第三代芳香化酶抑制劑治療女孩外周性性早熟的臨床分析
發(fā)布時(shí)間：2018-07-14 20:01
【摘要】：背景:性早熟是指男童在9歲前出現(xiàn)第二性征,女童在8歲前出現(xiàn)第二性征或10歲前月經(jīng)初潮。按照發(fā)病機(jī)理及臨床表現(xiàn)的不同,可以分為中樞性性早熟及外周性性早熟。中樞性性早熟(Central precocious puberty CPP)即下丘腦-垂體-性腺軸提前發(fā)動(dòng)、成熟,從而使內(nèi)、外生殖器發(fā)育和第二性征呈現(xiàn),為促性腺激素釋放激素依賴性性早熟。外周性性早熟(Peripheral precocious puberty PPP)則是由于體內(nèi)性甾體激素水平升高至青春期水平,并無性腺軸的真正發(fā)動(dòng),所以只有第二性征的出現(xiàn),而沒有完整的性發(fā)育程序性的過程。目前主張應(yīng)用第三代芳香化酶抑制劑來曲唑或選擇性雌激素受體調(diào)節(jié)劑他莫昔芬治療,通過抑制雄激素向雌激素的轉(zhuǎn)化而降低雌激素水平,或阻斷雌激素對(duì)相應(yīng)器官的影響,使陰道出血停止、防止骨骺提前閉合導(dǎo)致患兒最終身高受影響。目的:探討第三代芳香化酶抑制劑治療女孩外周性性早熟的療效及安全性方法:選擇于2013年9月至2016年12月就診于我院兒科內(nèi)分泌門診的11名1.2-6.8歲的外周性性早熟女孩,就診癥狀為乳房發(fā)育,陰道出血或分泌物,LH和FSH水平低下,除外分泌雌激素的腫瘤、先天性腎上腺皮質(zhì)增生癥、原發(fā)性甲狀腺功能低下、攝入過多外源性雌激素所致等情況。給予來曲唑片(江蘇省恒瑞醫(yī)藥股份有限公司,國藥準(zhǔn)字H19991001,規(guī)格為每片2.5 mg)口服治療,劑量為1-2mg/m2.d,分別于治療1月、3月后復(fù)查,通過比較治療前后性激素水平、Tanner分期,以及患者、家屬的主觀反映來評(píng)價(jià)來曲唑治療的有效性,若患兒治療期間乳房恢復(fù)正常,陰道出血或分泌物停止則予停藥。治療過程中,密切觀察患兒的一般情況,記錄來曲唑口服過程中出現(xiàn)的不良反應(yīng),以評(píng)估來曲唑治療女孩外周性性早熟的安全性。采用SPSS21.0統(tǒng)計(jì)學(xué)軟件對(duì)所觀察到的結(jié)果及實(shí)驗(yàn)室數(shù)據(jù)行數(shù)據(jù)處理分析。由于外周性性早熟發(fā)病率低,而且缺乏對(duì)照組數(shù)據(jù),所以每個(gè)病例都通過自身對(duì)照行前瞻性研究。結(jié)果:1入組兒童的基本資料本項(xiàng)研究共納入11例女孩,均為非促性腺激素釋放激素依賴性性早熟,發(fā)病年齡在1.2-6.8歲之間(4.6±2.0歲),表現(xiàn)為乳房發(fā)育、陰道出血或分泌物,LH和FSH水平低下,盆腔B超可見卵巢囊腫,5例女孩有骨齡資料,均為骨齡提前,其中2例女孩有顯著高的生長速率標(biāo)準(zhǔn)差。6例女孩有皮膚牛奶咖啡斑,9號(hào)女孩既往有骨折病史,且存在甲狀腺功能亢進(jìn)癥,10號(hào)女孩脛腓骨X片示骨纖維化,且存在甲狀腺功能亢進(jìn)癥。所有女孩均無腎上腺功能亢進(jìn)史,垂體MR檢測未見明顯異常。4名女孩曾接受過達(dá)那唑的治療,1名女孩曾接受過他莫昔芬治療,均在停藥半年到2年半后復(fù)發(fā),再次出現(xiàn)乳房發(fā)育,陰道出血或分泌物。2來曲唑治療1月后2.1基本情況的變化及比較經(jīng)過1個(gè)月的治療,6號(hào)女孩的乳房分期較前下降,其余女孩無明顯變化,除4號(hào)女孩外,所有女孩陰道出血或分泌物均較前減少或停止,2號(hào)、8號(hào)、11號(hào)病人在治療1月后卵巢囊腫消失,其余患兒,除4號(hào)、10號(hào)外卵巢囊腫均較前變小,4號(hào)病人治療1月后乳房較前增大,出血較前增多,盆腔B超示卵巢暗區(qū)較前增大,予停用來曲唑,10號(hào)病人治療1月后無變化,予來曲唑口服劑量加量。2.2盆腔超聲及性激素水平的變化患兒的平均卵巢容積(MOV)、雌二醇(E2)較前顯著下降,卵泡刺激素(FSH)較治療前升高,睪酮(T)、黃體生成素(LH)、子宮容積沒有變化。3來曲唑治療3月后3.1基本情況的變化及比較治療前后體重、Ht-SDS無顯著變化,身高較治療前增長,體質(zhì)指數(shù)(BMI)較治療前降低,經(jīng)過3個(gè)月的治療,6號(hào)、7號(hào)女孩的乳房分期較前下降,其余女孩無明顯變化,所有病例均未再出現(xiàn)陰道出血及分泌物。3.2盆腔超聲及性激素水平的變化6號(hào)、7號(hào)、11號(hào)女孩的MOV、子宮容積及卵巢囊腫均較前減小。1號(hào)女孩的MOV、子宮容積、卵巢囊腫在治療1月后較前降低,但在治療3月后有高于治療前的趨勢。與治療前相比,E2顯著降低(P=0.018),FSH有所升高(P=0.018),T、LH無變化(分別為P=0.735,P=1.0)。結(jié)論:1來曲唑治療外周性性早熟是有效的,可以減少陰道出血的量及頻率,降低雌激素水平,縮小平均卵巢容積,為治療女孩外周性性早熟提供了新的選擇。2來曲唑治療的安全性尚有待進(jìn)一步研究,治療過程中可能出現(xiàn)FSH水平的增高、卵巢囊腫的增大,需定期復(fù)查,除外中樞性性早熟及預(yù)防卵巢囊腫破裂或扭轉(zhuǎn)。3來曲唑治療外周性性早熟的劑量、療程仍需更多樣本及更長時(shí)間的研究來進(jìn)一步明確。
[Abstract]:Background: precocious precocious puberty refers to the second sex sex sign before 9 years of age. The girl has the secondary sex sign before the age of 8 or the menarche before the age of 10. According to the pathogenesis and the clinical manifestation, it can be divided into central precocious puberty and peripheral precocious puberty. Central precocious puberty CPP, the hypothalamus hypophysis - gonadal axis Dynamic and mature, so that the internal and external genitals are developed and the secondary sex is present, the gonadotropin releasing hormone dependent precocious puberty. Peripheral sexual precocious puberty (Peripheral precocious puberty PPP) is due to the level of steroid hormone levels in the body to puberty, and the real launch of the gonadotropin axis, so only the second sex sign appears. There is no complete procedural process of sexual development. Currently, the third generation aromatase inhibitor, trazole or selective estrogen receptor modulator tamoxifen, is used to reduce estrogen level by inhibiting the conversion of androgen to estrogen, or blocking the effect of estrogen on the corresponding organs, stopping the vaginal bleeding and preventing epiphysis. Objective: To explore the effect and safety of third generation aromatase inhibitors in the treatment of peripheral sexual precocious puberty in girls: 11 1.2-6.8 years old peripheral precocious girls aged from September 2013 to December 2016 in the pediatric endocrinology clinic of our hospital were selected for the symptoms of breast development and vagina Bleeding or secretions, low levels of LH and FSH, except for estrogen secreting tumors, congenital adrenocortical hyperplasia, primary hypothyroidism, excessive intake of exogenous estrogen, etc., were given to Letrozol Tablets (Jiangsu Heng Rui medical Limited by Share Ltd, Chinese medicine quasi word H19991001, specification for 2.5 mg per slice), The dose of 1-2mg/m2.d was treated in January and March respectively. The efficacy of letrozole was evaluated by comparing the level of sex hormone before and after treatment, Tanner staging, and the subjective reflection of the family members. In general, the adverse reactions occurring during the oral administration of letrozole were recorded to assess the safety of letrozole in the treatment of peripheral sexual precocious puberty. SPSS21.0 statistics software was used to analyze the observed results and laboratory data. The incidence of peripheral precocious puberty was low and the control group was lack of data. Results: a total of 11 girls were included in the basic data of 1 children, all of which were non gonadotropin releasing hormone dependent precocious puberty, the age of onset was between 1.2-6.8 years (4.6 + 2 years), showing breast development, vaginal bleeding or secretion, low levels of LH and FSH, and pelvic B ultrasound visible eggs. Nesting cysts, 5 girls have bone age data, all of which are early bone age, of which 2 girls have a significant high standard of growth rate,.6 girls have skin milk coffee spots, 9 girls have a history of fracture, hyperthyroidism, X shin and fibula in Girl 10, and hyperthyroidism. All girls have hyperthyroidism. No adrenal hyperfunction history, MR detection of pituitary MR had not been significantly abnormal.4 girls had been treated with dadazol, 1 girls had received tamoxifen treatment, all relapsed after half to 2 and a half years of drug withdrawal, recurrence of breast development, vaginal bleeding or secretion of.2 to cure 2.1 basic changes after the treatment of January, and compared 1 The breast staging of 6 girls declined more than that of the previous month, and the rest of the girls had no obvious changes. Except for girl No. 4, all the girls had vaginal bleeding or discharge more than before. The ovarian cysts disappeared after January, 2, 8 and 11. The remaining children, except 4 and 10, were all less ovarian cysts, and 4 patients were treated for the breast after January. More bleeding than before, pelvic B-ultrasound showed that the dark area of ovary was larger than before, and was given to trazole, and no change in 10 patients after January. The average ovarian volume (MOV), estradiol (E2) decreased significantly, and follicle stimulating hormone (FSH) was higher than that before the treatment in the patients with the oral dose of letrozole plus the changes of.2.2 pelvic ultrasound and sex hormone levels. Testosterone (T), luteinizing hormone (LH), the volume of uterus did not change.3, the changes in the 3.1 basic situation after March and the body weight before and after treatment, Ht-SDS had no significant change, the height was higher than before the treatment, the body mass index (BMI) was lower than before the treatment, after 3 months of treatment, 6, 7 girl's breast staging decreased, the rest of the girls were not clear. There was no recurrence of vaginal bleeding and the changes of.3.2 pelvic ultrasound and sex hormone levels in all cases, 6, 7, and 11 girls' MOV. The uterine volume and ovarian cysts were lower than the MOV, uterine volume and ovarian cysts in January. The ovarian cysts were lower than before in January, but after March, the trend was higher than that before treatment. E2 significantly decreased (P=0.018), FSH increased (P=0.018), T, LH did not change (P=0.735, P=1.0). Conclusion: 1 letrozole is effective in the treatment of peripheral sexual precocious puberty. It can reduce the amount and frequency of vaginal bleeding, reduce the level of estrogen, Suo Xiaoping's ovarian volume, and provide a new selection of.2 for the treatment of peripheral sexual precocious puberty in girls. The safety of letrozole still needs further study. The increase of FSH level and the increase of ovarian cysts in the treatment process should be reviewed regularly, except for central precocious puberty and prevention of rupture of ovarian cysts or reversing the dosage of.3 letrozole in the treatment of peripheral sexual precocious puberty. Step by step.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R725.8
本文編號(hào)：2122791
[Abstract]:Background: precocious precocious puberty refers to the second sex sex sign before 9 years of age. The girl has the secondary sex sign before the age of 8 or the menarche before the age of 10. According to the pathogenesis and the clinical manifestation, it can be divided into central precocious puberty and peripheral precocious puberty. Central precocious puberty CPP, the hypothalamus hypophysis - gonadal axis Dynamic and mature, so that the internal and external genitals are developed and the secondary sex is present, the gonadotropin releasing hormone dependent precocious puberty. Peripheral sexual precocious puberty (Peripheral precocious puberty PPP) is due to the level of steroid hormone levels in the body to puberty, and the real launch of the gonadotropin axis, so only the second sex sign appears. There is no complete procedural process of sexual development. Currently, the third generation aromatase inhibitor, trazole or selective estrogen receptor modulator tamoxifen, is used to reduce estrogen level by inhibiting the conversion of androgen to estrogen, or blocking the effect of estrogen on the corresponding organs, stopping the vaginal bleeding and preventing epiphysis. Objective: To explore the effect and safety of third generation aromatase inhibitors in the treatment of peripheral sexual precocious puberty in girls: 11 1.2-6.8 years old peripheral precocious girls aged from September 2013 to December 2016 in the pediatric endocrinology clinic of our hospital were selected for the symptoms of breast development and vagina Bleeding or secretions, low levels of LH and FSH, except for estrogen secreting tumors, congenital adrenocortical hyperplasia, primary hypothyroidism, excessive intake of exogenous estrogen, etc., were given to Letrozol Tablets (Jiangsu Heng Rui medical Limited by Share Ltd, Chinese medicine quasi word H19991001, specification for 2.5 mg per slice), The dose of 1-2mg/m2.d was treated in January and March respectively. The efficacy of letrozole was evaluated by comparing the level of sex hormone before and after treatment, Tanner staging, and the subjective reflection of the family members. In general, the adverse reactions occurring during the oral administration of letrozole were recorded to assess the safety of letrozole in the treatment of peripheral sexual precocious puberty. SPSS21.0 statistics software was used to analyze the observed results and laboratory data. The incidence of peripheral precocious puberty was low and the control group was lack of data. Results: a total of 11 girls were included in the basic data of 1 children, all of which were non gonadotropin releasing hormone dependent precocious puberty, the age of onset was between 1.2-6.8 years (4.6 + 2 years), showing breast development, vaginal bleeding or secretion, low levels of LH and FSH, and pelvic B ultrasound visible eggs. Nesting cysts, 5 girls have bone age data, all of which are early bone age, of which 2 girls have a significant high standard of growth rate,.6 girls have skin milk coffee spots, 9 girls have a history of fracture, hyperthyroidism, X shin and fibula in Girl 10, and hyperthyroidism. All girls have hyperthyroidism. No adrenal hyperfunction history, MR detection of pituitary MR had not been significantly abnormal.4 girls had been treated with dadazol, 1 girls had received tamoxifen treatment, all relapsed after half to 2 and a half years of drug withdrawal, recurrence of breast development, vaginal bleeding or secretion of.2 to cure 2.1 basic changes after the treatment of January, and compared 1 The breast staging of 6 girls declined more than that of the previous month, and the rest of the girls had no obvious changes. Except for girl No. 4, all the girls had vaginal bleeding or discharge more than before. The ovarian cysts disappeared after January, 2, 8 and 11. The remaining children, except 4 and 10, were all less ovarian cysts, and 4 patients were treated for the breast after January. More bleeding than before, pelvic B-ultrasound showed that the dark area of ovary was larger than before, and was given to trazole, and no change in 10 patients after January. The average ovarian volume (MOV), estradiol (E2) decreased significantly, and follicle stimulating hormone (FSH) was higher than that before the treatment in the patients with the oral dose of letrozole plus the changes of.2.2 pelvic ultrasound and sex hormone levels. Testosterone (T), luteinizing hormone (LH), the volume of uterus did not change.3, the changes in the 3.1 basic situation after March and the body weight before and after treatment, Ht-SDS had no significant change, the height was higher than before the treatment, the body mass index (BMI) was lower than before the treatment, after 3 months of treatment, 6, 7 girl's breast staging decreased, the rest of the girls were not clear. There was no recurrence of vaginal bleeding and the changes of.3.2 pelvic ultrasound and sex hormone levels in all cases, 6, 7, and 11 girls' MOV. The uterine volume and ovarian cysts were lower than the MOV, uterine volume and ovarian cysts in January. The ovarian cysts were lower than before in January, but after March, the trend was higher than that before treatment. E2 significantly decreased (P=0.018), FSH increased (P=0.018), T, LH did not change (P=0.735, P=1.0). Conclusion: 1 letrozole is effective in the treatment of peripheral sexual precocious puberty. It can reduce the amount and frequency of vaginal bleeding, reduce the level of estrogen, Suo Xiaoping's ovarian volume, and provide a new selection of.2 for the treatment of peripheral sexual precocious puberty in girls. The safety of letrozole still needs further study. The increase of FSH level and the increase of ovarian cysts in the treatment process should be reviewed regularly, except for central precocious puberty and prevention of rupture of ovarian cysts or reversing the dosage of.3 letrozole in the treatment of peripheral sexual precocious puberty. Step by step.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R725.8
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