Pull many drawers or Push them on a Desk

「physician order entry system」的圖片搜尋結果

 

A Physician Order Entry System is in the Same Design Structure as a Kitchen.  

A physician order entry system (POES)  is complicated.  It is just like a kitchen, there are a lot of drawers and closet. You must draw many drawers and open some closet to have your cookware, seasoning, and foods. Then you can process your work smoothly.

Many people have the same experience. They might forget something that they put them in which drawers. They should try to pull some drawers in order to find them. The Same situation can happen while physician operating an unfriendly and inhuman computer system. A physician they need open a lot of toolbars and seek many option buttons to find the medications and choose the right examination and test, such as whole blood, x-ray or sonography. However, a physician order entry system is really like a kitchen. You can not cook a meal in a novel kitchen and can do nothing in an unfamiliar POES.

If somebody is very intimate, they prepare some foods, eggs and flying pan on a desk. Around them, all seasonings are prepared. You could only cook them and have your meal. That is fine and sweet. A physician can also have the same feeling while they can make a diagnosis, then all concerned will quickly be pushed to a desk. They do not need to do a lot of work to search that they want, however, the medications and tests. It can facility their clinical work and help them to make good management and treatment. Truly, a simple tactics will help a physician to save a lot of time and improve the patients’ satisfaction. They can cease to complain that their physician sees a monitor more than them.  

There is few system is designed by a physician. Nevertheless, the engineering does not understand what a physician needs. Almost POES are designed as a kitchen. There are lots of choice button and many toolbars. A tree-based structure is deployed for physicians to find their option layer by layer, till they find it. A physician just like a cook should pull many drawers to find their options.  Is there any way that physician can have their needs quicker. Yes, it is why a system does not bring all the options on a desk that are concerned with the disease diagnosed. It means push all the options to them and let them have a one-stop shopping.

     

     「kitchen」的圖片搜尋結果

關於臨床資訊系統集成系統

過去醫院的資訊系統,只不過是一個透過系統,把一個散在很多單位的流程,整合起來。主要的目的是通過這樣的系統,可以把帳結的更清楚。

後來因為病歷的保存和運送量太大,檢驗資料把他們整合進去,現行的資訊系統,那是醫院資院的前世今生。

而臨床資料集成系統,當然是未來醫院的很重要的工作,在中國的北京的協合醫院,北京大學的醫院,他們引進了 Microsoft 和 Oracle 在做這方面的工作。

這個臨床資設集成系統,簡稱 Clinical Infomration Intergration System (CIS),聽起來好像是另一個很重大的系統改變,但是它就是物連網的觀念。

在臨床上,有許多的資料,就像血壓計,麻醉科也有一堆機器,婦產科的胎心音記錄,這種有時間序列的臨床資料,醫院的工作場域中,有許多許多的這種資訊。

過去都透過護理人員或底層的醫療工作人員,用手用筆,一筆筆設錄下來,單單的一個記錄,是沒有臨床意義,一定要透過一連續的資訊的收集,才能展現它們的功能。

 

這種臨床資料集成系統,也就像是另一個 PACS 系統,把過去這部份的資料匯編在病歷資料中,最重要的是,它能夠大量減輕護理工作人員的負擔,能讓更少的工作人員,做更多的事情。

基本上,這是人力和效能上的一個很大的指標。

但是這個資料集成的觀念,是很大的挑戰,但是對於醫療工作是一個很好的突破,收到學妹送來的一些資料,我看到這個走向在台灣的醫療工作職場,會帶來某些程度的變化。

要成功,還是需要臨床工作人員和資訊人員的良好溝通,有點難度,我祝福他們,有這個勇氣,有這個機會去嘗試。

臨床資訊系統之整合發展與實務探討

 

 

 

 

對於醫療資訊的前世,今生和未來

星期五,在 FB 上,收到 Alex Wang 的一個交友要求,Alex 一位15年未見的朋友,那時候,他在台北醫學大學醫療資訊研究所就讀,當時我們對於醫院的醫囑系統 CPOE (Computerized Physician Order Entry) 有一個很相同的見解,網頁化的工作環境,能夠在醫院的工作環境中,有很好的效能,比起當時,也可以說是現在還在所使用的 API 的工作環境,來的更友善。

我們共組了一個 Team,來開發這種介面,但是當時沒有成功,因為當時的 IE和 JAVA 的環境,還不成熟,所以這種的醫療工作環境,坎坎坷坷,無法成功的運行。

而今天在藍創的醫療資訊系統上,我們看到了這件事情的成功,界面和運行都非常的完美,但是在中國醫療院所,因為界面的太先進,流程不同於現行醫療人員的思考,還是麻煩一堆,但是這種時勢和走向,應該會是未來的大宗。

從台灣的藥歷檔,還有一些同一集團多院區的工作環境,基本上也都是採用這種設計架構,足見這種系統是比較好工作的方式。

15年了,看到過去自己的 idea 變成了真實的東西,有時候很感嘆,有時候很高興。

2005年到2007年,在美國,UMHS 的工作環境中,看到了一些醫療資訊系統,Go Public 和 Go Individual 的這些,如 Pre-Visit Questionnaire, Dynamic Structure Data Entry, Patient Education on Demand 和  Text in or Scrap out 等等在 Outpatient Service 上的概念,終於有人聽得懂了,可以在期刊發表了。 一些醫療網路行銷 (Medical Internet Intervention) 的故事,也可以出手去賣了。 這些都是我 5到10年內,累績的概念和想法。 很高興的,這些概念可以 Go Publishing 了。

那近五年,我的思考是那些,主要的在醫療資源整合的故事,上個世紀,ERP,SCM 運用在製造的產業,對於整個供應鋉和生產製造業,得到很明顯改善。但是在醫療或服務型的產業,進步微少,最主要的是服務業的產品,單個產品的差異性很大,但是醫療服務上,DRG 和臨床路徑的開展,我們可以預期一些 Disease-Based 的產品,和流程管控的一些概念,會逐漸變成長河。我會遠遠的看看,這些未來的醫療資訊和 Disease-Based 的產品和概念的成長,我希望下一代的醫療資訊,不再是大貓和小貓都走大洞的思考,而是大貓,小貓都走自己的洞,這些大貓,小貓,不是指人的個性化,而是疾病和針對醫療產品的個別化。

利用資訊做產品的展開,Bill of Material 和 ERP 的 Simulation 的思考,逐漸的會在醫療資訊上,扮演一個重要的角色。但是,不容易的是醫療產品的展開,需要有專業知識的醫療工作人員去進行開展,所以需要很高的資本的投入,我想這個故事,不會在台灣的這個環境開花結東,對岸可能有機會,歐美也可能會有這種環境吧。

另外的是 APP 的使用,個人化的病歷載具,會變成最紅最方便的工作,過去所提到的 Personal Medical Record 會變成主流,而取代最在 EMR 在醫療界所佔的地位。而資訊的流通量的增加,雲端的使用,和線上支付系統的成熟,會對未來醫療產品產生很大的變化,而且會有機會改變現行醫療服務和保險。

一般來說病人來醫院有三種重要的需求,其一是透過醫院取得他所需求的藥品,其二是醫院能提供治療性醫療產品,比如說換藥,復健或手術等這方面的醫療產品,其三是最重要的,而且近年來越來越重要的資訊需求,也就是透過醫療院所得到正確,被需要的疾病資訊。

(醫院的選擇  http://powwow.drlin.info/?p=238 )

過去,我們把所有的醫療服務,都放在醫院裏面,未來這些環結和產品,可以進行一種拆解,會型成一種上下流的關係,也就是所謂的生產鍊和醫院資源管理的架構的改變,取代過去醫療院所,盲目的管理人員騎著瞎掉的醫護人員,用著傳統企業管理的工具(不合適的鞍),或許在這方面,醫療資訊和醫院管理,才有機會站在一起。 這種需要跨組織的資訊架構,再十年吧,我們就可以看到這種的情型。

醫療保險的全流和服務流,也會有很大的改變,過去健保局,是集中對醫院支付的,醫院為一個 Pooling 旳地方,再把它分配給廠商,醫師和工作人員。未來這些服務會裂解,成為一個個的產品服務單元,保險對每產品單元的價值和醫師費 Physician Fee,藥品費用更合理的掌控 ,大型的醫療體系,會和醫師 Contract,成為一種開放醫院的架構,台灣大型醫院的存在,會再度的受到挑戰。 這種醫療資訊創造時代,領軍做資源分配的情境,才會出現,過去的那種 Capitation, DRG,Prospect Payment 這種公共衛生體制的不合理管控方式,才會汰舊換新。

再十五年吧,我們可以看到這樣的故事。

未來的醫療資訊,應該是開放的,流動的,可以變型的…..

產科的醫療困境

台灣的產科,到底出了什麼問題,或許大家只看到產科醫師的一個個出走,
到底產科出了什麼問題,有沒有機會去改善產科的醫療品質和產科醫師工作環境,和減少產科醫療風險。

健保上對於產科的支付,包含了兩個部份,生產前的產檢門診和入院生產的部份。

我們先來談一下,住院生產的部份,台灣健保在這個部份,很早就實施所謂的 DRGs 論案件計酬的方式,
2005年開始,無論自然生產和剖腹生產,都支付一個固定的價款,從 2009年後,取消所謂的最低醫療要求。

或許非產科醫師,大概很難了解,上面的這段文字,DRGs的支付方法,是為了減少支付的量,通常支付量是比正常醫療常規所有要的 7成左右,
過去為了保障醫療品質,會要求一個最低醫療需求(Minimal Requirement),但是後來取消了,只要醫師和醫院認為安全,可以減少某些醫療項目。

而絕大部份的產科醫師,在醫院中工作,因為整個產科醫院,需要高人力和高投資,現在受訓完成的產科醫師,通常無法負擔這個的開業成本,
也就是如果你是產科醫師的話,就可以認為你是醫院的員工,而非事業主。
在這種情況下,醫院為了利益極大化,也就是逼迫醫師,減少醫療項目,甚至於要求醫師做某些的風險操作,也就是在 DRGs 的部份,醫師如果在整個治療過程中,減少醫療服務的項目,能多些盈餘(DRGs 的支付是定額),讓醫師有更多的分紅。也就是逼迫或利誘醫師來得到更多的獲利。

   
 

通常在高風險病患的情況下,醫師會採用保護醫療的方式(Protect Medicine),也就是增加某些檢查,包括血液和超音波,或是胎心音監測,來改善醫療的瘉後和減少錯誤診斷或決策的風險,但是在這種 DRGs,你是透過多層次的代理的情況,你無法如此做,所以醫療的風險會密集增高。

現在產科,高齡的產婦增加,妊娠高血懕或糖尿病的風險高,胎兒先天畸型的機會大大升高,而那麼多年,產科的 DRGs 没有考慮到這些,健保的費用没有提升,
醫院和醫師又因為費用壓縮的問題,
所以高危產科的病患,可能處在高風險的情況而不自知,而醫師是知道風險所在,但是無法改變這種情境。

醫師在高被告風險,醫院高壓力和健保低費率,三方面壓力下,無任何保護自己的方法,所以除了那種愛心滿滿的醫師,在高度壓力下留下來,但是絕對是少數,
大多數醫師經過一段時間的產科工作,或有法律糾紛後,都會掛冠求去。

   
 

我們再來檢視產前檢查門診這個部份,台灣的產檢,都按照母嬰健康手册來操作,在 10次的產檢中,僅有一次的超音波檢查,而且不是高解析,一般超音波的機器,
無法排除畸形,而且胎心音的檢查是不支付,這些檢查的項目和現在醫療水平的要求,相差太多,可以告訴大家,整個產檢的設計,大架構有20年没有改過,思考一下,20年母嬰醫學有很大的進步,醫療的項目和醫療規範能不修正更新嗎,而現在的門診,病人的超音波,除了第20週的那次外,其它都是醫師免費的 Service,而且因為產檢基本上,醫院和醫師無利可圖,醫師們為了維持正常的營運,每診看診的病人,超過了40人,才能打平成本,很多的超音波,醫師無法自已操作,
都是一些技術員來操作,這些是醫療上的灰色地帶,這種醫療行為要醫師自行操作,但是通常我們只能看操作員所做出的影像報告來解釋病情。
醫師在產檢部份,高流量的病人,受限制的醫療服務,遇到高危的病人,很多的服務是無償提供,其實這種醫療情況,是非常不利產科醫師。

產科是一種高度教育的科目,因為是高風險,須要很大量和病人的溝通量,在一個診次要看到40-50個病人的情況下,你覺得你的產科醫師真的了解你的病情,你認為產科應該很好的衛生教育嗎,產科醫師也没有能力去改變這種情況,所以看診像打戰。
加上產科因為DRGs的支付,產檢是注定賠錢,產房需要高人力,器材的投入,這些都是需要錢,每年醫療設備的更換,產科的需求都常常被醫院忽視,超音波儀器已經老到瞎了,
解析度己經完完全全跟不上時代,在這護理人員缺額超高的情況下,產房的護理人員流動嚴重,相對於的產房的風險高漲,醫師要自己檢查產科生產的過程,所以日子更難過,
更辛苦。
所有產科醫師,對這樣子的情況,無可奈何。產科後繼無人,醫學中心没有住院醫師,晚上開刀只能請實習醫師做第一助手,在這種情況,大部份剖腹生產難可以,但是遇到困難的病患,真的叫天不應,叫地不靈,那種心力交淬,一個非產科醫師是無法体會的。

 
 

可以用一句話來形容,師老兵疲,缺馬少糧,宰相有權割地,孤臣無力回天,這就台灣產科的情況 ……

所以我就來中國執業了….

   

區域型醫療-虛擬型醫院

過去醫療單位,是一個獨立的團体,集中在某一個點,所有的資源,活動和服務,也都繞著這個點來發動,也就是過去的工廠,從原料到成品,都在一個生產線上完成。在過去資訊不對等,為了保證成品的品質,把所有的團隊,資源,信息綁在一個點上。大型醫院就是這種的代表,醫療是個高成本,高信息含量的工作,所以醫院的組織都傾向大型化保障運作的正常。過往,受限於信息傳輸的高成本,和醫療信息的不順利,這是個必然的現象。當信息系統已善,影像系統,醫療協作系統,和醫院的跨網路,跨組織的的管理工具的出現,例如雲系統,鷹眼系統(PACS)。這時候,新的醫療運營的組織架構,應該可以改善現在大小病都集中在某些大型的醫療機構,造成週邊小型的醫療點非常清閒,而中間大型的醫療單位,非常擁擠。提出一個以信息系統為架構,組織變革為輔助的方式,解決一個區域的醫療問題。婦產科和兒科,多數的醫療活動,重覆性高,是一個系統性,有序列的服務產品,可以拆開在不同的服務點,來進行服務。例如產檢,兒保,婦保的工作。透過一個連結地區的互聯網的系統,將週邊社區內健康中心和中心的婦幼醫院,他們共享同一個醫療信息系統,有完整的電子病歷,將醫療常規整合在標準作業流程中,有一個開放性的影像系統,一個中心檢驗和檢查系統,和一個完善的排程程序。讓產檢過程中,需要超聲波檢查的週數,前往中心的醫院進行產檢,而其它只要驗尿和抽血的其它週數,就在週邊的健康中心完成,等到足月生產時,再行前往中心醫院來待產和生產,等到生產完後,也可以回到健康中心來完成。但是產婦或病人對醫師的選擇,是這個系統成功的重要因素之一,人們認為健康中心的醫師或許在專業上,不如中心醫院的醫師,即使這個信息系統成功完成,這個系統仍然不會成功,這時候就要進行醫療組織的調整,來配合這個信息系統的運作,中心醫院的醫師,安排在週邊的健康中心看診,少部份的門診安排在中心醫院,她的產婦可以在健康中心追踪,需要做某些檢查時,可以安排在中心醫院她的門診來進行。也就是整個健康中心和中心醫院,屬於同一個健康體系,同一個組織架構,有同樣的升職和進修的機會,而病患的服務也可以透過這種系統,安全延續,不會有交接病患的風險。而某些昂貴的檢驗,透過內部的物流系統,進入中央檢驗室,而報告透過電子病歷和信息系統,傳到週邊的健康中心或通過簡訊系統,直接傳播給病患或產婦和組織內公共衛生的單位。過去公共衛生的單位,將轉型成為一個婦兒健康管理的中心,透過這個訊息系統,可以得到完整的基本資料,檢驗和影像,可以對整個區域內的婦兒健康,進行提升,也可以和臨床工作人員合作,提供婦兒一個完整的轉診和關懷的服務。透過整個系統,提供病患和產兒健康教育,健康管理和公共衛生的費用,可以得到醫療服務的分成和補貼。這樣的故事,在台灣的新竹地區和美國的密西根醫療系統,都有成功的例子。透過一個公司的架構,建構這樣平台和組織,是一種可行的辦法,引入部份的社會資本,配合國家的戰略,限制獲利的上限,強調必要的對健康管理和公共衛生的捐助,這樣的方式,可以在未來保障婦兒醫療的品質,也減低了政府在醫療上的高額花費,解決大量病患集中在中心醫院而造成過度擁擠的情況,改善週邊地區醫療的可近性,而且透過這樣的組織改造,能養成更多專業的醫療人員。

E-Prescribing Collaboration in Massachusetts

J.Am Med Inform Assoc. 2006:13:239-244

Ten barriers for E-Prescibing

1. Previous Negative Technology Experience

2.   Inital and Long-Term Cost

3.  Lost Productivity

4. Competing Priorities

5. Change Management Issues

6. Interoperability limitations

7. Information Technology IT requirements

8. Standards Limitations

9. Waiting for an "All in One Solution"

10 Confusion about competing product offerings including hospital/Integrated Delivery System (IDN)

Electronic Medical Record 的想法

最近在 Review EMR 的相關文章,新的 EMR 整合了各種的 Media 增加了 Medical Record 的豐富性,比起過去以 Text-Based 的病歷記錄來說,可讀性增加,Figure 和 Photo 的加入,使得醫師對於病人的情況掌握和回憶的程度較佳,而不再依賴醫師個人的記憶,提供了轉換醫師所造成的新醫師對病情熟悉程度降低的窘境。

但是較過去複雜的 Physician Order Entry System,各種 Media 所需要的輸入方式不同,需要填寫的內容增加,為了增加記載的豐富程度,卻增加了醫療人員書寫(記錄)病歷的時間,大幅增加。

病歷的記錄是重要且必要的,要維持醫療的品質,良好病歷是個很好的指標,但是對醫師對病人看診時間的長度,會有造成壓縮的情況,減少醫師問診的時間,可能導致門診品質的下降。

Medical Record Processing (Writing)的過程,才是最重要的,是否能以比較短,比較簡單的方式來完成,而這種方式能夠產生內容相對豐富,為了改善病歷的記錄方式,幾個比較可行的方法,現在正在推廣實驗中,Natural Language Processing (NLP) 就是一個聽寫系統,透過程式處理人(醫師)的聲音,將這些資料以文字的方式呈現,但是聽寫系統可能有錯誤解讀的情況,另一個重要的問題是,言語比起文字更為不精確,將言語真接翻釋成文字,將造成文字記載的程序性和結構性消失,使得閱讀和情境再生的能力下滑,Structure Data Entry (SDE),是另一種好方法,透過類似節構性問卷的方式,讓醫療人員,可以以簡單的點選方式,產生病歷記錄。

 

Dynamic Structure Data Entry 的方式,做為 Medical Record 收集資料的方法,結構化病歷的架構

2006年 BMC medical informatics and decision making  6.29 Dr. Bleeker

Structured data entry for narrative data in a broad specialty:
patient history and physical examination in pediatrics

嘗用 SDE 的方式,利用分割的畫面,以 Tree 和 電子表單的方式填寫,將嬰兒體重,溫度,常見的症狀,和一般需要的注載的部份,以 Tree 點選,再以電子表單的方式點選,再利用這些填寫的資料,整合為 Narrative 的病歷。

作者是用 OpenSDE Website 的觀念,SDE 的 Construct 可以隨著不同的科別,不同的需求,來更改,增加,修正架構,是一個 Very Flexibility 的方式,可以改善過去病歷記錄的上所遇問題。

 

2 Hypothesis:

1.  個別醫師看診的疾病種類,侷限在某些疾病上

2. 個別醫師看診時所開立的藥品處方和檢驗項目,和疾病種類有高度的相關

 

Flow Change

 

記載病歷 –>診斷 –> 開立處方和檢驗

Replaced with..

診斷 –> 記載病歷 –> 開立處方和檢驗

 

Model

Individual Interface (依照個別醫師的看診,記錄和處方的習慣 )

Disease Orientation  ( 自已慣看的疾病診斷的排序)

Disease Related History Taking (疾病相關的資料記載)

Disease related medication & laboratory examination. (疾病相關的藥品,檢驗的選擇)

Human Papillomavirus (US CDC Pink Book) Patient Information

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. The relationship

of cervical cancer and sexual behavior was suspected for more than 100 years and was established by epidemiologic

studies in the 1960s. In the early 1980s, cervical cancer cells were demonstrated to contain HPV DNA. Epidemiologic

studies showing a consistent association between HPV and cervical cancer were published in the 1990s. The first

vaccine to prevent infection with four types of HPV was licensed in 2006.

Human Papillomavirus

Human papillomaviruses are small, double-stranded DNA viruses that infect the epithelium. More than 100 HPV

types have been identified; they are differentiated by the genetic sequence of the outer capsid protein L1. Most HPV

types infect the cutaneous epithelium and cause common skin warts. About 40 types infect the mucosal epithelium;

these are categorized according to their epidemiologic association with cervical cancer. Infection with low-risk,

or nononcogenic types, such as types 6 and 11, can cause benign or low-grade cervical cell abnormalities, genital warts

and laryngeal papillomas. High-risk, or oncogenic, HPV types act as carcinogens in the development of cervical

cancer and other anogenital cancers. High-risk types (currently including types 16, 18, 31, 33, 35, 39, 45, 51, 52,

56, 58, 59, 68, 69, 73, 82) can cause low-grade cervical cell abnormalities, high-grade cervical cell abnormalities that

are precursors to cancer, and anogenital cancers. High-risk HPV types are detected in 99% of cervical cancers. Type 16

is the cause of approximately 50% of cervical cancers worldwide, and types 16 and 18 together account for about 70%

of cervical cancers. Infection with a high-risk HPV type is considered necessary for the development of cervical cancer,

but by itself it is not sufficient to cause cancer because the vast majority of women with HPV infection do not develop

cancer.

In addition to cervical cancer, HPV infection is also associated with anogenital cancers less common than cervical cancer, such as cancer of the vulva, vagina, penis and anus. The association of genital types of HPV with non-genital cancers is less well established, but studies support a role for these HPV types in a subset of oral cavity and pharyngeal cancers.

Pathogenesis

HPV infection occurs at the basal epithelium. Although the incidence of infection is high, most infections resolve

spontaneously. A small proportion of infected persons become persistently infected; persistent infection is the most

important risk factor for the development of cervical cancer precursor lesions. The most common clinically significant

manifestation of persistent genital HPV infection is cervical intraepithelial neoplasia, or CIN. Within a few years of

infection, low-grade CIN—called CIN 1—may develop, which may spontaneously resolve and the infection clear.

Persistent HPV infection, however, may progress directly to high-grade CIN, called CIN2 or CIN3. High-grade

abnormalities are at risk of progression to cancer and so are considered cancer precursors. A small proportion of highgrade abnormalities spontaneously regress. If left undetected and untreated, years or decades later CIN2 or 3 can progress to cervical cancer.

Infection with one type of HPV does not prevent infection with another type. Of persons infected with mucosal HPV,

5% to 30% are infected with multiple types of the virus.

Clinical Features

Most HPV infections are asymptomatic and result in no clinical disease. Clinical manifestations of HPV infection

include anogenital warts, recurrent respiratory papillomatosis, cervical cancer precursors (cervical intraepithelial neoplasia), and cancers, including cervical, anal, vaginal, vulvar, penile, and some head and neck cancer.

Laboratory Diagnosis

HPV has not been isolated in culture. Infection is identified by detection of HPV DNA from clinical samples. Assays for

HPV detection differ considerably in their sensitivity and type specificity, and detection is also affected by the anatomic

region sampled as well as the method of specimen collection. Currently, only the Digene Hybrid Capture®2 (hc2) High-

Risk HPV DNA Test is approved by the Food and Drug Administration for clinical use The hc2 uses liquid nucleic

acid hybridization and detects 13 high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Results are

reported as positive or negative and are not type-specific. The hc2 test is approved for triage of women with equivocal

Papanicolaou (Pap) test results (ASC-US, atypical cells of undetermined significance) and in combination with the

Pap test for cervical cancer screening in women over age 30. The test is not clinically indicated nor approved for use in men.

Epidemiologic and basic research studies of HPV generally use nucleic acid amplification methods that generate typespecific results. The PCR assays used most commonly in epidemiologic studies target genetically conserved regions in the L1 gene.

The most frequently used HPV serologic assays are VLPbased enzyme immunoassays. However, laboratory reagents

used for these assays are not standardized and there are no standards for setting a threshold for a positive result.

Medical Management

There is no specific treatment for HPV infection. Medical management depends on treatment of the specific clinical

manifestation of the infection (such as genital warts or abnormal cervical cell cytology).

Epidemiology

Occurrence

HPV infection occurs throughout the world.

Reservoir

Viruses in the papillomavirus family affect other species (notably rabbits and cows). However, humans are the only

natural reservoir of HPV.

Transmission

HPV is transmitted by direct contact, usually sexual, with an infected person. Transmission occurs most frequently

with sexual intercourse but can occur following nonpenetrative sexual activity. Studies of newly acquired HPV infection demonstrate that infection occurs soon after onset of sexual activity. In a prospective study of college women, the cumulative incidence of infection was 40% by 24 months after first sexual intercourse. HPV 16 accounted for 10.4% of infections.

Genital HPV infection also may be transmitted by nonsexual routes, but this appears to be uncommon. Nonsexual

routes of genital HPV transmission include transmission from a woman to a newborn infant at the time of birth.

Temporal Pattern

There is no known seasonal variation in HPV infection.

Communicability

HPV is presumably communicable during the acute infection and during persistent infection. This issue is difficult to

study because of the inability to culture the virus. Communicability can presumed to be high because of the

large number of new infections estimated to occur each year.

Risk Factors

Risk factors for HPV infection are related to sexual behavior, including the number of sex partners, lifetime history of

sex partners, and the partners’ sexual history. Most studies suggest that young age (less than 25 years) is a risk factor

for infection. Results of epidemiologic studies are less consistent for other risk factors, including young age at sexual

initiation, inconsistent condom use, number of pregnancies, genetic factors, smoking, lack of circumcision of male partner, and oral contraceptive use

Disease Burden in the United States

Anogenital HPV infection is
believed to be the most common sexually transmitted infection in the United States. An

estimated 20 million persons are currently infected, and an estimated 6.2 million new HPV infections occur annually.

HPV infection is common among adolescents and young adults. Prevalence among adolescent girls is as high as 64%.

Up to 75% of new infections occur among persons 15–24 years of age. Modeling estimates suggest that more than 80%

of sexually active women will have been infected by age 50.

HPV infection is also common in men. Among heterosexual men in clinic-based studies, prevalence of genital HPV

infection is often greater than 20%. Prevalence is highly dependent on the anatomic sites sampled and method of

specimen collection.

The two most common types of cervical cancer worldwide, squamous cell carcinoma followed by adenocarcinoma, are

both caused by HPV. The American Cancer Society estimates that in 2006 about 9,700 new cases of cervical cancer

will be diagnosed in the United States. Approximately 3,700 women will die as a result of cervical cancer. HPV is

believed to be responsible for nearly all of these cases of cervical cancer. HPV types 16 and 18 are associated with

70% of these cancers.

In addition to cervical cancer, HPV is believed to be responsible for 90% of anal cancers, 40% of vulvar, vaginal,

or penile cancers, and 12% of oral and pharyngeal cancers. Population-based estimates, primarily from clinics treating

persons with sexually transmitted infections, indicate that about 1% of the sexually active adolescent and adult population in the United States have clinically apparent genital warts. More than 90% of cases of anogenital warts are associated with the low-risk HPV types 6 and 11.

About 4 billion dollars are spent annually on management of sequelae of HPV infections, primarily for the management

of abnormal cervical cytology and treatment of cervical neoplasia. This exceeds the economic burden of any other

sexually transmitted infection except human immunodeficiency virus.

Prevention

HPV Infection

HPV transmission can be reduced but not eliminated with the use of physical barriers such as condoms. Recent studies

demonstrated a significant reduction in HPV infection among young women after initiation of sexual activity when

their partners used condoms consistently and correctly.

Abstaining from sexual activity (i.e., refraining from any genital contact with another individual) is the surest way to

prevent genital HPV infection. For those who choose to be sexually active, a monogamous relationship with an uninfected partner is the strategy most likely to prevent future genital HPV infections.

Cervical Cancer Screening

Most cases and deaths from cervical cancer can be prevented through detection of precancerous changes

within the cervix by cervical cytology using the Pap test.

Currently available Pap test screening can be done by a conventional Pap or a liquid-based cytology. CDC does

not issue recommendations for cervical cancer screening, but various professional groups have published recommendations.

The American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society

(ACS), and the U.S. Preventive Services Task Force (USPSTF) guidelines recommend that all women should

have a Pap test for cervical cancer screening within 3 years of beginning sexual activity or by age 21, whichever

occurs first. While the USPSTF recommends a conventional Pap test at least every 3 years regardless of age, ACS

and ACOG recommend annual or biennial screening of women younger than age 30, depending on use of

conventional or liquid–based cytology. According to these national organizations, women over age 30 with three

normal consecutive Pap tests should be screened every 2 to 3 years.

The use of HPV vaccine does not eliminate the need for continued Pap test screening, since 30% of cervical cancers

are caused by HPV types not included in the vaccine.

Human Papillomavirus Vaccine

Characteristics

The currently licensed vaccine is a quadrivalent HPV vaccine (Gardasil, Merck). The vaccine antigen is the L1

major capsid protein of HPV, produced by using recombinant DNA technology. The L1 protein is expressed

in Saccharomyces cerevisiae (yeast) cells, and the protein self-assembles into noninfectious, nononcogenic viruslike-

particles (VLP). Each 0.5-mL dose contains 20 μg HPV 6 L1 protein, 40 μg HPV 11 L1 protein, 40 μg HPV

16 L1 protein, and 20 μg HPV 18 L1 protein. The VLPs are adsorbed on 225 μg alum adjuvant. The vaccine also

includes sodium chloride, L-histidine, polysorbate 80, sodium borate, and water for injection. The quadrivalent

HPV vaccine contains no thimerosal or antibiotics. The vaccine is supplied in single-dose vials and syringes.

Immunogenicity and Vaccine Efficacy

The immunogenicity of the quadrivalent HPV vaccine has been measured by detection of IgG antibody to the HPV L1

by a type-specific immunoassay developed by the manufacturer.

In all studies conducted to date, more than 99.5% of participants developed an antibody response to all four

HPV types in the vaccine 1 month after completing the three-dose series. At that time interval, antibody titers against

HPV types 6, 11, 16, and 18 were higher than those that developed after natural HPV infection.

There is no known serologic correlative of immunity and no known minimal titer determined to be protective. The high

efficacy found in the clinical trials to date has precluded identification of a minimum protective antibody titer. Further

follow-up of vaccinated cohorts may allow determination of serologic correlates of immunity in the future.

HPV vaccine has been found to have high efficacy for prevention of HPV vaccine type–related persistent infection,

vaccine type–related CIN, CIN2/3, and external genital lesions in women 16–26 years of age. Clinical efficacy

against cervical disease was determined in two double-blind, placebo-controlled trials, using various endpoints. Vaccine

efficacy was 100% for prevention of HPV 16 or 18–related CIN 2/3 or adenocarcinoma in-situ (AIS). Efficacy against

any CIN due to HPV 6, 11, 16, or 18 was 95%. Efficacy against HPV 6, 11, 16 or 18–related genital warts was 99%.

Although high efficacy among females without evidence of infection with vaccine HPV types was demonstrated in

clinical trials, there was no evidence of efficacy against disease caused by vaccine types with which participants were

infected at the time of vaccination. Participants infected with one or more vaccine HPV types prior to vaccination

were protected against disease caused by the other vaccine types. However, prior infection with one HPV type did not

diminish efficacy of the vaccine against other vaccine HPV types.

There is no evidence that the vaccine protects against disease due to non-vaccine HPV types or provides a therapeutic

effect against cervical disease or genital warts present at the time of vaccination.

A subset of participants in the phase II HPV vaccine study has been followed for 60 months post-dose 1 with no evidence

of waning protection. Study populations will continue to be followed for any evidence of waning immunity.

HPV vaccine has been shown to be immunogenic and safe in males. However, no clinical efficacy data are available for

males. These studies are in progress.

Vaccination Schedule and Use

As of January 2007, ACIP recommendations for use of HPV vaccine have not been published. Recommendations included
here are provisional until published in the Morbidity and Mortality Weekly Report.

Quadrivalent HPV vaccine is licensed by the Food and Drug Administration for use among females 9–26 years of

age. The recommended age for routine vaccination in the United States is 11–12 years. The vaccine can be given as

young as 9 years of age at the discretion of the clinician.

The vaccine should be given at the same visit as other vaccines recommended for persons of this age (e.g., Tdap,

meningococcal conjugate, hepatitis B).

At the beginning of a vaccination program, there will be females older than 12 years of age who did not have the

opportunity to receive vaccine at age 11–12 years. Catch-up vaccination is recommended for females 13 through 26 years of age who have not been previously vaccinated or who have not completed the full series. Ideally, vaccine should

be administered before potential exposure to HPV through sexual contact; however, females who may have already

been exposed to HPV should be vaccinated. Sexually active females who have not been infected with any of the HPV

vaccine types will receive full benefit from vaccination.

Vaccination will provide less benefit to females if they have already been infected with one or more of the four HPV

vaccine types. However, it is not possible for a clinician to assess the extent to which sexually active females would

benefit from vaccination, and the risk of HPV infection may continue as long as persons are sexually active. Pap testing

or screening for HPV DNA or HPV antibody is not recommended prior to vaccination at any age.

HPV vaccine is administered in a three-dose series administered by intramuscular injection. The second and third

doses should be administered 2 and 6 months after the first dose. The minimum interval between the first and second

doses is 4 weeks. The minimum interval between the second and third dose of vaccine is 12 weeks. Doses administered at an interval shorter than the minimum interval should not be counted as valid and should be repeated.

If the HPV vaccine schedule is interrupted, the vaccine series does not need to be restarted. If the series is interrupted

after the first dose, the second dose should be given as soon as possible, and the second and third doses should be

separated by an interval of at least 12 weeks. If only the third dose is delayed, it should be administered as soon as possible.

Although no data are available yet on administration of quadrivalent HPV vaccine with vaccines other than

hepatitis B vaccine, the vaccine contains only HPV capsid protein and has no components that have been found to

adversely affect safety or efficacy of other vaccinations.

The vaccine can be administered at the same visit as other age-appropriate vaccines, such as Tdap and quadrivalent

meningococcal conjugate (MCV4) vaccines. Administering all indicated vaccines at a single visit increases the likelihood

that adolescents and young adults will receive each of the vaccines on schedule. Each vaccine should be administered

using a separate syringe at a different anatomic site.

HPV vaccine is not approved for use among females younger than 9 years or older than 26 years of age. Use of the vaccine in females younger than 9 years or older than 26 years is not recommended. Studies with females older than 26 years of age are ongoing. There are no current studies among children younger than 9 years of age.

Quadrivalent HPV vaccine is not licensed for use among males, and off-label use among males is not recommended.

While data on immunogenicity and safety are available for 9–15-year-old males, there are no data on efficacy in males

at any age. Efficacy studies among males are under way.

Females who have an equivocal or abnormal Pap test could be infected with any of more than 40 high-risk or low-risk

genital HPV types. It is unlikely that such females would be infected with all four HPV vaccine types, and they may not

be infected with any HPV vaccine type. Women younger than 27 years with a previously abnormal Pap test may be

vaccinated. Women should be advised that data do not indicate the vaccine will have any therapeutic effect on

existing HPV infection or cervical lesions.

Females who have a positive HPV DNA test (Hybrid Capture 2®)done in conjunction with a Pap test could be infected with any of 13 high-risk types. This assay does not identify specific HPV types, and testing for specific HPV types is not done routinely in clinical practice. Women younger than 27 years with a positive HPV DNA test may be vaccinated. HPV DNA testing is not a prerequisite for vaccination. Women should be advised that the vaccine will not have a therapeutic effect on existing HPV infection or cervical lesions. A history of genital warts or clinically evident genital warts indicate infection with HPV, most often type 6 or 11. However, these females may be infected with HPV types other than the vaccine types, and therefore they may receive HPV vaccine if they are in the recommended age group. Women with a history of genital warts should be advised that data do not indicate the vaccine will have any therapeutic effect on existing HPV infection or genital warts.

Because quadrivalent HPV vaccine is a subunit vaccine, it can be administered to females who are immunosuppressed

because of disease or medications. However, the immune response and vaccine efficacy might be less than that in

persons who are immunocompetent. Women who are breastfeeding may receive HPV vaccine.

Adverse Reactions Following

Vaccination

The most common adverse reactions reported during clinical trials of HPV vaccine were local reactions at the site of

injection. These were most commonly pain (84%), swelling (25%), and erythema (25%). The majority of injection-site

adverse experiences reported by recipients of quadrivalent HPV vaccine were mild to moderate in intensity. Fever was

reported within 15 days of vaccination by 10% of vaccine recipients and 9% of placebo recipients. No serious adverse

reactions have been reported.

A variety of systemic adverse reactions were reported by vaccine recipients, including nausea, dizziness, myalgia and

malaise. However, these symptoms occurred with equal frequency among both vaccine and placebo recipients.

Contraindications and Precautions

to Vaccination

A severe allergic reaction (acute respiratory distress or collapse) to a vaccine component or following a prior dose

of HPV vaccine is a contraindication to receipt of HPV vaccine. A moderate or severe acute illness is a precaution

to vaccination, and vaccination should be deferred until symptoms of the acute illness improve. A minor acute illness

(e.g., diarrhea or mild upper respiratory tract infection, with or without fever) is not a reason to defer vaccination.

HPV vaccine is not recommended for use during pregnancy. The vaccine has not been associated with adverse outcomes

of pregnancy or with adverse effects on the developing fetus. However, data on vaccination during pregnancy are limited.

Until further information is available, initiation of the vaccine series should be delayed until after completion of

the pregnancy. If a woman is found to be pregnant after initiating the vaccination series, the remainder of the threedose regimen should be delayed until after completion of the pregnancy. If a vaccine dose has been administered during pregnancy, no intervention is indicated. A vaccine in pregnancy registry has been established; patients and healthcare providers are urged to report any exposure to quadrivalent

HPV vaccine during pregnancy by calling (800) 986-8999.

Vaccine Storage and H

andling

HPV vaccine should be stored continuously at 35°–46°F (2°–8°C) and should be protected from light. The vaccine

should be removed from refrigeration immediately before administration. The vaccine must not be exposed to freezing

temperature. Vaccine exposed to freezing temperature should never be administered.

Selected References

American College of Obstetricians and Gynecologists.  Human papillomavirus vaccination. ACOG committee opinion No. 344. Obstet Gynecol 2006;108:699–705.

CDC. Provisional recommendations for the use of quadrivalent HPV vaccine. Available at http://www.cdc.

gov/nip/recs/provisional_recs/hpv.pdf (Publication of these recommendations is anticipated in early 2007.)

Dunne E, Markowitz L. Genital human papillomavirus infection. Clin Infect Dis 2006;43:624–9.

Koutsky LA, Kiviat NB. Genital human papillomavirus. In: Holmes KK, Sparling PF, Mardh PA, et al, eds. Sexually

Transmitted Diseases. 3rd ed. New York: McGraw-Hill; 1999:347–59.

Schiller J, Lowy D. Human papillomavirus vaccines for cervical cancer prevention. In: Plotkin SA, Orenstein, WA,

eds. Vaccines. 4th ed. Philadelphia: Saunders; 2003:1259–65.

Trottier H, Franco E. The epidemiology of genital human papillomavirus infection. Vaccine 2006;24(suppl1):51–15.

Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–44

Weinstock H, Berman S, Cates W, Jr. Sexually transmitted diseases among American youth: incidence and prevalence

estimates, 2000. Perspect Sex Reprod Health. 2004;36:6–10.

Winer R, Hughes J, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women.

N Engl J Med 2006;354:2645–54.

Winer R, Lee S, Hughes J, et al. Genital human papillomavirus infection incidence and risk factors in a cohort of

female university students. Am J Epidemiol 2003;157:218-26.

Equivalence, Superiority and Non-Inferiority

在新藥審查時,藥品的 Efficacy 的研究,時常使上面三個名詞,我的治療和原本的治療是 Equivalence, 是優於某種治療(Superiority),是不遜於那種治療的 (Not Inferiority)。

在統計學上,有單雙尾的問題,一篇 EMBA 的 Guidance 可以用來解說,這三種 Hypothesis and Analysis

 

95% CI, Mean 的落點,可以參考下面三個圖

 

 

 

 

 

荷爾蒙療法問與答

1、什麼是更年期?

更年期乃是婦女由生育年齡進入非生育年齡的過渡時期,婦女因卵巢功能隨年齡增加而逐漸退化,此時卵巢逐漸減少性荷爾蒙﹝包括雌激素、黃體素、雄激素﹞的產生,終致生理上的月經完全終止。正常來說,停經通常於45歲至55歲間完成。而在停經前後二到五年的過渡時期,稱為「更年期」。此時由於卵巢雌激素的分泌日漸減少,產生種種生理變化及一些不適症狀,如潮紅、盜汗、陰道尿道發炎、心悸、失眠、情緒不穩等,一般稱為「更年期症候群」或「停經症候群」,這些症狀大多發生在更年期早期。某些婦女如果接受兩側卵巢切除手術,使用治癌化學藥物的治療疾病、或接受骨盆區的放射線治療,則月經會停止,稱作「醫源性停經」。

更年期是女性生命週期中自然且必經的階段,婦女朋友要認識更年期,享受更年期,注重保健之道,才能留住風華、享受健康,提昇生活品質。

2、更年期婦女應如何自我保健?

二十一世紀的今天,對於預防保健的觀念,已由過去強調疾病篩檢與疫苗接種,轉為加強對個人健康行為的建立,因此,因此建議每個面臨更年期的婦女們都應採取健康的生活方式,而且應從年輕時就做起。建議如下

(一)定期身體健康檢查

1.每年定期做子宮頸抹片、骨盆腔的檢查。

2.每月做一次乳房的自我檢查,每年定期接受乳房超音波或乳房攝影檢查 。

(二)保持良好生活習慣:戒除不良的嗜好,如:抽煙、酗酒或飲用過量的咖啡,皆會妨礙鈣質吸收。

(三)注意營養均衡

1.多吃蔬菜水果,少油、鹽、糖,避免刺激性及辛辣食物。

2.攝取足夠的鈣質:除一般牛奶外,亦可多攝取其他含鈣量高的食物,如:小魚乾、深色蔬菜及黑芝麻等。

(四)持續規律的運動習慣

1.適度的戶外運動與日曬:陽光能幫助身體產生維他命D,維他命 D可以加強腸胃道對鈣的吸收,也可使骨骼再造速率加快。

2.運動項目要選擇適合個人的體能狀況(如游泳、太極拳、外丹功等),避免需要碰撞或快速移位的運動,以免摔倒。

3.有些負重運動(如慢跑、騎單車、步行、提重等)能增加骨質,但患有關節炎者,則應避免,以免增加關節負荷。

(五)心理良好的調適

1.自我成長:培養正當嗜好,擴大生活圈,加入社團活動或志工。

2.家庭關係:多關心自己,照顧配偶。

3.夫妻關係:夫妻培養共同的興趣,多做言語交談及心靈交流。

4.親子關係:多給子女生活空間,多溝通而非抱怨。

(六)雖然更年期使用荷爾蒙會有一些立即可見的效果及可預期效益,但長期使用可能會有一些健康上的考量。因此,荷爾蒙療法需依個人需求,並與醫師商討是否適用及如何使用等,以決定最好的選擇。

3、更年期婦女荷爾蒙治療是否有替代的方法?

目前,坊間有一些所謂含植物性雌激素的天然食物萃取物﹝如黃豆、全麥穀類、種子、某些蔬果等﹞、或中草藥等,均曾被用來治療短期的更年期症狀,然其效果及安全性仍待更多的科學之驗證。

最近的臨床報告,大豆異黃酮對於停經後潮紅和盗汗有些許的效果,但所需劑量要一般攝取食物量的200倍以上。已經證實無法改善骨質疏鬆的情況,也無法緩解陰道萎縮、乾燥所造成的性交疼痛和萎縮性發炎的情況。

對於停經後所造成的失眠等症狀,某些新型短效安眠藥品,退黑激素,短效鎮定劑等藥品,能夠適時減少停經後急性的精神症狀。

4、更年期婦女如何決定是否接受荷爾蒙療法?

一般而言,婦女若沒有更年期症狀,不需使用荷爾蒙治療。若有更年期症狀可考慮使用荷爾蒙治療,但應經醫師的健康評估、告知荷爾蒙療法的好處與風險,雙方充分討論,以決定如何治療。

目前已使用荷爾蒙療法的婦女,應與醫師仔細商量,了解利弊後再做是否繼續使用的決定。

5更年期荷爾蒙療法有哪些?

所謂更年期荷爾蒙療法,是指停經後婦女經由外界提供(口服、經皮、經陰道、經黏膜等)雌激素,以減輕更年期症狀及不適。就是補充自然停經或醫療引起的的女性荷爾蒙缺乏症;目前臨床上大致可分成4種方法:

1.單獨傳統劑量雌激素的荷爾蒙療法:因為雌激素易刺激子宮內膜增生,進而增加子宮內膜癌的風險,因此,只適用於子宮已經切除的婦女。

2.週期性順序型的荷爾蒙療法:此類型療法在週期中,每天皆服用雌激素,並在每一週期後段的十二至十四天添加服用黃體素。在服用黃體素結束後會有類似月經來潮的出血。

3.連續性合併型的荷爾蒙療法:每天合併使用雌激素與黃體素,原則上此種療法能避免類似月經來潮和出血現象,但臨床上仍有少部分婦女會產生少量不規則出血。

4.
超低劑量雌激素的單獨荷爾蒙療法:雌激素的使用約為傳統劑量的1/4量。這種超低劑量的單獨雌激素治療,極少發生子宮內膜增厚的變化。因不需使用黃體素,因此與乳癌、心臟血管疾病的發生較無相關。不會有陰道出血的現象。

6、更年期在何種情況下才要使用荷爾蒙?

更年期使用荷爾蒙的主要目的,在於治療「更年期症狀」,包括全身或臉部熱潮紅、夜間盜汗、失眠、陰道乾澀、心悸、煩躁等。

荷爾蒙過去常被使用於預防停經婦女骨質流失。然而,最近美國國家衛生院公布的研究報告顯示,長期使用連續性合併型的荷爾蒙療法,其風險大於其好處,主要原因是增加心血管疾病和乳癌的發生率,但也顯示對骨質保護及骨折減少的效益。因此,建議國內婦女,如以預防骨質流失為目的,而決定使用荷爾蒙療法之前,應先向醫師請教,充分了解使用後的利弊得失,千萬不可自行服用。

婦女在子宮切除後,可單獨使用雌激素,據
2006年,JAMA所刊載,美國22個醫學中心,20萬人的大型研究,證實單獨使用雌激素比不使用者,乳癌的發生機率較低,長期單獨使用雌激素的婦女,心臟血管和中風的發生機會,較不服用者來的低,骨折的機會也相對降低。

7、更年期使用荷爾蒙,對子宮有何影響?

研究顯示,子宮如果長期受傳統劑量的雌激素刺激而無黃體素的拮抗作用,罹患子宮內膜癌的機率會增加。因此,停經婦女如果子宮仍然完整,須使用雌激素合併黃體素的荷爾蒙療法或超低劑量的單獨雌激素荷爾蒙療法;如果子宮已經切除,只須單獨使用雌激素。有關藥物之使用,建議應與醫師討論。

未摘除子宮的婦女,單獨服用雌激素,恐導致子宮內膜癌,仍須合併使用黃體素,但可能有罹患乳癌的風險。

近年研發的雌激素新藥,對不同的雌激素受體有選擇性的結合,意思就是這種新藥不會刺激子宮內膜增厚,也就不須合併黃體素使用。這些新藥,亦能刺激骨骼上的雌激素受體。對於不能使用傳統荷爾蒙合併療法的婦女,此類雌激素能夠改善骨質疏鬆的問題。

8、更年期使用荷爾蒙,對心血管有何影響?

最近研究顯示,使用雌激素與黃體素連續性合併型的荷爾蒙療法,對心臟並無益處。因此,罹患心臟病的更年期婦女,不應期待使用合併型荷爾蒙療法,來減低心血管疾病併發症的風險。至於單獨使用雌激素的荷爾蒙療法,對心臟疾病並未產生正面或負面的影響。

2004年的JAMA報告,證實雌激素與黃體素合併型服用者,在最初使用的一年間,確實有提高心血管疾病的風險。長期服用荷爾蒙補充的病人,並沒有很明顯的心臟血管疾病,對於只服用單一雌激素的患者,反而有明顯減少心臟血管方面的風險。

9、更年期使用荷爾蒙,對骨骼有何影響?

雌激素減少,是更年期婦女骨質流失的主要危險因子。研究顯示,單獨使用雌激素或雌激素合併黃體素等荷爾蒙療法,皆可以預防骨質流失;也可以減少髖部及脊椎等處之骨折。然而,也有研究顯示,短期﹝三至五年﹞治療更年期症候群的荷爾蒙療法,並未能預防婦女在75-80歲時發生骨折,婦女如欲使用雌激素以維持骨密度,則必須長期使用,因為一旦停用,其對骨質健康的益處就會逐漸消失。

然而骨質疏鬆的成因相當複雜,荷爾蒙的減少並不是唯一的原因。更年期婦女可以透過生活方式的改變幫助減少骨質的流失,如:走路、跑步、舉重等運動;低脂、高鈣、高維他命D的飲食習慣;攝取足夠的陽光及減少飲酒及抽煙。事實上,預防骨質疏鬆最好的方法,應在女性年輕時就開始建立良好的生活習慣以儲存骨本。

近來有些活性維生素D3,副甲狀腺素,褔善美等的藥品,在臨床上己被證實能夠預防和治療骨質疏鬆的問題,荷爾蒙補充來防止骨質疏鬆的方式,己退居第二線。現在很少醫師會以荷爾蒙治療作為預防和治療骨質疏鬆的主力用藥。

未來長效型的雙磷酸鹽,服用一次可以維持三個月到半年的藥效,對於這類骨質疏鬆病人,將是ㄧ大福音。

10更年期使用荷爾蒙,對乳癌的發生率有何影響?

研究顯示,長期使用超過五年以上雌激素合併黃體素荷爾蒙的婦女,罹患乳癌的機率略高於一般同齡層婦女。單獨使用雌激素經過七年追蹤乳癌沒有增加而有稍許減少的現象。

根據最新的國外研究,有乳癌病史的婦女使用荷爾蒙可能會增加乳癌再發的機率。雖然國內目前並沒有具體統計數字,或相關研究證實相同結果,不過由於近年來國內乳癌發生率逐年增加,因此,凡是有乳癌病史的婦女應避免使用荷爾蒙。婦女無論有否使用荷爾蒙療法,亦都應定期進行乳癌篩檢及自我檢查。

最近的醫學報告,單獨使用雌激素的病患,乳癌發生的機會比完全不服用者來的低。過去有關合併型荷爾蒙補充療法所造成乳癌的研究中,黃體素都是以
MPA(medroxyprogesterone)為主,而近年來某些新療效的黃體素如DRSP (Drospirenone) 和 CPA (cyproterone
acetate) 。研究指出,含DRSP成份的避孕藥,能減少40%良型乳房纖維瘤的發生。而以DRSP 和 CPA
成份合併雌激素使用的荷爾蒙補充製劑,是否能有效降低乳癌發生的機會,仍待時間證實。但是,對於某些有嚴重更年期症候的婦女或急切需要合併型荷爾蒙補充的病人,如今有了更安全的用藥選擇,這是值得額手稱慶的事情。

11、更年期使用荷爾蒙,對卵巢癌的發生率有何影響?

近來一篇研究報告顯示,單獨使用傳統劑量雌激素超過十年以上,會增加卵巢癌的發生率,至於長期使用雌激素與黃體素合併的荷爾蒙療法,是否會增加卵巢癌的發生率,則還沒有定論。在2002年JAMA
的學術報告顯示,雌激素單獨使用超過10年以上,卵巢癌發生的比例略高於未使用者。但如果服用雌激素合併黃體素的婦女,卵巢癌發生與未使用者無差異。

12、更年期荷爾蒙療法,對有子宮內膜癌的婦女有何風險?

雌激素的主要功能,是促進女性特徵,同時刺激乳房及子宮的生長。因此,罹患子宮內膜癌的病人,使用更年期荷爾蒙療法恐會促進腫瘤的生長,故不建議使用。

13、更年期荷爾蒙療法,尚有哪些好處及風險?

雌激素對於停經症狀如熱潮紅、失眠及陰道乾澀等的改善,非常有效;也有助於改善婦女的情緒及精神狀況。

至於有關雌激素可以改善記憶減退、預防老人失智症的說法,至今並未獲得科學上的証明。

近來研究顯示,使用連續性合併型荷爾蒙療法五年的婦女,其大腸直腸癌的發生率,較未使用的對照組減少,但會增加肺栓塞、深部靜脈血栓、腦中風等的風險。

超低劑量單獨雌激素荷爾蒙治療者,對於更年期症狀改善及骨質流失造成的骨質疏鬆有所助益。不會增加子宮內膜癌、乳癌、心臟血管疾病的發生。但報告顯示,有可能增加中風的風險。

14、荷爾蒙不同的使用途徑,其效果是否會有差異?

大部分的研究對象多採用口服荷爾蒙,至於市面上其他使用途徑的荷爾蒙如:經皮膚吸收之貼片或雌激素凝膠、陰道乳液等,一般而言,對改善停經症狀如熱潮紅、失眠、陰道乾澀等的效果大致相同;但陰道乳液因吸收至全身血液的雌激素量很低,主要用於減少陰道萎縮,而無預防骨質流失的效果。

目前市面上口服荷爾蒙錠劑的劑量仍然偏高。超低劑量單獨雌激素的治療,採用經皮膚吸收之貼片、雌激素凝膠、或陰道乳液較能達到超低劑量單獨雌激素治療的目標。

15、荷爾蒙療法是否應該用於預防之途?

通常預防性治療需要經過嚴格的評估,始得為之。因此,建議更年期婦女不要使用荷爾蒙療法來預防心血管疾病、老人失智症等。荷爾蒙療法有助於預防更年期後產生的骨質疏鬆症,可考慮使用超低劑量單獨雌激素治療。傳統雌激素則建議使用於具骨質疏鬆高危險且有更年期症狀或無法使用非雌激素藥物之婦女。

依據世界衛生組織的建議,國人應建立健康的生活方式,來預防骨質疏鬆、心血管疾病或癌症等慢性疾病,這些健康的生活方式包括:戒菸、規律運動(如健走)、攝取富含鈣質及維他命等食物的均衡飲食、定期測量血壓、血醣、血中膽固醇等,一旦有異常則需早期治療。

名詞解釋:

一、雌激素:控制女性第二性徵的發展,如:乳房的發育、臀部的變寬,以及臀部與陰阜中的脂肪儲存;幫助卵巢濾泡的成熟,並使子宮內膜之黏膜增厚。

二、黃體素:由黃體所分泌,會減少子宮因雌激素所引起之自動收縮,讓子宮內膜作最好的預備,使受精卵能好好地植入內膜著床,使妊娠得以維持,故此荷爾蒙又稱妊娠荷爾蒙。

三、女性荷爾蒙一生的變化:分泌女性荷爾蒙最重要的器官是卵巢,初經的少女卵巢中約有三十萬個濾泡,隨著年齡的增加,每月濾泡的成熟與排卵,濾泡總數逐漸減少,接近停經的婦女幾乎不再有濾泡。卵巢在女性未進入青春期之前幾乎沒有發揮作用,到青春期之後就開始會有女性荷爾蒙的產生(包括雌激素及黄體素),濾泡排卵後形成黃體並分泌黄體素,因卵未受精而黃體萎縮,月經週期於焉來到。生育期是女性生殖的顛峰,在這段時間女性有豐沛的雌激素。而到了停經前後,卵巢的功能逐漸降低,雌激素的產生降低。

四、超低劑量雌激素:以二氫基女性素(17-b
estradiol)貼片為例。傳統雌激素劑量為0.05mg/天,低劑量為0.025mg/天,超低劑量為0.014mg/天。