The Association of age at Menarche and Adult Height With Mammographic Density in the International Consortium of Mammographic Density

Sarah V. Ward; Anya Burton; Rulla M. Tamimi; Ana Pereira; Maria Luisa Garmendia; Marina Pollan; Norman Boyd; Isabel dos-Santos-Silva; Gertraud Maskarinec; Beatriz Perez-Gomez; Celine Vachon; Hui Miao; Martín Lajous; Ruy López-Ridaura; Kimberly Bertrand; Ava Kwong; Giske Ursin; Eunjung Lee; Huiyan Ma; Sarah Vinnicombe; Sue Moss; Steve Allen; Rose Ndumia; Sudhir Vinayak; Soo-Hwang Teo; Shivaani Mariapun; Beata Peplonska; Agnieszka Bukowska-Damska; Chisato Nagata; John Hopper; Graham Giles; Vahit Ozmen; Mustafa Erkin Aribal; Joachim Schüz; Carla H. Van Gils; Johanna O. P. Wanders; Reza Sirous; Mehri Sirous; John Hipwell; Jisun Kim; Jong Won Lee; Caroline Dickens; Mikael Hartman; Kee-Seng Chia; Christopher Scott; Anna M. Chiarelli; Linda Linton; Anath Arzee Flugelman; Dorria Salem; Rasha Kamal; Valerie McCormack; Jennifer Stone

Disclosures

Breast Cancer Res. 2022;24(49) 

In This Article

Results

Participant Characteristics

Characteristics of the participants, overall and by ethnic group, are shown in Table 1. The mean age at mammogram was 52.7 years (standard deviation (SD) = 8.2 years), which was relatively consistent across all groups except the Mestizo women, who were, on average, approximately 10 years younger. The mean age at menarche was also similar across all ethnic groups and, on average, occurred at a 13.2 years (SD = 1.7 years). Height varied slightly across the ethnic groups, with average height notably shorter in the East Asian, South Asian and Mestizo groups. There were more post-menopausal than pre-menopausal women in all ethnic groups except the Mestizo group, consistent with their younger age, and there were substantially more parous (90%) than nulliparous (10%) women.

Age at Menarche

Forest plots depicting population group-specific associations for age at menarche with each of the MD measures, along with meta-analyses results for overall associations, are presented in Figures 1 (PD) and 2 (DA). Overall, a small positive association was observed between the square-root change in both PD (β = 0.02, 95% CI 0.00, 0.03) and DA (β = 0.03, 95% CI 0.01, 0.05) with each yearly increase in age at menarche. Results were highly consistent across all studies for √PD (I 2 = 12.1%) but less so for √DA (I 2 = 32.4%), although both were considered to have low heterogeneity overall.

Pooled analyses of all participants (Table 2) showed very similar overall effect estimates to the meta-analyses. Later age at menarche was associated with increased √PD in all women (β = 0.057, SE = 0.008, P < 0.001). Results were attenuated when adjusted for BMI (β = 0.023, SE = 0.008, P = 0.003), similar to meta-analysis estimates. Adjustment for height did not alter the effect estimate substantially. Stratified analyses showed that this association was primarily driven by women with a BMI under 25 kg/m2 and by parous women. The association was present at both pre- and post-menopausal ages.

Similar results were observed for DA; later age at menarche was also associated with an increase in √DA for all women (β = 0.032, SE = 0.010, P = 0.002). The association with √DA was also more evident in parous women and women with lower BMI (BMI ≤ 25: P < 0.001) and did not differ by menopausal status. Results were generally unaffected after adjusting for age at first birth or age at menopause.

Height

Population group-specific and meta-analyses results for the association of MD measures with height are shown in Figures 3 (PD) and 4 (DA). Overall, there was no strong evidence of an association between √PD and height across studies (β = − 0.04 per 10 cm height increment, 95% CI − 0.08, 0.01), but there was evidence of an overall increase for √DA per 10 cm increase in height (β = 0.08, 95% CI 0.02, 0.14). Heterogeneity across population groups was relatively low for each MD measure (√PD, I 2 = 22.6%; √DA, I 2 = 20.9%).

Pooled results for both measures of MD and their association with adult height are presented in Table 3. For height and PD, the association was positive without adjustment for BMI or when adjusted for the study-specific weight-for-height index (Additional file 1: Table S2), but inversely associated when adjusted for BMI. The latter appeared to reflect the strong inverse association of height and BMI in almost all population groups (Additional file 1: Table S1). In the stratified analyses (adjusted for BMI), the height-√PD associations were largely negative, regardless of parity or menopausal status. When subset by the method of height measurement, an association was only observed in those women who had self-reported their height.

Consistent with the meta-analysis, an increase was observed in √DA with increased height (β = 0.059, SE = 0.028, P = 0.034) and this association was slightly stronger without adjustment for BMI (β = 0.069, SE = 0.028, P = 0.012). When stratified by BMI category, women in all but the highest (> 30 kg/m2) categories had an increased √DA with increased height. When analysed by height ascertainment method, the height-√DA association was stronger when height was measured (β = 0.084, SE = 0.034, P = 0.015) as opposed to self-reported (β = 0.020, SE = 0.047, P = 0.676). The association with √DA was stronger in parous women, overall (β = 0.090, SE = 0.030, P = 0.002), and in both pre- (β = 0.099, SE = 0.047, P = 0.034) and post-menopausal parous women (β = 0.090, SE = 0.039, P = 0.019).

No differences in results were observed for any outcome measures when adjusted for age at first birth in parous women or age at menopause in the post-menopausal group.

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