下丘脑性性腺功能减退症的临床研究

发布时间：2018-03-05 19:43

本文选题：低促性素性腺功能减退症　切入点：hCG/FSH联合治疗　出处：《上海交通大学》2014年博士论文　论文类型：学位论文

【摘要】：【目的】观察hCG/FSH联合治疗和戈那瑞林脉冲治疗是否能有效促进男性低促性素性腺功能减退症（idiopathic hypogonadotropic hypogonadism, IHH）患者精子生成、第二性征发育。探究戈那瑞林脉冲治疗和hCG/FSH联合治疗相比，对诱导男性患者精子生成、第二性征发育是否具有优势性。【方法】纳入上海交通大学医学院附属瑞金医院内分泌代谢科收治的16例男性IHH患者，使用hCG/FSH联合治疗（hCG2000IU，biw，im6个月后，加用FSH75IU，tiw，im）。同期纳入90例男性IHH患者，使用戈那瑞林脉冲治疗，剂量为10μg-15μg/90min皮下注射。观察治疗后患者激素水平、第二性征发育、精子生成和配偶自然受孕情况。 48例确诊为IHH男性患者，按1:2人数入组。双促治疗组16人，使用hCG/FSH联合治疗；脉冲治疗组32人，使用戈那瑞林脉冲治疗。比较两组患者治疗18个月后在激素水平、第二性征发育、精子生成、配偶自然受孕等方面是否具有差异。【结果】 hCG/FSH联合治疗后患者T上升至正常范围，第二性征发育，治疗18个月后14名患者中11名有精子生成，精子密度中位数为3.03×106/ml。戈那瑞林脉冲治疗后患者LH、FSH出现脉冲式波动，T水平上升，第二性征发育。治疗1年时生精率为60.61%，精子密度中位数为2.75×106/ml；2年时生精率达76.47%，精子密度中位数为14.04×106/ml。患者首次精子生成时间、首次精子密度达到20×106/ml时间均与睾丸初始体积有关（r=-0.448，P=0.001；r=-0.600，P=0.001）。治疗12、18个月时有精子生成和无精子生成患者的初始睾丸体积有统计学差异。9名已婚患者中8名配偶自然受孕，已婚怀孕率为88.89%，平均诱导怀孕时间为（15.38±1.92）月。 hCG/FSH联合治疗与脉冲治疗的疗效比较研究显示，患者的睾酮水平、第二性征发育、精子密度和诱导精子生成所需时间两组无统计学差异。治疗18个月后78.6%双促组和77.0%脉冲组患者精子最大密度1×106/ml。脉冲组患者精子密度较双促组增高(21.57×106/ml vs3.03×106/ml, P=0.11)。双促组中1名患者已婚，其配偶成功自然受孕；脉冲组中8名患者已婚，其中7名患者配偶自然受孕，已婚怀孕率为87.5%。【结论】 hCG/FSH联合治疗和戈那瑞林脉冲治疗均能诱导男性IHH患者第二性征发育、精子生成，使配偶自然受孕，是安全、有效促进生育能力的治疗方法。戈那瑞林脉冲治疗诱导男性IHH患者精子生成所需时间与初始睾丸体积有关，睾丸体积越大，诱导精子生成所需时间越短。两种治疗方法对诱导男性IHH患者精子生成速度、最终精子密度以及第二性征发育无明显差别，可根据患者自身需求选择治疗方案。脉冲治疗因治疗后精子密度相对更高，对部分促性腺激素治疗效果不佳患者有效，且耐受性、依从性更好，与hCG/FSH联合治疗相比仍具有优势性。
[Abstract]:[purpose]. To observe whether the combination of hCG/FSH and gonadotropin pulse therapy can effectively promote the spermatogenesis and the development of secondary sexual characteristics in patients with idiopathic hypogonadotropic hypogonadism (IHHH), and to explore the comparison between gonarelin pulse therapy and hCG/FSH combined therapy. Whether secondary sexual development is dominant in inducing spermatogenesis in male patients. [methods]. Sixteen male IHH patients admitted to the Department of Endocrinology and Metabolism of Ruijin Hospital affiliated to Shanghai Jiaotong University were treated with hCG/FSH combined with hCG/FSH for 6 months. 10 渭 g-15 渭 g / 90 min subcutaneous injection was used to observe the hormone level, secondary sexual development, spermatogenesis and natural conception of the spouse after treatment. 48 male patients diagnosed as IHH were enrolled in the group according to 1: 2, 16 patients in the double promoting treatment group were treated with hCG/FSH combined therapy, and 32 patients in the pulse treatment group were treated with gonarelin pulse therapy. The hormone levels in the two groups were compared after 18 months of treatment. There are differences in secondary sexual development, spermatogenesis, and natural conception of spouses. [results]. After 18 months of treatment, 11 of the 14 patients had spermatogenesis, the median sperm density was 3.03 脳 10 ~ 6 / ml 路L ~ (3) 3 脳 10 ~ (-6) ml. The spermatogenesis rate was 60.61%, the median sperm density was 2.75 脳 10 6 / ml, the spermatogenic rate was 76.47% and the median sperm density was 14.04 脳 10 6 / ml at 2 years after treatment. The initial sperm density of 20 脳 10 6 / ml was related to the initial testicular volume. The initial testicular volume was significantly different between the patients with spermatogenesis and azoospermia at 12,18 months after treatment. The average pregnancy induction time was 15.38 卤1.92 months. A comparative study of the effects of hCG/FSH combination therapy and pulse therapy showed that testosterone levels, secondary sexual development, There was no significant difference between the two groups in sperm density and the time required to induce spermatogenesis. After 18 months of treatment, the maximum sperm density of the 78.6% and 77.0% pulse groups was 1 脳 10 6 / ml. The sperm density of the pulse group was increased by 21.57 脳 10 6 / ml vs3.03 脳 10 6 / ml, P < 0. 11%. In the pulse group, 8 patients were married, 7 of them were naturally pregnant, and the married pregnancy rate was 87.5%. [conclusion]. The combination of hCG/FSH therapy and ganarelin pulse therapy can induce secondary sexual development and spermatogenesis in male patients with IHH. It is safe for spouses to conceive naturally. The duration of sperm production in male patients with IHH is related to the initial testicular volume. The larger the testis volume, the shorter the time required to induce spermatogenesis. There was no significant difference in the rate of sperm production, the final sperm density and the development of secondary sexual characteristics in male patients with IHH, but they could be selected according to the needs of the patients. It is effective in some patients with poor gonadotropin treatment and has better tolerance and compliance. It is still superior to hCG/FSH combined therapy.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R711.6

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