Age at Natural Menopause and Development of Chronic Conditions and Multimorbidity

Results From an Australian Prospective Cohort

Xiaolin Xu; Mark Jones; Gita D. Mishra


Hum Reprod. 2020;35(1):203-211. 

In This Article

Abstract and Introduction


Study Question: Is age at natural menopause (ANM) associated with the development of multiple chronic conditions (multimorbidity) in postmenopausal life?

Summary Answer: Women with premature menopause experience increased odds of developing individual chronic conditions and multimorbidity.

What is Known Already: ANM is considered as a marker of age-related morbidity and mortality in postmenopausal life. Multimorbidity affects more than 60% of older women and has been recognized as the most common 'chronic condition'. Few studies have examined the association between ANM and the development of multimorbidity.

Study Design, Size, Duration: A prospective national cohort study of 11 258 Australian women, aged 45–50 years in 1996. Women were followed from 1996 to 2016.

Participants/Materials, Setting, Methods: Information about ANM and 11 chronic conditions (diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer) were estimated approximately every 3 years. Multimorbidity is defined as 2 or more of these 11 conditions. Generalized estimating equations were used to link the categorical ANM with individual chronic conditions and multimorbidity.

Main Results and the Role of Chance: Among 5107 women reporting ANM, 2.3% experienced premature menopause (≤40 years) and 55.1% developed multimorbidity. Compared with women who experienced menopause at age 50–51 years, women with premature menopause had twice the odds of experiencing multimorbidity by age 60 (OR = 1.98, 95% CI 1.31 to 2.98) and three times the odds of developing multimorbidity in their 60s (OR = 3.03, 95% CI 1.62 to 5.64). Women with premature menopause also experienced higher incidence of most individual chronic conditions.

Limitations, Reasons for Caution: The main limitation of this study was the use of self-reported data, but with repeated assessments from prospective study design and the validity of most of the chronic conditions from hospital data, the potential for non-differential misclassification is minimized.

Wide Implications of the Findings: To our knowledge, this is the first study to assess the association of premature menopause and development of multimorbidity in a larger national cohort of mid-aged women. Health professionals should consider comprehensive screening and assessment of risk factors for multimorbidity when treating women who experienced premature menopause.

Study Funding/Competing Interest(S): The Australian Longitudinal Study on Women's Health was supported by the Australian Government Department of Health. X.X. is funded by an International Postgraduate Research Scholarship from the Australian government and a UQ Centennial Scholarship from The University of Queensland. G.D.M. is supported by the National Health and Medical Research Council Principal Research Fellowship (APP1121844). None of the authors has any conflicts of interest to declare.


As life expectancy is more than 80 years for women in high-income countries, a third of a woman's life is spent after menopause. The postmenopausal status coincides with increased risks for a range of chronic conditions (Gartlehner et al., 2017). The timing of final menstrual period (age at menopause) differs largely in women and is considered as a marker of age-related morbidity and mortality in postmenopausal life (Jaspers et al., 2015; Mishra et al., 2017). For instance, empirical evidence has uncovered the associations between a woman's age at menopause and her subsequent risk of cardiovascular disease (de Kat et al., 2017), diabetes (Pandeya et al., 2018, Slopien et al., 2018), chronic lung diseases (Campbell et al., 2018; Matulonga-Diakiese et al., 2018), osteoporosis, cognitive function and dementia (Ryan et al., 2014; Georgakis et al., 2016), mental disorders (de Kruif et al., 2016) and premature death (Ossewaarde et al., 2005). However, few studies have examined the association between age at menopause and the development of multiple chronic conditions (also known as multimorbidity).

Loss of ovarian hormones (primarily estrogen) due to menopause affects multiple organs and systems, which further leads to multimorbidity (van Dijk et al., 2015; Rocca et al., 2018). Multimorbidity affects more than 60% of elderly women and has been recognized as the most common 'chronic condition' in older persons (Tinetti et al., 2012; Xu et al., 2017). Multimorbidity is now an emerging research and practice focus for women's postmenopausal health (van Dijk et al., 2015). For instance, Rocca and colleagues found that women who underwent oophorectomy before age of 46 years (premature or early surgical menopause) also experienced an increased risk of accumulation of multimorbidity (number of 18 chronic conditions) compared to women who experienced natural menopause (hazard ratio = 1.22; 95% CI, 1.14–1.31) (Rocca et al., 2016; Rocca et al., 2017). However, there is a paucity of prospective data on the association between age at menopause and the development of multimorbidity among women with natural menopause.

Understanding age at natural menopause (ANM) in relation to the development of chronic conditions and multimorbidity could lead to new strategies to prevent and manage these chronic conditions and multimorbidity (Lobo et al., 2014; van Dijk et al., 2015). In this article, we used data from a prospective cohort of mid-aged women over 20 years to determine whether ANM is associated with the development of individual chronic conditions and multimorbidity.