Testosterone Replacement Therapy with Long-Acting Testosterone Undecanoate Improves Sexual Function and Quality-of-Life Parameters vs. Placebo in a Population of Men with Type 2 Diabetes
Testosterone Replacement Therapy with Long-Acting Testosterone Undecanoate Improves Sexual Function and Quality-of-Life Parameters vs. Placebo in a Population of Men with Type 2 Diabetes
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DOI：
10.1111/jsm.12146
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发表时间：
2013-06-01
影响因子：
3.5
通讯作者：
Wilkinson, Peter
中科院分区：
文献类型：
--
作者：
Hackett, Geoffrey;Cole, Nigel;Wilkinson, Peter
简介 性功能障碍，特别是勃起功能障碍 (ED)，在 2 型糖尿病男性中很常见，发生率高达 75%。患有糖尿病的男性性腺功能减退症的患病率也很高，而低睾酮水平与性功能障碍和口服治疗 ED 的反应降低有关。目的 本研究旨在确定在 30 周的治疗期和 52 周的开放标签药物治疗期间，用长效十一酸睾酮 (TU) 替代睾酮对性功能、情绪和生活质量与安慰剂的影响。这项研究是在 2 型糖尿病男性初级保健人群中进行的，这些男性接受初级保健医生的例行就诊。方法 在常规糖尿病就诊时对 7 个全科诊所的男性糖尿病人群进行筛查，以检测总睾酮水平为 12nmol/L 或更低或游离睾酮水平为 250pmol/L 或更低的有症状男性。 211 名男子接受了筛查。一项双盲安慰剂对照研究在 199 名患有 2 型糖尿病和性腺功能减退症的男性中进行，接受 1,000 毫克 TU 或匹配安慰剂治疗 30 周，然后进行 52 周开放标签随访。主要结局指标国际勃起功能指数（IIEF）作为主要结局指标，用于评估性功能障碍，而老年男性症状（AMS）、医院焦虑和抑郁量表以及全球疗效问题作为次要结局指标，用于评估情绪和自我报告的生活质量。结果 长效 TU 睾酮替代疗法在 30 周时改善了性功能的所有领域（勃起功能 [EF]，P=0.005；性交满意度，P=0.015；性欲，P=0.001；总体满意度，P=0.05；性高潮，P=0.04），早在 6 周就获益。在没有抑郁症的男性中，AMS 评分的改善显着（P=0.02），并且基线时抑郁症的存在与性功能和心理评分的反应显着降低相关。性功能的所有反应持续显着改善长达 18 个月，EF 评分较基线提高 4.31。在一个由 35 名服用 5 型磷酸二酯酶抑制剂的男性组成的小队列中，双盲阶段没有任何变化，但在 52 周开放标签治疗期间 EF 结构域改善了 9 个百分点。 30 周后，接受积极治疗的患者和接受安慰剂的患者分别有 46% 和 17% 的患者认为治疗改善了他们的健康状况，开放标签治疗后这一比例达到 70%。肥胖较少和老年患者对睾酮治疗的反应更好。没有明显的不良事件。结论 TU 显着改善了 IIEF 的所有领域，患者报告的 30 周生活质量在 52 周开放标签延伸后更显着。肥胖程度较低的患者和没有共存抑郁症的患者的改善最为明显。对于患有 2 型糖尿病的男性，治疗试验的时间可能需要比当前指南建议的 3-6 个月长得多。
Introduction Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. Aim This study aimed to determine the effect of testosterone replacement with long-acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open-label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. Methods The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12nmol/L or less or with free testosterones of 250pmol/L or less. Two hundred eleven men were screened. A double-blind placebo-controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000mg of TU or matching placebo followed by 52-week open-label follow on. Main Outcome Measures The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self-reported quality of life. Results Testosterone replacement therapy with long-acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P=0.005; intercourse satisfaction, P=0.015; sexual desire, P=0.001; overall satisfaction, P=0.05; and orgasm, P=0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P=0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological scores. All responses in sexual function continued to improve significantly up to 18 months with an improvement in EF score of 4.31 from baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors, there was no change during the double-blind phase but a nine-point improvement in EF domain during 52-week open-label treatment. After 30 weeks, 46% vs. 17% of patients on active therapy vs. placebo felt that the treatment had improved their health, reaching 70% after open-label therapy. Less obese and older patients responded better to testosterone therapy. There were no significant adverse events. Conclusion TU significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks and more significantly after 52-week open-label extension. Improvement was most marked in less obese patient and those without coexisting depression. In men with type 2 diabetes, trials of therapy may need to be given for much longer than 3-6 months suggested in current guidelines.