Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
Department of Women's Health, Research Centre for Women's Health and University Women's Hospital of Tuebingen, University Hospitals of Tuebingen, Tuebingen, Germany.
Climacteric. 2023 Jun;26(3):263-270. doi: 10.1080/13697137.2023.2196002. Epub 2023 Apr 17.
Estrogens are in the list of carcinogenic chemicals from the World Health Organization (WHO). However, estrogens require additional factors such as stromal factors or progestogens to increase the ratio of proliferation/apoptosis for initiation of replication errors and consequent mutations to occur. These mutations require at least 5-10 years to develop into clinically detectable cancer, whereby this review is focused on breast cancer. The US National Cancer Institute highlighted a second mechanism of carcinogenicity: certain estrogen metabolites are capable of inducing DNA damage, even in low concentration. They can be assessed in the tissue and circulation. However, those deleterious reactions require excessive unrestricted oxidative cell stress, for example in industrial areas with heavy pollution. We have shown that this can be avoided using transdermal instead of oral estradiol treatment, especially important in smokers. The spectrum of metabolites is also influenced by other exogenous factors such as nutrition, physical activity and certain diseases. Reduction of breast cancer risk as demonstrated in the Women's Health Initiative (WHI) was explained by pro-apoptotic estrogen effects working after a certain 'time gap'. In addition, certain estrogen metabolites are carcinoprotective, if no genetic polymorphisms would impair their beneficial activities. Thus, since additional factors are required for both main pathways of carcinogenicity and because estrogens can even have carcinoprotective effects, we cannot agree with the statement from the WHO.
雌激素被世界卫生组织（WHO）列入致癌化学物质清单。然而，雌激素需要额外的因素，如基质因素或孕激素，以增加增殖/凋亡的比例，从而引发复制错误和随后的突变。这些突变需要至少 5-10 年才能发展为临床可检测到的癌症，因此本综述重点关注乳腺癌。美国国家癌症研究所强调了致癌作用的第二种机制：某些雌激素代谢物能够诱导 DNA 损伤，即使在低浓度下也是如此。它们可以在组织和循环中进行评估。然而，这些有害反应需要过度的不受限制的氧化细胞应激，例如在污染严重的工业区。我们已经表明，使用透皮而不是口服雌二醇治疗可以避免这种情况，尤其是对吸烟者而言。代谢物的谱也受到其他外源因素的影响，如营养、体育活动和某些疾病。妇女健康倡议（WHI）中证明的乳腺癌风险降低可以通过特定的“时间间隔”后发挥促凋亡雌激素作用来解释。此外，如果没有遗传多态性会损害其有益活性，某些雌激素代谢物具有抗癌作用。因此，由于致癌作用的两种主要途径都需要额外的因素，并且雌激素甚至可能具有抗癌作用，因此我们不能同意世界卫生组织的声明。
