Kendall A, Dowsett M, Folkerd E, Smith I
Academic Department of Biochemistry, Royal Marsden Foundation NHS Trust, London, UK.
Ann Oncol. 2006 Apr;17(4):584-7. doi: 10.1093/annonc/mdj127. Epub 2006 Jan 27.
Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer.
Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women.
Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women.
The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.
芳香化酶抑制剂(AI)在早期乳腺癌中的应用日益广泛,人们对其深度抑制雌激素所带来的长期副作用的关注度也在不断提高。萎缩性阴道炎导致的泌尿生殖系统副作用通常采用阴道雌激素制剂进行治疗。一般认为这些制剂导致的雌激素全身吸收极少。我们对7名正在使用阴道雌激素制剂且同时接受AI治疗乳腺癌的绝经后女性的血清雌二醇、促卵泡生成素(FSH)和促黄体生成素(LH)水平进行了跟踪监测。
在基线时以及开始使用阴道雌二醇后的第2、4、7 - 10和12周对血清进行雌二醇、FSH和LH分析。雌二醇采用专门为测量绝经后女性低水平雌二醇而开发的检测方法进行测定。
血清雌二醇水平从与AI治疗相符的基线水平≤5 pmol/l升至2周时的平均72 pmol/l。到4周时,大多数患者(中位数为16 pmol/l)降至<35 pmol/l,不过有两名女性出现了显著的进一步升高。
阴道雌二醇片(爱斯妥)至少在短期内会显著提高全身雌二醇水平。这会逆转芳香化酶抑制剂对乳腺癌女性患者雌二醇的抑制作用,因此该药物是禁忌的。