How can polycystic ovarian syndrome (PCOS) cause endometrial cancer?

Daniel A. Dumesic, MD
Reproductive Endocrinology
There are two mechanisms that can link polycystic ovary syndrome (PCOS) to endometrial carcinoma (cancer). If women do not ovulate, they do not make a hormone called progesterone, which is intended to clean up the lining of the uterus every month with the menses.

In the absence of ovulation, estrogen is produced and the endometrium (lining of the uterus) continues to grow. Because progesterone is not being made, there’s no stop signal to the growth of the endometrium. Over many years, one will experience long-term irregular bleeding and ultimately an increased risk of endometrial carcinoma, which is originating from this endometrium that’s constantly been growing over the long term without a mechanism to really stop its growth. That’s the common mechanism associated with endometrial carcinoma in PCOS.

A second mechanism involves insulin, which is also a hormone that causes cell proliferation. Many PCOS women have a type of insulin-resistance that is independent and additive with that of obesity so that their insulin levels in the circulation are increased. This elevation in circulating insulin levels can continuously stimulate the cells lining the uterine cavity and may also increase the risk of developing endometrial carcinoma.
Irregular menstrual periods and the absence of ovulation cause women with polycystic ovarian syndrome (PCOS) to produce estrogen, but not progesterone. Without progesterone, which causes the endometrium to shed each month as a menstrual period, the endometrium may grow too much and undergo cell changes. This is a pre-cancerous condition called endometrial hyperplasia. If the thickened endometrium is not treated, over a long period of time it may turn into endometrial cancer.

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