Title: Is progesterone yet another disappointing neuroprotectant?
題目：孕激素是另一個令人失望的神經保護劑？
Author 作者: Wan-Tsu Wendy Chang
翻譯：鄭辛甜 校對：肖鋒

Is progesterone yet another disappointing neuroprotectant?
Traumatic brain injury (TBI) affects more than 1.7 million persons in the U.S. annually. The incidence of TBI is increasing globally, especially in developing countries. Despite improvement in trauma systems and critical care, the morbidity and mortality associated with severe TBI remain high.
Progesterone has been shown in preclinical and phase 2 randomized clinical trials to have pluripotent neuroprotective properties and improve mortality in TBI.
每年美國有超過170萬人遭受創傷性腦損傷（TBI）。TBI的發病率在全球范圍內不斷增加，尤其是在發展中國家。盡管創傷系統和重癥護理有所改善，重癥腦外傷的發病率和病死率居高不下。孕激素已在臨床前和II期隨機臨床試驗中被證明具有不同程度的神經保護功能，用以改善TBI的病死率。
Two multicenter phase 3 trials were recently completed and published in the December 25th issue of the New England Journal of Medicine. However, their results were disappointing.
近期2項多中心III期臨床試驗已完成，發表在12月25日的NEJM上。然而，研究結果令人失望。
• The Progesterone for the Treatment of Traumatic Brain Injury (PROTECT III) trial, funded by the NIH, looked at progesterone administered within 4 hours after injury in patients with moderate to severe TBI.
• 由NIH資助的孕激素對創傷性腦損傷的治療（PROTECT III）試驗中，中度至重度顱腦損傷患者傷后4小時內給予孕激素。
• The Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SYNAPSE) trial, funded by BHR Pharma, looked at progesterone administered within 8 hours after injury in patients with severe TBI.
• 由BHR制藥公司資助的神經保護劑孕激素在重癥創傷性腦損傷患者中的（SYNAPSE）試驗，研究重癥創傷性腦損傷患者傷后8小時內給予孕激素。
Both studies used the Glasgow Outcome Scale (GOS) or Extended
Glasgow Outcome Scale (GOS-E) at 6 months as their primary outcome. The GOS and GOS-E capture the degree of recovery from brain injury in terms of disability, stratified into levels by death, vegetative state, severe disability, moderate disability, and good recovery.
兩項研究均采用傷后6個月GOS評分或擴展GOS評分（GOS-E）作為主要指標。GOS和GOS-E評分根據傷殘情況評估腦損傷恢復程度，分為死亡、植物狀態、嚴重殘疾、中等殘疾和恢復良好。

Progesterone was not found to have any benefit in functional outcome at 6 months.
研究均未發現孕激素對患者6個月的功能恢復有任何益處。
Both of these studies were well designed and conducted. However, they were based on small effect sizes of the phase 2 trials. In addition, they had very favorable outcome rates in the placebo group, thereby making it hard to demonstrate a benefit by their sample sizes.
兩項研究都是精心設計和進行的。然而，它們都是基于小型的II期臨床試驗。此外，兩項研究中的安慰劑組有非常好的結局，使得根據它們目前的樣本量很難得出孕激素有益的結論。
There has been a long history of failed neuroprotectant trials likely due to the complex and variable injury mechanisms involved in TBI. The currently available outcome measures are also insensitive to the targeted mechanistic endpoints. More research is needed to understand not only potential therapies but also how to select appropriate patients for these therapies.
神經保護劑試驗失敗的歷史已有很久，這可能是由于TBI復雜多變的損傷機制。目前可用的觀測指標也對針對機制效果不敏感。需要更多的研究來了解不僅是潛在的治療方法也是如何選擇合適的患者進行這些治療。

Take Home Point: Progesterone does not have any clear benefit in TBI at this time.
要點：孕激素目前未被證實對創傷性腦損傷有任何明確的益處。

References 參考文獻：
Wright DW, Yeatts SD, Silbergleit R, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014;371(26):2457-2466.
Skolnick BE, Maas AI, Narayan RK, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014;371(26):2467-2476.