Anuja Dokras, MD., PhD. Professor Obstetrics and Gynecology Director PENN PCOS Center University of Pennsylvania, USA.

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1 Anuja Dokras, MD., PhD. Professor Obstetrics and Gynecology Director PENN PCOS Center University of Pennsylvania, USA.

2 Mood Disorders Based on the Diagnostic and Statistical Manual (DSM) V depressive disorders include Major Depressive Disorder (MDD) Dysthymic Disorder Dysphoric Mood Dysregulation Disorder Premenstrual Dysphoric Disorder Depression Not Otherwise Specified (NOS) Worldwide prevalence 3-18%

3 National Institute of Mental Health Mood Disorders

4 Prevalence of Depression in an Urban South Indian Population The Chennai Urban Rural Epidemiology Study (Cures 70) PLoS ONE 4(9): e7185, 2009.

5 Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement Cost of mental health services in the US was $56.5 billion in 2006

6 Fert Steril, 2007

7 Common Symptoms of Depression

8 OR % CI Obstet Gynecol, 2011

9 Prevalence of Depression in women with PCOS in Kashmir 110 PCOS/40 controls Indian J Psychol Med (1):66-70

10 Updated Meta-Analysis Depressive Symptoms in PCOS OR %CI Cooney et al, unpublished

11 Moderate and Severe Depressive Symptoms OR % CI Cooney et al, unpublished

12 Does Obesity lead to Depression? OR % CI Women who are obese have a 50% higher odds of developing depression than women who are normal weight Luppino et al, 2010

13 Meta-Analysis - BMI Controlled Studies OR % CI Cooney et al, unpublished

14 Screening Tools PHQ Patient Health Questionnaire PRIME-MD PHQ Primary Care Evaluation of Mental Disorders PHQ MINI NPI - Psychiatric Neuropsychological Interview SCL Symptom check list (German version) DACL - Depression Adjective Check List MMPI Minnesota Multiphasic Personality inventory BDI Becks Depression Inventory

15 Longitudinal Risk of Depression - PCOS Overall prevalence 40% with 19% conversion rate

16 Does this high risk group need more frequent screening? PLOS One 9(5) e97041

17 Frequency of Screening Optimal timing and interval for screening is not known Pragmatic approach is to screen all patients who have not been screened previously Follow up screening co-morbidities, life events, family history

18 Anxiety Disorders (DSM V) Separation Anxiety Disorder Selective Mutism Specific Phobia Social Anxiety Disorder (Social Phobia) Panic Disorder Panic Attack (Specifier) Agoraphobia Generalized Anxiety Disorder Substance/Medication-Induced Anxiety Disorder Anxiety Disorder Due to Another Medical Condition Other Specified Anxiety Disorder Unspecified Anxiety Disorder

19 National Institute of Mental Health Anxiety Disorders

20 Meta-Analysis Anxiety Symptoms in PCOS Dokras et al, 2011, Fert &Steril

21 Updated Meta-Analysis Anxiety Symptoms OR 4.74 ( ) Cooney et al, unpublished

22 Moderate and Severe Anxiety Symptoms OR 4.15 ( ) Cooney et al, unpublished

23 Anxiety Symptoms - BMI Controlled Studies Cooney et al, unpublished

24 Screening Tools for Anxiety HADS - Hospital Anxiety and depression scale BSA-S - Brief Scale for Anxiety 11 BAI Beck anxiety Inventory >11 STAI-gr Greek version - State-Trait Anxiety Inventory (global) PRIME-MD PHQ Primary care evaluation of mental disorders patient health questionnaire MINI NPI MINI neuropsychiatric interview SCL-90-R Symptom check list German verison

25 Coexisting Mood and Anxiety Disorders Patients with GAD have a high prevalence of social phobia, specific phobia, panic disorder and major depression (National comorbidity survey, Wang et al, 2005). In the general population between 35-50% of individuals with major depression also meet criteria for GAD. In 20 of the studies included in our systematic review for anxiety, the subjects were also screened for depression and in 16 studies the prevalence of abnormal depression scores was significantly higher than in controls.

26 Health-Related Quality of Life in PCOS Veltman Verhulst et al, 2012 Hum Reprod

27 Treatments Anti-depressants/Anti-anxiety medications Psychological Counselling Weight loss Interventions Hormonal Contraception Metformin

28 JCEM Nov 2015

29 OWL-PCOS Trial Infertile Overweight/Obese Women with PCOS Phase I 4 months Lifestyle Modification LS Continuous OCP Combined LS+OCP Phase 2 Ovulation Induction with Clomiphene: 4 cycles PRIMARY OUTCOME: Live Birth

30 OWL-PCOS Trial P<0.05 P<0.02 Depressive Symptoms Anxiety Symptoms

31 OWL PCOS STUDY Change in PCOSQ scores 0 7 low high a p<0.05, b p<0.01

32 Adolescents OCP+LS or OCP+ Metformin

33 Effect of Diet /Exercise on Depression and HRQOL

34 Summary Screening for depression and anxiety At first visit, then if risk factors present Referral to specialist Treatment of both mood disorder and PCOS symptoms

35 Acknowledgements PENN Laura Cooney, MD Shailly Sani, MD Iris Lee, M4 AE-PCOS Task Force on Mood/Anxiety Disorders Anuja Dokras (USA) Helena Teede (Australia) Bulent Yildiz (Turkey) Elisabet Stener-Victorin (Sweden) Rong Li (China) Duru Shah (India) Sasha Ottey (USA) Jane Speight (Australia)

36 Updated QoL in PCOS 13 studies identified with 3149 women with PCOS 2 used different scoring systems: not included in study comparison 9/13 used Rotterdam Highly variable clinic or RCT populations- mostly infertile women PCOSQ/ MPCOSQ scores with domains related to emotional, menstrual (2/11), infertility (2/11), weight (5/11), hirsutism (2/11) Most troublesome domains related to QoL depended on population Need community based QoL study across ethnic and age ranges

37 Controlling for variables The majority of people with GAD reported substantial interference with their life, a high degree of professional help seeking, and a high use of medication to relieve their symptoms Coexisting GAD in depressed patients may worsen the outcome by increasing the risk of suicide, worsening overall symptoms, conferring a poorer response to treatment, increasing the number of medically unexplained symptoms, and increasing functional disability

38 Impact of Low Glycemic Index Diet Marsh et al, 2010

39 AE-PCOS Task Force on Mood and Anxiety Disorders

40 Eating Disorders DSM V Anorexia Nervosa Bulimia Nervosa Binge Eating Disorder Pica Rumination Disorder Avoidant/Restrictive Food Intake Disorder (ARFID) Other Specified Feeding or Eating Disorder (OSFED) Unspecified Feeding or Eating Disorder (UFED)

41 Eating Disorders in PCOS OR %CI

42 Common Mental Disorders - India A review of 8 epidemiological studies on CMD in South Asia shows that the prevalence in primary care was 26.3% (95% CI 25.3%-27.4%) Patel V. The epidemiology of common mental disorders in South Asia. NIMHANS J 1999;17:307-27

43 PCOS and emotional wellbeing: Recommendations from the first evidence based guidelines: Depression and/or anxiety should be routinely screened and assessed by all appropriately qualified health professionals in women with PCOS Disordered eating, including eating disorders, negative body image and psychosexual dysfunction should be considered in women with PCOS If a woman with PCOS is positive on screening, practitioners should further assess and appropriate management should be offered Range of simple tools identified / available to screen and assess in clinical practice

44 Change in Prevalence of Depressive /Anxiety Symptoms Depressive symptoms OCP group % to 4.4% (OR 0.30, 95% CI: 0.09, 0.99, p<0.05) LS group % to 15.9% (OR 0.64, 95% CI: 0.34, 1.22, p=0.17). Combined group- 11.6% vs. 11.9% Anxiety symptoms LS Group % to 4.7% (OR 0.30, 95% CI: 0.10, 0.85) p=0.02) OCP Group - 6.7% to 2.2% (OR 0.32, 95% CI: 0.06, 1.64, p=0.17). OWL PCOS Study JCEM Nov 2015

45 Zhuang, 2013 Karabacak, 2004 Antidepressants In PCOS

46 Effect of OCP on Mood/Anxiety and HRQOL Cinar et al, 2012, Human Reprod

47 Longitudinal studies Risk Factors Obesity/body image Diabetes/IR Future Directions Biochemical Hyperandrogenism Acne, hirsutism, hair loss Therapeutic options other than anti-depressants/ anxiolytics

48 Mood Disorders - Women The prevalence of MDD in women 18-44year ranged from 12-14% with the mean age of onset of 30.4years. The prevalence of depressive disorders in a multicenter study of obstetric-gynecologic patients was reported to be ~12% Hasin et al, 2005, Kornstein et al, 2006