Androgens and the Female Brain: The Relationship between Testosterone Levels, Depression, Anxiety, Cognitive Function, and Emotion Processing in Females with Polycystic Ovarian Syndrome

Abstract

Background: Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder in reproductive-aged females, with the main hormonal abnormality being androgen (testosterone) excess. Although it is well-established that there is a higher prevalence of depression in PCOS, little research has examined the direct relationship between androgen levels, depression and associated cognitive impairment. The current study conducted a simultaneous investigation of the relationship between androgen levels, mood, cognitive function and emotion processing in females with PCOS, before and after 12 weeks of anti-androgen treatment. Elucidating the relationship between androgens and mood in females could have significant benefit in determining optimal treatment for the subset of females whose symptoms of depression may be related to an underlying androgen excess.

Objectives: • To describe differences between the PCOS (n = 53) and non-PCOS control (n = 54) groups on measures of mood, anxiety, cognitive function and emotion processing, • To determine whether correlations exist between androgen levels and symptoms of depression and anxiety, cognitive function, and emotion processing in the entire sample with varying androgen levels, • To determine whether symptoms of depression relate to aspects of cognitive function and emotion processing, • To determine whether anti-androgen treatment is associated with changes in mood, anxiety, cognitive function and emotion processing in the PCOS group.

Methods: Fifty-three females with PCOS and 54 age-matched females without PCOS completed an assessment of androgen levels from blood samples, depression-rating scales, and cognitive and emotion processing measures at two-time points; baseline and 12 weeks. The PCOS group commenced anti-androgen treatment following baseline assessment.

Results: • Females with PCOS had more symptoms of depression but not anxiety, and showed worse performance on the cognitive domains of psychomotor speed and emotion processing compared with the control group. • Higher testosterone levels were significantly associated with worse mood and worse cognitive function in sub-tests within the domains of verbal and visuospatial learning and memory, psychomotor speed and emotion processing across the entire sample. • Significant correlations were found between worse mood and anxiety and poorer cognitive performance on aspects of verbal and visuospatial learning and memory, and attention and executive function measures. • Anti-androgen treatment was associated with significant improvements in psychomotor speed and aspects of emotion processing in the PCOS group. • Following anti-androgen treatment, a significant improvement was observed in symptoms of depression and anxiety and on performance on verbal and visuospatial learning and memory and emotion processing measures within the PCOS group. • Improvement in symptoms of mood was associated with improved performance on measures of psychomotor speed, attention and executive function and improved recognition accuracy of fearful and disgusted faces within the PCOS group.

Conclusions: Females with PCOS showed greater symptoms of depression and worse cognitive function compared with non-PCOS control participants. Additionally, higher testosterone levels were associated with greater symptoms of depression and worse cognitive performance. Anti-androgen treatment appeared to have a significantly beneficial effect on mood and aspects of cognitive function in the PCOS group. Results from the current study thus provide preliminary evidence that testosterone excess in females with PCOS is associated with greater depressive symptoms and worse cognitive function, which may be benefited by anti-androgen treatment.