The impact of menstruation and menopause on mental health is a historically neglected area which is now receiving much needed attention from the public, policy makers and researchers. This article summarises what is known about reproductive factors and bipolar, and outlines some upcoming research in this area.

Sex differences in bipolar

Overall, bipolar affects both men[1] and women similarly in terms of age at onset, how common it is, and how severe it is (1). The nature of episodes is a little different: women are more likely to be diagnosed with bipolar type II, more likely to have mixed episodes and probably more likely to have depressive episodes. The biggest difference is the impact of childbirth: this is a major trigger for new onset and relapse of bipolar in women. On the other hand, men with bipolar who are becoming fathers do experience mood episodes, but these are most likely to occur during pregnancy, and mania or psychosis are much less common (2).

How are reproductive factors relevant to men?

Both male and female bodies make oestrogen, testosterone and progesterone – there are no “female” or “male” hormones. There are, however, differences in levels of hormones and women experience larger fluctuations than males. Genetic evidence suggests oestrogen receptors and a sex hormone receptor regulator influence risk for bipolar across sexes (3). So, understanding more about how sex hormones influence bipolar in women is likely to help understand how hormones influence bipolar in men too. As a general principle, sex and gender-specific approaches help men as well as women – men too may need approaches tailored to their biology and circumstances which may be obscured by being analysed in a mixed sex group.

Reproductive factors and bipolar

The reason some women experience a severe postpartum episode of bipolar is unknown. One theory is an altered sensitivity to the normal changes in sex hormones that occur during childbirth. Childbirth is the most substantial time of hormonal change a woman can experience. However, other reproductive stages are also times of hormonal fluctuation, such as the menstrual cycle and menopause. An emerging concept is that some women with bipolar are “hormonally sensitive” and are vulnerable to mood episodes during times of hormonal fluctuation across the life course (4).

Menstrual cycle and bipolar

The majority of people who menstruate notice some degree of change in mental or physical symptoms across their menstrual cycle. At least 1 in 50 women experience debilitating mood symptoms in the days before their period (5). The most recent versions of the psychiatric classification systems (the DSM-5 and ICD-11) now recognise this with the new diagnosis of Premenstrual Dysphoric Disorder (PMDD). Approximately 1 in 2 women with bipolar report significant variation in their mood across the menstrual cycle (6), but the pattern of this may be different to that seen in PMDD. Some research suggests the days around ovulation can be more problematic than the days before the period (7). Women with bipolar who report premenstrual mood symptoms are more likely to also report postpartum mood episodes and perimenopausal mood episodes (8). However, there are no clinical guidelines on how to manage menstrual cycle mood symptoms in bipolar specifically, but UK guidelines for managing severe premenstrual syndrome (9) advise exercise, CBT and combined hormonal contraception. SSRIs are also first line treatments, but women with bipolar would need to apply a high degree of caution with these.

Menopause and bipolar

The relationship between menopause and bipolar is a really common question I get from people with lived experience. This area also needs more research. The evidence so far is that the years shortly before or after the final menstrual period are a time of increased risk for new onset bipolar (10).

What about if you already have bipolar? In the region of two thirds of women with bipolar report an increase in symptoms during the perimenopause – the years leading up the menopause when periods have become irregular (4, 8). These are most likely to be depressive symptoms rather than hypomania or mania (11). This mirrors what is seen in women without bipolar, when around 1 in 2 perimenopausal women experience depressive and cognitive symptoms (“brain fog”) (12). The good news is that in the general population these symptoms tend to get better once a woman is postmenopausal, although what happens in bipolar is little studied. There are no specific clinical guidelines for managing bipolar symptoms during perimenopause, but the NICE guidelines for menopause (13) recommend consideration of CBT and hormone replacement therapy (HRT) for depressive symptoms or hot flushes. Although there are no controlled trials investigating HRT in bipolar specifically, giving oestrogen to women with schizophrenia alongside their usual treatment has been found to be of benefit, which is reassuring.

Upcoming research on reproductive factors and bipolar

Alongside people with lived experience, we have designed a number of research projects to try to answer some important questions about reproductive factors in bipolar.

The first study is called “Meno-BD”.  It aims to find out more about why some women with bipolar experience mental health symptoms around the time of menopause. Specifically, it aims to investigate changes in how brains get their energy during the menopausal transition. Watch this space for more details.

We also plan to look at long term physical health outcomes in women who have had a postpartum psychosis, and explore psychiatric admissions in the typical age for perimenopause. We are also assessing how common it is to have a diagnosis of both bipolar disorder and PMDD using the new large research cohort Our Future Health.

We think considering reproductive factors in bipolar is a big opportunity for improving care. If you have suggestions for future work in this area, please let us know at menoBD@ed.ac.uk .

Author bio:

Dr Katie Marwick is a Senior Clinical Research Fellow at the University of Edinburgh and an Honorary Consultant Psychiatrist with NHS Lothian. Clinically, she works in the NHS Lothian Premenstrual Disorder Clinic and inpatient perinatal psychiatry.

References

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[1] This article uses men to refer to those assigned male at birth and women to refer to those assigned female at birth. Some content will also be relevant to those of different, non-binary or no gender.

Women and Bipolar / Reproductive Factors and Bipolar Disorder by is licensed under a