Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index

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1 Hum. Reprod. Advance Access published November 19, 2009 Human Reproduction, Vol.00, No.0 pp. 1 7, 2009 doi: /humrep/dep384 ORIGINAL ARTICLE Psychology and counselling Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index E. Jedel 1, M. Waern 2, D. Gustafson 2,3, M. Landén 4, E. Eriksson 5, G. Holm 6, L. Nilsson 7, A.-K. Lind 7, P.O. Janson 7, and E. Stener-Victorin 8,9 1 Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden 2 Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 3 Rush University Medical Center, Chicago, IL, USA 4 Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden 5 Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 6 Department of Metabolism and Cardiovascular Disease, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 7 Department of Obstetrics and Gynecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 8 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Box 434, Gothenburg, Sweden 9 Correspondence address. Tel: þ ; Fax: þ ; elisabet.stener-victorin@neuro.gu.se background: Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). methods: Women with PCOS (n ¼ 30) and controls (n ¼ 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Åsberg Depression Rating Scale (MADRS-S). results: Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1 24 versus 5.0, 0 28, P, 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0 5 versus 0, 0 2, P, 0.001), worry (1.5, 0 4 versus 0, 0 6, P ¼ 0.004), phobias (1, 0 4 versus 0, 0 3, P, 0.001), and pain (1, 0 3 versus 0, 0 2, P, 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0 27 versus 5.5, 0 24, P ). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. conclusions: Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group. Key words: anxiety / depression / polycystic ovary syndrome / body mass index Introduction Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, polycystic ovaries, oligomenorrhea and/or amenorrhea (Rotterdam, 2004; Azziz et al., 2009), and occurs in women of reproductive age with prevalence estimates of at least 6.5% (Norman et al., 2007). Women with PCOS also tend to be overweight or obese (Yildiz et al., 2008), which may contribute to clinical hyperandrogenism via either insulin resistance aggravation or alterations in sex steroid hormone synthesis (Moran et al., 2008). Overproduction of androgens also leads to hirsutism, another common feature of PCOS (Mofid et al., 2008). In addition to the gynecological, endocrine and metabolic features of PCOS, a number of psychological correlates have been identified. Quality of life and psychological well-being are reduced in women with PCOS (Elsenbruch et al., 2003; Coffey et al., 2006; Barnard et al., 2007). Women with PCOS appear to have poorer psychological health-related quality of life than women with a number of other physical conditions including asthma, epilepsy, & The Author Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 2 Jedel et al. diabetes and back pain (Coffey et al., 2006). Depression is more prevalent in women with PCOS (Hollinrake et al., 2007; Kerchner et al., 2009); and higher scores on self-reported depression symptoms have been observed in women with PCOS who do not fulfill criteria for clinical depression (Elsenbruch et al., 2006). Eating disorders and suicidal behavior are also overrepresented among women with PCOS (Månsson et al., 2008). Anxiety may be common in women with PCOS (Himelein and Thatcher, 2006; Månsson et al., 2008; Benson et al., 2009a). In addition, a lifetime history of social phobia was observed in 27% of women with PCOS recruited at departments of gynecology and internal medicine (Månsson et al., 2008). This psychiatric disorder was associated with the highest odds of PCOS when compared with age-matched controls. Focusing on anxiety symptom burden rather than diagnosis, clinically significant anxiety levels were observed in one-third of women taking part in an internet-based survey posted on the homepage of the German PCOS patient support group (Benson et al., 2009a). While there is compelling evidence that women with PCOS are at increased risk of psychological ill-health, pathophysiological correlates of this vulnerability remain unclear. There are several reports linking specific PCOS features, such as infertility (Tan et al., 2008), hirsutism (Hahn et al., 2005) and acne (Barnard et al., 2007), to decreased mental well-being. Neuroendocrine dysfunction has been suggested, but results are inconclusive (Weiner et al., 2004; Månsson et al., 2008). Possible confounding effects of obesity have been suggested. After reviewing the literature on health-related quality of life in women with PCOS, it has been concluded that concerns regarding body weight have a particularly negative influence on quality of life, more so than hirsutism or acne (Jones et al., 2008). Depression (Adali et al., 2008) and anxiety (Månsson et al., 2008) symptoms are associated with higher body mass index (BMI) and waist-to-hip ratio (WHR) (Adali et al., 2008) in women with PCOS. Relationships may be further confounded by the use of psychotropic medications, which may induce weight gain. In the current study, we explore depression- and anxiety-related symptoms in a case control study of PCOS. To avoid potential obesity-related confounding, we matched cases and controls on age, body weight and BMI. We also excluded women with ongoing medication. Our hypothesis was that anxiety and depression symptom burden would be greater in women with PCOS than in matched community controls. Materials and Methods Participants This case control study was conducted from November 2005 to September 2008 at the Sahlgrenska Academy, University of Gothenburg, Sweden. Potential PCOS cases were recruited by advertising for women with PCOS and/or any of the following: body weight concerns, excess body hair and/ or irregular menstrual periods. Potential controls were recruited by advertising for women without PCOS or any of the symptoms listed for potential PCOS cases. All potential participants underwent gynecological examination and two-dimensional vaginal ultrasound to confirm case control status. Diagnostic inclusion criteria for women with PCOS were as follows: 12 or more 2 9 mm ovarian follicles and/or ovarian volume exceeding 10 ml in one or two ovaries; clinical signs of hyperandrogenism and/or oligo/amenorrhea. Two or more criteria were required for inclusion. Women with related disorders (congenital adrenal hyperplasia, Cushinǵs syndrome and androgen secreting tumors) (Rotterdam, 2004) were excluded. Potential controls were excluded on the basis of the gynecological examination if they had polycystic ovaries, menstrual irregularities (cycles,28 days or.35 days), acne or excess body hair. Acne was determined by an affirmative response to the question Do you have acne? and excess body hair was measured by the Ferriman-Gallwey instrument (Ferriman, 1961). Facial and body hair on upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, upper arm and/or upper thigh were evaluated by asking participants to mark 0 for no excess body hair, 1 for an insignificant amount of excess body hair, 2 for a moderate amount of excess body hair, 3 for a considerable amount of excess body hair or 4 for a substantial amount of excess body hair (Ferriman, 1961). Item ratings are summed yielding a minimum value of 0 and a maximum value of 36 (Ferriman, 1961). Exclusion criteria for all participants were difficulties in reading or writing the Swedish language, self-reported current physical/psychiatric disease, any pharmacological treatment within the past 12 weeks and breastfeeding within 24 weeks preceding inclusion. This procedure yielded 30 cases. Comparison subjects (n ¼ 30) were selected to achieve matching by age (+5 years), body weight (+5 kg) and BMI (+2 kg/m 2 ). All participants gave their oral and written consent. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee, University of Gothenburg, Gothenburg, Sweden. Procedure Initial examination of all participants included a case history and twodimensional vaginal ultrasound (HDI 5000, ATL, Bothell, WA, USA) performed by gynecologists. Anthropometrics included body weight, body height, waist and hip circumferences. Body weight and body height were measured in an upright position with light clothing and no shoes. BMI was calculated as body weight (kg) divided by body height (m) squared. Waist circumference was measured in centimeters at the midpoint between the iliac crest and lower rib margin at the end of expiration, while standing without clothing. Hip circumference was measured in centimeters at the widest point between waist and thighs. WHR was calculated as the ratio of waist and hip circumferences. Menstrual cycles were reported in days. Oligomenorrhea was defined as more than 35 days between cycles with fewer than eight menstrual bleedings in the past year. Amenorrhea was defined as absent menstrual bleeding or no menstrual bleeding in the past 90 days. For all participants, fasted blood samples were drawn between 7.30 and 8.30 am. Endocrine parameters measured included total testosterone and sex hormone-binding globulin (SHBG). Analyses were carried out in an accredited laboratory at the Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden. In brief, total testosterone was measured by competitive immunochemistry with chemiluminescence technology (ADVIA Centaur w TSTO ready pack w primary reagents, Bayer Health Care, Terrytown, NY, USA) and SHBG was measured by chemiluminiscent microparticle immunoassay (Abbott SHBG reagent pack, Abbott Laboratories Diagnostic Division, Chicago, IL, USA). Free androgen index was calculated as total testosterone/shbg 100. Psychometrics The self-reported version of the Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) (Svanborg and Åsberg, 1994) was used to assess psychiatric symptoms within a time frame of the last 3 days. The CPRS-S-A is easy to administer, takes 5 30 min to complete and has been shown to be clinically useful (Svanborg and

3 Anxiety and depression in PCOS 3 Åsberg, 1994). A research member was present when the participant completed the computerized instrument. For the purpose of this study, two scales were extracted from the CPRS-S-A (Svanborg and Åsberg, 1994). Anxiety symptoms (shown in Table II) were self-reported with the Brief Scale for Anxiety (BSA-S) (Tyrer et al., 1984) and symptoms of depression (shown in Table III) were measured using the Montgomery Åsberg Depression Rating Scale (MADRS-S) (Montgomery and Åsberg, 1979). The latter instrument, which is widely utilized in both clinical and research settings in Sweden, has been shown to be equivalent to the Beck Depression Inventory as a self-report scale (Svanborg and Åsberg, 2001). MADRS-S and BSA-S each include nine individual items, two of which are present in both scales (Svanborg and Åsberg, 1994). All items are rated on a 6-point Likert scale: 0 represents absence of symptoms; 2, a potentially pathological deviation; 4 represents a pathological condition and 6, an extremely pathological condition (Åsberg and Montgomery, 1978). Item ratings are summed yielding a maximum value of 54 for each scale. Statistical analyses Prediction Application Software (PASW) Statistics 17 (formerly SPSS Statistics) and Statistical Analysis Software (SAS) were used for statistical analyses. Due to skewed distributions, the goodness of matching on age, body weight and BMI was assessed using Wilcoxon signed rank test. In addition, a variety of background factors were compared in cases and controls using either Paired Student s t-test or Wilcoxon signed rank test. Two different strategies were used to compare symptomatology in women with and without PCOS. First, BSA-S and MADRS-S scores were treated as ordinal variables and the Wilcoxon signed rank test employed to test for differences. Thereafter, categorical variables were created for each item. An individual symptom was considered to be present when a woman rated herself 2 on the corresponding BSA-S or MADRS-S item. A MADRS-S score of 11 or more was utilized to denote depression symptom burden of potential clinical relevance, based on previous clinical reports suggesting that a score of 10 or less corresponds to a broadly defined state of remission (Zimmerman et al., 2004). Similarly, a cut-off of 11 was used to indicate an anxiety symptom burden of potential clinical significance. The odds of being a case given a score 2 on individual MADRS-S and BSA-S symptoms, or 11 on the entire BSA-S or MADRS-S, were obtained using Conditional exact logistic regression models. The odds ratio (OR) and 95% confidence interval (95% CI) are presented. Results were considered statistically significant at P, To minimize type I error due to multiple comparisons, a Bonferroni correction was used, dividing 0.05 by the items used in the individual analyses when appropriate (Curtin and Schulz, 1998). Results Characteristics of cases and controls All participants lived in Sweden and spoke Swedish fluently. Eighty three percent (n ¼ 25) of the women with PCOS and 90% (n ¼ 27) of the controls were born in Scandinavia. Seventy three percent (n ¼ 22) of the women with PCOS reported Ferriman-Gallwey score 8 (median, range: 10.5, 0 27) and were defined as hirsute women (Hatch et al., 1981). Acne was reported by 63% (n ¼ 19), and oligo/amenorrhea was reported by 63% (n ¼ 19) of the women with PCOS, were of 20% (n ¼ 6) reporting oligomenorrhea and 43% (n ¼ 13) reporting amenorrhea. As expected, free androgen index was higher in women with PCOS compared with controls (Table I). Also, WHR was higher in women with PCOS compared with controls, while no other sociodemographic Table I Sociodemographics and characteristics of a community sample of women with PCOS and controls matched for age, body weight and body mass index PCOS median (min max) Controls median (min max) Wilcoxon signed rank or % (n) or % (n) test, P-value Age (years) 28.0 ( ) 27.8 ( ) Body weight (kg) 69.4 ( ) 70.9 ( ) BMI (kg/m 2 ) 24.8 ( ) 24.7 ( ) Waist circumference (cm) 83.2 ( ) 83.6 ( ) WHR 0.81 ( ) 0.78 ( ) Free androgen index ( ) 2.1 ( ),0.001 Cigarette smoking (ever/never) 7 (2) 7 (2) Physical exercise 2 days/week 40 (12) 63 (19) Married or cohabitating 43 (13) 40 (12) Biological children 13 (4) 7 (2) Employment status: full-time 47 (14) 27 (8) Part-time 20 (6) 10 (3) Student 30 (9) 60 (18) Unemployed 0 (0) 3 (1) Sick-leave 3 (1) 0 (0) BMI, body mass index; WHR, waist-to-hip ratio. 1 Free androgen index was calculated as total testosterone/shbg 100.

4 4 Jedel et al. Table II Individual items and sum total for the BSA-S in a community sample of women with PCOS and controls matched for age, body weight and BMI PCOS median (min max) Controls median (min max) Wilcoxon signed rank test, P-value BSA-S sum total 10.5 (1 24) 5.0 (0 28), Feelings of unease 2.0 (0 6) 1.0 (0 5) Irritability and anger 1.0 (0 6) 1.0 (0 4) Sleep 2.0 (0 5) 0.0 (0 2), Concern about health 1.0 (0 4) 1.0 (0 5) Worry about unimportant matters 1.5 (0 4) 0.0 (0 6) Phobias 1.0 (0 4) 0.0 (0 3), Physical discomfort 1.0 (0 6) 0.0 (0 5) Pain 1.0 (0 3) 0.0 (0 2), Panic attacks 0.0 (0 5) 0.0 (0 2) P-value of 0.05 for accepting statistical significance among individual items was divided by 9 and set to Table III Individual items and sum total for the MADRS-S in a community sample of women with PCOS and controls matched for age, body weight and BMI PCOS median (min max) Controls median (min max) Wilcoxon signed rank test, P-value MADRS-S sum total 10.0 (0 27) 5.5 (0 24) Mood 1.0 (0 4) 0.0 (0 4) Feelings of unease 2.0 (0 6) 1.0 (0 5) Sleep 2.0 (0 5) 0.0 (0 2), Appetite 0.0 (0 4) 1.0 (0 3) Ability to concentrate 1.0 (0 4) 0.0 (0 5) Initiative 0.5 (0 4) 0.0 (0 4) Emotional involvement 1.0 (0 6) 0.0 (0 5) Pessimism 1.0 (0 4) 0.0 (0 5) Zest for life 0.0 (0 4) 0.0 (0 2) P-value of 0.05 for accepting statistical significance among individual items was divided by 9 and set to and clinical characteristics differed between cases and controls (Table I). Symptoms of anxiety and depression The anxiety score was higher in women with PCOS than in the control group (Table II). Higher median scores were observed among women with PCOS on several individual symptoms including sleep, worry about unimportant matters, phobias and pain compared with controls (Table II). No difference was observed for depression scores (Table III). The only depression-related item that differentiated cases and controls was sleep, which was reported above as this symptom is also present in the BSA-S. In the categorical analysis regarding individual items rated 2 or more, sleep, phobias and pain were more often observed in women with PCOS compared with controls (Table IV). A score of 11 on the sum total BSA-S was observed in 63% of women with PCOS versus 13% of controls (Exact OR 13.00, 95% CI: , P ¼ 0.002). A score of 11 on the sum total MADRS-S was observed in 53% of the women with PCOS versus 20% of controls (Exact OR 3.00, 95% CI: , P ¼ 0.078). Discussion Not only anxiety symptom burden but also several specific anxiety-related symptoms (reduced sleep, worry, phobias and pain) distinguished women with PCOS from a control group matched on age, body weight and BMI. Our results confirm and expand on recent findings from an uncontrolled Internet-based self-report survey posted on the homepage of the German PCOS patient support group (Benson et al., 2009a). Strengths of the present study include the community recruitment procedure that allowed inclusion

5 Anxiety and depression in PCOS 5 Table IV Odds of having PCOS by individual depression and anxiety items rated at 2 based on the BSA-S and MADRS-S in a community sample of women with PCOS and controls matched for age, body weight and BMI PCOS, % (n) Controls, % (n) P-value OR 95% CI Mood 2 37 (11) 33 (10) , 4.20 Feelings of unease 1,2 60 (18) 27 (8) , Irritability and anger 1 47 (14) 37 (11) , 3.94 Sleep 1,2 57 (17) 3 (1), , 1 3 Appetite 2 30 (9) 23 (7) , 4.66 Ability to concentrate 2 33 (10) 27 (8) , 47 Initiative 2 33 (10) 20 (6) , 6.84 Emotional involvement 2 43 (13) 20 (6) , Pessimism 2 40 (12) 17 (5) , Concern about health 1 27 (8) 37 (11) , 2.10 Worry about unimportant matters 1 50 (15) 17 (5) , Phobias 1 43 (13) 7 (2) , 1 3 Physical discomfort 1 43 (13) 30 (9) , 9.08 Pain 1 47 (14) 7 (2), , 1 3 Panic attacks 1 10 (3) 3 (1) , Zest for life 2 17 (5) 3 (1) , Item included in BSA-S. 2 Item included in MADRS-S. 3 1 ¼ less than five women reporting the symptom. of PCOS cases without previous health-care contact and rigorous inclusion/exclusion criteria. All potential participants underwent gynecological examination and vaginal ultrasound to confirm case control status. The matching procedure controlled for possible confounding effects of obesity. Despite the fact that women with current psychiatric disorders/psychotropic medication were excluded, a relatively large proportion (63%) of the women with PCOS had anxiety of potential clinical relevance. This suggests an unmet need for treatment and/or counseling, which could improve mental health and well-being in women with PCOS. Regarding specific anxiety symptoms, half of the women with PCOS reported worry, a proportion more than twice that of the control group. While it was beyond the scope of this paper to diagnose anxiety disorders, we note that worry is a cardinal symptom in generalized anxiety disorder (GAD). A recent clinical study demonstrated a lifetime diagnosis of GAD in 17% of PCOS women (Månsson et al., 2008). Women with this diagnosis have feelings of tension, worry and apprehension concerning everyday events and problems, indicating a mental health problem that goes beyond previously reported worries related to fertility (Trent et al., 2003; Tan et al., 2008). Phobic symptoms were reported by almost half of the women with PCOS in this study. These included feelings of unreasonable fear in specific situations, such as buses, grocery stores, crowds, feeling enclosed and being alone (Åsberg et al., 1978). High free androgen index has been related to life time incidence of phobias in PCOS (Månsson et al., 2008). The majority of cases in this study scored 8 on the Ferriman-Gallwey instrument, exceeding the suggested cut-off for hirsutism; (Hatch et al., 1981) and acne was reported by almost two-thirds of the women with PCOS. We did not test for a relationship between endocrine measures and phobic symptoms in the current study due to the small sample size. Almost half of the women with PCOS reported pain, compared with less than 10% of the women in the control group. Previous studies evaluating health-related quality of life in PCOS demonstrated an association with pain, but this did not remain after adjusting for multiple comparisons (Elsenbruch et al., 2003; Hahn et al., 2005), which emphasized the need to further investigate pain as part of the syndrome. We showed a significant difference on self-reported pain between women with PCOS and controls matched by age and BMI even after adjusting for multiple comparisons. Women with anxiety might have increased muscle tension that might in part explain the finding concerning pain among the women with PCOS. Muscle tension is a subjective experience with possible negative influences on physical as well as psychological health (Pluess et al., 2009), and we suggest regular pain assessment in women with PCOS to optimize care and treatment. Over half of the women with PCOS in this study reported sleep concerns. A partial explanation for this finding might be that sleep apnea is common in obese women with PCOS (Vgontzas et al., 2001). Androgen excess together with subnormal estrogen levels and visceral adiposity may be involved in sleep disturbances (Tasali et al., 2008). The sleep disturbance item, which is incorporated in both the BSA-S and in the MADRS-S, was the only MADRS-S symptom that differed between women with PCOS and controls after correction for multiple comparisons. Somewhat unexpectedly, we could not demonstrate a significant difference in MADRS-S scores between cases and controls, nor could we show an

6 6 Jedel et al. overrepresentation of the specific depressed mood item in women with PCOS. While both low study power and the exclusion of women with ongoing disorders/treatment may play a role, it is also possible that anxiety symptoms as assessed by the CPRS-S-A (Svanborg and Åsberg, 1994) are stronger correlates of PCOS than depression symptoms captured by the same instrument. What might be the physiological underpinnings of the associations observed in the current study? Several of the symptoms such as worry, phobias and sleep disturbances that were overrepresented among women with PCOS suggest increased arousal. In addition, high sympathetic nerve activity has been observed in women with PCOS compared with controls, observations explained by high testosterone concentrations (Sverrisdottir et al., 2008). A disturbed stress response has been observed in mentally healthy women with PCOS. Women with PCOS showed a greater increase in heart rate as compared with BMI-matched controls after exposure to public speaking stress, suggesting autonomic hyperactivity (Benson et al., 2009b). Greater increases in adrenocorticotropic hormone and cortisol were observed, suggesting hyper-reactivity of the hypothalamic pituitary adrenal (HPA) axis (Benson et al., 2009b). Methodological issues Limitations of this study include small sample size and multiple comparisons, both of which were taken into consideration when choosing statistical methods. While cases and controls were matched on age and BMI, there were other, non-significant differences between the two groups that might have affected results. A larger proportion of the women in the control group were students and therefore may be more likely to engage in regular physical exercise, thus confounding results given the wellknown relationship between physical exercise, depression and anxiety (De Moor et al., 2006). Both cases and controls were in relatively good health as potential participants were excluded if self-reported current physical/psychiatric disease or medication use. Women with ongoing hormonal or other treatment were also excluded. Thus, these observations cannot be generalized directly to those who are on treatment. Symptoms of anxiety and depression were self-reported using the CPRS-S-A. While good concordance between expert and selfreported versions of this instrument has been demonstrated in psychiatric outpatients (Mattila-Evenden et al., 1996), the psychometric properties of the self-reported scale in community samples of relatively young women with milder psychopathology are yet unclear. There is some evidence that self-reports may work better for the detection of anxiety symptoms than depression (Mattila-Evenden et al., 1996) and this, in combination with low study power, might help to explain part our failure to show a relationship with specific depression symptoms other than sleep disturbance. In summary, not only overall anxiety symptom burden but also several individual anxiety symptoms distinguished women with PCOS from a control group matched on age, body weight and BMI. A better understanding of anxiety symptoms in this syndrome is needed, as are strategies to identify and alleviate symptoms of mental ill-health in this vulnerable patient group. Authors Role E.J., M.L., E.E., G.H., L.N. A.-K.L., P.O.J. and E.S.-V. conceived and designed the trial. E.J., G.H., L.N. A.-K.L., P.O.J. and E.S.-V. performed the trial. E.J., M.W., D.G. and E.S.-V. analyzed the data. E.J., M.W., D.G. and E.S.-V. wrote the paper. Funding This study was financed by grants from Osher Center for Integrative Medicine, Swedish Medical Research Council ( VP A), EU P7 project LipiDiDiet Grant agreement (211696), Novo Nordisk Foundation, Ekhaga Foundation, Wilhelm and Martina Lundgrenś Science Fund, Hjalmar Svensson Foundation, Magnus Bergvall Foundation, Tore Nilson Foundation, Åke Wiberg Foundation, Swedish Diabetes Association Research Foundation, Adlerbert Research Foundation, Swedish Federal Government under the letters of understanding agreement of Medical Education (ALFFGBG ) and Regional Research and Development agreement (VGFOUREG-5171, and 7861). References The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19: Adali E, Yildizhan R, Kurdoglu M, Kolusari A, Edirne T, Sahin HG, Yildizhan B, Kamaci M. 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Quality of life, psychosocial well-being, and sexual

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