GnRH泵治疗女性特发性低促性腺激素性性腺功能减退症的有效性和安全性

Effectiveness and safety of pulsatile GnRH pump therapy on female patients with IHH

目的 分析和总结应用促性腺激素释放激素（GnRH）戈那瑞林脉冲式皮下注射泵治疗女性特发性低促性腺激素性性腺功能减退症（IHH）患者经验,以提高对女性IHH的治疗水平.方法 对2013年1月—2015年3月在北京协和医院内分泌科门诊治疗的5例女性IHH患者进行GnRH泵（10 μg/90 min）皮下脉冲输注治疗,并且随诊≥12周.观察患者促性腺激素、性激素水平变化及月经来潮情况.本研究通过北京协和医院伦理审查委员会批准.结果 女性IHH患者用泵治疗前黄体生成素（LH）为（2.2±2.0）U/L,卵泡刺激素（FSH）为（3.7±2.7） U/L,雌二醇（58±13） pmol/L;用泵1周后LH（5.4±2.5） U/L,雌二醇（260±97） pmol/L,均较治疗前显著升高（P =0.028、0.011）,FSH（6.3±1.0）U/L,也较治疗前升高,但差异无统计学意义（P=0.162）.有4例患者在治疗后35 ～ 55 d月经来潮,随后均有规律月经周期,其中长期随诊的2例患者自然妊娠.另1例患者在治疗20周后仍无月经来潮,遂调整GnRH脉冲间隔,1个月后月经来潮.结论 GnRH泵治疗对女性IHH患者有效.恒定脉冲间隔的GnRH泵治疗方案,可使多数女性IHH患者月经来潮甚至自然妊娠.对疗效不佳者,应调整GnRH脉冲间隔,模拟女性生理性周期性性激素变化,可能促进月经来潮.

Objective To investigate the therapeutic effect of pulsatile GnRH （gonadorelin） pump on female patients with idiopathic hypogonadotropic hypogonadism （IHH）.Methods In this retrospective study,five female IHH patients were recruited.Patients were treated with pulsatile gonadorelin （10 μg per 90 min） via a pump for at least 12 weeks.Serum gonadotropins and sex steroid levels were measured,and menses were recorded.Results After one-week treatment,luteinizing hormone （LH） level increased from （2.2 ± 2.0） U/L to （5.4 ± 2.5） U/L （P =0.028）,follicle-stimulating hormone （FSH） level increased from （3.7 ± 2.7） U/L to （6.3 ± 1.0） U/L （P =0.162）,and estradiol （E2） level increased from （58 ± 13） pmol/L to （260 ± 97） pmol/L（P =0.011）.Menstrual bleeding was observed in 4 patients after starting treatment for 35-55 days and two natural pregnancies were reported.No menstrual bleeding was reported in another patient.The frequency of pulsatile GnRH had to be adjusted according to endogenous GnRH secretion during the follicular phase of normal women and regular menses were induced.Conclusions Pulsatile GnRH is effective in treating female IHH.A constant frequency of pulsatile GnRH is suitable for most of IHH patients.However,for those who failed to produce regular menses,adjusting pulsatile frequency to imitate the physiological rhythm of GnRH may be an alternative option.