The Menopause and Mental Disorders

The menopause and its consequences have begun to receive much-needed attention over recent years. However, uncertainty abounds. Surprisingly little is known about this natural change that affects around half the world’s population. In the absence of facts, fear and speculation can mushroom.

High quality research can help narrow the problem space, providing information to individuals and clinicians. Around 20% of women experience the menopausal transition simply as a cessation of periods (Brinton et al., 2015). The remainder are symptomatic in some way, with around 50% experiencing changes to mood, sleep or cognition (Brinton et al., 2015). These symptoms are often problematic, inconvenient or distressing, but only a subset will meet the threshold of a mental disorder such as a depressive episode. What proportion is unclear.

The impact of the menopause on severe mental illnesses such as schizophrenia and bipolar has received even less attention. In women with established bipolar disorder, prospective studies of around 100 women found that the perimenopause is a time of symptom worsening for the majority, with an increase in both depressive and manic symptoms (Marsh et al., 2015; Marsh et al., 2008). In schizophrenia, the evidence is more circumstantial.

The study by Shitomi-Jones and colleagues at Cardiff University published recently in Nature Mental Health is a welcome addition to the existing scarce literature on the association of menopause with mental disorder. It utilised the large, prospective, well characterised dataset in the UK Biobank to test the hypothesis that the perimenopause is a time of increased risk of new onset psychiatric disorders compared to the late premenopausal stage.

Methods

Sample Postmenopausal female participants (sex but not gender was assessed) in the UK Biobank were included in the primary analyses. Females were excluded if they had experienced early menopause (< 40 years) or if their age of menopause could not be determined due to surgery (post hysterectomy, oophorectomy or uterine ablation), hormonal medication (intrauterine system or oral contraception) or inconsistent answers. People using hormone replacement therapy were not excluded.

Psychiatric diagnoses and age at onset were obtained using a combination of interviews with research nurses at baseline and a self-report questionnaire completed by a subset (about 30%) of participants 5-10 years after recruitment. ‘Major depressive disorder’ required participants to have at least 2 cardinal symptoms of depression (as defined by DSM-5) and at least 5 in total. ‘Mania’ referred to diagnoses of mania, bipolar or manic-depression. ‘Schizophrenia spectrum disorder’ referred to schizophrenia or any other type of psychosis. ‘Any psychiatric disorder’ included depression, mania, psychosis, anxiety, substance use, PTSD, OCD, eating disorders and insomnia.

Results

The first onset of a psychiatric disorder during the perimenopause was reported by 0.88% of females. This is equivalent to a rate of 2.33 new cases per 1,000 person years. Rates of first onset psychiatric disorder in the postmenopausal period (0.50%) were similar to the premenopausal period (0.59%) at 1.53 and 1.66 cases per 1,000 person years respectively. The risk varied by nature of psychiatric disorder, with the largest increase in perimenopausal risk seen for new onset mania with a relative risk of 2.12 (95% CI 1.30 to 3.52).

Conclusions

A major take-home message from this study is that 99% of females did not experience a new onset psychiatric condition during the two years either side of their final menstrual period. This is reassuring. However, for those who are in some way vulnerable, the two years either side of the final menstrual period represent a time of increased risk for new onset bipolar and major depressive disorder.

Strengths and Limitations

The key strengths of this study are firstly the large sample size and secondly being able to assess age at menopause using participant’s self-report rather than relying on age as a proxy. A partially addressed limitation of this study is selection bias. The study performed a number of supplementary sensitivity analyses, which found largely similar effects of perimenopause on new onset psychiatric disorders in participants at extremes of these characteristics within the UK Biobank.