Alvarez-Vasquez R B, Axelrod D, Frenkel K, Newman M C, Sepkovic D W, Bradlow H L, Zumoff B
Division of Endocrinology and Metabolism, Beth Israel Medical Center, New York, NY 10003, USA.
Horm Metab Res. 2003 Jun;35(6):358-61. doi: 10.1055/s-2003-41357.
Whether postmenopausal hormone-replacement therapy (HRT) increases the risk of breast cancer remains controversial, despite numerous epidemiological studies. We approached the question from a biochemical rather than an epidemiological direction - we hypothesized that if estrogen administration increases the risk of breast cancer, it should also alter a known estrogen biomarker of risk towards what has been observed in patients who already have breast cancer. The specific biomarker we studied was the ratio of the urinary excretion of two principal estradiol metabolites, 2-hydroxyestrone and 16 alpha-hydroxyestrone, which is markedly decreased in women with breast cancer and women with familial risk for breast cancer. We studied 34 healthy postmenopausal women not on HRT and 19 women on HRT (Premarin 0.625 mg daily plus Provera, 2.5 mg daily, in women with a uterus and Premarin alone in women without a uterus); treatment duration ranged from 3 months to 15 years. We also studied four women with recently diagnosed, untreated breast cancer. The women with breast cancer showed a significantly lower 2-hydroxyestrone to 16 alpha-hydroxyestrone ratio than control women on HRT (1.35 +/- 0.13 vs. 2.71 +/- 0.84; p < 0.0001). There was no significant difference in the metabolite ratio between healthy women on HRT and women not on HRT (2.82 +/- 0.92 vs. 2.71 +/- 0.84). There was no significant difference between women receiving Premarin alone and women receiving Premarin plus Provera (2.46 +/- 0.84 vs. 3.13 +/- 0.90), and neither differed significantly from women not on HRT (2.71 +/- 0.84). The finding that the ratio of women on HRT was not decreased to or toward the ratio in women with breast cancer can be interpreted, we believe, as a suggestive item of biochemical evidence that HRT is not a risk for breast cancer.
尽管进行了大量流行病学研究，但绝经后激素替代疗法（HRT）是否会增加患乳腺癌的风险仍存在争议。我们从生化而非流行病学的角度来探讨这个问题——我们假设，如果给予雌激素会增加患乳腺癌的风险，那么它也应该会改变一种已知的雌激素风险生物标志物，使其向已患乳腺癌患者中观察到的情况转变。我们研究的特定生物标志物是两种主要雌二醇代谢物（2-羟雌酮和16α-羟雌酮）的尿排泄率之比，乳腺癌患者和有乳腺癌家族风险的女性中该比值显著降低。我们研究了34名未接受HRT的健康绝经后女性以及19名接受HRT的女性（有子宫的女性每日服用0.625mg结合雌激素加2.5mg甲羟孕酮，无子宫的女性仅服用结合雌激素）；治疗持续时间从3个月到15年不等。我们还研究了4名近期诊断为未治疗乳腺癌的女性。乳腺癌女性的2-羟雌酮与16α-羟雌酮比值显著低于接受HRT的对照女性（1.35±0.13对2.71±0.84；p<0.0001）。接受HRT的健康女性与未接受HRT的女性之间的代谢物比值无显著差异（2.82±0.92对2.71±0.84）。仅接受结合雌激素的女性与接受结合雌激素加甲羟孕酮的女性之间无显著差异（2.46±0.84对3.13±0.90），且两者与未接受HRT的女性均无显著差异（2.71±0.84）。我们认为，接受HRT的女性的该比值未降至或趋向于乳腺癌女性的比值这一发现，可以解释为HRT不是乳腺癌风险的一项生化证据。
