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Predictive factors for pituitary response to pulsatile gnrh therapy in patients with congenital hypogonadotropic hypogonadism

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Asian Journal of Andrology 2018年第4期20卷 319-323页

作者： Jiang-Feng Mao Xi Wang Jun-Jie Zheng Zhao-Xiang Liu Hong-Li Xu Bing-Kun Huang Min Nie Xue-Yan Wu Department of Endocrinology Peking Union Medical College Hospital Key Laboratory of Endocrinology Ministry of Health Beijing 100730 China

pulsatile gonadotropin-releasing hormone （gnrh） may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism （CHH） by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile gnrh therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile gnrh therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile gnrh therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone （LH） response subgroups according to their LH level （LH 〈2 IU 1-1 or LH P_2 IU 1-1） 1 month into pulsatile gnrh therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after gnrh therapy. Among all patients, LH increased from 0.4±0.5 IUI^-1 to 7.5±4.4 IUI^-1 and follicle-stimulating hormone （FSH） increased from 1.1±0.9 IUI^-1 to 8.8±5.3 IU 1-1. A Cox regression analysis showed that basal testosterone level （6 = 0.252, P = 0.029） and triptorelin-stimulated FSH60min（13 = 0.518, P = 0.01） were two favorable predictors for pituitary response to gnrh therapy. Nine patients （9/82, 11.0%） with low LH response to gnrh therapy were classified into the poor LH response subgroup. After pulsatile gnrh therapy, total serum testosterone level was 39± 28 ng dl^-1 versus 248±158 ng d1^-1 （P=0.001）, and testicular size was 4.0±3.1 ml versus 7.9±4.5 ml （P= 0.005） in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH60min. and basal total serum testosterone are favorable predictors of pituitary LH response to gnrh therapy.

关键词： congenital hypogonadotropic hypogonadism pulsatile gnrh therapy treatment

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pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism

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Asian Journal of Andrology 2017年第6期19卷 680-685页

作者： Jiang-Feng Mao Zhao-Xiang Liu Min Nie Xi Wang Hong-Li Xu Bing-Kun Huang Jun-Jie Zheng Le Min Ursula Brigitte Kaiser Xue-Yan Wu Department of Endocrinology Peking Union Medical College Hospital Key Laboratory of Endocrinology Ministry of Health Beijing 100730 China Internal Department Division of Endocrinology Diabetes and Hypertension Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA.

Both pulsatile gonadotropin-releasing hormone （gnrh） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile gnrh and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the gnrh group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the gnrh group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the gnrh group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the gnrh group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the gnrh group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the gnrh group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the gnrh group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile gnrh therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.

关键词： combined gonadotropin therapy congenital hypogonadotropic hypogonadism pulsatile gnrh therapy spermatogenesis

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