ncpow 2010-6-11 00:25
使用viagra可能增加突發性聽力喪失
使用viagra可能增加突發性聽力喪失
作者：Nancy Fowler Larson
出處：WebMD醫學新聞
May 23, 2010 — 根據一項發表於5月份耳鼻喉、頭頸部手術學誌的研究結果，使用sildenafil（Viagra）的男性們比較可能發生突發性聽力喪失。
最近超過數十件報告指出，突發性聽力喪失與使用雙磷酸酯酶第五型抑制劑（PDE-5is）之間是有關的。PDE-5is的例子包括：
* Sildenafil（Viagra與Revatio；輝瑞藥廠）
* Vardenafil（Levitra；拜耳藥廠，先靈葆雅與葛蘭素史克藥廠）以及
* Tadalafil（Cialis；禮來藥廠）
在2007年，大約根據30個研究報告，美國食品藥物管理局(FDA)要求廠商警告消費者這些藥物可能造成聽力喪失。部分研究已經評估解釋這個潛在因果關係的作用機轉；然而，目前還沒有進一步的研究檢驗這些藥物與聽力喪失之間的關係。
試驗作者、伯明罕阿拉巴馬州立大學公共衛生學院流行病學部門Gerald McGwin醫師表示，就我所知，目前並沒有流行病學研究評估使用PDE-5is與聽力喪失的關係。為了協助填補目前文獻中的這個缺憾，這項研究評估美國一個以群眾為基礎的樣本，檢視兩者之間的關係。
透過邏輯性迴歸，這項研究比較有或沒有聽力喪失的受試者，使用PDE-5i之後，校正可能影響因子前後的影響。這個群體包括40歲以上，從2003年到2006年醫療資源使用專家小組普查取出來的11,525位男性（加權後249,217,013位）；在這兩年期間，受試者們提供5次有關於流行病學資訊、健康、健康照護活動以及處方藥物的訪談資訊。他們也自行通報任何聽覺障礙與使用助聽器的資料。
結果顯示，聽力受損的整體發生率為17.9%，這個百分比隨著年齡增長而增加。大約有2%受試者使用特定種類的PDE-5i藥物，其中80.3%使用sildenafil。未經校正的結果顯示，使用PDE-5i的受試者，發生聽力喪失的機率高出兩倍（3.0%相較於1.4%）；在校正流行病學資料與健康因子後，這些發現仍然是相當的。
* 那些聽力喪失的受試者比較常使用PDE-5i（勝算比[OR]為2.23；95%信賴區間[CI]為1.36-3.66）。
* 使用PDE-5i藥物與聽力喪失比較常跟sildenafil有關（OR為2.05；95% CI為1.23-3.43）。
* 聽力喪失與tadanafil或是vardenafil沒有具意義的關係（OR分別為1.40[95% CI為0.49-4.04]及0.88[95% CI為0.35-2.22]）。
McGwin醫師表示，PDE-5i與聽力喪失之間的關係可能是藥物促進鼻勃起組織的傾向，這可能提高中耳壓力。
McGwin醫師寫到，也有報告指出，使用PDE-5i可能會加強一氧化氮的效果，這被證實與許多耳部疾病有關，或是透過活化態細胞內環狀鳥嘌呤核苷單磷酸鹽（cGMP）刺激效應。PDE-5i透過阻斷cGMP降解，堆積透過特定磷酸酶進行蛋白磷酸化的轉錄因子誘發基因表現，這些已經被證實與耳部毛細胞損傷有關。
雖然tadanafil顯示出與聽力受損有些微關係，但上升幅度並未達到統計上顯著差異。McGwin醫師承認，受試者有限地使用tadanafil與vardenafil可能使得這項研究未能探索這兩個藥物與聽力受損可能的關聯性。
PDE-5i藥物與聽力受損之間仍然有許多問題。除此之外，McGwin醫師表示，目前這項發現確實證實了FDA的警訊。
McGwin醫師寫到，有鑑於聽力喪失大部分是不可逆的，且其對於生活品質的影響突顯了有關於使用PDE-5i藥物相關病理角色之更多研究的需求。此時，應謹慎對待使用這些藥物的病患，特別是使用sildenafil者，醫師應提醒他們相關聽力受損的病徵與症狀，並鼓勵他們立即尋求醫療協助，以避免造成永久性的傷害。
這項研究作者表示擔任使用viagra與非動脈缺血性聽神經病變病理專家審查的法律諮詢。沒有報告其他相關資金上的往來。
Viagra Use May Increase the Risk for Sudden Hearing Loss
By Nancy Fowler Larson
Medscape Medical News
May 23, 2010 — Men who have taken sildenafil (Viagra; Pfizer) are more likely to experience sudden sensorineural hearing loss, according to an study published in the May issue of the Archives of Otolaryngology–Head Neck Surgery.
More than 2 dozen recent reports have indicated an association between sudden sensorineural hearing loss and phosphodiesterase type 5 inhibitors (PDE-5is). Examples of PDE-5is include the following:
sildenafil citrate (Viagra and Revatio; Pfizer),
vardenafil (Levitra; Bayer Pharmaceuticals, Schering-Plough, and GlaxoSmithKline), and
tadalafil (Cialis; Eli Lilly).
In 2007, based on roughly 30 case reports, the FDA required manufacturers of these drugs to warn consumers of possible hearing loss. Some studies have evaluated mechanism of action to explain the potential causal association; however, deeper examinations of the possible relationship between the drugs and hearing loss have not been conducted.
"To my knowledge, no epidemiologic studies to date have evaluated the association between PDE-5i use and [hearing loss]," writes study author Gerald McGwin, PhD, from the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham. "To help fill this void in the current literature, this study evaluates this relationship in a population-based sample of men in the United States."
Using logistic regression, the study compared subjects with and without hearing loss against the use of PDE-5i both before and after adjustment for possible confounding factors. The cohort consisted of 11,525 men (249,217,013 weighted), aged 40 years and older, chosen from the 2003 to 2006 Medical Expenditure Panel Survey. During a 2-year period, the participants provided information in 5 total interviews about their demographics, health, healthcare activities, and prescription medications. They also self-reported any hearing difficulty and use of hearing aids.
The results showed that the overall incidence of hearing impairment was 17.9% — a percentage that increased with age. Roughly 2% of the subjects had taken some type of PDE-5i drug, 80.3% of whom used sildenafil. Unadjusted results showed that taking PDE-5i was more than twice as common among those with hearing loss (3.0% vs 1.4%); the percentages remained nearly the same after adjustments for demographics and health factors, among other findings.
Those with hearing loss more often used PDE-5i (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.36 - 3.66).
The relationship between PDE-5i drugs and hearing loss was confined to sildenafil (OR, 2.05; 95% CI, 1.23 - 3.43).
No meaningful relationship to hearing loss was seen with tadalafil or vardenafil (ORs, 1.40 [95% CI, 0.49 - 4.04] and 0.88 [95% CI, 0.35 - 2.22], respectively).
Dr. McGwin posited that the relationship between PDE-5i and hearing loss might be a result of the drugs' tendency to promote congestion of nasal erectile tissue, which can then elevate middle ear pressure.
"It has also been suggested that PDE-5i may intensify the effects of nitric oxide, which has been implicated in a number of otologic diseases, or simulate the effects via activated intracellular cyclic guanosine monophosphate (cGMP)," Dr. McGwin writes. "The PDE-5i function by blocking the degradation of cGMP, the accumulation of which induces gene expression via transcription factors by protein phosphorylation by specific kinases, which themselves have been associated with damage to cochlear hair cells."
Although tadalafil demonstrated a slight association with hearing impairment, the rise was not statistically significant. Dr. McGwin acknowledged that the limited use of tadalafil and vardenafil by participants may have prevented the study from finding their possible association with hearing impairment.
Many questions remain about PDE-5i drugs and hearing loss. Still, according to Dr. McGwin, the current findings do substantiate the use of US Food and Drug Administration warnings.
"The largely irreversible nature of [hearing loss] and its impact on quality of life underscore the need for additional research regarding the etiologic role of PDE-5i use," Dr. McGwin writes. "In the interim, it is prudent that patients using these medications, specifically sildenafil, be warned about the signs and symptoms of hearing impairment and be encouraged to seek immediate medical attention to potentially forestall permanent damage."
The study author reported that legal counsel has retained him as an expert witness in cases related to the relationship between Viagra and nonarteritic ischemic optic neuropathy. No other relevant financial relationships were disclosed.
Arch Otolaryngol Head Neck Surg. 2010;136:488-492.