Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, Saghir A
Good Hope Hospital, Sutton Coldfield, UK.
Int J Clin Pract. 2014 Feb;68(2):203-15. doi: 10.1111/ijcp.12235. Epub 2013 Dec 20.
The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established. Current Endocrine Society and European Association of Urology guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes and in men suffering from erectile dysfunction. It is recognised that a range of physical symptoms appear as the testosterone level falls but few studies have addressed the threshold at which symptoms improve with physiological replacement. We report the first double-blind placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess the metabolic changes with testosterone replacement.
The type 2 diabetes registers of seven general practices were screened to establish the prevalence of low testosterone and the associations with diabetes control. Of 550 eligible patients approached, 488 men (mean age 62.6) consented to take part in screening with a morning testosterone level, assessed between 8 and 11 am. This identified 211 patients for a double-blind placebo-controlled study of long acting testosterone undecanoate (TU) 1000 mg lasting 30 weeks followed by 52 weeks of open label use. The population was divided into a SEVERE group with either total testosterone (TT) of 8 nmol/l or less or free testosterone (FT) 180 pmol/l or less or a MILD group with TT 8.1-12 nmol/l or FT 181-250 pmol/l.
Men in the SEVERE group increased mean through TT from 7.73 nmol/l at baseline to 9.93 at 30 weeks and the MILD group from 10.47 to 11.94. The SEVERE group showed marked improvement in sexual function, but no significant improvement in metabolic parameters. The MILD group showed no improvement in sexual function, but significant improvement in weight, body mass index, waist circumference and Hospital Anxiety and Depression Scale. Improvement was seen in all parameters during 52 weeks open label treatment where trough TT levels approached 15 nmol/l. Baseline prostate-specific antigen (PSA) was lower in the SEVERE group and increased with TU for 30 weeks and then stabilised. There was no increase in PSA with treatment in the MILD group.
Testosterone undecanoate significantly improves sexual parameters and Ageing Male Symptom Score, but not metabolic factors at 30 weeks in men with SEVERE testosterone deficiency syndrome (TDS). In men with MILD TDS, significant improvements in metabolic but not sexual parameters were seen, suggesting that there are threshold levels for response to testosterone replacement therapy and that trials of therapy need to achieve sustained therapeutic levels to be effective. PSA showed minor rises, but only for 30 weeks in the SEVERE group.
2型糖尿病男性患者中，睾酮缺乏与胰岛素抵抗之间的关联已得到充分证实。目前，美国内分泌学会和欧洲泌尿外科学会的指南建议对所有2型糖尿病男性患者以及患有勃起功能障碍的男性进行睾酮水平检测。人们认识到，随着睾酮水平下降会出现一系列身体症状，但很少有研究探讨通过生理替代使症状改善的阈值。我们报告了第一项专门针对男性2型糖尿病人群进行的双盲安慰剂对照研究，以评估睾酮替代治疗后的代谢变化。
筛查了7家普通诊所的2型糖尿病登记记录，以确定低睾酮的患病率及其与糖尿病控制的关联。在550名符合条件的患者中，488名男性（平均年龄62.6岁）同意参与筛查，于上午8点至11点之间评估其早晨睾酮水平。这确定了211名患者参与一项双盲安慰剂对照研究，使用长效十一酸睾酮（TU）1000mg，持续30周，随后进行52周的开放标签使用。将人群分为重度组，其总睾酮（TT）为8nmol/l或更低，或游离睾酮（FT）为180pmol/l或更低；以及轻度组，其TT为8.1 - 12nmol/l或FT为181 - 250pmol/l。
重度组男性的平均TT水平从基线时的7.73nmol/l升至30周时的9.93nmol/l，轻度组从10.47nmol/l升至11.94nmol/l。重度组性功能有显著改善，但代谢参数无显著改善。轻度组性功能无改善，但体重、体重指数、腰围及医院焦虑抑郁量表评分有显著改善。在52周的开放标签治疗期间，所有参数均有改善，此时谷值TT水平接近15nmol/l。重度组的基线前列腺特异性抗原（PSA）较低，使用TU 30周后升高，然后稳定。轻度组治疗期间PSA无升高。
对于患有重度睾酮缺乏综合征（TDS）的男性，十一酸睾酮在30周时显著改善了性功能和老年男性症状评分，但未改善代谢因素。对于患有轻度TDS的男性，代谢参数有显著改善，但性功能参数无改善，这表明睾酮替代治疗存在反应阈值，且治疗试验需要达到持续的治疗水平才能有效。PSA有轻微升高，但仅在重度组持续30周。
