Elsevier

Maturitas

Volume 67, Issue 1, September 2010, Pages 60-66
Maturitas

Defining menopausal status in epidemiologic studies: A comparison of multiple approaches and their effects on breast cancer rates

https://doi.org/10.1016/j.maturitas.2010.04.015Get rights and content

Abstract

Objectives

Menopausal status is a common covariate in epidemiologic studies. Still, there are no standard definitions for menopausal status using observational data. This study assesses distinctions between menopausal status definitions using commonly collected epidemiologic data, and explores their impact on study outcomes using breast cancer rates as an example.

Study design

Using survey data from 227,700 women aged 40–64 who received screening mammograms from the Breast Cancer Surveillance Consortium, we classified menopausal status under five different definitions: one complex definition combining multiple variables, two definitions using age as a proxy for menopausal status, one based only on menstrual period status, and one based on age and menstrual period status.

Main outcome measures

We compared the distribution of menopausal status and menopausal status-specific breast cancer incidence and detection rates across definitions for menopausal status.

Results

Overall, 36% and 29% of women were consistently classified as postmenopausal and premenopausal, respectively, across all definitions. Menopausal status-specific breast cancer incidence and detection rates were similar across definitions. Rates were unchanged when information regarding natural menopause, bilateral oophorectomy, hormone therapy, and timing of last menstrual period were sequentially added to definitions of postmenopausal status.

Conclusions

Distinctions in menopausal status definitions contribute to notable differences in how women are classified, but translate to only slight differences in menopausal status-specific breast cancer rates.

Introduction

Given that menopausal status is an important risk factor for breast cancer [1], [2], [3], and risk factors for breast cancer differ according to menopausal status [4], [5], [6], [7], many breast cancer studies include menopausal status as a covariate of interest. However, determining menopausal status can be complicated: the transition from premenopause to postmenopause is often several years in length, varies in symptomology and duration, and may not be measurable by menstrual patterns in women with a history of hysterectomy or menopausal hormone therapy (HT) use [8], [9], [10], [11]. Given these complexities, there is no standardized definition for menopausal status in epidemiologic studies.

Biologically, menopause is defined as the permanent cessation of ovulation, marked by the end of menstruation [8], [9]. The menopausal transition is marked by changes in estradiol and follicular stimulating hormone (FSH) levels and in the regularity and length of menstrual cycles [9], [10], [11]. Consensus guidelines for staging natural menopausal status developed by the Stages of Reproductive Aging Workshop (STRAW) make use of prospectively collected menstrual diaries and blood specimens, and assessment of physical symptoms to characterize stages in the menopausal transition [9]. Highlighting the complexity of this transition, STRAW describes eight reproductive stages spanning early reproductive years through demise, differentiated by menstrual cyclicity, changes in FSH, and vasomotor symptoms. While STRAW guidelines provide an informative framework, their applicability to population-based studies is limited by the fact that this staging was not intended to apply to women who smoke, have a body mass index >30 kg/m2, or have had a hysterectomy. Additionally, in epidemiologic studies, it is rarely feasible to prospectively collect menstrual diaries or serum samples, especially if data collection is retrospective or based on a single questionnaire. Most studies instead define menopausal status as a dichotomous variable based on current age, time since last menstrual period, history of menopausal surgeries (i.e., hysterectomy, oophorectomy), and HT use, with information collected via self-report or medical record review. Availability of these data elements differs between studies, as does the manner in which they are applied to classify menopausal status. Some studies define menopausal status based on a complex combination of multiple criteria; for example, in the Nurses’ Health Study, women are considered postmenopausal if they have not had a menstrual period for >12 months due to natural causes, have had a bilateral oophorectomy, or have had a hysterectomy without bilateral oophorectomy and are aged ≥56 (non-smokers) or ≥54 (smokers) [12]. Conversely, in the absence of detailed information, some epidemiologic studies consider age alone as a crude proxy for menopausal status (e.g., age <50/≥50 years) [13].

We undertook an analysis to characterize the distinctions and concordance between epidemiologic definitions of menopausal status using data from the Breast Cancer Surveillance Consortium (BCSC). We also evaluated whether using different definitions for menopausal status resulted in appreciable differences in rates of breast cancer incidence and detection.

Section snippets

Methods

The BCSC is a collaborative effort between seven geographically dispersed mammography registries. Details regarding the BCSC are provided elsewhere [14]. This study was restricted to the four BCSC registries with detailed self-reported information regarding menopausal status: Group Health (western Washington State), the New Hampshire Mammography Network, the San Francisco Mammography Registry, and the Vermont Breast Cancer Surveillance System. Although the list of data elements and the

Results

The distributions of study population characteristics are illustrated in Table 2. The majority of the study population was non-Hispanic white (78%) and college-educated (51%). Overall, 57% of women reported their menstrual periods had stopped due to natural menopause (56%) or other reasons (including surgical amenorrhea) (44%). Under the complex definition, 53% (N = 119,982) of women were classified as postmenopausal, 7% (N = 17,022) as having ‘surgical/other amenorrhea’, 5% (N = 10,749) as

Discussion

Our results indicate that differences in the criteria used to define menopausal status affect how women are classified as premenopausal or postmenopausal and the distribution of certain characteristics, such as age, within menopausal status groups. These differences did not translate into marked differences in menopausal status-specific breast cancer incidence or detection rates. Within the age range of this analysis, there was little difference between premenopausal versus postmenopausal rates

Ethical approval

Each registry within the Breast Cancer Surveillance Consortium (BCSC) and the BCSC Statistical Coordinating Center have received institutional review board approval for either active or passive consenting processes or a waiver of consent to enroll participants, link data, and perform analytic studies. All procedures are Health Insurance Portability and Accountability Act compliant, and all registries and the Statistical Coordinating Center have received a Federal Certificate of Confidentiality

Competing interests

No competing interests have been declared by any of the authors included on this manuscript.

Funding

Data collection for this work was supported by a NCI-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). This publication was supported by grant number T32 CA09168 from the National Cancer Institute (NCI), NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI, NIH.

Contributors

Amanda I. Phipps, MPH, Erin J.A. Bowles, MPH, and Diana S.M. Buist, PhD, participated in the study design, writing, and editing of this manuscript and have seen and approved the final version and had no conflicts of interest to report; Laura Ichikawa, MS, participated in the study design, analysis, writing, and editing of this manuscript and has seen and approved the final version and had no conflicts of interest to report; Patricia A. Carney, PhD, Karla Kerlikowske, MD, and Diana L.

Acknowledgements

We thank the BCSC investigators, participating mammography facilities, and radiologists for the data they have provided for this study. A complete list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: http://breastscreening.cancer.gov/. The collection of cancer incidence data used in this study was supported in part by several state public health departments and cancer registries throughout the U.S. For a full description of these sources,

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