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Age at menopause, duration of reproductive years, time since menopause and depression – is there an association and what might explain it?


Bristol Medical School

, Applications accepted all year round Self-Funded PhD Students Only

About the Project

Rationale
Depression is a major cause of disability and is a leading contributor to the global burden of disease. At onset of menarche, girls experience steep rises in depressive symptoms, and by mid-adolescence they have double the risk of experiencing an episode of depression than boys. This female excess of depression persists through their reproductive years, but sex differences in depression attenuate in older age. Some studies have found that a later age at menopause and a longer reproductive period, are associated with lower levels of depression in post-menopausal women. However, several important limitations make this evidence difficult to interpret: the majority of studies are cross-sectional; they relied on retrospective reports of age at menopause, and they did not take account of episodes of pre-menopausal depression. This is important because previous depressive episodes predict subsequent episodes, and there is evidence that depression is associated with an earlier age at menopause. Some studies did not adjust for important confounders such as pre-menopausal health problems and stressful experiences.

Later age at menopause may reflect a greater lifetime exposure to oestrogen. Oestrogen is thought to have an antidepressant effect in women, and there is a reduction in oestrogen levels toward the menopausal transition. Studies to date have not always accounted for other factors affecting lifetime oestrogen exposure (e.g. oral contraceptive use, breastfeeding, number of pregnancies) or the role of hormone replacement therapy. Menopause has both physical and psychosocial consequences, but few studies have sought to uncover the psychosocial mechanisms that might explain why women experience increased depression at menopause.

Aims & Objectives
The overall aim of this PhD project is to examine the relationship between age at menopause (and/or time since menopause, lifetime exposure to oestrogen) and risk of post-menopausal depression. The study will address limitations of earlier studies by examining this relationship in well characterised prospective cohorts; adjusting for a range of confounders including pre-menopausal depression, and using linked health record data (where available) to validate self-reports of depression. Potential explanatory pathways will also be investigated.

Methods
The project will be based on the ALSPAC mothers’ cohort in the first instance, as well as other longitudinal cohorts with relevant data such as UK Biobank, BWHHS, and NSHD. Mendelian randomization approaches will be used to improve causal inference by using a genetic instrument for age at menopause. Potential mechanisms will be investigated using appropriate mediation methods (e.g. SEM, gformula). There is also scope for using existing qualitative data to explore women’s experiences of the menopausal transition as part of this project, should the student wish to do so.

References

Salk RH, Hyde JS, Abramson LY. Gender Differences in Depression in Representative National Samples: Meta-analyses of Diagnoses and Symptoms. Psychol. Bull. 2017;143(8):783-822

Bleil ME, Adler NE, Pasch LA, et al. Depressive symptomatology, psychological stress, and ovarian reserve: a role for psychological factors in ovarian aging? Menopause. 2012;19(11):1176-1185.

GeorgakisMK, Thomopoulos TP, Diamantaras AA, Kalogirou EI, Skalkidou A, Daskalopoulou SS, Petridou ET. Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2016 Feb;73(2):139-49.

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