FDA调查睾酮的心血管风险

美国食品药品管理局(FDA)正在重新评估已批准睾酮药物的心血管安全性，并要求医生和患者报告这类药物的副作用。

两项最新观察性研究显示，接受睾酮制剂治疗的男性患者心梗(MI)、卒中和死亡风险增加，这促使FDA开展此次调查，并发布相关警告。

FDA警告称，正在应用睾酮产品的患者在未与医生沟通之前不应停止用药。FDA尚未得出已批准睾酮制剂增加心血管风险的结论，最终推荐意见有待这次评估完成后发布。

一项针对55,593例男性患者医疗保险资料的队列研究显示，与上一年相比，年龄≥65岁男性开始应用睾酮后90天内MI风险加倍，而对于有心脏疾病史的年轻男性，其风险增加近2倍(PLoS ONE 2014 Jan. 29 [doi: 10.1371/journal.pone.0085805])。

统计方法及软件开发公司Consolidated Research总裁William D. Finkle及其同事报告称，无心脏病史的年轻男性，应用睾酮药物后心血管风险未见增加。研究者报告无相关利益冲突。

另外一项针对8,709例低睾酮水平男性患者的回顾性队列研究显示，与未接受睾酮治疗者相比，1,223例睾酮治疗者接受治疗1年内MI、卒中或死亡风险增加30%，治疗后2年相对风险是未治疗者的3倍，而3年则近6倍，德州大学西南医学中心的Rebecca Vigen医生及其同事报告称(JAMA 2013;310:1829-36)。

此外，无论有无冠脉疾病史，睾酮治疗男性的心血管风险均增加，且风险似乎不受血压等心血管风险因素差异或预防用药影响。该研究由美国退伍军人事务部资助，Vigen医生及其同事报告无相关利益冲突。

美国国立卫生研究院(NIH)于2010年曾报告，一项纳入老年男性(包括部分心血管疾病患者)的睾酮治疗临床研究被提前终止，原因是与安慰剂组相比，治疗组患者心血管事件增加。

FDA要求医疗专业人士和患者应将与睾酮产品相关的副作用报告至FDA MedWatch不良事件报告系统，或致电800-332-1088或传真至800-FDA-0178。

FDA已批准的睾酮产品包括局部用凝胶剂、透皮贴剂、口腔给药系统和注射剂，且仅用于与低或无睾酮水平相关疾病的男性，睾酮制剂没有被批准用于治疗无医学病症的睾酮水平低下男性。

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By: SHERRY BOSCHERT, Cardiology News Digital Network

The Food and Drug Administration is reassessing the cardiovascular safety of approved testosterone treatments and urged physicians and patients to report side effects.

Two recent observational studies that reported increased risks of MI, stroke, and death in men taking prescribed testosterone products prompted the FDA to open its investigation and to publish the alert about its actions.

Patients on prescribed testosterone products should not discontinue them without talking with their health care providers, the FDA cautioned. The agency has not concluded that approved testosterone formulations increase cardiovascular risk. Final recommendations are pending the completion of its evaluation.

The risk of MI doubled within 90 days of starting testosterone, compared with the previous year, in men aged 65 years or older and nearly tripled in younger men who had a prior history of heart disease, a cohort study of claims data for 55,593 men reported (PLoS ONE 2014 Jan. 29 [doi: 10.1371/journal.pone.0085805]).

Younger men with no history of heart disease showed no increased cardiovascular risk after filling a testosterone prescription, William D. Finkle and his associates reported. The National Cancer Institute funded the study. Mr. Finkle is owner of Consolidated Research, Los Angeles, a company that develops statistical methods and software. He and his associates reported having no relevant financial disclosures.

A separate retrospective cohort study of 8,709 men with low testosterone levels, 1,223 of whom were treated with testosterone, found a 30% increased risk for MI, stroke, or death within 1 year of starting testosterone compared with the men not on testosterone. The relative risk was threefold higher at 2 years and nearly sixfold higher at 3 years, reported Dr. Rebecca Vigen of the University of Texas at Southwestern Medical Center, Dallas, and her associates (JAMA 2013;310:1829-36).

The elevated risk with testosterone therapy was seen both in men who had existing coronary artery disease and in those who did not, and the risk did not appear to be affected by differences in cardiovascular risk factors such as blood pressure or by the use of preventive medications.

The Department of Veterans Affairs funded the study. Dr. Vigen and her associates reported having no relevant financial disclosures.

An earlier clinical trial of testosterone therapy in older men that included many men with cardiovascular disorders was halted early after an increase in cardiovascular events in the testosterone group compared with the placebo group was found, the National Institutes of Health reported in 2010.

The FDA urged health care professionals and patients to report side effects involving testosterone products to the FDA MedWatch program by filing a report online, calling 800-332-1088, or faxing to 800-FDA-0178.

FDA-approved testosterone products deliver the hormone by topical gel, transdermal patch, buccal system, and injection, and are indicated only for men with low or no testosterone levels associated with a medical condition. No testosterone products are approved to treat men with low testosterone levels that are not associated with a medical condition.