An aggregated analysis of hormonal factors and endometrial cancer risk by parity

Abstract

Background: Nulliparity is associated with an increased risk of endometrial cancer. It is less clear whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies to date have been too small to test the hypothesis that endometrial cancer risk factors may be associated more strongly with risk among nulliparous women compared with parous women.

Methods: Data were aggregated on 26,936 postmenopausal, Caucasian, nulliparous women (360 endometrial cancers) and 146,583 postmenopausal, Caucasian, parous women (1378 endometrial cancers) from 4 US prospective studies (1979-2006). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in stratified analyses.

Results: The risk of endometrial cancer was higher among nulliparous women than among parous women, as expected (nulliparous vs parous: HR, 1.42; 95% CI, 1.26-1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ between nulliparous versus parous women: For both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity: A body mass index ≥30 kg/m(2) (vs <25 kg/m(2) ) increased the risk of endometrial cancer 3-fold among nulliparous women (HR, 3.04; 95% CI, 2.34-3.94) and parous women (HR, 2.88; 95% CI, 2.52-3.29).

Conclusions: The results from this large, pooled analysis of data from 4 large prospective studies suggested that nulliparity does not modify the risks of endometrial cancer associated with established hormone-related risk factors.

Figure 1

Calendar year of follow-up and endometrial cancer case numbers among postmenopausal Caucasian nulliparous and parous women in the four studies included in the aggregated analysis Nulliparous women represented by dashed (- - - -) lines. Parous women represented by solid lines.

Figure 2

Ages at menarche and menopause and body mass index and endometrial cancer risk stratified by parity in the aggregated sample of postmenopausal Caucasian women Hazard ratios (HRs) and 95% confidence intervals (CI) estimated using Cox proportional hazards models with age as the underlying time scale with separate models fit to nulliparous and parous women. Models include all variables presented in Figures 2 and 3 as well as study, birth year, calendar year of entry, diabetes, and smoking status. Parous models further adjusted for number of births. P-values are presented for the heterogeneity between parous and nulliparous women based on a Wald type chi-square test. HRs for nulliparous women represented by white boxes. HRs for parous women represented black boxes. 2a. In PLCO, age at menarche categorized as <14 and ≥14 years.

Figure 3

Use of oral contraceptives and menopausal hormone therapy and risk of endometrial cancer stratified by parity in the aggregated sample of postmenopausal Caucasian women Hazard ratios (HRs) and 95% confidence intervals (CI) estimated using Cox proportional hazards models with age as the underlying time scale with separate models fit to nulliparous and parous women. Models include all variables presented in Figures 2 and 3 as well as study, birth year, calendar year of entry, diabetes, and smoking status. Parous models further adjusted for number of births. P-values are presented for the heterogeneity between parous and nulliparous women based on a Wald type chi-square test. HRs for nulliparous women represented by white boxes. HRs for parous women represented black boxes. 3a. In NIH-AARP, never use includes <1 year 3b. In PLCO, duration of E + P use categorized as <6 years and ≥6 years. Analyses restricted to subset of women who reported never or current use from NIH-AARP or entry into PLCO and USRT after 1995. Follow-up censored at June 30, 2002.

Figure 4

Joint associations of body mass index, oral contraceptive use, and menopausal hormone therapy use with parity in the aggregated sample of postmenopausal Caucasian women. Hazard ratios (HRs) and 95% confidence intervals (CI) estimated using Cox proportional hazards models with age as the underlying time scale with separate models fit to nulliparous and parous women. Models include all variables presented in Figures 2 and 3 as well as study, birth year, calendar year of entry, diabetes, and smoking status. HRs for nulliparous women represented by white boxes. HRs for parous women represented black boxes. 4b. In NIH-AARP, never use includes <1 year 4c. In PLCO, duration of E + P use categorized as <6 years and ≥6 years. Analyses restricted to the subset of women who reported never or current use from NIH-AARP or entry into PLCO and USRT after 1995. Follow-up censored at June 30, 2002.