Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
Translational & Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, UK.
Lancet Healthy Longev. 2023 Oct;4(10):e561-e572. doi: 10.1016/S2666-7568(23)00169-1.
Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment.
We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005.
9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory).
In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity.
National Institute for Health and Care Research Health Technology Assessment Programme.
睾酮替代疗法已被证实可改善 40 岁以下患有病理性性腺功能减退症的男性的性功能。然而，目前尚不清楚睾酮是否能缓解年龄较大的男性和肥胖男性的性功能障碍，尽管睾酮正越来越多地用于这些患者群体。我们旨在评估患有低睾酮症的男性亚组是否能从睾酮治疗中获得任何症状改善。
我们进行了系统评价和荟萃分析，以评估年龄在 18 岁及以上、基线血清总睾酮浓度低于 12nmol/L 的男性中，与安慰剂相比，睾酮治疗与症状改善相关的特征。我们检索了主要电子数据库（MEDLINE、Embase、科学引文索引和 Cochrane 对照试验中心注册库）和临床试验注册库，以查找 1992 年 1 月 1 日至 2018 年 8 月 27 日发表的英文报告。我们向所有确定试验的研究者请求了匿名的个体参与者数据。本次分析的主要（心血管）结局已在前次报告中发表。在本报告中，我们介绍了 12 个月时的次要结局，包括性功能、生活质量和心理结局。我们采用单阶段个体参与者数据荟萃分析，使用随机效应线性回归模型，以及整合未提供个体参与者数据的研究的个体参与者数据和汇总数据的两阶段荟萃分析。本研究已在 PROSPERO、CRD42018111005 上注册。
通过数据库检索共鉴定出 9871 条引文。排除重复项和不符合纳入标准的出版物后，评估了 225 篇全文的纳入情况，其中 109 篇出版物报告了 35 项主要研究（共 5601 名参与者）被纳入。其中，17 项试验提供了个体参与者数据（3431 名参与者；中位年龄 67 岁[IQR 60-72]；3281[97%]名参与者年龄≥40 岁）与安慰剂相比，睾酮治疗可增加 15 项国际勃起功能指数（IIEF-15）总分（平均差异 5.52[95%CI 3.95-7.10]；τ=1.17；n=1412）和 IIEF-15 勃起功能子评分（2.14[1.40-2.89]；τ=0.64；n=1436），达到轻度勃起功能障碍的最小临床重要差异。这些效果似乎与参与者年龄、肥胖、糖尿病或基线血清总睾酮无关。然而，在接受睾酮治疗期间达到的绝对 IIEF-15 评分受患者年龄和基线血清总睾酮的限制。与安慰剂相比，睾酮治疗可显著改善男性衰老症状评分，以及一些 12 项或 36 项简短表格调查生活质量子评分，但不能显著改善心理症状（通过贝克抑郁量表评估）。
在基线血清睾酮水平低于 12nmol/L 的年龄在 40 岁或以上的男性中，短期至中期的睾酮治疗可能为轻度勃起功能障碍提供有临床意义的治疗，无论患者年龄、肥胖或低睾酮程度如何。然而，由于基线症状更为严重，在接受睾酮治疗期间，性功能的绝对水平可能在年龄较大的男性和肥胖男性中较低。
英国国家卫生与保健优化研究所卫生技术评估计划。
