本研究目的為探討停經婦女在有無接受荷爾蒙補充治療（Hormone Replacement Therapy,HRT）或接受不同給藥方式的HRT情況下補充魚油，對於受試者尿液中女性荷爾蒙代謝物2-hydroxyestrone(2OHE1)、16α-hydroxyestrone(16αOHE1)濃度及其比值2OHE1/16αOHE1 ratio的影響，以了解魚油和HRT對於停經婦女女性荷爾蒙代謝的影響
作用。
受試者為停經一年以上、身體健康且無服用魚油製品的自願者47名，依其原本有無使用HRT或使用HRT方式分為(1)沒有接受HRT，non-HRT組；(2)接受HRT而僅服用estrogen，HRT(E)組；(3)接受HRT而同時服用estrogen及progestin，HRT(E+P)組；(4)接受HRT的對照組，HRT-SO組等四組，實驗期間HRT-SO組每日服用4顆富含單元不飽和脂肪酸的葵花油(共含1g C18:1脂肪酸)作為安慰劑，其餘三組每天服用魚油4顆（共含2克的n-3脂肪酸）共28天。實驗前後各採集一次空腹血液及早晨起床後第一次尿液，進行血漿及紅血球脂肪酸組成及尿液中2OHE1 、16αOHE1、TBARs(Thiobarbituric acid reactive
substance)等含量的測量。
由魚油或葵花油補充前的數據顯示，接受HRT的停經婦女尿液中經creatinine濃度校正的2OHE1量與16aOHE1量及2OHE1/16aOHE1比值皆高於沒有接受HRT者，其中2OHE1量的差異達到顯著水準。以2OHE1含量佔2OHE1與16aOHE1總量的百分比，表示等量estrone在人體內進行兩個主要代謝途徑：estrone 2-hydroxylation與estrone 16a-hydroxylation的比例，有接受HRT的停經婦女體內進行estrone 2-hydroxylation的程度皆顯著高於沒有接受HRT的停經婦女，接受不同治療方式HRT的停經婦女尿液中2OHE1量沒有差異，因單獨使用estrogen的停經婦女16aOHE1絕對量較合併使用estrogen與progestin的停經婦女低，所以其2OHE1/16aOHE1比值顯著較高。在魚油補充後停經婦女不論有無接受荷爾蒙補充治療或接受何種治療方式尿液中2OHE1量均下降、16aOHE1量均上升，2OHE1/16aOHE1比值下降，其中HRT(E)組2OHE1與2OHE1/16aOHE1比值的變化量達顯著差異。魚油補充會增加尿液中TBARs量，顯示停經婦女體內氧化程度因魚油補充而上升。有趣的發現是尿液中TBARs增加量與2OHE1下降量間存顯著的負相關性。服用葵花油的停經婦女在實驗後尿液中2OHE1量上升，16aOHE1量顯著下降，2OHE1/16aOHE1比值上升；這些變化皆與服用魚油形成的結果相反。本研究顯示補充魚油使停經婦女尿中
2OHE1/16aOHE1比值下降，也許對乳癌危險指標有不利影響。

HRT(Hormone replacement therapy) might increase the risk of breast cancer,while fish oil seems to have protective effect against breast cancer. To investigate the effect of fish oil and HRT on the distribution of urinary estrogen metabolites in postmenopausal women, four groups of healthy postmenopausal women were recruited: (1) without HRT, non-HRT; (2) with HRT by taking estrogen only, HRT(E); (3) with HRT by taking estrogen and progestin, HRT(E+P) ; (4) 8 women with HRT were randomly chosen to take sunflower oil capsules as the placebo, HRT-SO. The first three groups were given 4g fish oil capsules per day (2g n-3 fatty acids) for 28 days. First morning urine samples were collected before and after oil supplementation, and the content of 2OHE1 and 16αOHE1 adjusted by creatinine and the ratio of 2OHE1 to 16αOHE1 (as an index of breast cancer risk) were measured. (1)Comparing the influence of HRT on estrogen metabolism before oil supplement, the data indicated that proportion of estrogen metabolized toward 2-hydroxylation was more in women with HRT than in those without HRT. Among the women taking HRT, urinary 16αOHE1 content was lower and 2OHE1/16αOHE1 ratio was higher in those taking estrogen than in those takiing combination of estrogen and progestin. (2)After fish oil supplementation, urinary 2OHE1/creatinine content , the percentage of 2OHE1 content in urinary 2OHE1 and 16αOHE1 and the ratio of 2OHE1 to 16αOHE1 decreased and reached a significant difference in HRT(E) and urinary 16αOHE1/creatinine, estriol/creatinine and TBARs/creatinine content increased compared with those before oil supplement but did not reach a significant difference.A significant negative correlation was found between the change of 2OHE1 and TBARs.In contrast, sunflower oil treatment induced the changes of above parameter in opposite dirrection. The results suggest that fish oil supplementation decreases the ratio of urinary 2OHE1 to 16αOHE1that might imply negative effect on the incidence of breast cancer.

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