion of treatment,and compared the clinical characteristics of the two groups of RP-PP and SP-PP.ResultsA total of 212 girls were enrolled,of which 211(99.53%)were diagnosed with central precocious puberty(CPP)and one with peripheral precocious puberty(PPP).135 girls underwent brain MRI examination,and the results showed none had pathological brain lesions requiring surgical intervention.Ninety-five girls(44.81%)developed RP-PP and 117 girls(55.19%)developed SP-PP.31 girls(14.62%)with RP-PP were treated with gonadotropin-releasing hormone analogs(GnRHa)because of deteriorated predicting adult height.The RP-PP girls showed more advanced bone age,higher level of basal luteinizing hormone(LH),larger ovarian volume and larger uterine volume comparing with SP-PP.Receiver Operating Characteristic(ROC)analyses revealed that the difference between bone age and chronological age(BA-CA)was the best approach to identify girls with RP-PP.ConclusionThe incidence of serious endocrine diseases in girls with breast development between age 7-8 years is very low.Nearly half of the girls showed rapid progress in puberty,but majority of girls do not need treatment.Bone age is the useful initial test to identify girls with RP-PP who are much more likely require treatment.