睪固酮治療的最初6個月血栓風險最高


  【24drs.com】研究者提醒,服用睪固酮治療的男性在治療的最初6個月時,血栓風險顯著增加,而之前的研究因為研究方法的問題忽視了這項風險。
  
  這篇線上發表於11月30日的BMJ期刊的研究指出,開始睪固酮治療後的最初6個月內,靜脈血栓栓塞(venous thromboembolism,VTE)風險增加達63%,相當於每10,000 人-年增加10個案例。
  
  研究團隊指出,雖然VTE風險增加是暫時的且絕對值依舊相對較低,這些結果支持美國食品藥物管理局[在2014年]要求的,睪固酮製劑應增加靜脈血栓栓塞風險之一般警告。
  
  第一作者、德國法蘭克福流行病學統計與資訊研究院Carlos Martinez醫師表示,睪固酮治療的好處必須大於風險,這項評估最好由主治醫師,特別是內分泌科醫師和患者一起處理。
  
  他接著表示,重點在於瞭解睪固酮治療的潛在風險,以作出對特定患者之最佳治療決策,增加相關警覺也很重要,以更迅速診斷和治療任何靜脈血栓栓塞。
  
  他指出,應告知患者深部靜脈栓塞[DVT]和肺栓塞[PE]的症狀與徵兆,例如:腳痛、腳腫脹、呼吸急促等,並告訴他們,如果發生這類症狀,應將這些告訴醫師以玆注意。
  
  男性的睪固酮治療處方已大幅增加,主要是性功能障礙和/或性能力衰退,自本世紀以來,美國的人均處方增加了10倍、加拿大增加了40倍,此數據包含網路銷售量。
  
  雖然以前的研究報告結果,對於睾固酮使用是否與增加VTE風險方面互相矛盾,本次研究的作者們指出,這些研究都沒有探討睪固酮的使用時機與期間,可能會遮蔽了開始治療之後的靜脈血栓栓塞風險,如同口服避孕藥的情況。
  
  為了進一步探討,研究團隊檢視了19,215名確認有VTE的男性以及909,530名年齡匹配的對照組,這些資料來自英國370所一般開業機構的292萬名患者,將他們的記錄與醫院出院診斷和住院手術連結,另外包括所有原因死亡率的資訊。
  
  VTE案例包括8394例DVTs、10,787例PEs以及65例未特定VTEs,研究資料來源族群的VTE發生率是每10,000人-年有15.8例。
  
  有0.36%的VTE患者以及0.14%的對照組確認曾使用睪固酮,患者與對照組最近的使用報告分別是0.11%和0.09%。
  
  治療者目前使用的睪固酮製劑最常見的有:肌肉注射製劑(54.2%)、經皮製劑(36.2%)以及口服製劑(7.8%)。
  
  納入共病症與所有匹配因素的邏輯回歸分析指出,目前使用睪固酮與沒有使用睪固酮者的VTE整體校正比率為1.25,表示VTE額外增加的比率比基礎比率15.8/10,000人-年還要多出3.9/10,000人-年。
  
  將分析限於治療持續期間最長為6個月時,研究團隊發現,目前使用睪固酮與沒有使用睪固酮者的VTE整體校正比率為1.63,代表額外增加的VTE發生率是比基礎比率多出10.0/10,000人-年。
  
  目前使用睪固酮與沒有使用睪固酮者,治療後6個月的VTE校正比率是1.00,而最近的睪固酮治療相較於沒有治療的此一比率為0.68,並不顯著。
  
  最長6個月的睪固酮治療中,在有病理性性腺功能減退和無病理性性腺功能減退者觀察到的VTE增加風險比率,分別是1.52與1.88,而在有已知VTE風險因素與無該因素者的比率則分別是1.41和1.91。
  
  研究者指出,因為無法檢視使用睪固酮的時機與期間,由於一種稱為易感耗竭的現象,之前的研究可能會忽略開始治療時的VTE風險高峰期。
  
  雖然暫時性風險增加的潛在機轉未知,研究團隊認為,它可能涉及纖維蛋白溶解的初始減少,與之前未診斷的血栓形成-低纖維蛋白溶解和/或因為勃起功能障礙導致的心血管風險增加有關,隨後是繼發性反應而增加纖維蛋白溶解,然後中和增加的風險。
  
  然而,Martinez醫師強調,測量治療的時機和持續期間是藥物安全的關鍵因素,這在荷爾蒙治療和靜脈血栓栓塞之情況下是高度相關的。
  
  他指出,治療日期和事件總是在臨床試驗中收集,在適當情況下,希望將治療持續期間納入分析。
  
  資料來源: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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