睾固酮治疗的最初6个月血栓风险最高


  【24drs.com】研究者提醒,服用睾固酮治疗的男性在治疗的最初6个月时,血栓风险显著增加,而之前的研究因为研究方法的问题忽视了这项风险。
  
  这篇在线发表于11月30日的BMJ期刊的研究指出,开始睾固酮治疗后的最初6个月内,静脉血栓栓塞(venous thromboembolism,VTE)风险增加达63%,相当于每10,000 人-年增加10个案例。
  
  研究团队指出,虽然VTE风险增加是暂时的且绝对值依旧相对较低,这些结果支持美国食品药物管理局[在2014年]要求的,睾固酮制剂应增加静脉血栓栓塞风险之一般警告。
  
  第一作者、德国法兰克福流行病学统计与信息研究院Carlos Martinez医师表示,睾固酮治疗的好处必须大于风险,这项评估最好由主治医师,特别是内分泌科医师和患者一起处理。
  
  他接著表示,重点在于了解睾固酮治疗的潜在风险,以作出对特定患者之最佳治疗决策,增加相关警觉也很重要,以更迅速诊断和治疗任何静脉血栓栓塞。
  
  他指出,应告知患者深部静脉栓塞[DVT]和肺栓塞[PE]的症状与征兆,例如:脚痛、脚肿胀、呼吸急促等,并告诉他们,如果发生这类症状,应将这些告诉医师以玆注意。
  
  男性的睾固酮治疗处方已大幅增加,主要是性功能障碍和/或性能力衰退,自本世纪以来,美国的人均处方增加了10倍、加拿大增加了40倍,此数据包含网络销售量。
  
  虽然以前的研究报告结果,对于睾固酮使用是否与增加VTE风险方面互相矛盾,本次研究的作者们指出,这些研究都没有探讨睾固酮的使用时机与期间,可能会遮蔽了开始治疗之后的静脉血栓栓塞风险,如同口服避孕药的情况。
  
  为了进一步探讨,研究团队检视了19,215名确认有VTE的男性以及909,530名年龄匹配的对照组,这些资料来自英国370所一般开业机构的292万名患者,将他们的记录与医院出院诊断和住院手术连结,另外包括所有原因死亡率的信息。
  
  VTE案例包括8394例DVTs、10,787例PEs以及65例未特定VTEs,研究资料来源族群的VTE发生率是每10,000人-年有15.8例。
  
  有0.36%的VTE患者以及0.14%的对照组确认曾使用睾固酮,患者与对照组最近的使用报告分别是0.11%和0.09%。
  
  治疗者目前使用的睾固酮制剂最常见的有:肌肉注射制剂(54.2%)、经皮制剂(36.2%)以及口服制剂(7.8%)。
  
  纳入共病症与所有匹配因素的逻辑回归分析指出,目前使用睾固酮与没有使用睾固酮者的VTE整体校正比率为1.25,表示VTE额外增加的比率比基础比率15.8/10,000人-年还要多出3.9/10,000人-年。
  
  将分析限于治疗持续期间最长为6个月时,研究团队发现,目前使用睾固酮与没有使用睾固酮者的VTE整体校正比率为1.63,代表额外增加的VTE发生率是比基础比率多出10.0/10,000人-年。
  
  目前使用睾固酮与没有使用睾固酮者,治疗后6个月的VTE校正比率是1.00,而最近的睾固酮治疗相较于没有治疗的此一比率为0.68,并不显著。
  
  最长6个月的睾固酮治疗中,在有病理性性腺功能减退和无病理性性腺功能减退者观察到的VTE增加风险比率,分别是1.52与1.88,而在有已知VTE风险因素与无该因素者的比率则分别是1.41和1.91。
  
  研究者指出,因为无法检视使用睾固酮的时机与期间,由于一种称为易感耗竭的现象,之前的研究可能会忽略开始治疗时的VTE风险高峰期。
  
  虽然暂时性风险增加的潜在机转未知,研究团队认为,它可能涉及纤维蛋白溶解的初始减少,与之前未诊断的血栓形成-低纤维蛋白溶解和/或因为勃起功能障碍导致的心血管风险增加有关,随后是继发性反应而增加纤维蛋白溶解,然后中和增加的风险。
  
  然而,Martinez医师强调,测量治疗的时机和持续期间是药物安全的关键因素,这在荷尔蒙治疗和静脉血栓栓塞之情况下是高度相关的。
  
  他指出,治疗日期和事件总是在临床试验中收集,在适当情况下,希望将治疗持续期间纳入分析。
  
  资料来源:http://www.24drs.com/
  
  Native link:Blood Clot Risk Highest in First 6 Months of Testosterone Therapy

Blood Clot Risk Highest in First 6 Months of Testosterone Therapy

By Liam Davenport
Medscape Medical News

Men taking testosterone therapy face a significantly increased risk of blood clots in the first 6 months after starting treatment, warn researchers who say that previous studies may have missed the risk due to methodological issues.

The research, which was published online in the BMJ on November 30, shows that the risk of venous thromboembolism (VTE) is increased by 63% in the first 6 months after starting testosterone therapy, corresponding to an additional 10 cases per 10,000 person-years.

The team notes that, although the increase in VTE risk is transient and "still relatively low in absolute terms," the results "support the addition of the general warning for risk of venous thromboembolism with testosterone products required by the US Food and Drug Administration [in 2014]."

Lead author Carlos Martinez, MD, Institute for Epidemiology, Statistics and Informatics, Frankfurt, Germany told Medscape Medical News that the "benefits of testosterone treatment must be weighed against the risks," the evaluation of which is "best handled by the treating physician and in particular the endocrinologist, together with the patient."

He continued: "It is important to understand the potential risks of testosterone treatment in order to be able to make informed decisions about the best treatment for any particular patient, and it is also important to increase awareness of the risks in order to have more rapid diagnosis and treatment of any venous thromboembolism.

"Patients should be informed of the symptoms and signs of deep vein thrombosis [DVT] and pulmonary embolism [PE] — for example, leg pain, leg swelling, or shortness of breath, and be told that, if such symptoms occur, they should bring these to the attention of a doctor," he added.

Large Increase in Prescribing of Testosterone in Men

There has been a large increase in the prescribing of testosterone therapy in men, primarily for sexual dysfunction and/or decreased energy, since the turn of the century, with a 10-fold increase in prescriptions per capita in the United States and a 40-fold increase in Canada, a figure that includes internet sales.

While previous studies have reported contradictory results in terms of whether testosterone use is associated with an increased risk of VTE, the current researchers note that none of those studies "investigated the timing and duration of testosterone use, which could have masked a risk of venous thromboembolism soon after the start of treatment, as seen with oral contraceptives."

To investigate this further, the team examined data on 19,215 males with confirmed VTE and 909,530 age-matched controls from a source population of 2.92 million individuals registered at 370 UK general practices. Their records were linked to hospital-discharge diagnosis and in-hospital procedures, as well as information on all-cause mortality.

The VTE cases included 8394 DVTs, 10,787 PEs, and 65 unspecified VTEs. The incidence rate for VTE in the source population was 15.8 per 10,000 person-years.

Current testosterone use was identified in 0.36% of VTE patients and 0.14% of controls, while recent use was reported in 0.11% and 0.09% of patients and controls, respectively.

The most common testosterone preparations for currently treated individuals were intramuscular preparations (54.2%), transdermal preparations (36.2%), and oral preparations (7.8%).

Logistic regression analysis taking into account comorbidities and all matching factors indicated that the overall adjusted rate ratio of VTE for current vs no testosterone treatment was 1.25, suggesting an additional excess VTE incidence rate of 3.9 per 10,000 person-years over the base rate of 15.8 per 10,000 person years.

Confining the analysis to a treatment duration of up to 6 months, the team found that the adjusted rate ratio of VTE for current vs no treatment was 1.63, indicating an additional excess VTE incidence rate of 10.0 per 10,000 person-years over the base rate.

The adjusted rate ratio of VTE after 6 months of treatment for current vs no treatment was 1.00, while that for recent testosterone treatment vs no treatment was 0.68, which was not significant.

The increased risk of VTE seen with up to 6 months of testosterone treatment was observed in patients with and without pathological hypogonadism, at rate ratios of 1.52 and 1.88, respectively, and in those with and without known VTE risk factors, at rate ratios of 1.41 and 1.91, respectively.

Previous Studies Could Have Missed Peak VTE Risk at Start of Testosterone Therapy

The researchers point out that, having failed to examine the timing and duration of testosterone use, previous studies could have missed the transient peak in VTE risk at the start of treatment due to "a phenomenon known as depletion of susceptibles."

While the mechanism underlying the transient increased risk is not known, the team suggests that it may involve an initial decrease in fibrinolysis, associated with previously undiagnosed thrombophilia-hypofibrinolysis and/or increased cardiovascular risk due to erectile dysfunction, followed by a secondary response to increase fibrinolysis, which then neutralizes the increased risk.

Nevertheless, Dr Martinez emphasized that "measuring the timing and duration of treatment is a crucial element in drug safety and highly pertinent in the context of hormonal therapy and venous thromboembolism."

He added: "The dates of treatment and of events are always collected in clinical trials, and one would hope that the duration of treatment is included in the analysis, where appropriate."

The authors declare no relevant financial relationships for the submitted work. Dr Martinez has received personal fees from Boehringer Ingelheim and grants from CSL Behring, Bayer, and Bristol-Myers Squibb. Other disclosures for the coauthors are listed in the paper.

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BMJ. Published online November 30, 2016.

    
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