更年期婦女的婦科腫瘤與荷爾蒙療法 台北榮民總醫院婦科主任

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Oral Estrogen and Estrogen/Progestin Products ＊

Gels, Creams, Patches, and Other

Hormone Products ＊

For postmenopausal conditions:

Risk Factors for Uterine Cancer

There are various types of uterine cancer. The most common is endometrial cancer, which begins in the lining (endometrium) of the uterus. It is often referred to as uterine cancer.

Key risk factors for uterine cancer are: ■ Age–usually occurs after age 50 ■ Endometrial hyperplasia–an increase in cells in the lining of the uterus ■ Hormone therapy–using estrogen without progesterone ■ Obesity and related conditions

■ Tamoxifen–taken to prevent breast cancer ■ Race–white women are more likely than African American women to

develop uterine cancer ■ Colorectal cancer–those who have an inherited form are at a higher

risk of developing uterine cancer ■ Factors that increase exposure to estrogen–not having children,

starting menstruation at an early age, entering menopause late

Breast Cancer Risk Factors

About 80 percent of breast cancer cases occur after age 50. One of every eight American women who

live to be 85 develops breast cancer. Some factors increase the risk for breast cancer. However, most women who develop breast cancer do not have any of the risk factors.Key factors that increase the risk of

developing breast cancer are:■ Personal history–if you’ve had it once, you’re more likely to develop it again■ Family history–if your mother, sister, or daughter had breast cancer, especiallyat an early age, you’re more likely to develop it■ Other breast changes (not including ordinary “lumpiness”)–such as atypical hyperplasia (an irregular pattern of cell growth)■ Genetic alterations–changes in certain genes, including BRCA1 and BRCA2 mutations

Other factors also may increase the risk of

developing breast cancer.

These include:

■ Race–white women are more likely to develop it

than African American or Asian women

■ Estrogen exposure–risk is somewhat increased for

those who began menstruation early (before age 12),

had menopause late (after age 55), never had

children, or took hormone therapy for long periods

■ Late childbearing–having a first child after about

age 30

■ Radiation therapy–if given to the chest more than

10 years ago, especially in women younger than age

30

■ Breast density–breasts with a high proportion of

lobular and ductal tissue,which is dense and in

which breast cancers usually appear

■ Alcoholic beverage consumption

WHI Findings On Estrogen Progestin Therapy

Compared with a placebo, after about 5 years of use, estrogen plus

progestin resulted in:

Increased risks 26% increase in breast cancer 41% increase in strokes 29% increase in heart attacks Doubled rates of blood clots in legs and lungs

Increased benefits 37% less colorectal cancer 34% fewer hip fractures No difference Number of deaths

Estrogen Plus Progestin Pills vs. Placebo Pills

Risk Factors for Stroke

Main risk factors are:■ High blood pressure■ Diabetes■ Cigarette smokingOther risk factors include:■ Family history–stroke appears torun in some families, whetherdue to genetics and/or sharedlifestyle■ Heavy consumption of alcoholicbeverages■ High blood cholesterol■ Menopause

Risk Factors for Colorectal CancerAbout 30,000 women a year die of colorectal cancer–it is the third-leading cause of cancer deaths for women,after lung and breast cancers.Factors that increase the risk of colorectal cancer include:■ Age–risk increases after age 50■ Diet–eating a diet high in fat and calories, and low in fiber■ Polyps–these are benign growths on the inner wall of the colon and rectum■ Personal medical history–having had cancer of the ovary, uterus, or breast; also having had colorectal cancer once increases the chance of developing it again■ Family medical history–having first-degree relatives (parents, siblings, or children) with colorectal cancer, especially at a young age; risk increases even more if many family members have had colorectal cancer■ Ulcerative colitis–a condition in which the lining of the colon becomes inflamed

Postmenopausal Hormone Therapy and Ovarian Cancer Risk

Early studies of postmenopausal hormone therapy found inconsistent results about its effect on the risk of ovarian cancer: Some reported increased risk with estrogen use, while others reported no effect or even

a protective one. Most of those studies were relatively small and did not take into account the key risk factors for ovarian cancer .

More recently, two large observational studies have indicated that long- term estrogen use increases the risk of ovarian cancer. It’s important to keep in mind that observational studies do not prove that a treatment causes a disease. The evidence from these studies is cautionary, not definitive.

Risk Factors for Ovarian CancerAbout 1 in 57 American women will develop ovarian cancer.Most will be over age 50, but younger women also can develop the disease.

Here are some factors that increase or decrease the risk of ovarian cancer:Increases risk– Age–risk increases as a woman ages Family history of ovarian cancer–higher risk if mother or sister has had ovarian

cancer; somewhat higher risk if other relatives, such as grandmother, aunt, or cousin, have developed ovarian cancer

Postmenopausal hormone therapy–may increase risk Fertility drugs Personal history of breast and/or colon cancerDecreases risk– Oral contraceptives–the longer the use, the lower the riskmay be and the decrease

may last after use has ended Childbearing and breast-feeding Tubal ligation (sterilization) or hysterectomy Prophylactic (to prevent or protect) oophorectomy (surgery to remove one or both

ovaries)

Increased Risk of Ovarian Cancer Is Linked to Estrogen Replacement Therapy

Posted Date:Tuesday, July 16, 2002

Researchers from the National Cancer Institute (NCI) have found that women in a large study who used estrogen replacement therapy after menopause were at increased risk for ovarian cancer. The report was published in the July 17, 2002, issue of JAMA.*

The scientists followed 44,241 women for approximately 20 years. Compared to postmenopausal women not using hormone replacement therapy, users of estrogen-only therapy had a 60 percent greater risk of developing ovarian cancer. The risk increased with length of estrogen use. The women, who were followed from 1979 to 1998, were former participants in the Breast Cancer Detection Demonstration Project, a mammography screening program conducted between 1973 and 1980.

"The main finding of our study was that postmenopausal women who used estrogen replacement therapy for 10 or more years were at significantly higher risk of developing ovarian cancer than women who never used hormone replacement therapy," said James V. Lacey, Jr., Ph.D., lead author of the study from NCI's Division of Cancer Epidemiology and Genetics. The relative risk for 10 to 19 years of use was 1.8, which translates to an 80 percent higher risk than non-users, and increased to 3.2 (a 220 percent higher risk than non-users) for women who took estrogen for 20 or more years.

Talking With Your Doctor

It’s important to be involved in your health care. Ask questions and express your

concerns. Here are some questions that may help you talk with your health care

provider about hormone therapy:

Why am I taking hormone therapy? Or why should I take hormone therapy?

Which hormone therapy am I on? What are my risks for heart disease, breast cancer, and osteoporosis? Should I stop taking the hormone therapy? What’s the best way for me to stop? What side effects will I have? Is there an alternative therapy that I can use long-term? What alternatives can help me prevent heart disease? What alternatives can help me prevent osteoporosis? What can I do to keep menopausal symptoms from returning?

Check It Out

Here’s a prescription for better health:

Blood pressure–healthy women should have it checked every 2 years; others may need it

Checked more often.

Lipoprotein profile–checks blood levels of LDL, HDL,total cholesterol, and triglycerides; healthy women should have it once every 5 years.

Blood glucose–tests blood levels of glucose (a sugar) and indicates risk for diabetes; healthy women age 45 and older should have it, especially if they are overweight; if it’s normal and women are healthy and not overweight, it should be taken again in 3 years, while others will need it more often.

Overweight and obesity check–this is done by calculating your body mass index (BMI) and Measuring your waist circumference. BMI is a measure of your weight relative to your height, while waist circumference measures abdominal fat. Box 22 tells you how

to calculate BMI. A BMI of 25 or higher is overweight or obese. For women, a waist circumference of more than 35 inches indicates an increased risk for heart disease and

other conditions. Your health care provider also will check you for other risk factors and conditions associated with obesity to determine the best treatment.

■ Mammogram–a special x ray of the breast; Healthy women age 40 and older should be screened for breast cancer with ammography once every 1 to 2 years; studies show screening is especially important for those aged 50-69; women also should do breast Selfexams and have their doctor or health care provider do a clinical breast exam during routine physical exams.

■ Pap Smear–this test checks a sample of cervical cells for changes that may lead tocancer; begin by having it as part of an annual gynecological exam and, if normal 3 years in a row, talk with your doctor about how oftento have it after that.

■ Colonoscopy–examines the inside of the

colon and rectum using a thin, lighted tube

called a colonoscope; healthy women should

have it once every 5 years starting at age 50.

■ Bone density–this x ray measures bone

Thickness and strength; postmenopausal

women with one or more risk factors for

osteoporosis (besides menopause) or who

suffer fractures, and women age 65 and older

regardless of added risk factors should have

this test.

■ Electrocardiogram (EKG or ECG)–this tests

the heart’s electrical activity as it beats;

women over age 40 should have a baseline

EKG.

8.. 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。　　更年期使用荷爾蒙，可以改善婦女的情緒及精神狀況。此外有關雌激素可以減少記憶減退、預防老人失智症的說法，至今還沒有獲得科學上的確證。　　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。

9.. 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。

荷爾蒙治療有助於心臟的健康 ?荷爾蒙治療可增加心臟衰竭患者的存活率

　　 Sept ． 30 ， 2003 －－新研究顯示，罹患心臟衰竭的女性若使用荷爾蒙治療會活得比較久！這項發現並非來自於荷爾蒙治療的臨床試驗，反而是 JoAnn Lindenfeld博士在回顧一個有關荷蒙治療的臨床試驗資料而得，這個臨床試驗的目的在調查服用降壓藥物來治療嚴重心臟衰竭者的存活率，其中共有 490 名年齡在 50歲或 50歲以上的女性參與這項研究。

　　結果發現，罹患心臟衰竭的女性接受荷爾蒙治療3年後可減少 40% 的死亡機率，而在調整其它相關的心臟危險因子後，接受荷爾蒙治療的心臟衰竭女性其3年存活率可由 58% 增加至 78% 。

　　這個研究是於美國進行的，人種與生活習慣與國人均不盡相同，各種疾病的發生率也有所不同，例美國婦女乳癌高峰期在 60～ 65歲，而台灣地區婦女乳癌高峰期平均 48 歲，又西方婦女乳癌罹患率及罹患乳癌的危險因子，如肥胖、高熱量食物，都高於台灣婦女，根據衛生署癌症登記年報及美國國家癌症研究院的統計數字顯示：國內乳癌發生率每十萬人為 31.48 人，而美國乳癌發生率每十萬人為 139.13 人，台灣乳癌發生率為美國 1/4～ 1/5 ，因為這些東西方的差異，所以未必能將此研究完全套用於國人。同時研究也顯示雌激素不會引起基因的突變而將正常的乳房細胞變為惡性的乳癌細胞，只是可能將潛在的乳癌危險提早表現。然而此重要的歸女更年期關懷研究報告值得我們作為參考的依據，雖然它是否可推翻以前的研究報告並做成定論仍需討論。例如，此研究並未評估荷爾蒙療法對治療更年期症狀與陰道萎縮的效益，而且約 30% 婦女在進入研究前已使用超過五年的荷爾蒙，因此研究中使用四年後乳癌增加的時間尚待進一步研究分析。

　　這個報導 (WHI) 的研究是以 16608位平均 63.3歲的婦女，經過 5.2年的研究，結果發現：

心臟病 每年每萬人增加 7人

中風 每年每萬人增加 8

乳癌 每年每萬人增加 8人

肺栓塞 每年每萬人增加 8人

但這個研究也證實了一些好處，例如：

大腸直腸癌 每年每萬人增少 6人

髖骨骨折 每年每萬人增少 5人

　　這篇報導的重要性，不在於全盤否定補充荷爾蒙，因為對個別婦女而言，絕對風險仍相當低，不應引起社會如此的恐慌，而此研究應在強調補充荷爾蒙必須經過更謹慎的評估與追蹤，因為報告中也指出短期使用荷爾蒙仍有很多好處，根據過去很多篇研究都證實補充荷爾蒙對更年期婦女的熱潮紅、盜汗、心悸、失眠、陰道乾澀萎縮、萎縮性尿道炎等症狀的緩解，仍是最有效的治療方法，而且對骨質疏鬆症的預防及降低大腸直腸癌也都是再次被肯定。

美國婦產科協會對於『女性健康關懷研究』 (WHI) 的 estrogen 與 典 progestin 合併療法的研究結果所提出之聲明美國婦產科醫師協會 (ACOG) 在今天的一項聲明中指出，將組成一個專案小組對荷爾蒙補充療法進行研究，此專案小組將由各種專長的醫學專家所組成，其任的醫學專家所組成，其任務為根據最近有關停經婦女　estrogen/progestin合併療法的研究結果做出館床實務上的建議。

ACOG 的專案小組將由 Isaac Schiff醫師所主持， Schiff醫師為 年期 ACOG的更年期照護雜誌所屬醫學諮詢委員會的主席，同時也領導了波士頓麻州總醫院的婦產科。

　　 ACOG的專案小組在六月成立之後，將會儘速完成其研究複查的工作，並根據最近有關女性 estrogen 與 progestins合併療法的研究發現，以及美國國家衛生研究院 (National Health Institute) 所屬之國家心臟、肺部和血液協會在今天所發表的聲明做出較慎密的思考 ;該聲明指出該單位已經止了一項針對健康停經女性所進行之 estrogen/progestin合併療法優缺點評估的大型研究。此為期 8.5 年的臨床試驗在進行到 5.2年時被緊急喊停，因為該療法會造成惡性乳癌的發生率增加。

　　女性健康關懷研究 (WHI) 的部分臨床試驗也發現使用 estrogen 與 progestin合併療法 ( 每日劑量 :0.625 毫克conjugated estrogens加上 2.5 毫克 medroxyprogesterone( 醋酸監 ) 的參與者其冠心疾病、肺部栓塞的發生機率也都含比安慰劑組稍微上升。雖然研究中確實發現此合併療法的好處包括髖骨骨折及大腸直腸癌的發生率都含下降，但是整體而言，其所帶來的風險卻大於上述的效益。WHI試驗中單獨使用 estrogen的部分仍繼續進行著，因為研究報告指出單獨使用 estrogen的實驗組並沒有出現乳癌罹患率上升的情形。

　　完整的研究報告將含刊登在 2002 午 7 月 17 B 出刊的美國替學期刊 (JAMA) 或走今天在 JAMA的網站 (WWW jama.com) 上就可查詢到該篇文章。

2004 年　台灣更年期婦女荷爾蒙補充　　　　療法與整體照護建議

　　對於婦女更年期症狀的緩解，荷爾蒙補充治療是目前最常使用且最有效的治療方法之一，過去歷年以來的臨床證據也顯示此療法提供相當的利益。然而，近日刊登於報紙的美國國家衛生研究院 (US NIH)所進行的婦女更年期關懷研究 (WHI, Women’s Health Initiatives) 報導，有關於荷爾蒙補充療法會增加乳癌、心臟病、血栓等的危險性，造成更年期婦女的不知何去何從，榮總婦科大夫參考更年期醫學會的建議，才提出看法。

因此：

１、目前正接受荷爾蒙治療的婦女不要貿然停藥，且　　應諮詢醫師，以便評估個人利弊，採取適當處置。

２、荷爾蒙補充治療仍是緩解婦女更年期症狀最有效　　的方法，如熱潮紅、盜汗、心悸、失眠、陰道萎　　縮乾澀、尿道萎縮等，服用荷爾蒙治療，四年以　　內乳癌危險性並未增加，如有更年期症狀，短期　　仍可建議使用。

３、長期使用 (4 年以上 )荷爾蒙，則需進一步針對骨質　　密瘦、乳癌、心臟病等進行利益風險評估。

４、子宮切除的更年期婦女，由美國的婦女更年期關懷研　　究 (WHI Study) 報告指出，目前追蹤 5.2年，仍未發現危險性增加，該研究繼續進行中，單獨使用雌激素療法仍可考慮繼續治療。

５、對停經並保有子宮的婦女，可以使用其他藥物或方法　　降低心管管疾病，建議不要為了預防心血管疾病而處方荷爾蒙補充療法。

６、醫師應提供專業諮詢，告知婦女荷爾蒙補充療法的利　　益與可能帶來的風險，以決定是否需使用。

７、建議婦女定期的就醫檢查，每年做子宮頸抹片、乳房　　的檢查、 血液的檢查，並依照醫師的處方用藥。醫師不僅為婦女緩解更年期症狀，更會提供更年期婦女整體的醫療照護。

You are invited—Dr. Chao