Clinical Analysis Of The Treatment In Girls With Peripheral Precocious Puberty Using Third Generation Aromatase Inhibitors

Background:Ovarian cyst,McCune-Albright syndrome(MAS)are the common causes of peripheral precocious puberty(PPP)in girls.Ovarian cyst estrogen secreting,causes breast development,vaginal bleeding or discharge,and suppressed levels of LH and FSH,thus girls present with non gonadotropin dependent precocious puberty.The disease is mainly symptomatic treated.By reducing the concentration of estrogen or blocking estrogen effects on target organs,we can stop the bleeding and prevent epiphyseal closure in advance which will influence the adult height.There are two approachs to treat PPP:The third generation aromatase inhibitors(AIs)such as letrozole and anastrozole,and selective estrogen receptor modulators,such as tamoxifen.Objective:To assess the efficacy and safety of the treatment in girls with peripheral precocious puberty using the third generation aromatase inhibitors.Methods:The subjects were 11 girls aged 1.2-6.8 years old with peripheral precocious puberty which were referred to Pediatrics Endocrinology from 2013 September to 2016 December.They presented with the similar symptoms,such as breast development,vaginal bleeding or discharge,and suppressed levels of LH and FSH.Estrogen secreting tumors,congenital adrenal hyperplasia,primary hypothyroidism,caused by excessive intake of exogenous estrogen were excluded.Subjects were evaluated at baseline and 1-month and 3-months after treatment with letrozole 1.0-2.0mg/m2.d.Sex hormone levels,Tanner stage,and the subjective appraisal of patient and parents before and after the treatment were compared to evaluate the effectiveness of letrozole treatment.At the same time,Patients’ general conditions were closely observed and adverse adverse effects were recorded in order to evaluate the safety of AIs.All the observation data and laboratory tests data were processed by SPSS21.0 statistical software.Because of the low incidence of PPP,and lack of data in the control group,the study is a prospective study with each case served as her own control.Results: 1 The basic data of enrolled girlsThe subjects were 11 girls with peripheral precocious puberty who initially presented with breast development,vaginal bleeding or discharge,suppressed levels of LH and FSH,and ovarian cyst at ages 1.2-6.8 years old.All the girls who had bone age(BA)data had advanced BA and 2 of them had significantly increased growth rate SD scores.Six girls had café-au-lait pigment.Patient 9 had a sustained fracture on the left tibia and also suffered hyperthyroidism.Patient 10 had a fibrous dysplasia in tibiofibula which was certified by X-ray,she also suffered hyperthyroidism.Four girls had been treated with danazol and one girl tamoxifen and all relapsed at half a year to 2.5years after drug withdrawal.2 Letrozole treatment for 1 month 2.1 The basic data changes and comparisons after letrozole treatment for 1month.Patient 6 had a decrease in breast stage.Except for patient 4,all girls had no or less vaginal bleeding or discharge.Patient 2,8 and 11’s ovarian cysts disapeared after 1-month therapy and except for patient 4 and patient 10,other six girls’ ovarian cysts minified compared with pre-treatment.Patient 4 had greater breast,vaginal more bleeding and larger ovarian cyst after 1-month treatment,so we stoped the therapy of letrozole.Patient 10 had no change after treatment,so we gave her a higher dose of letrozole.2.2 The change of plevic ultrasound and the change of sex hormone levelsAfter 1-month treatment,the mean ovarian volume(MOV)and E2 were significantly decreased.T,LH,uterine volume had no change.While,FSH increased when compared with pre-treatment.3 Letrozole treatment for 3 months 3.1 The basic data changes and comparisons after letrozole treatment for 3months.Height were increased and BMI were decreased after 3 months treatment of letrozole.There were no changes in weight and Ht-SDS after 3 months treatment of letrozole.Patient 6 and 7 had decrease in breast stage.All girls had no vaginal bleeding or discharge.3.2 The change of plevic ultrasound and sex hormone levelsPatient 6 and 7 had a decrease in MOV,and ovrian cyst.There had a decrease in MOV,uterine volume and ovrian cystin patient 1 after 1 month treatment,but it tended to increase after 3 months therapy.E2 were significantly decreased.T,LH,had no change.While,FSH increased when compared with pre-treatment.Conclusions:1 The study suggests that letrozole is a effective therapy in girls with PPP.It can reduce the amount and frequency of vaginal bleeding,lower the estrogen levels and reduce the average ovarian volume.Letrozole offers an alternative therapy for girls with PPP.2 It remains to study whether letrozole treatment is safety.The present study indicates that FSH levels increased,ovarian enlargement may occur during therapy.Patients should be observed regularly to rule out the central precocious puberty and ovarian cyst rupture or reverse.3 A greater number of subjects are needed before the doses and periods of letrozole treatment be confirmed.