不孕不育 糖尿病 肥胖症與多囊症之迷
Scientists know this much about polycystic ovary syndrome: It is one of the most common causes of infertility. It's linked to diabetes and several other troubling health problems. It affects as many as 5 million U.S. women.
關於多囊卵巢綜合症，科學家知道的也就是這些：它是不孕不育的最常見原因之一。它與糖尿病和另外多種惱人的健康問題有關。它影響着多達500萬的美國女性。But the condition, also known as PCOS, largely remains a mystery. Researchers are trying to better understand the disorder, which is generally defined by an excess production of the hormone testosterone, irregular ovulation and cysts-fluid-filled sacs-within the ovaries. Some teams are trying to improve its treatment to lessen its impact on women's reproductive health and metabolism, or how the body uses or makes energy.
但多囊症總體上還是一個迷。研究人員正在努力更好地理解這一病症。它大體上被定義爲睾丸激素分泌過多、排卵不規律、卵巢內存在囊腫（積液囊）。有些團隊希望改進治療方案，減輕它對女性生殖健康和新陳代謝（身體使用或產生能量的過程）的影響。'We really need better options,' says Esther Eisenberg, project scientist of the Reproductive Medicine Network, a research collaboration set up and funded through the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
尤尼斯・肯尼迪・施萊佛美國國家兒童健康與人類發育研究所(Eunice Kennedy Shriver National Institute of Child Health and Human Development)設立並資助的研究協作團體“生殖醫學網絡”(Reproductive Medicine Network)項目科學家埃絲特・艾森伯格(Esther Eisenberg)說：“我們真的需要更好的選擇。”
Even the diagnosis of PCOS can be tricky because the syndrome doesn't look the same in everyone. What is called PCOS is likely a number of different diseases that manifest similar symptoms, such as acne, excess facial- and body-hair growth in reproductive-aged females, insulin resistance and abnormal menstrual periods, according to experts.
多囊症的診斷有時候都很困難，因爲這一綜合症並不是在每個人身上都表現得一樣。據專家說，所謂多囊症可能是一系列表現爲相似症狀的不同疾病，這些症狀包括痤瘡、育齡婦女面部和身體毛髮過旺、胰島素抵抗、月經不調等。Over 60% of women with PCOS are overweight or obese. Excess hair growth, called hirsutism, also can differ by ethnicity, as can body weight. Such demographic differences can cause doctors to have difficulty identifying PCOS in those patients. And since most girls have irregular periods when they first start menstruating, misdiagnosis may be more likely to occur with young adolescents.
六成以上多囊症婦女都存在過重或肥胖的問題。毛髮生長過旺（稱爲“多毛症”）的情況可能因爲種族的不同而不同，體重問題也是如此。這些人口學差異可能導致醫生在診斷這些病人的多囊症時發生困難。由於大多數女孩在剛開始來月經時都存在經期不正常的問題，在青少年身上或許更有可能發生誤診。Insulin resistance, an inability to properly process sugar, is common, regardless of body weight. This can greatly raise the risk in PCOS patients of developing diabetes. The uterine lining may build up excessively, which is related to the lack of ovulation, and endometrial cancer risk appears to be increased as well. And women with PCOS often have trouble conceiving because they may not ovulate regularly, and may be more likely to miscarry. There also are concerns about an increased risk of heart disease, although no definitive data support that notion.
胰島素抵抗（無法有效處理糖分）是常見病徵，與體重無關。它可以極大地提高多囊症患者患上糖尿病的風險。子宮內膜可能會過度生長，而這與排卵缺乏有關。患子宮內膜癌的風險似乎也會增加。多囊症女性之所以存在生育困難，是因爲她們的排卵可能不規律，流產的概率也可能更大。另外還有心臟病風險增加的擔憂，不過沒有確切數據支持這樣一種說法。Researchers fear a general rise in obesity is causing a spike in PCOS, too, though they don't have enough longitudinal data to say definitively.
研究人員擔心，肥胖率的總體上升也在造成多囊症患病率的猛增。不過他們沒有足夠的縱向數據來得出確切的結論。PCOS appears to have a genetic component that may be triggered or influenced by environmental factors, like weight gain, later in life. But scientists are still trying to determine exactly what goes wrong. The symptoms of PCOS are at least in part due to excess androgens, the family of hormones to which testosterone belongs.
多囊症似乎含有一種遺傳成分，這種成分可能會受到年齡增大時體重增加等環境因素的誘發或影響。但科學家仍在試圖明確究竟是什麼地方出了問題。多囊症的症狀至少在一定程度上是因爲雄激素（指包括睾丸激素在內的一系列激素）過多。The womb environment also appears critical to its development. Daniel Dumesic, a professor of reproductive endocrinology and infertility at the University of California, Los Angeles, and his colleagues found that by exposing mother monkeys with high doses of testosterone, their female offspring developed PCOS-like features after birth, including higher testosterone levels.
子宮環境似乎也是形成多囊症的關鍵。加州大學洛杉磯分校(University of California, Los Angeles)生殖內分泌與不孕不育教授丹尼爾・杜麥西克(Daniel Dumesic)及其同事發現，將母猴暴露於高劑量的睾丸激素，它們的雌性後代在出生之後出現了類似於多囊症的特徵，比如更高的睾丸激素水平。They now are studying whether the bodies of women with PCOS, because of excess testosterone, store fat in tissues where it shouldn't be. Dr. Dumesic hypothesizes that this may impact the function of the ovary and perhaps fertility.
現在他們在研究多囊症患者的身體是否會因爲睾丸激素而在本不應儲存脂肪的組織中儲存脂肪。杜麥西克假想，這一點可能會影響卵巢功能和生育能力。Christopher McCartney, a professor of medicine at the University of Virginia, is examining whether the high levels of testosterone could increase the body's secretion of another chemical, called luteinizing hormone, or LH, at puberty, contributing to the development of PCOS. LH, in turn, is needed for the ovaries to produce testosterone, so high levels of LH may be helping produce additional testosterone, leading to a vicious cycle, Dr. McCartney says.
弗吉尼亞大學(University of Virginia)醫學教授克里斯托弗・麥卡特尼(Christopher McCartney)正在檢驗高水平的睾丸激素是否有可能增加體內另一種化學物質“促黃體生成素”在青春期的分泌，從而促進多囊症的形成。麥卡特尼說，促黃體生成素又是卵巢產生睾丸激素所需的物質，所以高水平的促黃體生成素可能是在幫助形成過多的睾丸激素，構成了一種惡性循環。Why the syndrome increases the risk of diabetes remains unclear. One possibility is that because the body doesn't respond well to insulin, it overcompensates to make more of it, which leads to increased levels of luteinizing hormone and lower levels of follicle-stimulating hormone, as well as increased ovarian production of androgens.
多囊症增加糖尿病風險的原因仍舊不明。有一種可能性是，因爲身體對胰島素的反應不敏感，作爲補償它便過多地生成胰島素。過多的胰島素會導致促黃體生成素水平提高、促卵泡生成素水平下降、卵巢雄激素分泌增加。Together, these slow or prevent ovulation, according to Richard Legro, a professor of obstetrics and gynecology and public health sciences at Penn State University College of Medicine in Hershey, Pa.
據賓州赫希市賓夕法尼亞州立大學醫學院(Penn State University College of Medicine)婦產科與公共衛生學教授理查德・勒格羅(Richard Legro)說，這些因素會一起延緩或阻止排卵。'It's likely that the menstrual and reproductive dysfunction is a harbinger of later metabolic abnormalities like diabetes,' Dr. Legro says.
勒格羅說：“月經和生殖障礙可能是糖尿病之類後期代謝異常的先兆。”Treatments include hormonal contraceptives to prompt ovaries to stop producing testosterone and other hormones, plus anti-androgen medications like flutamide, usually used to treat prostate cancer, and insulin sensitizers for metabolic issues. Metformin, which isn't an insulin sensitizer but is used to treat high blood sugar, is given as well on a case-by-case basis. Some of these treatments carry risks and most, with the exception of metformin, can't be used when women are trying to get pregnant.
治療辦法包括服用激素避孕藥，促使卵巢停止產生睾丸激素和其他激素，服用通常用於治療前列腺癌的氟他胺等抗雄激素藥物，以及針對代謝問題服用胰島素增敏劑。本身不是增敏劑但用於治療高血糖的二甲雙胍也可酌情讓病人服用。這些治療方法中的一部分存在風險，除了二甲雙胍之外，大多數治療方法都不能在婦女準備懷孕的時候使用。Lourdes Ibáñez, a professor of pediatrics at the University of Barcelona, has been studying combination treatments for PCOS. She found that metformin, an insulin sensitizer called pioglitazone and flutamide taken together performed better than oral contraceptives. Oral contraceptives appeared to actually worsen the girls' metabolic abnormalities.
巴塞羅納大學(University of Barcelona)兒科教授洛德斯・伊瓦涅斯(Lourdes Ibanez)一直在研究多囊症的組合治療。她發現，二甲雙胍、胰島素增敏劑“?格列酮”和氟他胺一起服用的效果好於口服避孕藥。口服避孕藥似乎還加重了女孩的代謝異常。Six months after the 18-month treatment, no one in the combination therapy group has relapsed but 50% of those in the oral contraceptive groups have, according to a paper Dr. Ibáñez published in 2013 in the Journal of Clinical Endocrinology & Metabolism.
根據伊瓦涅斯2013年發表在《臨牀內分泌和代謝雜誌》(Journal of Clinical Endocrinology & Metabolism)上的論文，經過18個月的治療並觀察六個月之後，組合治療組裏面無人復發，而口服避孕藥組裏面50%的人復發。She is also studying whether the symptoms of PCOS can be prevented in girls at high risk for the condition. She conducted a tiny pilot study of 38 girls who were born with a low birth weight and had precocious puberty, which are often precursors to PCOS.
她也正在研究能不能阻止患多囊症風險較高的女孩出現多囊症症狀。她對38名出生體重低、性早熟（常常是多囊症的先兆）的女孩展開了一項微型試點研究。She began treating them with metformin between ages 8 to 12. At 18 years old, the rate of detectable symptoms in the treated group was 5%, compared with 50% of those in the untreated group. She hopes to run a larger trial to further explore the possibility of prevention.
她在她們八歲到12歲的時候開始用二甲雙胍治療。在18歲的時候，治療組出現可觀測症狀的比例爲5%，未治療組的比例爲50%。她希望開展一場規模更大的試驗，以進一步探索預防多囊症的可能性。Scientists also have focused on improving fertility in women with PCOS. With clomiphene citrate, the most commonly used agent for ovulation induction in women with PCOS, only about half the women who ovulate end up having babies, according to NICHD's Dr. Eisenberg.
科學家也一直在集中精力改善多囊症婦女的生育能力。據艾森伯格說，在服用多囊症患者最常用的排卵誘導劑枸櫞酸氯米芬（克洛米芬）的情況下，只有大約一半成功排卵的婦女最後生了孩子。Dr. Eisenberg, Penn State's Dr. Legro and the Reproductive Medicine Network have been running a clinical trial to improve fertility. In a presentation to the American Society for Reproductive Medicine in October, they showed that early results indicate a medication called letrozole, a drug commonly used for in vitro fertilization, appears to result in more live births than clomiphene.
艾森伯格、賓大的列格羅以及生殖醫學網絡已經在做一次旨在提高生育率的臨牀試驗。他們在2013年10月份向美國生殖醫學會(American Society for Reproductive Medicine)做報告的時候表示，初步結果表明，常常用於體外授精的來曲唑產生的活胎數量似乎高於枸櫞酸氯米芬。One of those success stories was Lindsey Maloney, from Fredericksburg, Va. She had so much facial hair she started waxing it off in the fifth grade and always struggled with her weight because of insulin resistance. She had her period only once in the seventh grade and was first diagnosed with PCOS at 15.
弗吉尼亞州弗雷德裏克斯堡的琳賽・馬洛尼(Lindsey Maloney)便是成功例子之一。由於面部毛髮過多，她在上五年級的時候便開始動手脫毛；而因爲胰島素抵抗，她又總是因爲體重問題而煩惱。她只在上七年級的時候有過一次例假，15歲時第一次診出多囊症。When Ms. Maloney, now a 29-year-old school counselor, got engaged to her now-husband, her fertility worried her. When the couple heard about Dr. Legro's study, Ms. Maloney enrolled and drove three hours to Hershey once a month for drugs to help her ovulate. She was randomly assigned to the letrozole group, she says.
馬洛尼現年29歲，是一名中學輔導員。在跟現在的丈夫訂婚時，她因爲自己的生育能力而擔憂。夫妻二人聽說列格羅的研究時，馬洛尼加入了研究，每個月開車三小時到赫希去服用幫助她排卵的藥物。她說，她被隨機分配到服用來曲唑的小組。They now have a 2-year-old girl, Briley. Ms. Maloney and her husband are trying for a second child on their own and haven't had any luck yet.
現在他們的女兒布里利(Briley)已經兩歲了。馬洛尼和丈夫正在嘗試自行孕育第二個孩子，目前尚未成功。Ms. Maloney has been taking metformin since she was a teenager, sees an endocrinologist every three months and buys supplements and organic foods without hormones in them, but her symptoms have remained, she says.
馬洛尼說，她從十幾歲以來一直在服用二甲雙胍，每三個月都要看一次內分泌科醫生，她還購買補充劑和沒有激素的有機食品，但症狀依然沒有消失。'It's not just on your ovaries. It's a whole mess of endocrine problems that you have,' she says.
她說：“不只是卵巢的問題，而是一大堆內分泌問題。”
