荷爾蒙補充療法及癌症 Hormone Replacement Therapy and Cancers 黃思誠台大醫院婦產科

停經後的荷爾蒙補充療法 (HRT) 可以治療停經後症候群, 如潮紅心悸失眠等, 也可以防止及治療骨質疏鬆常用藥物口服動情激素 ( 如 premarin), 經皮膚吸收動情激素 (estradiol) 黃體素 ( 如 provera) 動情激素及黃體素混合經皮膚吸收劑動情激素及 androgen 混合劑

1896 The Landau Clinic in Berlin: ovarian extracts 1900 preparations from organs and animal urinary sources 1938 synthesis of diethylstilbestrol (DES) 1942 natural conjugated equine estrogens.

1960 及 1970 年代, 動情激素療法非常流行, 認為可以保持青春及預防慢性疾病 1975 年 Smith 報告, 使用動情激素療法時, 子宮內膜癌發生率增加 4.5 倍 1980 及 1990 年代, 荷爾蒙使用持續增加

Breast cancer and HRT 1. 51 observational studies: short term use(<5 year): no increase long term use ( 5 years): 35% increased 2. combined estrogen progestin preparations appear to increase breast cancer risk. 3. In NHS (Nurses` Health study, 20 years) for each year of use, the risk of breast cancer rose by 9% for combination and by 3.3% for estrogen alone.

Breast cancer and HRT 4. Invasive breast cancer in HT users were more likely to be node positive, more likely to have spread. The percentage of abnormal mammograms was higher. 5. Estrogen progestin therapy induces the development of breast cancer relatively rapidly and at the same time delays detection, perhaps by increasing breast tissue.

WHI(Women s Health Initiative) 50 79 years old women) 2002 年 Estrogen progestin arm(16,000 women with intact uterus)terminated after 5.2 years became of unfavorable risk benefit ratio. Estrogen only arm(10,000 women with hysterectomy)terminated after 6.8 years became of excessive risk of stroke.

HERS (The Heart and Estrogen/progestin Replacement Study). 0.625 mg oral conjugated equine estrogen 2.5 mg medroxyprogesterone acetate daily PEPI (The Postmenopausal Estrogen/Progestin Interventions Study).

自從 2002 年 WHI(Women s Health Initiative) 之報告後, 荷爾蒙補充療法必要時以短期低劑量使用, 不超過 5 年為宜, 對於已切除子宮的患者, 給予動情激素 (estrogens) 治療, 對於仍有子宮的患者, 給予動情激素及黃體素 (progestins) 的混合療法只給予動情激素的患者, 不會增加乳癌發生率給予動情激素及黃體素混合的患者, 乳癌發生率會增加

台灣女性乳癌. 子宮體癌. 結腸直腸乙狀結腸連結部及肛門癌年齡標準化發生率之長期趨勢 1979 2006 年

台灣地區女性十大癌症比率 1997 2006

服用荷爾蒙之患者, 乳房方面必須定期做乳房攝影 (mammography) 或乳房超音波檢查 ; 子宮方面, 必須定期做子宮超音波檢查或子宮鏡檢查

BI RADS Categorization(all modalities) (Breast Imaging Reporting and Data System) BI RADS 1 no findings risk of cancer 0% BI RADS 2 benign findings risk of cancer 0% BI RADS 3 probably benign findings risk of cancer <2% BI RADS 4 probably malignant findings risk of cancer ~30% BI RADS 5 highly suspect findings risk of cancer ~95% BI RADS 6 histologically verified cancer

Breast sonar:birads Category 3

Breast sonar:birads Category 4

mammography BI RADS Categorization Clinical findings right 1 left 1 Ultrasound right 1 left 1 Mammography right 3 left 1 MR Mammography right 1 left 1 BI RADS Total right 3 left 1

Population studies examining the safety of hormone replacement therapy(hrt)after breast cancer

對於乳癌之患者或高危險患者, 目前無 FDA approved 之製劑, 對於植物性女性荷爾蒙仍須小心 SERM(selective estrogen receptor modulator) Tamoxifene Raloxifene

Raloxifene(evista) Counters estrogenic effects in breast Acting like estrogen in bone Do not promote excess growth of uterine tissue

Endometrial cancer 1. 30 observational studies: uses of unopposed estrogen: 1 5 year uses 3X 10 year uses 10X 2.DEPI: unopposed estrogen for 3 years. 24% of women developed atypical endometrial hyperplasia. 1% for placebo 3.HERS and WHI: Daily combined regimen: no increase in the risk.

Evaluation of abnormal bleedihg sonography:if the endometrial thickness< 5mm, the risk of endometrial hyperplasia or cancer is low. Endometrial biopy Hysteroscopy D&C

hysteroscopic finding and histologic picture Complex hyperplasia

hysteroscopic finding and histologic picture Endometrial adenocarcinoma

colorectal cancer 1. 18 observational studies: 20% reduction in risk of colon cancer 19% reduction in risk of rectal cancer 2. administration of estrogen decreases the secondary production of bile acids, compounds that are believed to initiate or promote malignant change in the colonic epithelium. 3. estrogen decreases serum levels of insulin like growth factor 1, a mitogen that may be associated with colorectal cancer.

The risk for colorectal cancer is decreased among women currently receiving postmenopausal hormone therapy, but the apparent reduction diminishes substantially upon cessation of therapy

Screening Test for fecal occult blood Flexible signoidoscopy and colonoscopy

另外, 在亞洲 ( 如中國日本 ) 食用含高量植物性動情激素 (phytoestrogens) 食物, 如大豆類, 可能降低乳癌及子宮內膜癌, 但此仍有待更嚴謹的研究證實, 目前無 FDA 認可之植物性動情激素製劑, 對於植物性女性荷爾蒙的使用, 仍須小心

植物動情激素 (isoflavon, 大豆異黃酮 ) 大豆製品 Flaxseed red clover dong quai Black cohosh

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荷爾蒙補充療法及癌症 Hormone Replacement Therapy and Cancers 黃思誠 台大醫院婦產科

荷爾蒙補充療法及癌症 Hormone Replacement Therapy and Cancers 黃思誠台大醫院婦產科