Sex hormones and fear inhibition: A novel exploration of why women are so vulnerable to anxiety disorders

Principal investigator: Dr Bronwyn Graham

Institution: University of New South Wales

Funding Period: 2014-2017

Women are twice as likely to develop anxiety disorders as men, but little is known as to why. Whist some existing psychological treatments (Such as exposure therapy) work for many people, they don’t work for everyone.

The project

This project investigates the connection between hormones and anxiety and to find out if natural variations in hormones, such as oestrogen, make anxiety more likely and does this affect the way people respond to treatment.

Oestrogen levels are low during the early phase of the menstrual cycle, and even lower when women are taking hormonal contraceptives, such as the pill. Up to 80% of women will use hormonal contraception at some point in their lives so it is important to understand the effect they have on treatment outcomes. 

The process

Research has already shown that sex hormones can affect the mechanisms that control fear. With this in mind, the project was designed in two parts.

Part one examined fear responses in two groups of women. One group had spider phobia, and the other group had no phobia. In each group, half were at a time of high oestrogen, and half at a time of low oestrogen. They were then given one of the two methods of psychological treatment: exposure therapy or cognitive reappraisal.

Part two was a clinical trial that investigated the effectiveness of Cognitive Behavioural Therapy (CBT) for spider phobia for 90 women throughout their natural hormonal cycle. Women’s oestrogen levels were measured on the day of treatment. Their self-reported fear, and behavioural avoidance of spiders was measured 1-week and 12-weeks after treatment. 

The outcome

Bronwyn found that women with anxiety, who had low levels of the hormone oestrogen, were less likely to get better – and stay better – following psychological treatment. This means that if we can schedule treatment when oestrogen is highest (in the second week of the menstrual cycle), it could end up being more effective – enabling more people to cope with anxiety, based on their personal situation.

Key Findings:
- Women with higher estradiol levels showed faster and more sustained recovery from fear and anxiety after exposure therapy;
- Women using hormonal contraception (lower estradiol) had poorer treatment outcomes and less self-initiated exposure to phobic stimuli;
- The hormonal status of women is a significant factor in the effectiveness of anxiety treatments.
Outputs:
- Multiple publications, conference presentations, and new collaborations;
- Completion of a clinical trial demonstrating the importance of timing exposure therapy with periods of high estradiol for optimal results;
- Development of new clinical protocols and ongoing research into hormonal influences on other anxiety-related processes.

Papers

Top publication: Li SH, Graham BM (2017) Why are women so vulnerable to anxiety, trauma-related and stress-related disorders? The potential role of sex hormones . The Lancet Translational psychiatry 

Other papers:

Graham et al, 2014: Bridging the gap: Lessons we have learnt from the merging of psychology and psychiatry for the optimisation of treatments for emotional disorders. Science Direct
Graham et al, 2015: Teens that fear screams: A comparison of fear conditioning, extinction, and reinstatement in adolescents and adults. Journal of Developmental psychobiology
Graham, Richardson, 2015: Fibroblast Growth Factor 2 as a New Approach to Fighting Fear. Jama Psychiatry.
White, Graham, 2016: Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction. Science Direct.
Graham, 2016: Estradiol is associated with altered cognitive and physiological responses during fear conditioning and extinction in healthy and spider phobic women. Journal of behavioural neuroscience.
Graham et al, 2017: High endogenous estradiol is associated with enhanced cognitive emotion regulation of physiological conditioned fear responses in women. Journal of Psychneuroendocrinology.
Graham et al, 2018: The association between estradiol levels, hormonal contraceptive use, and responsiveness to one-session-treatment for spider phobia in women. Journal of Psychneuroendocrinology.

Talking about working with MQ, Bronwyn said:

“I have found MQ as a whole organisation to be extremely supportive. The annual meetings were a joy to attend- it is a very rare occurrence to be in the same room as so many like-minded people who support scientifically rigorous and daring investigations into all aspects of mental health. The meetings really stood out for me as a point of difference compared to other funding bodies as they opened up opportunities for meaningful collaboration that have proved fruitful.”

The impact

Scientific Impact:
- First translation of basic hormonal research into clinical settings for anxiety treatment;
- Provided evidence that uniquely female factors (menstrual phase, contraceptive use) should be considered in treatment planning;
- Raised awareness of the need for sex-specific research in mental health.
Societal Impact:
- Findings featured in national and international media, public lectures, and outreach activities;
- Contributed to public dialogue about mental health and the importance of personalised treatment approaches for women;
- No direct impact on policy or services yet, but the research lays the groundwork for future improvements in treatment responsiveness for women with anxiety disorders.
Personal and Career Impact:
- The MQ Award enabled the Bronwyn to transition from preclinical to clinical research, secure further grants, and achieve promotions and recognition in the field.

Dr Bronwyn Graham

Dr Bronwyn Graham is Associate Professor of Psychology at the University of New South Wales, and an editorial board member for the Journal of experimental psychology.

Bronwyn’s research aims to identify the neurobiological causes of anxiety disorders, with the ultimate goal to improve treatments.

In 2020 Bronwyn was awarded the Aubrey Lewis Award from Biological Psychiatry Australia.