Do we know what causes endometrial cancer?

The exact cause of endometrial cancer isn't fully understood, but several factors significantly increase the risk. These include prolonged exposure to estrogen without the counterbalancing effects of progesterone (e.g., due to early menarche, late menopause, obesity, infertility treatments, or conditions like polycystic ovary syndrome), genetic predisposition (certain gene mutations increase susceptibility), a history of certain other cancers (like breast or colon cancer), and certain lifestyle factors (such as lack of exercise and a diet high in saturated and trans fats). While some cases may be attributed to random genetic mutations, the interplay of these risk factors contributes significantly to the development of endometrial cancer.

The exact cause of endometrial cancer isn't fully understood, but several factors are known to increase the risk significantly. These are often grouped into two categories: factors that increase estrogen exposure and factors that decrease progesterone exposure. The interplay of these factors is crucial. Here's a breakdown:

• Increased Estrogen Exposure: Prolonged exposure to estrogen without the counterbalancing effects of progesterone is a major risk factor. This can be due to:
  • Early menarche (first period) and late menopause: Longer reproductive lifespan means more exposure to estrogen.
  • Obesity: Fat cells produce estrogen, leading to higher levels.
  • Polycystic ovary syndrome (PCOS): This condition often leads to hormonal imbalances, including high estrogen levels.
  • Tamoxifen use: While used to treat breast cancer, tamoxifen can stimulate the uterus and increase the risk of endometrial cancer.
  • Nulliparity (never having given birth): Pregnancy and breastfeeding reduce estrogen exposure.
  • Late first pregnancy: Delaying pregnancy means more years of exposure to unopposed estrogen.
  • Hormone replacement therapy (HRT): Especially estrogen-only therapy. Combined HRT (estrogen and progesterone) is less risky.
• Decreased Progesterone Exposure: Progesterone helps to counteract the effects of estrogen on the uterine lining. Factors that decrease progesterone include those listed above (leading to relative estrogen excess) as well as:
  • Anovulation: Absence of ovulation means less progesterone production.
• Genetics: A family history of endometrial cancer or certain genetic mutations (like Lynch syndrome) significantly increase the risk.
• Other Factors: Although less well understood, other factors may play a role, including:
  • Race: Endometrial cancer is more common in white women than in other racial groups.
  • Diet: A high-fat diet is linked to increased risk.
  • Physical inactivity: Lack of exercise is associated with higher risk.
  • Diabetes: Type 2 diabetes is linked to increased risk.

It's important to note that having one or more risk factors doesn't guarantee developing endometrial cancer. Many women with risk factors never develop the disease, while some women with no known risk factors do. Research continues to explore the complex interplay of these factors and identify additional contributing elements.