女性神经性厌食症患者的瘦素水平及其在生殖功能调节中的作用

Leptin level and its role in the regulation of reproductive function in females with anorexia nervosa

目的研究青年女性神经性厌食症(AN)患者血清瘦素水平与下丘脑-垂体-性腺(HPG)轴功能改变的相互关系。方法测定16例新诊断的女性神经性厌食症患者的身体组成成分、性激素、瘦素等水平,分析其与生殖功能间的相关性。其中4例患者接受了24 h血清瘦素节律的研究。经18周综合治疗后,再次评价AN患者身体组成成分、血清瘦素、性激素水平,并分析其与月经周期恢复的相互关系。另设26例年龄匹配的健康女性为正常对照。结果(1)16例AN患者均发生闭经,13例为继发性闭经,3例为原发性闭经,14例患者LH低于正常参考范围的下限(1．5 U／L),12例患者FSH低于正常参考范围的下限(4．6 U／L),其中5例患者FSH和LH低于0．01 U／L。(2)治疗前16例AN患者体重指数(BMI)、体脂、血清瘦素水平较正常对照组显著降低[分别为(13．6±3．5)kg／m2 vs(20．2±2．2)kg／m2;(16．14±1．99)％vs (23．20±2．64)％;(1．21±0．36)μg/L vs(7．70±4．15)μg／L,均P<0．01];AN组瘦素水平与BMI、体脂含量呈正相关(分别为r=0．526,P=0．015;r=0．628,P=0．003),调整BMI和体脂的影响后,AN组的血清瘦素水平仍显著低于正常对照组(P<0．01)。血清瘦素水平与年龄、体重、FSH、LH未见相关性。(3)24 h血清瘦素节律提示AN患者瘦素分泌曲线较正常人低平。(4)经18周治疗,11例患者体重上升>15％,瘦素水平较未治疗时显著上升(P<0．01),16例患者月经周期均未恢复。结论女性AN患者血瘦素水平较正常人群显著降低,并保持与BMI、体脂含量的相关性,经治疗后瘦素水平上升,但月经周期迟迟不能恢复。AN人群性腺功能低下可能与血瘦素水平的降低存在一定关系。

Objective To explore the relationship between serum leptin level and the hypothalamuspituitary-gonad （HPG） axis in female adolescents with anorexia nervosa （AN）. Methods Sixteen newly diagnosed female adolescents with AN in Shanghai and Zhejiang province were investigated, and their serum leptin, FSH, LH and body composition were measured before and after 18 weeks treatment, and their menorrhea cycles were observed. The rhythm of 24 h serum leptin secretion was studied in 4 patients with AN. Twenty-six, healthy females with normal weight and without contraceptive medication were studied as controls. Results （ 1 ） All of 16 patients had amenorrhea, 3 primary amenorrhea and 13 secondary amenorrhea. At admission LH in 14 patients and FSH in 12 patients were below the low limit of the normal reference range （1.5 U/L and 4.6 U/L respectively） , and among them 5 patiend had both 〈 0.01 U/L of FSH and LH. （2） At admission body mass index （BMI） , body fat and serum leptin level were significantly lower in patients with AN as compared with those in normal controls [（13.6±3.5）kg/m^2 vs （20.2±2.2）kg/m^2, P〈0.01; （16.14±1.99）% vs （23.20±2.64）%; （1.21 ± 0.36）μg,/L vs （7.70 ±4.15）μg,/L, all P 〈0.01 ]. The leptin levels were positively correlated with the BMI and body fat （ r =0.526, P = 0. 015 ; r = 0. 628, P = 0. 003）. After adjustment for BMI and body fat, the patients with AN still showed lower level of leptin than the normal controls （ P 〈0.01 ）. No correlationship between age, weight, FSH, LH and leptin levels was found. （3） The rhythm of 24 h serum leptin secretion indicated a relatively fiat curve in patients with AN. （4） After 18 weeks treatment, 11 patients showed 〉 15% weight gain and significantly increased serum leptin level （ P 〈 0.01 ）. None of the individuals with AN had resumption of menses. Conclusion In AN population, the leptin level, which is significantly lower as compared with the normal controls, correlates with BMI and body fat. The increase in leptin after weight gain occurs prior to resumption of mense. Leptin plays an important role in HPG axis activation in the resumption of reproductive function. Leptin alone is not sufficient in inducing gonadotropin secretion, but may provide a permissive signal for HPG axis activation.