2009-12-18

Japan: Rape simulator games and the normalization of sexual violence

出處:Say NO – UNiTE

“Women are stupid creatures who don’t know how to do anything other than cook us dinner. This just proves their stupidity; they need to realize that the word ‘equality’ was a word created by men for men, and was never meant to be used by, referred to, or given to women.” (Online game blogger responding to Equality Now’s Women’s Action against rape simulator games in Japan)


"By the way I played RapeLay (doing the 13 year old was best).” (Email to Equality Now)


“The only way to defeat women’s rights and make things to the advantage of Men again is to brutally, publically, murder women’s rights activists en masse. Don’t you want young females of child bearing age as your wives (females gain the ability to have children at age 12, 13, or 14 commonly)? Yes you do. Don’t you want her to obey you? Yes you do. Don’t you want her to be nice to you? Yes you do (whatever “nice” means… probably quiet suffices). The only way you have a shot at getting any of that is if all feminists and those who support them are dead or ineffectual (dead really helps here as well).” (U.S. online gamer railing against Equality Now’s Women’s Action)


In May 2009 Equality Now launched a Women’s Action on rape simulator games produced and sold in Japan. The Action highlighted the game RapeLay which was produced by Illusion Software and sold on Amazon Japan. RapeLay shows a schoolgirl around 12 years old travelling on a commuter train. A man who has been following her gropes and sexually molests her. Eventually the train stops and she runs frightened into a public toilet, followed by her assailant who handcuffs and rapes her. The assailant takes her prisoner and repeatedly rapes her in various locations. Her mother and teenaged sister suffer the same fate. This family is targeted for rape as punishment because the older sister had previously reported to the police the attempted sexual assault of another woman by the rapist. The aim of the RapeLay game is for the player repeatedly to rape the mother and her daughters until they begin to “enjoy” the experience.


Japan ratified the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) in 1985 and was last examined by the CEDAW Committee, which reviews government compliance with CEDAW, on 24 July 2009. The CEDAW Committee expressed concern at the “normalization of sexual violence in [Japan] as reflected by the prevalence of pornographic video games and cartoons featuring rape, gang rape, stalking and sexual molestation of women and girls.” The Committee also stated that it was concerned about the stereotypical depictions of women in the media and that, “the over-sexualized depiction of women strengthens the existing stereotypes of women as sex objects and continues to generate girls’ low self-esteem.” In its concluding observations the CEDAW Committee strongly urged the Japanese government to “ban the sale of video games or cartoons involving rape and sexual violence against women which normalize and promote sexual violence against women and girls.” The new Japanese government, elected in August 2009, has the opportunity and responsibility actively to address the concerns expressed by the CEDAW Committee by banning all media which promote violence against women and girls.


Since Equality Now issued its original Action, Japan’s Ethics Organization of Computer Software (EOCS), the industry’s self regulatory body whose job it is to rate computer software, has reportedly banned its members from producing games containing certain forms of violence against women. EOCS is a voluntary organization with a large but not universal membership. It is not yet clear what aspects of violence against women its rules will address and to what extent they will be applied. However, online gaming magazines suggest that due to the international attention, game makers in Japan are merely changing titles and pictures on game covers to make them appear innocuous and/or preventing anyone from outside Japan from accessing their websites, but are not addressing the actual content of these games. The Japanese government must take decisive steps to ban outright games that promote violence against women and girls and to address the objectification of women and promotion of violence against women in various media including in pornography.


Amazon Japan and Illusion Software have now withdrawn RapeLay from sale, however both continue to sell similar extreme pornography games in the form of cartoons known as hentai which include women and girls being raped, gang raped, stalked, molested, sexually assaulted and groped. In a furious backlash against moves to restrict the normalization of sexual violence against women and girls, Equality Now has been targeted through online blogs and emails with hundreds of abusive and sometimes threatening communications, including seemingly credible videos of real girls actually being gang raped. The videos were passed on to the Japanese police who initially refused to investigate, stating that, based on the officers’ analysis of the shape of the girls’ pubic hair, the girls were over eighteen, therefore the tapes were not considered child pornography. Only after Equality Now impressed upon the police that actual (and not enacted) gang rape videos are in fact sold on the open market in Japan, did they finally agree to re-examine the tapes, but it remains unclear what, if any, action has been taken including to trace the sender of the videos. The failure by the police even to contemplate that a serious crime might have taken place remains a deep concern.


The hostile responses provoked by Equality Now’s advocacy against extreme pornography, including the examples above, underscore the urgent need to address all instances of discrimination against women and girls, including the promotion of sexual violence. Article 5 (a) of CEDAW, which obligates States Parties to “modify the social and cultural patterns of conduct of men and women, with a view to achieving the elimination of prejudices and customary and all other practices which are based on the idea of the inferiority or the superiority of either of the sexes or on stereotyped roles for men and women” is just one of many clear international standards adopted by the international community. In the same way that it would be unacceptable to promote violence against religious or ethnic groups, so it is unacceptable to promote violence and discrimination against women.


In addition to Japan’s obligations under CEDAW, Article 14 of the Japanese Constitution guarantees equality under the law and states that there shall be no “discrimination in political, economic or social relations because of race, creed, sex, social status or family origin.” Computer games such as RapeLay and real rape “pornography” videos condone and promote gender stereotypes and gender-based discriminatory attitudes. As the CEDAW Committee has noted, these, in turn, contribute to gender-based violence.


Recommended Actions


Please write to the Japanese government officials below, calling on them to comply with Japan’s obligations under CEDAW, including the recent strong exhortation of the CEDAW Committee to ban games and cartoons that normalize and promote sexual violence against women and girls. In your letter to the Minister of Justice ask her also to inquire about the requested investigation into the apparent gang rape video sent by Equality Now to the Tokyo police department, and ask that her office investigates this and other actual rape videos to ensure that all those involved are prosecuted to the full extent of the law. Please also continue to write to Illusion Software asking it to withdraw immediately from sale all games which involve rape, stalking or other forms of sexual violence or which otherwise denigrate women. Suggest that corporations have a responsibility to consider, as good business practice, any negative impact their activities may have on society and the public interest. Please write a similar letter to Amazon Japan.


Mr. Tadashi Yoshimura
Managing Director
Illusion Software
1-10-1 Nishikanagawa Kanagawa-ku
Yokohama-city, Kanagawa 221-0822, Japan
Tel: (+81) (0)4-5322-1551
Email: illuon@illuon.jp, info@illuon.jp


Sample letter to Illusion Software


Mr. Jasper Cheung
President of Amazon Japan K.K
2-15-1 Shibuya, Shibuya-ku, Tokyo 150-000-2, Japan
Email: via website


Sample letter to Amazon Japan


Prime Minister Yukio Hatoyama
2-3-1 Nagata-Cho, Chiyoda-ku,
Tokyo 100-0014, Japan
Tel: (+81)(0)3-3581-0101
Fax: (+81)(0)3-3581-3883
Email: via website


Ms. Mizuho Fukushima
Minister of State for Consumer Affairs, Declining Birthrate and Gender Equality
Room 708, 4-gokan,
Chuogodo Chosya, 3-1-1 Kasumigaseki,
Chiyoda-ku,Tokyo 100-8970, Japan
Tel: (+81)(0)3-5253-2111
E-mail: via website


Sample letter to government officials


Ms. Keiko Chiba
Minster of Justice
1-1-1 Kasumigaseki,
Chiyoda-ku, Tokyo 100-8977, Japan
Tel: (+81)(0)3-3580-4111
Fax: (+81)(0)3-3592-7393
Email: webmaster@moj.go.jp


Sample letter to the Minister of Justice

Date: 12/04/2009
Time: 7:00 PM
Action Type: Awareness Raising
Sponsored By: Equality Now
PHOTOS

2009-12-14

何謂『多囊性卵巢症候群』?


轉貼自:高雄榮總婦產部生殖醫學中心

何謂『多囊性卵巢症候群』?

多囊性卵巢症候群最早是在西元1935年Stein 及Leventhal 兩位學者首度發表七例這種症候群,包括「無月經」(amenorrhea),多毛症(hirsutism),肥胖(obesity),以及合併卵巢呈現多發性的囊狀腫大(enlarged polycystic ovaries)等症狀,將臨床症狀與多囊性卵巢做一個結合,長久以來,關於所謂的多囊性卵巢症候群的診斷標準始終莫衷一是,因為這類病患的臨床症狀變化多端、表現也是相當的異質性。

多囊性卵巢形成的原因目前尚未有明確的結論,但是可以由一個簡單的觀念加以詮釋,每個月經週期,卵巢在月經初期開始會有濾泡逐漸長大,待其成熟之後,會將卵子釋放出來,這個過程便為「排卵」。若在濾泡生長的過程中,發生男性賀爾蒙上昇,就會影響濾泡的生長速度,並使其無法排卵,這個沒有釋放卵子的濾泡就會逐漸堆積於卵巢之中,同時也會逐漸影響日後的排卵,並形成超音波影像下所謂的「多囊性卵巢」。
依據Adam於1985年在Lancet所表之文章的定義,在超音波檢查時,可以發現這些囊腫大小約2-8mm (數目經常大於20顆),通常排列於卵巢回音部分較強之基質周圍,圍繞成如項鍊般的特徵("black pearl necklace" sign) ,形成所謂的多囊性卵巢 。 臨床上,大約有百分之二十的婦女可以在超音波檢查時發現這種超音波表徵,其中約有三分之一至一半合併有臨床症狀,是屬於所謂的「多囊性卵巢症候群」,所以多囊性卵巢症候群的發生率大約百分之六至十之間。
有人認為多囊性卵巢有遺傳的傾向,在親屬中有糖尿病,肥胖,三酸甘油酯過多,不孕症,月經異常,多毛症或高血壓的病史者比較容易罹患多囊性卵巢症候群。
這種常見的症候群,臨床表現未必一致,在早期這種症候群的診斷大多以卵巢囊狀腫大為其依據,但是有些正常排卵的婦女也有常出現這種解剖上的變化,同時某些疾病,如「庫辛氏症候群」(Cushing’s disease),「卵巢或腎上腺腫瘤」也可能出現與此症候群類似的變化。另外,某些婦女臨床表現出「多囊性卵巢症候群」之症狀,但其卵巢並無囊狀的腫大。所以目前有些人是以「雄性素過多與慢性不排卵症候群」(syndrome of hyperandrogenic chronic anovulation)來說明這個症候群的含意,認為與其由卵巢之解剖上的變異來探討其病因與表現,反而不如著重於這種症候群所代表的賀爾蒙系統的異常。

多囊性卵巢症候群之致病原因

多囊性卵巢症候群是一種原因不明的內分泌系統的異常,特徵是不適當的「性腺刺激素釋放激素」(GnRH) 分泌頻率異常所引發持續性的黃體化激素(LH)上昇,通常血清濃度會超過10 mIU/mL。當LH分泌過多的時候,對濾泡之發育及卵之成熟則有很大的負面影響:
1. 刺激膜細胞(theca cell)合成過多雄性激素,並抑制顆粒細胞(granulose cell)內由FSH誘導之芳香環轉化酵素(FSH-induced aromatase)的活性,使estrogen之分泌量下降進而導致濾泡萎縮。
2. 導致早發性黃體化現象(premature luteinization),繼而引起黃體化而未破裂之濾泡(luteinized unruptured follicle, LUF)。
3. 導致黃體機能不全。
4. 提早抑制OMI (卵子成熟抑制因子) 之作用,加速卵泡之成熟,使卵泡在排卵時已成為過度老化之細胞。

目前有越來越多的證據顯示,多囊性卵巢症候群與胰島素有密切的關係.就是身體組織對胰島素產生抗拒力(insulin resistance),也就是說,身體組織或細胞對於胰島素的反應性下降,迫使體內必須分泌更多的胰島素,才能維持血糖的正常,如此所引發的效應,就是所謂的「代償性的高胰島素血症」(compensatory hyper-insulinemia)。
高胰島素血症容易引起卵巢雄性素製造增加,特別是睪丸酮(testosterone),另外就是會使「血清性腺賀爾蒙結合球蛋白」(SHBG)減少,如此便使血清內游離的睪丸酮濃度上昇。高濃度的雄性素會干擾「腦下垂體-卵巢軸線」(pituitary-ovarian axis),造成LH濃度上昇,不排卵,無月經與不孕症。
此外,卵巢與腎上腺所產生的雄性素(androgens)也隨之上揚。通常血清中睪丸酮 (testosterone)的濃度約在70-120ng/dL之間,而androstenedione的濃度約在3-5ng/mL之間。約有一半的病人其DHEA-S的血清濃度也會上昇。
血清中的濾泡刺激素(FSH)的濃度通常沒有太大的變化,所以約有一半的病人其LH/FSH的比率通常會超過3倍。約有百分之二十的多囊性卵巢症候群患者,其「泌乳素」(prolactin)的濃度會有輕微上昇的現象,濃度約在20-30ng/mL之間。其原因可能與GnRH釋放頻率增加或相對多巴胺(dopamine)的濃度減少有關。泌乳素上昇可能會干擾正常的排卵。

多囊性卵巢症候群所造成的賀爾蒙變化總結如下:
1. 不適當的「性腺刺激素釋放激素」(GnRH)分泌頻率異常所引發持續性的黃體化激素(LH)上昇。
2. 身體組織對對「胰島素產生抗性」(insulin resistance)產生「代償性高胰島素血症」(compensatory hyperinsulinemia)。
3. 卵巢與腎上腺所產生的雄性素(androgens)增加。
4. 「泌乳素」(prolactin)的濃度會有輕微上昇的現象。
 

多囊性卵巢症候群之臨床症狀

一、慢性不排卵與不孕症(Anovulation and Infertility):
多囊性卵巢症候群最常見的症狀還是「慢性不排卵」與「不孕症」。慢性不排卵的症狀包括:月經不規則,月經過少或無月經,其間或有偶發性的月經過多合併大量陰道出血。
這種月經的不規則,通常開始於初經,因為沒有排卵,所以月經來臨前的一些不適症狀比較不會出現;由於慢性不排卵,子宮內膜便暴露於長期動情素的單向刺激,而無黃體素的制衡,發生子宮內膜增生甚至子宮內膜癌的機率也就可能增高。幸運的是:若發生子宮內膜癌,通常是屬於比較低度的細胞變化,同時期別也較早。
慢性不排卵表示卵巢濾泡生成的異常,即或偶有自發性的排卵,其卵子品質也會受到影響,受孕率也隨之下降,所以容易導致不孕。

二、雄性素過多(Hyperandrogenemia):
A.肥胖(Obesity)—大約有百分之四十的患者會有肥胖的症狀,這種肥胖與正常婦女的肥胖有些差異,正常婦女的肥胖是下半身的梨子型肥胖,而這些雄性素偏高的婦女肥胖常是上半身與腹部的蘋果型肥胖。
肥胖(obesity)會改變體內生物化學反應的途徑及新陳代謝之狀態,最常見的是引起胰島素抗性(insulin resistance)現象,而造成血中循環的胰島素濃度增加,胰島素本身可加速腦下垂體下垂體LH的分泌,也會抑制IGFBP-l之合成,所以因胰島素抗性所造成之高胰島素血症(hyper-insulinemia)會導致LH分泌增加及IGFBP-l之合成減少,而此二者都會促進卵巢雄性素的分泌,最後演變成PCOS。另外,肥胖婦女之脂肪組織多,性腺外 (周邊組織)的E1轉化作用(extra-glandular-conversion of E1)較頻繁,所以血中之E1濃度較高,也是造成LH分泌的原因之一。肥胖對於多囊性卵巢症候群扮演了一個相互影響重要的角色,因為肥胖的人, 常導致「性腺賀爾蒙結合球蛋白」(SHBG)的減少,而相對增加了血清中「游離睪丸酮」(unbound testosterone)的濃度,使得男性化的表徵較易出現。
此外,肥胖的人,因為容易增加由周邊脂肪組織將男性素轉化成動情素,也增加了慢性動情素刺激的機會,發生月經異常的比率就大為增加。
B.多毛症(Hirsutism)—多囊性卵巢所導致的多毛症,主要是於身體的中線容易發現過多的毛髮生長,就其臨床表徵而言,可能因種族而有不同的變異,例如西方人可能有百分之七十的多囊性卵巢症候群患者或有多毛或肥胖的症狀,反之,只有百分之十的東方人會出現明顯的多毛或肥胖等症狀。
是否會出現多毛的症狀,與周邊毛囊組織中的5α-還原脢(5α-reductase)的接受器濃度有關,因為這種5α-還原脢會將睪丸酮轉變為更具活性的DHT(dihydrotestosterone)與3α-diol-G。
C.痤瘡(Acnes)—對於一些經由傳統治療無效的痤瘡(Acne) 患者,也常發現有多囊性卵巢症候群的存在。這些痤瘡主要發生在臉部與恥骨聯合上方部位,其他常見的部位包括胸部,大腿內側與會陰部等。
D.黑色棘皮病—雄性素過多症的另外一個常見的特徵就是所謂「黑色棘皮病」或「黑色角化病」 (acanthosis nigricans),也就是在全身,腋下, 胯下,或有皺摺的皮膚處,呈現過度色素化(hyperpigmentation)的現象。

三、 抗胰島素(Insulin-resistance)
多囊性卵巢的患者,比較容易形成一種所謂類似糖尿病的狀況,這些病患在以後的日子裡,也比較容易罹患糖尿病。許多研究也顯示,多囊性卵巢症候群和肥胖、糖尿病,或是心臟血管疾病,有密切的關係。

多囊性卵巢症候群與青春期變化之關係
 
青春期(Puberty)之少女常有不規則的月經週期,也常合併有雄性素過高血症(hyperandrogenemia)及多囊性卵巢(PCO),因此多囊性卵巢症候群(PCOS)可能與青春期之變化有密切之相關性。最近的資料顯示,"胰島素抗性"(insulin resistance)及"代償性高胰島素血症(compensating hyper-insulinemia)是青春期變化的一種正常現象。
性器官之成熟(sexual maturation)與軀體之生長(somatic growth)是青春期的兩大變化。青春期,生長激素(growth hormone, GH)大量分泌,拮抗了胰島素的作用,引起胰島素抗性,而胰臟代償性的分泌導致高胰島素血症,繼而抑制第一型類胰島素生長因子結合蛋白(IGFBP-l)的分泌,造成第一型類胰素生長因子(IGF-I)的活性增加,同時,GH的目標細胞在GH的作用下也會分泌IGF-I,(實際上,IGF-I是執行GH促生長作用的物質),IGF-I是促進生長的蛋白質,可刺激軀體之生長。胰島素抗性只限於葡萄糖之新陳代謝作用,並不會影響到胺基酸的新陳代謝,相對地,代償性高胰島素血症實際上可增強蛋白質的新陳合成作用,更有利於軀體之生長,另一方面,IFG-1能加強FSH與LH的作用而增加卵巢合成性類固醇的能力,繼而促進濾泡內顆粒細胞的增生及濾泡的發育,最後達到性器官成熟、(具有排卵功能的卵巢)的目的。
臨床觀察發現高胰島素血症(hyper-insulinemia)可導致雄性素過多症(hyper-androgenemia)及多囊性卵巢症候群(PCOS)。
胰島素之刺激卵巢分泌雄性素是經由IGF-I的type 1 receptor,因IGF-I的type-1 receptor對insulin的結合力弱,所以必需有相當高濃度的insulin才能誘發刺激作用。體外實驗證實insulin及IGF-I都能刺激正常卵巢以及多囊性卵巢的雄性素製造(包括testosterone與androstenedione),同時發現對PCO之卵巢只要給予insulin便能刺激雄性素之合成,但對正常的卵巢,則還需LH之共同作用才能刺激雄性素之合成,而且每單位重量之多囊性卵巢所產生的雄性素之量比正常卵巢來得多,這些資料都顯示多囊性卵巢對insulin的反應較一般正常卵巢更為敏感。
許多在青春期(puberty)出現激素分泌之改變(endocrine changes),不但可以在POCS的病人身上發現,而且其改變還更為嚴重,即激素之分泌有過度異常之情形:
(a)卵巢型態之改變:正常早期青春期少女的卵巢常出現許多小囊(multicysts),但在排卵之機能確立之後會逐漸消失;而PCOS之病人其卵巢亦有多囊,但中間的基質組織有過度增厚之現象(超音波之診斷) 。
(b)PCOS病人之FSH與LH的分泌很類似青春期少女FHS與LH分泌過度之現象:PCOS病人其基礎LH血清值上升,LH/FSH ratio也增加,對GnRH刺激之反應也有過度分泌LH之現象,這些臨床觀察都可在青春期之變化時發現,只不過是更為明顯罷了。
(c)腎上腺分泌雄性素之機能亢進:腎上腺合成雄性素的途徑需要一種酵素稱為細胞色素P450c17(cytochrome P450c17),這種酵素實際上是扮演著催化兩種不同反應的酵素,一是17b-hydroxylase,另一是17,20-desmolase,在這酵素的作用下,DHEA androstenedione才能被合成。青春期時,這種酵素的活性大大地被增加,這是因為青春期之前,腎上腺已有皮質官能初昇(adren-arche)之變化,這變化最主要就是活化cytochrome P450c17之17,2O-desmolase的活性,於是DHEA及androstenedione能開始大量被合成,如此有助於卵巢之成熟,但過多的DHEA及androstenedione分泌會導致雄性素過多症(hyperandrogenism),反而加速卵巢濾泡之萎縮(follicuIar atresia)及抑制雌二醇(E2)之合成,這便是PCOS臨床表徵,所以PCOS似乎是一種過度青春期變化的狀態(a state of hyperpuberty)。

 
分子生物學及基因方面的發展與證據

目前臨床醫師與科學家已將多囊性卵巢的治病原因之研究方向,轉移至基因的層面。當今研究的方向著重於底下幾大類之基因族群:
1. 與類固醇之合成與作用有關的基因,CYP11A,CYP17,CYP21,Androgen receptor gene (雄性激素受器基因), 及Sex-hormone Binding Globulin(性荷爾蒙結合蛋白基因)。
2. 與醣類之代謝與利用有關之基因,如Insulin gene (胰島素基因),Insulin Receptor gene (胰島素受器基因),Insulin Receptor substrate gene(胰島素受體受質基因)及Calpain 10 gene。
3. 與性激素作用及調控有關之基因,如Dopamine Receptor gene(多巴胺受體基因) 及Follistatin gene。
4. 與MHC有關之基因。
其中以CYP11A, Insulin gene(胰島素基因)及Insulin Receptor gene(胰島素受器基因)最有潛力。

多囊性卵巢的診斷
歐洲婦產科界對於多囊性卵巢的定義,最主要是根據超音波檢查發現在一個介面下可以看到單側卵巢至少有五個直徑2-8mm 的濾泡排列於超音波回音甚強的卵巢中央基質周圍,而且伴隨著寡月經或無月經等月經異常,或同時有多毛症、青春痘與雄性禿等雄性素過高現象謂之;對於抽血來檢測體內荷爾蒙狀態的步驟則認為非診斷所必須。
相對地,北美婦產科界的對於多囊性卵巢症候群的定義遵循的是1990年美國國家衛生院會議所推薦的診斷標準,包括有雄性素過高的血液生化證據或臨床症候以及卵巢排卵功能異常(需排除其他特定疾病所致,如泌乳素過高、先天性腎上腺增生、腎上腺腫瘤、與庫欣氏症候群等等),所以超音波的檢查則非診斷所必須。
可想而知,即使雙方定義上有交疊的部分,關於多囊性卵巢症候群的疾病盛行率會因不同的國家、不同的民族、不同的研究者、不同的報告,而有相當大的歧異性。
所以在國際的診斷共識是在2003年歐洲與美國的專家在荷蘭鹿特丹開會,為多囊性卵巢症候群的診斷標準定義為,以下面三項中有兩項符合即是:(1)排卵稀少;(2)外表或血中男性荷爾蒙過高;(3)超音波發現多囊性卵巢(單側或雙側卵巢有10個以上的濾泡)
Revised diagnostic criteria of polycystic ovary syndrome.
Revised 2003 criteria (2 out of 3)
1.Oligo- or anovulation,
2.Clinical and/or biochemical signs of hyperandrogenism,
3.Polycystic ovaries and exclusion of other etiologies (congenital adrenal hyperplasia, androgen-secreting tumors, Cushing’s syndrome) 2003 Rotterdam PCOS consensus. Fertil Steril 2004.
當然,在多囊性卵巢症候群患者需排除是否有「分泌雄性素的腫瘤」存在或是有「先天性腎上腺增生」的可能,所以應先接受total testosterone,17-OH-progesterone與DHEA-S的血清檢驗。
篩檢testosterone表示卵巢與腎上腺雄性素的分泌狀態,若testosterone指數超過200ng/dL,應即考慮是否有來自卵巢或腎上腺的腫瘤。
血清DHEA-S代表腎上腺所分泌的雄性素來源,若指數超過700ng/dL表示可能有腫瘤。17-OH-progesterone在多囊性卵巢很少會超過300ng/dL,若超過300ng/dL則考慮先天性腎上腺增生,最常見的是21-hydroxylase deficiency,此時應接受ACTH刺激試驗以進一步診斷。若是11-β-hydroxylase deficiency,會同時有高血壓與鹽類滯留;若是3-β-hydroxylase deficiency,會合併有血清DHEA-S的明顯上昇。
台灣關於多囊性卵巢症候群的盛行率到底多少?一直沒有明確可信的數據,西方的診斷標準是否可以全然適用於台灣婦女的身上不無疑問,比如說以多毛症的表現而言,東方女性可能因為先天毛囊數目與皮膚某種還原?基因上的差異,臨床表徵上不像西方婦女常見,不過,上述的診斷流程或許可以開闢出一條清晰的溝通道路吧。

 
 
多囊性卵巢的治療
 
 
治療多囊性卵巢症候群,除了使用藥物以外,最重要的就是減重,以及改善生活作息,包括良好的飲食習慣與適量的運動。許多臨床的研究證明,經過適當的減重5-10%以後,多囊性卵巢症候群的症狀就會改善,可以減少藥物的使用或是停藥。
多囊性卵巢的治療主要針對四個方面:痤瘡,多毛症,月經異常與不孕症。
痤瘡與多毛症:
有些PCOS之病人臉上長滿青春痘,臨床醫師則視是否有感染的情形給予口服及外用之抗生素。如果排除是感染的可能性,認為是雄性素過高造成的痤瘡,可以使用含有抗雄性素黃體素成分的避孕藥或是直接使用抗雄性素藥物。
其中避孕藥中的Diane-35含有抗雄性素的黃體素成分CPA 2mg,治療3個月後對於痤瘡會有明顯的改善,治療6個月後對於多毛症會有明顯的改善;此外新一代的避孕藥Yasmin含有另一類抗雄性素的黃體素dropspirenone 3mg,亦具有同樣的效果。所以對於一些不急於懷孕PCOS病人,服用estrogen-progesterone combination的口服避孕藥是一個理想治療方式。因為它會使LH的濃度逐漸恢正常,使卵巢分泌雄性激素的活性降低。同時經由動情素的作用,也會使SHBG增加,所以血清內游離的睪丸酮濃度就會降低。口服避孕藥中的其中黃體素的成分會直接抑制5-α還原脢的活性,並會與男性素的接受器競爭其結合位置,抑制男性素的活性。
動情素可抑制腎上腺之活性,減少雄性激素的分泌。動情素亦可抑制睪固酮在皮膚中活化成DHT,故能改善多毛症、脂溢以及粉刺等相關症狀。由於服用口服避孕藥可促使子宮內膜成週期性的剝落,使原本長期不排卵的病人免於子宮內膜癌的威脅。
抗雄性素藥物中現較常用的包括Spironolactone,Cimetidine及CPA(Cyproterone acetate)當有DHEA-S濃度上昇時,合併使用類固醇dexamethasone也有助益。Spironolactone有對抗男性素的效果,主要作用是在毛囊細胞內抑制DHT的接受器。CPA為合成hydroprogesterone;具有對抗男性荷爾蒙、抗腦下垂體激素及黃體素的特性。它對抗男性荷爾蒙主要的機轉是經由阻礙男性荷爾蒙與細胞核位置形成複合體,並與男性荷爾蒙在細胞質接受器上行競爭性抑制,同時它亦具有抗性腺激素的特性,故可少男性荷爾蒙的製造。另外也有人使用flutamide或finasteride來治療多毛的症狀。
※胰島素抗性(Insulin resistance):

在治療所謂「胰島素抗性」方面,最近有人主張使用一些治療糖尿病的藥物,也可以得到很好的效果,例如Metformin與Troglitazone。通常在使用這些藥物二至三個月之後,就可見療效,包括體重減輕,脫髮減少,面部與身體的毛髮生長速度減慢,月經正常,回復排卵生育能力等。
Troglitazone(Rezulin),是一種thiazolidinedione的衍生物,可以經由細胞核接受器peroxisome proliferator activated receptors(PPARs)影響脂肪酸的代謝,使其不與葡萄糖競爭氧化代謝,而使局部細胞組織對胰島素的抗拒力降低,達到降低血糖與的效果,也同時減少代償性的高胰島素血症的發生率。
副作用包括:頭痛(11%),疼痛(10%),無力(6%),暈眩(6%)與噁心(6%)。
Metformin(即glaucophage)是一種biguanide的降血糖藥物,主要作用在藉由無氧葡萄糖代謝路徑,將腸道中的葡萄糖轉變成乳酸,減少葡萄糖的吸收,並減少肝臟中葡萄糖的製造,同時也增加組織對胰島素的敏感度,幫助胰島素清除過多的血糖,並且有降低三酸甘油酯與膽固醇的效用。在卵巢方面,Metformin可以降低卵巢中細胞色素P450c17-α的活性,改善男性素過高的情形。
副作用:約有百分之二十至三十的人會有上腹灼熱感,腹瀉,食慾不振等。有非常少數(1/100000 patient-years)的人會發生「乳酸血症」(lactic acidosis),對於腎臟功能不佳者,如「肌酸酐大於1.5」或「肌酸酐清除小於60%」者,應該非常謹慎使用。
以上這兩種藥物,是否能夠於懷孕中使用?目前並無足夠的人體證據證實其會導致胎兒畸形,目前美國FDA將其歸諸於Class B的分類中,認為並不會影響懷孕的安全。
※刺激排卵

刺激排卵通常先使用clomiphene citrate約75~80%可以成功的排卵,其中只有40%患者得以受孕,若反應不理想可以合併使用Metformin約可達到80-90%可以成功的排卵,如果再無反應才使用上「人類停經後性腺刺激素」Human menopausal gonadotropin(HMG) 或FSH或腦下垂體阻斷素 (GnRHa)。
若病人同時合併DHEA-S濃度增加者,可以加入dexamethasone(0.25-0.5mg/day)可以增加排卵率與懷孕率。
至於使用電燒或雷射治療卵巢的多發性囊腫,即所謂的腹腔鏡卵巢燒灼術Laparoscopic ovarian diathermy (LOD, laparoscopic ovarian drilling)是否具有療效,根據英國雪菲爾大學Amer et al的研究認為兩側卵巢各鑽4個洞,每個洞使用的電燒能量為30瓦特持續5秒為150焦耳,4個洞之總能量為600焦耳,可達到67 % 的排卵率。加拿大多倫多大學的Tulandi et al的建議為兩側卵巢各鑽10-12個洞,每個洞使用的電燒能量為40瓦特持續2秒為80焦耳,10-12個洞之總能量為800-1200焦耳亦可達到67 % 的排卵率。至於卵巢的楔狀切 除術,目前已經很少使用,因為除了療效不確定之外,同時可能造成術後的沾連,並且目前的排卵藥物效果不錯,所以手術治療越來越少施行了,目前的適應症為對藥物無反應者才使用手術治療,且建議使用腹腔鏡卵巢燒灼術較為適合。
哈佛大學Barbieri等學者建議對於PCOS患者的誘導排卵可以參考如下的流程循序使用:(1)如果BMI過高,儘可能減重,即使減少5%的體重,也可以增加許多自然排卵的機會、(2)使用clomiphene(如果DHEAS比較高可以再加上glucocorticoid)、(3)單獨使用胰島素活化物如Metformin、(4)胰島素活化物加上clomiphene、(5)性腺激素、(6)胰島素活化物加上性腺激素、(7)卵巢手術、(8)試管嬰兒。而奧地利JCEM的主編 Norman 則建議對於PCOS患者的誘導排卵流程如下(1)生活作息改變,儘可能減重 (2) 單獨使用胰島素活化物 Metformin(up to 2500 mg/day) (3)、使用胰島素活化物 Metformin加上clomiphene(up to 200 mg/day) (4) 腹腔鏡卵巢燒灼術 (5)性腺激素、(6) 試管嬰兒, 由近期的研究看來,不論是在何種治療階段,適度的使用胰島素活化劑於誘導排卵,在臨床反應上效果不錯。





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