The WHO claims estrogens are ‘carcinogenic’: is this true?

Abstract

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.

摘要

雌激素在世界卫生组织（WHO）的致癌化学品清单中。然而, 雌激素需要额外的因素, 如基质因子或孕激素, 以增加增殖/凋亡的比率, 从而引发复制错误和随后发生的突变。这些突变至少需要5-10年才能发展成为临床可检测的癌症, 因此本综述主要针对乳腺癌。美国国家癌症研究所（US National Cancer Institute）强调了致癌性的第二种机制：某些雌激素代谢物即使在低浓度下也能诱导DNA损伤。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。我们已经证明, 使用经皮治疗而不是口服雌二醇治疗可以避免这种情况, 这对吸烟者来说尤其重要。代谢产物谱也受其他外源因素的影响, 如营养、体力活动和某些疾病。女性健康倡议（WHI）中显示的乳腺癌风险降低是由促凋亡雌激素效应在特定“时间间隔”后发挥作用所解释的。此外, 某些雌激素代谢产物具有抗癌保护作用, 如果没有遗传多态性, 则会损害其有益活性。因此, 由于致癌性的主要途径都需要额外的因素, 而且雌激素甚至可以具有癌症保护作用, 我们不能同意世界卫生组织的说法。

Keywords:

• World Health Organization
• estrogens
• carcinogenicity
• breast cancer
• proliferation
• apoptosis
• estrogen metabolism

Potential conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

National Menopause Health Care Specialist Construction Unit of China [(2020)30]; first batch of Beijing maternal and child health specialist demonstration units ‘menopausal health specialist’ [(2017)35]; Beijing Municipal Administration of Hospitals’ Ascent Plan [No. DFL20181401].