Polycystic Ovarian Syndrome (PCOS) is the most common endocrine-related dysfunction in women of reproductive age.  Multiple studies have observed a higher prevalence of psychiatric illness, including depressive disorders, anxiety disorders, and bipolar disorder in women with PCOS  The nature of this association is not fully understood.  Some have hypothesized that the hormonal dysregulation seen in women with PCOS may increase vulnerability to psychiatric illness.  Others have questioned whether the medications used to treat psychiatric illness, specifically mood stabilizers, may increase risk for PCOS. In order to help distinguish these two possibilities, a recent study has looked at the temporal association between PCOS and psychiatric illness. 

In this study, patients diagnosed with PCOS (n = 7175) by an obstetrician-gynecologist were identified in the Taiwan National Health Insurance Research Database. A comparison group consisted of age-matched women without PCOS (n = 28,697).  New-onset psychiatric illness (emerging after the diagnosis of PCOS) were identified in the medical record, as indicated by a psychiatrist).  Women were included between 2000 and 2012, then followed until the end of 2013.

Compared to unaffected controls, women with PCOS had a significantly increased risk of developing bipolar disorder after adjusting for age, medical comorbidity,  and different treatment options (1.05 vs. 0.12 per 1,000 person-years, HR: 8.29, 95% CI: 4.65–14.7). 

Women with PCOS who were treated with metformin showed a significantly reduced risk of developing bipolar disorder compared to non-users (HR: 0.36, 95% CI: 0.16–0.81).  PCOS patients treated with hormone therapy also showed a lower risk of developing bipolar disorder compared to non-users; however, the reduction in risk was not as large as seen with metformin and was not statistically significant (HR: 0.68, 95% CI: 0.35–1.32).

This study brings us a bit closer to understanding the interplay between PCOS and mood and anxiety disorders.  This study suggests that PCOS may increase risk for bipolar disorder. While PCOS is associated with hormonal dysregulation, the authors point out that PCOS is also associated with  systemic inflammation as indicated by elevation of multiple markers of inflammation.  They speculate that inflammation may play an important role in increasing vulnerability to bipolar disorder.  Very interesting.   

One of the most interesting findings is that in women with PCOS, treatment with metformin seems to decrease the risk for developing bipolar disorder.  Hormonal therapy demonstrated a less robust reduction in risk which was not statistically significant. Metformin is an oral hypoglycemic agent which corrects glucose resistance in women with PCOS; metformin also has direct anti-inflammatory effects which the authors suggest may contribute to decreasing risk for bipolar disorder.  

Many women with PCOS, especially when it is relatively mild, are not aware that they have PCOS.  Some women have mild symptoms and do not receive any specific treatment. The approach varies, and interventions for more severe symptoms include dietary modifications, oral contraceptives, progestins, spironolactone, and metformin.  Although this study needs to be replicated in other populations, the finding that metformin may reduce the risk of bipolar disorder in women with PCOS argues for considering using this medication more widely.

 

Ruta NOnacs, MD PhD

 

Chen S-F, Yang Y-C, Hsu C-Y, Shen Y-C. Risk of bipolar disorder in patients with polycystic ovary syndrome: a nationwide population-based cohort study. J Affect Disord. 2020;263: 458-462.