男性精神分裂症患者服用氯丙嗪、利培酮及喹硫平影响下丘脑-垂体-性腺轴及性功能的比较

Comparison of the effects of chlorpromazine, risperidone and quetiapine on hypothalamic-pituitary-gonadal axis and sexual function in male patients with schizophrenia

目的:抗精神病药物引起的性功能障碍可能与下丘脑-垂体-性腺轴激素水平变化有关。探讨喹硫平、利培酮及氯丙嗪对男性精神分裂症患者下丘脑-垂体-性腺轴激素水平及性功能影响的差异。方法:选择2003-10/2004-10在南京医科大学附属脑科医院住院的精神分裂症患者75例,随机分为喹硫平组、利培酮组及氯丙嗪组,每组25例,各组患者在年龄、文化程度、病程、经济状况、夫妻关系及基线阳性与阴性症状量表评分等方面基线值均无明显差异。患者法定监护人知情同意。喹硫平组、利培酮组和氯丙嗪组分别予以喹硫平(200mg/片)、利培酮(1mg/片)和氯丙嗪(25mg/片)进行干预。应用放免法检测各组患者治疗前、治疗后4周及8周血清促卵泡素、黄体生成素、催乳素、睾酮水平。治疗前由配偶提供患者基线性功能资料,待患者精神症状缓解后可进一步完善评估。利用自制男性性功能量表评估疗前、治疗后8,12及16周的性功能状况(量表分为性欲、性唤起、性高潮及性满意度4项因子分,性功能总体因子分为上述4项分值总和)。结果:进入结果分析氯丙嗪组、利培酮组及喹硫平组分别为17,19和19例。①血清催乳素水平:氯丙嗪组治疗8周后显著高于基线值(F=3.120,P=0.05);利培酮组在治疗4周及8周后均显著高于基线值(F=23.770,P<0.01);喹硫平组在治疗4周及8周后与基线值差异均无显著性意义(P>0.05)。②血清睾酮及黄体生成素水平:利培酮组在治疗8周后显著低于基线值(F=2.560,8.340,P<0.05～0.01);喹硫平组在治疗4周及8周后与基线值差异均无显著性意义(P>0.05)。③性欲减退发生率:喹硫平组在入组8周后显著低于氯丙嗪组及利培酮组犤21.1%,58.8%,63.2%,(F=5.386,6.909,P<0.05)犦。④性唤起困难发生率:喹硫平在入组后的8,12及16周显著低于氯丙嗪组犤(21.1%,21.1%,15.8%),(64.7%,70.6%,70.6%),(F=7.034,8.916,11.085,P<0.05～0.01)犦,在第8及16周显著低于利培酮组犤63.2%,57.9%,(F=6.909,7.238,P<0.05)犦。结论:利培酮和氯丙嗪均能引起较明显的催乳素水平升高,对性欲及性唤起也有不同程度的影响。服用利培酮后,还可能出现黄体生成素及睾酮水平下降。而喹硫平对血清催乳素水平及性功能的影响较小。

AIM： Sexual disturbance caused hy antipsychotic drugs may be associated with the changes of hormone level of hypothalamic-pituitary-gonadal axis.The study was designed to investigate the differences of the effects of quetiapine, risperidone and chlorpromazine on the hormone level of hypothalamic-pituitary-gonadal axis and sexual function in male patients with schizophrenia.METHODS： Seventy-five patients with schizophrenia, who were hospitalized in the Brain Hospital affiliated to Nanjing Medical University between October 2003 and October 2004, were randomly divided into quetiapine group （n=25）. risperidone group （n=25） and chlopromazine group （n=25）,and there were no obvious differences in age. educational background, disease course, economic status, relationship between husband and wife, and baseline score of positive and negative syndrome scale among the groups.All the patients participated in this study with the permission of their legal guardians, and they were treated with quetiapine （200 mg per tablet）,risperidone （1 mg per tablet） and chlorpromazine （25mg per tablet） respectively. The serum levels of follicle-stimulating hormone, luteinizing hormone, prolactin and testosteone of patients in each group were determined with radioimmunoassay before treatment and 4 and 8 weeks after treatment. The baseline data of the patients＇ sexual function were provided hy their spouse before treatment, anti then further consummated and evaluated after their psychiatric symptoms were relieved, Before treatment and 8, 12 and 16 weeks after treatment, the conditions of sexual function were assessed with the self-designed male sexual function scale （including scores of 4 items of sexuality, sexual arousal, sexual orgasm and sexual satisfactory degree, and the total lector score of sexual function was the sum-up of the above 4 factor scores）.RESULTS： There were 17, 19 and 19 cases involved in the analysis of results in the quetiapine group, risperidone group and chlorpromazine group respectively.① Serum level of prolactin： It was significantly higher in the chlorpromazine group 8 weeks after treatment than the baseline level （F=3.120, P =0.05）; It was significantly higher in the risperidone 4 and 8 weeks after treatment than the baseline level （F=23.770, P 〈 0.01）;There were insignificant differences in the quetiapine group 4 and 8 weeks after treatment as compared with the baseline level （P 〉 0.05）, ②Serum levels of luteinizing hormone and testosteone; Those were significantly lower in the risperidone group 8 weeks after treatment than the baseline level （F=2.560, 8.340, P 〈 0.05 to 0.01）; There were insignificant differences in the quetiapine group 4 aud 8 weeks after treatment as compared with the haseline level （P 〉 0.05）. ③ The occurrence rate of hyposexuality； Eight weeks after entering the groups, it was significantly lower in the quetiapine group than in the chlorpromazine group and risperidone group [21.1%, 58.8%, 63.2%. （F=5.386, 6,909, P 〈 0.05）],④ The occurrence rate of difficulty in sexual arousal： It was significantly lower in the quetiapine group than inn the chlorpromazine group 8,12 and 16 weeks after entering the groups [（21,1%,21.1%,15.8%）, （64.7%,70.6%,70.6%）, （F=7.034, 8.916. 11.085. P 〈 0.05 to 0.01）]; It was significantly lower in the quetiapine group at 8 and 16 weeks than in the risperidone group [63.2%, 57.9%. （F=6.909. 7.238. P 〈 0.05）].CONCLUSION： Both risperidone and chlorpromazine can lead to the obvious increase of prolaetin level, and has different influence on sexuality and sexual arousal. After taking risperidone, the levels of luteinizing hormone and testosteone are decreased; Quetiapine has little influence on the serum level of prolactin and sexual function,