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  簡 介
  宗 旨
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  願 景
  第九屆委員介紹
  主任委員上任序言
  章 程
勃起功能障礙:代謝症候群病人如何治療?

恩主公醫院泌尿科高銘鴻醫師 高銘鴻

1.前言
隨著世界工業化程度越高,飲食精緻化,熱量攝取過高以及生活型態改變,所以帶來的高血壓,高血糖與高血脂等身體狀況,逐漸成為現代人健康的隱憂。而代謝症候群(Metabolic syndrome,簡稱MetS),則是高血壓,高血糖,高血脂與肥胖的總和,它並非單一疾病,而是各種危險疾病的集合體。

代謝症候群的成因主要來自於胰島素抗性(insulin resistence),造成高胰島素血症與接續的血脂過高與代謝問題[1]。在諸多定義中,最常被使用的則是,美國國家膽固醇教育計畫成人治療指引第三版2001年NCEP-ATP III 針對心血管疾病發生風險,向下修正後的診斷標準,我國國民健康局於2004年在專家學者建議下,參酌我國國情,訂定代謝症候群定義,作為我國之臨床診斷準則,接著在2007/1/18作了最新的修正。在以下五個危險因子中,若包含3項或以上者,即可判定為代謝症候群。

  1. 中心肥胖(Central obesity): 腰圍:男性 大於或等於90 公分;女性 大於或等於 80 公分
  2. 血壓上升:收縮壓大於130毫米水銀汞柱或舒張壓大於85 毫米水銀汞柱
  3. 高密度脂蛋白膽固醇 (HDL-C)過低: 男性 小於40 mg/dl;女性 小於50 mg/dl
  4. 空腹血糖值(Fasting glucose)大於或等於100 mg/dl
  5. 三酸甘油脂(Triglyceride)大於或等於150 mg/dl

許多研究指出代謝症候群會增加心血管疾病以及第二型糖尿病等慢性疾病的危險性,且會造成死亡率上升,近年來世界各國盛行率上升,已成為重要的公共衛生議題。而代謝症候群對於心血管疾病有重大影響,因此陰莖的血管在代謝症候群的影響也會受到影響,而近來的研究也指出代謝症候群與勃起功能障礙有關[2]。

勃起功能障礙(Erectile dysfunction)在男性中是常見的問題,影響生活品質巨大,隨著年齡上升,勃起功能障礙的比率也越高[3]。在許多文獻中指出,族群裡勃起功能障礙的盛行率從30-50%不等[3,4,5]。在代謝症候群的病人中,勃起功能障礙的盛行率為79-96%,而有勃起功能障礙的病人,則有29-66%患有代謝症候群[6]。代謝症候群的病人如果心血管危險因子越多,則國際勃起功能指標量表(International Index of Erectile Function,以下簡稱為IIEF)的分數則越低[7,8]。

在陰莖多卜勒超音波底下發現最大收縮流速有下降的趨勢,而代謝症候群中的高血壓與肥胖程度是陰莖動脈血行動力學惡化的獨立預測因子[9]。而代謝症候群中的肥胖因子,跟其他代謝症候群的危險因子有密切相互關聯[10],除此之外肥胖也容易造成男性病人性腺低下(hypogonadism)[11]。有代謝症候群的病人得到性腺功能低下機會是沒有代謝症候群的三倍[12],而性腺功能低下跟心血管疾病,升高的LDL-C與降低的HDL-C也是密切相關[13]。

脂肪組織有芳香酶(Aromatase),會不可逆地將睪固酮轉化為雌激素,而雌激素同時也會抑制促黃體生成素(luteinizing hormone, LH)分泌,進而降低血液中睪固酮濃度[14]。有研究證實雌激素會降低陰莖內的壓力與阻礙血管內皮一氧化氮(Nitric oxide,NO)的釋放[15,16],性腺功能低下可能是代謝症候群與勃起功能障礙之間兩者的連結[17],而其中最重要的可能與胰島素抗性有關。因此,代謝症候群、男性性腺功能低下與勃起功能障礙三者關係密切,而其中的危險因子眾多,單獨治療可能無法逆轉其中錯縱複雜的關聯,而臨床上治療應該以多面向(Multi-modality)的策略來出發。

2.治療策略
治療代謝症候群相關的勃起功能障礙分為治標跟治本,治標的概念為快速增加陰莖內的血流,治本的概念是改善血管功能,而在眾多代謝症候群的危險因子中男性賀爾蒙隱隱扮演連結各危險因子的角色。所以三個目標是改善代謝症候群的因子,回復血中男性賀爾蒙的濃度,快速增加陰莖內血流。治標與治本的方法能達成三個目標的部分,所以需要多方面著手。

改變生活型態(Lifestyle modification)
改變生活型態要從飲食跟運動著手,最終的目的就是減重,改善心血管危險因子,增加睪固酮,進而改善勃起功能障礙。

1)改變飲食
富含脂肪的飲食會增加身體內氧化的壓力與發炎指數[18]。在相同的熱量下,富含蔬果與纖維的飲食相較富含脂肪飲食的造成身體發炎指數則較低[19]。而改變飲食最被推薦的為地中海型飲食,含豐富蔬果,堅果,橄欖油,與omega-3脂肪酸。研究指出在持續地中海型飲食兩年後,對於代謝症候群中的所有危險因子指數皆有下降,血液中發炎指數CRP同時也降低,血管內皮功能也能改善[20]。另一篇研究更指出堅持地中海飲食兩年後,代謝症候群危險因子與IIEF分數都被改善了[21]。

2)運動
一項研究指出,三年內規律的運動可以降低40到59歲族群代謝症候群的發生率[22]。研究指出每天進行30分鐘中等強度的運動,可以增加血中睪固酮的濃度[23],並改善代謝症候群病人勃起功能[24]。而運動與飲食雙管齊下,研究顯示合併飲食與運動後改善心血管功能與性功能還有增加睪固酮濃度[25,26]。

藥物治療
1)第五型磷酸二酯酵素抑制劑(phosphodiesterase type 5 inhibitor, PDE5 inhibitors)
PDE 5 inhibitor已經成為治療勃起功能障礙的第一線用藥,在所有族群中約有70%的病人會有效果。而對於病人同時有代謝症候群於勃起功能障礙的情況時,研究指出單獨使用Verdenafil,對於勃起功能障礙也有明顯的改善[27,28]。持續三個月每日服用5mg Tadalafil在代謝症候群合併勃起障礙的病人,最近的一篇研究指出在病人的IIEF會有改善的情形,甚至連血中睪固酮濃度也會上升[29]。但是過去有研究也指出,代謝症候群的危險因子越多,對於Sildenafil的治療勃起障礙效果則會打折扣[30],所以改善代謝症候群的體質才是治本的方法,但是還沒辦法改變前先從治標開始。

2)睪固酮補充療法
許多研究指出男性性腺功能低下與代謝症候群與勃起功能障礙有密不可分的關係,也有人認為男性性腺功能低下是連接代謝症候群與勃起功能障礙的重要關鍵。而已經有許多文獻提到補充睪固酮可以改善代謝症候群的危險因子狀態[31,32]。在一篇研究中甚至還指出對於糖尿病病人合併性腺功能低下,有超過三分之一的病人在補充睪固酮之後,糖化血色素與腰圍皆有所改善[33]。除了補充睪固酮提升血中濃度外,在許多對於PDE 5 inhibitor效果不好的男性性腺功能低下病人,合併睪固酮補充療法與PDE5 inhibitors治療,對於這些病人勃起功能的情形會比單獨使用PDE 5 inhibitor改善[34,35]。在一篇研究指出,之前對Sildenafil效果不佳的病人,合併補充Testosterone後,多卜勒超音波發現進入陰莖的血流有明顯上升。合併使用對於原本血中睪固酮濃度偏低的病人則特別有效果[36]。但臨床醫師必須謹記在心的是必須告知病人補充睪固酮會造成造精功能低下進而導致不孕,所以必須用在沒有生育打算與沒有禁忌症使用之病人。

3)其他藥物
芳香酶抑制劑Aromatase inhibitor
芳香酶在脂肪組織中可以將睪固酮轉化成雌激素,因此芳香酶抑制劑可以抑制睪固酮的轉化,維持血液中睪固酮的濃度。因此可以當作代謝症候群引起的勃起功能障礙的睪固酮補充的替代療法[37]。但是芳香酶抑制抑制劑的副作用極大如骨質疏鬆並增加骨折風險[38],如要使用則必須同時使用能增加骨密度的藥物。

Clomiphene citrate
Clomiphene citrate是種選擇性雌激素受體調節物(selective estrogen receptor modulator),它可以藉由阻斷雌二醇的副回饋而增加促濾泡激素(FSH)與促黃體激素(LH)分泌,進而增加血中睪固酮濃度[39,40]。因此對於有症狀的睪固酮低下病人合併代謝症候群與勃起功能障礙的病人會有好處。

減肥藥
美國國立衛生研究院National Institutes of Health (NIH)建議BMI大於27~30的病人並有合併症時,需要進行減重,而減肥藥是選項之一。而使用藥物減肥有兩種類型,分別是食慾抑制劑與抑制營養吸收劑。食慾抑制劑的代表是Sibutramine(諾美婷),在一篇統合性分析中發現Sibutramine相較於安慰劑或是其他藥物可以大約多減4公斤[41]。但是諾美婷可能會增加心血管疾病的風險,目前在台灣與世界上多國已被下架而無流通[42,43]。

抑制營養吸收劑以Orlistat(羅氏鮮)作為代表,機轉為脂肪酶的抑制劑進而降低食入的三酸甘油脂的吸收,過去的研究指出可以達到下降10%的體重[44]。在一篇比較Sibutramine與Orlistat的研究中,結果顯示兩者都能降低體重。Orlistat組呈現血壓,血脂、心跳都有下降的情形,但是在Sibutramine組心跳則有顯著的上升[45]。在另一篇研究中,在服用Orlistat六個月後,相較於未服用藥物組別腰圍則減少7公分[46]。雖然Orlistat能降低代謝症候的危險因子,但是如何影響代謝症候群相關的睪固酮濃度與性功能障礙則需要更多的研究。

減重手術(Bariatric Surgery)
減重手術對於病態性肥胖(Morbid obesity)的減重效果極佳並且改善代謝症候群中的危險因子如高血糖症、血脂異常與高胰島素血症[47,48]。相較於生活型態改變與藥物治療,在BMI介於30-35與第二型糖尿病的病人,減重與血糖控制效果較好並且穩定[49]。在一篇最近的系統性回顧與統合性分析中指出接受過減重手術病人後,IIEF-5分數有5.66分的提升,對性功能有顯著的改善(95% CI = 7.88-3.45, I2 = 35%, P < .00001),在IIEF的勃起功能分數也有4.1分的顯著改善(95% CI = 6.10-2.10, I2 = 0%, P < .0001)[50]。而在最近的一篇研究則指出在病態性肥胖合併勃起功能障礙的病人接受減重手術後,術後一個月則可發現早期勃起功能IIEF分數上的改善,在3個月與6個月IIEF則有持續性的進步[51]。

3.結論
因代謝症候群引起的勃起功能障礙,兩者關係與男性性腺功能低下密不可分,所以要治療勃起功能障礙,要從解決代謝症候群的危險因子與男性賀爾蒙低下開始,改變生活方式如藉由飲食與運動,藥物治療則可在男性賀爾蒙低下病人使用睪固酮補充療法或合併PDE 5 inhibitors,而其他藥物目前證據力不強或是副作用大,只能使用在少數特定病人上,最後,減重手術是可以強而有效減重並改善性功能與賀爾蒙狀態,對於嚴重肥胖的病人,提供一個治療上的選擇。

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