What is the highest risk factor for endometrial cancer among age, polycystic ovary syndrome, hypertension, and multiparity?

Highest Risk Factor for Endometrial Cancer

Age is the most important risk factor for endometrial cancer among the options provided. 1

Evidence-Based Risk Hierarchy

Age as the Primary Risk Factor

• Uterine cancer is primarily a disease of postmenopausal women, and consequently age is the most important risk factor, with a median age at diagnosis of 60 years 1
• Age represents a non-modifiable, universal risk factor that supersedes other demographic, reproductive, medical, and lifestyle factors in determining baseline endometrial cancer risk 1

PCOS as a Significant but Secondary Risk Factor

• Women with PCOS have a nearly threefold increased risk of endometrial cancer (OR 2.79-2.89) due to chronic anovulation causing unopposed estrogen stimulation 2
• Research studies confirm a 2.7 to 4-fold increased risk, though this association is partially attenuated when adjusted for BMI 3, 4, 5
• The BMI-adjusted odds ratio drops from 2.79-2.89 to 2.2, indicating that obesity independently contributes to the risk beyond PCOS itself 2

Hypertension as an Obesity-Associated Factor

• Hypertension is identified as an obesity-associated risk factor for endometrial cancer, but it functions primarily as a marker of metabolic dysfunction rather than an independent primary risk factor 6
• The relationship between hypertension and endometrial cancer is confounded by obesity, diabetes, and hyperinsulinemia 6

Multiparity as a Protective Factor

• Nulliparity (not multiparity) is the classical risk factor for endometrial cancer, with multiple pregnancies providing protective effects due to progesterone exposure 6
• This option represents the opposite of a risk factor—multiparity actually reduces endometrial cancer risk 1

Clinical Context and Pitfalls

Common pitfall: Confusing the magnitude of relative risk with population-attributable risk. While PCOS confers a higher relative risk (2-4 fold) compared to age-related baseline risk, age remains the most important risk factor because:

• It affects all women universally 1
• The absolute incidence increases dramatically with age regardless of other risk factors 1
• Other risk factors (PCOS, obesity, hypertension) modify risk on top of the age-related baseline 1, 6

Answer: A. Age