The Time Effectiveness Of Gonadotropin Replacement Therapy For Improving The Sencondary Sexual Characteristics And Sex Hormone Levels In Multiple Pituitary Hormone Deficiency

1. Background and ObjectiveMultiple pituitary hormone deficiency (MPHD) is the decreased secretion of growth hormone and one or more of the other pituitary hormones from which gonadotropin is the most common deficiency hormone. There is still no clinical standardized criteria for the treatment of hypogonadism. At present, the frequently used treatment is to give sex steroid replacement therapy improving the secondary sexual characteristics at adolescence and start gonadotropin replacement therapy when fertility is demanded. Human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) are usually used. Sex steroid replacement therapie has no good to fertility, and even impairs fertility and target height. The purpose of this study is to observe the gonadal development of MPHD with different start times of treatments (e.g. at adolescence and post adolescence).2. Objects and MethodsObjects60MPHD children with gonadotropin deficiency were enrolled in this study, at the outpatients pediatric endocrine clinic of**hospital from2007.02to2013.02. They were divided into2groups according to the age of the start time of treatment:1. Group of adolescence, in this group,26boys aged greater than or equal to12years old and less than16years old,3girls aged range from11to14years old, a total of29cases;2. Group of post adolescence,26boys aged greater than or equal to16years old and5girls eldly than14years old with a total of31cases.MethodsAll the boys were given hCG and hMG, and all the girls given hMG, im, every three days with hCG1000～2000u and hMG75u every time,3-month as a course of treatment. Different hormone replacement therapies were given to keep target hormones and clinical manifestations normal. All the patients came back for examination every three months, and were followed up for at least6months, of which43cases followed for9months and8cases for36months.Observed IndicatorsSerum hormone levels(follicle-stimulating hormone FSH, luteinizing hormone LH, estradiol E2, testosterone To), physical examination(height H, breast development stage, pubic hair stage, penis length and perimeter, testicular volume), imaging examinations (B-mode ultrasound of uterine, ovarian, testicular; bone age BA, hypothalamic-pituitary MRI scans) and other relevant tests (such as semen analysis) were taken at the beginning and3months,6months after treatment.3. Results(1)Group of adolescence:The basic value FSH0.52±0.53mIU/ml LH0.14±0.27mlU/ml E23.8±8.2pg/ml, To0.09±0.21ng/ml;3months after treatment FSH, E2, To were significantly higher compared to the basic value(P<0.01, P<0.001, P<0.01, respectively),6months after treatment FSH, LH, E2, To were all significantly increased, FSH3.49±3.57mIU/ml (P<0.01), LH2.11±3.2mIU/ml (P<0.01), E221.77±13.44pg/ml (P<0.001), To3.97±2.71ng/ml (P<0.001). The increased value of FSH, LH, E2, and To between3months and6months after treatment has no significant difference (P>0.05). All patients were at Tanner stage I (T Ⅰ), and5person enter T Ⅱ and one T Ⅲ. The length and perimeter of penis were significantly increased (P<0.001), testicular volume increased to5.64±2.38ml from1.18±0.91ml (P<0.001), the effective rate was96.2%. B-mode ultrasound showed girls’ uterine volume increased and the ovarian follicle.(2) Group of post adolescence:The basic value FSH0.95±0.82mIU/ml, E2the LH0.21±0.37mIU/ml, E29.85±12.07pg/ml, To0.89±1.83ng/ml;3months after treatment E2, To significantly higher than that of basic value(P<0.001, P<0.01, respectively),6months after treatment FSH, E2and To significantly increased, FSH2.11±1.85mIU/ml (P<0.01), LH0.25±0.56mIU/ml (P>0.5), E228.17±23.06pg/ml (P<0.01), To3.28±3.38ng/ml (P<0.01). The increased value of LH, E2, and To between3months and6months after treatment has no significant difference (P>0.05). FSH increased significantly (P<0.05). After6months treatment,7out of9moved from TⅡ to T Ⅲ,11out of22to TⅡ. The penis length and perimeter were significantly increased (P<0.001), testicular volume increased from4.73±2.16ml to 2.40±1.75ml (P<0.001),76.9%efficiency. In this group, there were two girls of menarche,9men had nocturnal emission and1person have been married and has a son.(3) Between the two groups:The FSH and LH increased value of adolescent group of both3months and6months after treatment were significantly higher than that of post adolescent group (P<0.05). The E2and To increased value has no significant difference between the two groups (P>0.1), such as the growth value of penis length and girth. Testicular volume of adolescent group increased significantly (P<0.01) compared with the post adolescent group.(4) Patients with different pituitary hormone deficiency were distributed with no difference in the two groups (P>0.1). When other hormones level had been maintained normal, the sex hormone level and secondary sexual characteristics changes has no significant difference (P>0.05) between MPHD children with different pituitary hormones deficiency.(5) The Ht and BA of adolescent group was less than that of post adolescent group neither before nor after treatment, while its PAH is always higher (P<0.05). The increased value of BA had no significant difference (P>0.1) between those two sets, though the adolescent group has a bigger Ht increased value (P<0.01).(6) With or without the PSIS, the basic value, secondary sexual characteristics and the therapeutic had no significant difference (P>0.05), a similar result came out in the presence or absence of dystocia history.(7) The increases of LH and testicular volume were negatively correlated with the start time of treatment (for LH, R>0.3, P<0.05;for testicular volume R>0.4, P<0.01).4. Conclusion(1) Start gonadotropin replacement therapy both of adolescence and post adolescence can improve secondary sexual characteristics and sex hormone levels, and begin the therapy at adolescence more beneficial to the recovery of gonadal function. The eld the age of the start of the treatment, the worse the effect.(2) Begin the therapy at adolescence doesn’t damage the PAH, it’s conducive for target height. (3) When other hormone level had been maintained normal, the sex hormone level and secondary sexual characteristics changes has no significant difference between those with different pituitary hormones deficiency MPHD children.