一篇最近的透视文章声称排卵周期期间黄体酮分泌是乳腺癌的原因。然而，我们对该出版物中开发的大部分证据提出质疑。首先，缺乏证据表明黄体酮对乳腺细胞具有诱变性。致癌应指的是通过突变引发，而不是促进。其次，在正常长度的月经周期中，亚临床排卵紊乱相当常见。第三，作者将潜在的致癌效应归因于月经周期中分泌的黄体酮而不是孕期中的黄体酮。他们没有讨论黄体酮/孕激素替代治疗在乳腺癌证据方面的作用。他们辩称，在遗传性原发性闭经中，乳腺癌的假定较低风险可能是由于缺乏黄体酮，尽管这些女性接受了含有黄体酮/孕激素的激素替代疗法。第四，他们主张黄体酮对多个可能与癌症起源有关的基因具有调控作用。特别是，他们将 Mayer-Rokitansky-Küster-Hauser 综合征女性的乳腺癌风险降低归因于黄体酮刺激的 Wnt4 基因缺陷。然而，这种缺陷只存在于小部分患者中。因此，提出的黄体酮乳腺癌风险是不具有说服力的，我们在这个评论中一一讨论了这些观点。

A recent Perspective article asserted that progesterone secretion during ovulatory cycles is the cause of breast cancer. However, we challenge most of the evidence developed in this publication. First, there is a lack of evidence that progesterone is mutagenic for breast cells. Cause of a cancer should mean initiation by mutation, as opposed to promotion. Second, subclinical ovulatory disturbances occur rather frequently in normal-length menstrual cycles. Third, the authors attribute a potential carcinogenic effect to progesterone secreted during menstrual cycles but not to progesterone during pregnancy. They did not discuss breast cancer evidence from progesterone/progestin therapeutics. They argue that in genetic primary amenorrhea, a hypothetic lower risk of breast cancer could be due to the lack of progesterone, despite the progesterone/progestin in hormone replacements these women receive. Fourth, they advocate a regulatory effect of progesterone on several genes potentially involved in cancer genesis. In particular, they attribute a lower risk of breast cancer in women with Mayer-Rokitansky-Küster-Hauser syndrome to a defect in the progesterone-stimulated Wnt4 gene. However, this defect is only present in a small subset. Thus, the postulated progesterone breast cancer risk is unconvincing, which we discuss point by point in this commentary.