Genetic evidence for causal relationships between age at natural menopause and the risk of ageing-associated adverse health outcomes.
Int J Epidemiol
; 52(3): 806-816, 2023 06 06.
Article
em En
| MEDLINE
| ID: mdl-36409989
ABSTRACT
BACKGROUND:
A later age at natural menopause (ANM) has been linked to several ageing-associated traits including an increased risk of breast and endometrial cancer and a decreased risk of lung cancer, osteoporosis and Alzheimer disease. However, ANM is also related to several proxies for overall health that may confound these associations.METHODS:
We investigated the causal association of ANM with these clinical outcomes using Mendelian randomization (MR). Participants and outcomes analysed were restricted to post-menopausal females. We conducted a one-sample MR analysis in both the Women's Health Initiative and UK Biobank. We further analysed and integrated several additional data sets of post-menopausal women using a two-sample MR design. We used ≤55 genetic variants previously discovered to be associated with ANM as our instrumental variable.RESULTS:
A 5-year increase in ANM was causally associated with a decreased risk of osteoporosis [odds ratio (OR) = 0.80, 95% CI (0.70-0.92)] and fractures (OR = 0.76, 95% CI, 0.62-0.94) as well as an increased risk of lung cancer (OR = 1.35, 95% CI, 1.06-1.71). Other associations including atherosclerosis-related outcomes were null.CONCLUSIONS:
Our study confirms that the decline in bone density with menopause causally translates into fractures and osteoporosis. Additionally, this is the first causal epidemiological analysis to our knowledge to find an increased risk of lung cancer with increasing ANM. This finding is consistent with molecular and epidemiological studies suggesting oestrogen-dependent growth of lung tumours.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoporose
/
Fraturas Ósseas
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Int J Epidemiol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos