Ovarian cancer incidence trends in relation to changing patterns of menopausal hormone therapy use in the United States

Abstract

Purpose: After a report from the Women's Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002.

Methods: Using the North American Association of Central Cancer Registries database (1995 to 2008; N = 171,142 incident ovarian cancers), we applied standard analytic approaches and age-period-cohort (APC) models to estimate ovarian cancer incidence rate changes before (1995 to 2002) and after (2003 to 2008) the WHI report.

Results: Among women age ≥ 50 years, age-standardized ovarian cancer incidence declined by 0.8% per year (95% CI, -1.8% to -0.5% per year) before the WHI announcement; after the WHI report, the rate declined by 2.4% per year (95% CI, -2.5% to -2.2% per year). APC models confirmed an accelerated decline in ovarian cancer incidence after the WHI report, adjusted for age and birth cohort effects. This sudden change was notable among women most likely to have used MHT (ie, women age 50 to 69 years, white women, and residents of regions with highest MHT prescription frequency). The largest changes were found for the endometrioid histologic subtype.

Conclusion: After a marked reduction in MHT use around 2002, ovarian cancer incidence rates demonstrated an accelerated decline, with the largest changes for endometrioid carcinomas. This strong temporal association, although not proving a causal role of hormones in ovarian carcinogenesis, suggests that future analytic research supporting cancer control efforts should clarify the role of hormonal exposures on the development and behavior of subtypes of ovarian cancer.

Fig 1.

Age-standardized ovarian cancer incidence rates in the United States (North American Association of Central Cancer Registries Incidence, 1995 to 2008). Age standardized to the 2000 US population.

Fig 2.

Age-period-cohort effects among US women age ≥ 50 years (North American Association of Central Cancer Registries Incidence, 1995 to 2008). Point estimates are shown in blue, with 95% CIs shaded in gold. (A) The significance of period deviations was assessed by contrasting the three time periods before the Women's Health Initiative (WHI; 1995 to 1996, 1997 to 1998, and 1999 to 2000) with the three time periods after WHI (2003 to 2004, 2005 to 2006, and 2007 to 2008). P value is for change in the slopes of the period deviations, adjusted for age and cohort effects. (B) Period relative risks were calculated as rate ratios adjusted for age and birth cohort effects, comparing the ovarian cancer incidence rates for a given time period with the rate of a referent period (the 2002 time period in this analysis). The period relative risks declined from more than 1.0 before the 2002 referent period, after which the period relative risks were significantly less than 1.0.

Fig 3.

Age-period-cohort period relative risks among US women age ≥ 50 years (North American Association of Central Cancer Registries Incidence, 1995 to 2008). The period relative risks by (A) age at ovarian cancer diagnosis, (B) race, (C) histologic subtype, and (D) US geographic regions associated with high (West South Central) and low (Mid-Atlantic) menopausal hormone therapy frequency. For most strata, the period relative risks declined from more than 1.0 before the 2002 referent period, after which the period relative risks were less than 1.0 (see text for further details).