A study published in Nature Mental Health shows that women during perimenopause, the time around menopause, may be at higher risk of developing mania or major depressive disorder.

Study: Investigation of the early signs of mania, schizophrenic disorders and major depressive disorders in the perimenopausePhoto credit: SpeedKingz/Shutterstock.com

background

Perimenopause refers to the years around the last menstrual period when the ovaries gradually stop functioning.

Approximately 80% of women experience neuropsychiatric symptoms during this time, including mood symptoms, cognitive dysfunction, sleep disturbances, and most commonly, hot flashes.

Only a handful of studies suggest that perimenopause may increase the risk of developing psychiatric complications, including major depressive disorder, schizophrenia spectrum disorders, and bipolar disorder.

Previous studies examining the influence of reproductive aging on psychiatric disorders have some significant limitations related to the difficulties in accurately determining ovarian aging.

Many epidemiological studies use chronological age as an indicator of menopausal age, but this assumption may not be accurate because menopausal age has a range of more than 20 years.

In this study, scientists examined the links between perimenopause and the risk of first-time onset of mental disorders, including mania, major depressive disorder, and schizophrenia spectrum disorders.

Study design

The study analysed data from the UK Biobank containing information on the timing of menopause and psychiatric history of 128,294 female participants. This information was collected through interviews by trained nurses and self-administered online questionnaires.

The incidence rates of new-onset psychiatric disorders (mania, major depressive disorder, and schizophrenia spectrum disorders) during perimenopause were calculated and compared with the reference period before menopause (late reproductive stage).

Perimenopause was defined as the four years surrounding the last menstrual period, and premenopause was described as six to ten years before the last menstrual period.

Important observations

The study evaluated data from 128,294 participants from the UK Biobank. The average age of the participants at menopause was 50 years.

Approximately 0.59% of study participants had their first psychiatric disorder in the premenopausal phase, 0.88% in the perimenopausal phase, and 0.50% in the postmenopausal phase (six to ten years after the last menstruation).

These estimates corresponded to incidence rates of 1.53, 2.33, and 1.66 per 1,000 person-years during the pre-, peri-, and postmenopausal periods, respectively.

Compared to the premenopausal period, significantly higher incidence rates of psychiatric disorders were observed in the perimenopausal period. In contrast, comparable incidence rates were observed in the pre- and postmenopausal periods.

Psychiatric disorder-specific incidence rates

Compared with the premenopausal period, significantly higher incidence rates of major depressive disorders and mania were observed during the perimenopausal period.

During postmenopause, the frequency of manic disorders returned to premenopausal levels. However, a significantly lower frequency of major depressive disorders was observed during postmenopause than during premenopause.

No significant association was observed between perimenopause and the incidence of schizophrenia spectrum disorders.

A significant increase in the frequency of other diagnoses was observed during peri- and postmenopause compared to premenopause.

Other diagnoses included anxiety or panic attacks, substance abuse or addiction, post-traumatic stress disorder, eating disorders, stress, obsessive-compulsive disorder or insomnia.

The observed association between perimenopause and an increased incidence of psychiatric disorders remained unchanged even after accounting for potential confounders such as material deprivation, physical health status, obesity, frequency of alcohol consumption, and previous or never smoking.

However, in underweight participants and smokers, the observed association was no longer significant.

Significance of the study

The study shows that perimenopause can significantly increase the risk of first-time onset of mental disorders in women. The strongest effects of perimenopause were observed in the frequency of mania.

Women without a history of mania have more than twice the risk of experiencing mania for the first time during perimenopause than before or after menopause. Hormonal changes during perimenopause may be responsible for the onset of mania.

Regarding major depressive disorders, the study found an increased incidence rate during perimenopause. In postmenopause, the incidence rate decreased but remained high.

This suggests that in addition to the hormonal changes during perimenopause, age-related biopsychosocial challenges also play a role in the development of major depressive disorders in women.

The study found no significant association between perimenopause and the risk of first-onset schizophrenia spectrum disorders. This result contradicts the much-discussed effect of hypoestrogenism on the development of first-onset schizophrenia.

Considering the study results, scientists advise clinicians and researchers to consider interpersonal variability in reproductive aging rather than using chronological age as a proxy.

They emphasize diagnostic accuracy and suggest that all psychiatric symptoms occurring in perimenopause should not be considered depressive symptoms that are etiologically related to perimenopause.

They also mention that future studies focusing on large cohorts of people with a history of mental disorders are needed to improve their risk prediction and reduction in the context of reproductive aging.