Increased Incidence of Endometrial Cancer Following the Women's Health Initiative: An Assessment of Risk Factors

Abstract

Background: The Surveillance, Epidemiology, and End Result (SEER) database shows a variable increase in endometrial cancer incidence over time. The objective of this review was to examine published endometrial cancer rates and potential etiologies.

Methods: Endometrial cancer incidence was obtained from the SEER Program database from 1975 through 2014, and a test for trend in incidence was calculated. Changes in risk factors thought to be associated with endometrial cancer, including age, obesity, diabetes, diet and exercise, reproductive factors, and medications (hormone therapy [HT] including Food and Drug Administration [FDA]-approved and non-FDA-approved [compounded] estrogens and progestogens, tamoxifen, and hormonal contraceptives) were found through PubMed searches. Temporal trends of risk factors were compared with endometrial cancer trends from SEER.

Results: Although endometrial cancer rates were constant from 1992 to 2002 (women 50-74 years of age), they increased 2.5% annually with a 10% increase from 2006 to 2012 (trend test 0.82). Use of approved prescription estrogen-progestogen combination products decreased after the publication of the Women's Health Initiative (WHI) data, whereas other risk factors either remained constant or decreased during the same time; however, compounded bioidentical HT (CBHT) use increased coincident with the endometrial cancer increase.

Conclusion: Endometrial cancer rate increases after the first publication of WHI data in 2002 may be associated with the decreased use of approved estrogen-progestogen therapy, the increase in CBHT use, and the prevalence of obesity and diabetes; potential relationships require further evaluation.

Keywords: compounded bioidentical hormone therapy; endometrial cancer; hormone therapy; menopause.

FIG. 1.

Age-adjusted endometrial cancer incidence per 100,000 from SEER for (A) all women between 1975 and 2014 and (B) in women ≥50 years for 2000–2014. SEER, Surveillance, Epidemiology, and End Result.

FIG. 2.

Prevalence of women using hormone therapy by formulation between 2000 and 2009.

FIG. 3.

Age-adjusted prevalence of overweight (BMI 25 to <30 kg/m²), obese (BMI ≥30 kg/m²), or extremely obese (BMI ≥40 kg/m²) women 20–74 years of age between 1960 and 2012. BMI, body mass index.