||BACKGROUND: Women with polycystic ovary syndrome (PCOS) have symptoms of depression and anxiety and impaired health related quality of life (HRQoL). Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women. METHODS: Seventy-two PCOS women were randomly assigned to 16 weeks of 1) acupuncture (n = 28); 2) exercise (n = 29); or 3) no intervention (control) (n = 15). Outcome measures included: change in Montgomery Asberg Depression Rating Scale (MADRS-S), Brief Scale for Anxiety (BSA-S), Swedish Short-Form 36 (SF-36), and PCOS Questionnaire (PCOSQ) scores from baseline to after 16-week intervention, and to 16-week post-intervention follow-up. RESULTS: A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group. The SF-36 domains role physical, energy/vitality, general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up. Within the exercise group the role physical decreased after treatment, while physical functioning and general health perception scores increased at follow-up. The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups, and at follow-up in acupuncture and exercise groups. At follow-up, improvement in the infertility domain was observed within the exercise group. CONCLUSION: There was a modest improvement in depression and anxiety scores in women treated with acupuncture, and improved HRQoL scores were noted in both intervention groups. While not a primary focus of the trial, these data suggest continued investigation of mental health outcomes in women treated for PCOS.Trial registration numberClinicalTrials.gov Identifier: NCT00484705.