Testosterone Modulation of Response to Phosphodiesterase Inhibitors

睾酮对磷酸二酯酶抑制剂反应的调节

• 批准号: 7285676
• 负责人: SHALENDER BHASIN
• 金额: $ 31.85万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-07 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285676
• 关键词: Achievement; Affect; Aftercare; Age; Age-Years; Androgens; Arts; Attention; Blood flow; Citrate; Citrates; Clinical; Clinical Trials; Daily; Dialysis procedure; Disease; Dose; Double-Blind Method; Elderly; Equilibrium; Erectile dysfunction; Functional disorder; Gel; High Prevalence; Hour; Incidence; Individual; Life; Liquid Chromatography; Longitudinal Studies; Maintenance; Measurement; Measures; Methods; Moods; Motivation; Muscle Rigidity; Nitric Oxide Synthase; Normal Range; Numbers; Oral; Penile Erection; Performance; Phosphodiesterase Inhibitors; Physical Dialysis; Placebo Control; Placebos; Prevalence; Probability Samples; Quality of life; Randomized; Randomized Clinical Trials; Range; Rate; Recurrence; Regulation; Research Design; Research Personnel; Role; Score; Serum; Sex Behavior; Sex Functioning; Sexual Dysfunction; Sildenafil citrate; Smooth Muscle; Stimulus; Subjects Selections; Supplementation; Surveys; Testing; Testosterone; Therapeutic; Thinking; Treatment Protocols; Venous; Visual; Week; Well in self; base; desire; improved; intimate behavior; man; men; middle age; older men; programs; randomized placebo controlled trial; response; satisfaction; sildenafil; size; tadalafil; tandem mass spectrometry; vardenafil

DESCRIPTION (provided by applicant): Androgen deficiency and erectile dysfunction (ED) are 2 common, but independently distributed, disorders that co-exist in a significant proportion of men with ED. The role of androgen deficiency in the pathophysiology of sexual dysfunction in men with ED remains misunderstood. The primary objective of this study is to determine whether testosterone replacement in men with low testosterone levels who present with ED improves therapeutic response to sildenafil citrate by improving erectile function, stimulating sexual desire, improving partner intimacy, affectivity balance, and sense of well being, and augmenting penile rigidity. We will conduct a double-blind, placebo-controlled, parallel-group, randomized clinical trial in men, 40-70 years of age, who present with mild to moderate ED and have androgen deficiency defined as total testosterone levels (measured by liquid chromatography tandem mass spectrometry, LC-MS/MS) below 300 ng/dL and/or free testosterone levels by equilibrium dialysis below 50 pg/ml. During the 6-week control period, the eligible men will initially take 50 mg sildenafil citrate, as often as necessary, but no more than once daily for 3-weeks or 8 doses, whichever is greater; at which point the dose will be increased to 100-mg in those not responding to 50-mg dose. After an additional 3-weeks on a stable, optimized, dose of sildenafil citrate, men would be randomized to receive the optimized dose of sildenafil citrate plus placebo gel or sildenafil citrate plus a replacement dose (100 mg daily) of testosterone gel. The dose of testosterone gel (100 mg) was selected to increase testosterone concentrations into the mid-normal range for young men (approx. 650-700 ng/dL). Erectile function assessed by IIEF, sexual encounter profile (subject and partner), global efficacy assessment, impact of ED on quality of life by ED Impact scale and Life Satisfaction Survey, overall sexual activity, sexual desire by MSHQ and sexual desire domain of IIEF, partner interaction and intimacy, affectivity balance by DeRogatis Affectivity Balance Scale, penile rigidity in response to a visual erotic stimulus after sildenafil citrate administration would be evaluated at baseline, and after 12-weeks of treatment. Careful attention to subject selection, potential confounders, effect size and power considerations, state-of-the-art methods, randomized, placebo-controlled study design, and a multi-disciplinary team of investigators would help elucidate the effects of testosterone in men with ED. The proposed study would provide a rational basis for testosterone administration in a significant subset of men with erectile dysfunction, and also provide an excellent opportunity for making further gains in our understanding of the role of testosterone in the regulation of sexual function in men.

描述（由申请人提供）：雄激素缺乏和勃起功能障碍 (ED) 是两种常见但独立分布的疾病，在相当大比例的 ED 男性中同时存在。雄激素缺乏在男性 ED 性功能障碍病理生理学中的作用仍然被误解。本研究的主要目的是确定睾酮水平低且患有 ED 的男性进行睾酮替代治疗是否可以通过改善勃起功能、刺激性欲、改善伴侣亲密感、情感平衡和幸福感来改善柠檬酸西地那非的治疗反应。并增强阴茎硬度。我们将对 40-70 岁男性进行一项双盲、安慰剂对照、平行组、随机临床试验，这些男性患有轻度至中度 ED，并且雄激素缺乏定义为总睾酮水平（通过液相色谱法测量）串联质谱法 (LC-MS/MS) 低于 300 ng/dL 和/或平衡透析游离睾酮水平低于 50 pg/ml。在 6 周的控制期内，符合条件的男性最初将根据需要经常服用 50 毫克枸橼酸西地那非，但每天不超过一次，持续 3 周或 8 剂，以较大者为准；此时，对于那些对 50 毫克剂量没有反应的患者，剂量将增加至 100 毫克。再服用稳定、优化剂量的柠檬酸西地那非 3 周后，男性将被随机接受优化剂量的柠檬酸西地那非加安慰剂凝胶或柠檬酸西地那非加替代剂量（每天 100 毫克）睾酮凝胶。选择睾酮凝胶的剂量（100 毫克），以将年轻男性的睾酮浓度提高到正常范围的中间值（约 650-700 ng/dL）。 IIEF 评估的勃起功能、性经历概况（受试者和伴侣）、总体功效评估、ED 对生活质量的影响（通过 ED 影响量表和生活满意度调查）、整体性活动、MSHQ 的性欲和 IIEF 的性欲领域，伴侣互动和亲密关系、DeRogatis情感平衡量表的情感平衡、枸橼酸西地那非给药后对视觉色情刺激的阴茎硬度将在基线和之后进行评估治疗12周。仔细关注受试者选择、潜在的混杂因素、效应大小和功效考虑因素、最先进的方法、随机、安慰剂对照研究设计以及多学科研究团队将有助于阐明睾酮对患有以下疾病的男性的影响：埃德。拟议的研究将为相当一部分患有勃起功能障碍的男性提供睾酮注射的合理依据，并且还为我们进一步了解睾酮在男性性功能调节中的作用提供了绝佳的机会。