A study published in Nature Mental Health reveals that women may be at higher risk of developing mania and major depressive disorder during perimenopause, which is the period of time around menopause.
Study: Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause. Image Credit: SpeedKingz/Shutterstock.com
Background
Perimenopause refers to the years around the final menstrual period when the ovaries gradually stop working.
About 80% of women develop neuropsychiatric symptoms during this period, including mood-related symptoms, cognitive dysfunction, sleep disturbances, and, most commonly, hot flashes.
Only a handful of studies have suggested that perimenopause may increase the risk of developing psychiatric complications, including major depressive disorder, schizophrenia spectrum disorders, and bipolar disorder.
Previous studies investigating the effect of reproductive ageing on psychiatric disorders exhibit some major limitations, which are associated with the difficulties in accurately determining ovarian aging.
Many epidemiological studies use chronological age as a proxy for menopausal age, which might not be accurate as there is an over-20-year range variation in age at menopause.
In this study, scientists have explored the associations between perimenopausal periods and the risk of first-onset psychiatric disorders, including mania, major depressive disorder, and schizophrenia spectrum disorders.
Study design
The UK Biobank data was analyzed in the study, which included information on menopausal timing and psychiatric history of 128,294 female participants. This information was collected through interviews conducted by trained nurses and self-reported online questionnaires.
Incidence rates of first-onset psychiatric disorders (mania, major depressive disorder, and schizophrenia spectrum disorders) during perimenopause were calculated and compared with the reference premenopausal period (late reproductive stage).
Perimenopause was defined as four years around the final menstrual period, and premenopause was described as six to ten years before the final menstrual period.
Important observations
Data from 128,294 participants from the UK Biobank was analyzed in the study. The mean age of participants at menopause was 50 years.
Among study participants, about 0.59% reported their first onset of a psychiatric disorder during the premenopausal period, 0.88% reported the same during the perimenopausal period, and 0.50% reported the same during the postmenopausal period (six to ten years after the final menstrual period).
These estimates corresponded to the incidence rates of 1.53, 2.33 and 1.66 per 1,000 person-years during pre-, peri-, and post-menopausal periods.
Significantly higher incidence rates of psychiatric disorders were observed during the perimenopausal period compared to that during the premenopausal period. In contrast, comparable incidence rates were observed during pre- and post-menopausal periods.
Psychiatric disorder-specific incidence rates
Significantly higher incidence rates of major depressive disorder and mania were observed during perimenopausal period compared to the premenopausal period.
The incidence rate of mania returned to the premenopausal level during postmenopause. However, for major depressive disorder, a significantly lower incidence rate was observed during postmenopause compared to that during premenopause.
No significant association was observed between perimenopause and incidence rates of schizophrenia spectrum disorders.
A significant induction in the incidence rate of other diagnoses was observed during peri- and post-menopause compared to that during premenopause.
Other diagnoses included anxiety or panic attacks, substance abuse or dependency, post-traumatic stress disorder, eating disorders, stress, obsessive-compulsive disorder or insomnia.
The observed association between perimenopause and increased incidence rates of psychiatric disorders remained unchanged after adjusting for potential confounding factors, including material deprivation, physical health status, obesity, alcohol intake frequencies, and previous or never smoking habits.
However, the observed association became non-significant for underweight participants and current smokers.
Study significance
The study reveals that perimenopause can significantly increase the risk of first-onset psychiatric disorders in women. The highest effect of perimenopause has been observed on the incidence rates of mania.
Women without a history of mania exhibit more than 2-fold higher risk of developing mania for the first time during perimenopause compared to that during pre- and post-menopause. Hormonal changes that occur during perimenopause might be responsible for triggering mania onset.
Regarding major depressive disorder, the study finds an increased incidence rate during perimenopause, which reduced but remained high during postmenopause.
This indicates that aging-related biopsychosocial challenges play a role in triggering major depressive disorder in women, in addition to perimenopause-related hormonal changes.
The study could not find any significant association between perimenopause and risk of first-onset schizophrenia spectrum disorders. This finding contradicts the widely discussed effect of hypoestrogenism on the development of first-onset schizophrenia.
Considering the study findings, scientists advise clinicians and researchers to consider interpersonal variability in reproductive aging rather than using chronological age as a proxy.
Stressing on diagnostic accuracy, they suggest that all psychiatric symptoms with onset at the perimenopause should not be considered depressive symptoms etiologically related to the perimenopause.
They also mention that future studies focusing on large cohorts of people with a history of mental disorders are necessary to improve their risk prediction and mitigation associated with reproductive aging.
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