Table 6 Current recommendations for clinical practice and research gaps identified by this review

 Healthy lifestyle behaviours encompassing healthy eating and regular physical activity should be recommended in all those with PCOS to achieve and/or maintain healthy weight and to optimise hormonal outcomes, general health, and QoL across the life course.

CCR

• Improves sustainability of weight loss interventions.

• Identifies subgroups who respond to weight loss with clinically relevant metabolic and reproductive improvements (this requires the inclusion of more clinical reproductive outcomes in RCTs).

• Defines weight loss thresholds for improvements in different PCOS features (metabolic, reproductive and psychological).

• Characterises the degree of metabolic and reproductive improvements related to different lifestyle factors (diet, physical activity and behavioural) independent of weight changes.

• Considers effects of weight gain prevention on limiting the progression/worsening of PCOS features.

• Investigates how different dietary, physical activity and behavioural interventions affect engagement, adherence and sustainability of lifestyle change.

• Investigates efficacy and effectiveness of healthy lifestyle changes independent of weight change.

 Lifestyle intervention (preferably multicomponent including diet, exercise and behavioural strategies) should be recommended in all those with PCOS and excess weight, for reductions in weight, central obesity and IR.

EBR

 Achievable goals such as 5% to 10% weight loss in those with excess weight yields significant clinical improvements and is considered successful weight reduction within six months. Ongoing assessment and monitoring is important during weight loss and maintenance in all women with PCOS.

CPP

 SMART (Specific Measurable, Achievable, Realistic and Timely) goal setting and self-monitoring can enable achievement of realistic lifestyle goals.

CPP

 Psychological factors such as anxiety and depressive symptoms, body image concerns and disordered eating, need consideration and management to optimise engagement and adherence to lifestyle interventions.

CPP

 Health professional interactions around healthy lifestyle, including diet and exercise, need to be respectful, patient-centred and to value women’s individualised healthy lifestyle preferences and cultural, socioeconomic and ethnic differences. Health professionals need to also consider personal sensitivities, marginalisation and potential weight-related stigma.

CPP

 Healthy lifestyle may contribute to health and QoL benefits in the absence of weight loss.

CPP

 Healthy lifestyle and optimal weight management appears equally effective in PCOS as in the general population and is the joint responsibility of all health professionals, partnering

with women with PCOS. Where complex issues arise, referral to suitably trained allied health professionals needs to be considered.

CPP

 A variety of balanced dietary approaches could be recommended to reduce dietary energy intake and induce weight loss in women with PCOS and overweight and obesity, as per general population recommendations.

CCR

• Low GI/GL diets may provide benefits in reducing weight and IR in women with PCOS. Further research needs to assess additional risk factors including reproductive function and CVD risk.

• Identify and define the optimal diet for PCOS management by comparing a range of different dietary approaches (e.g. DASH, Mediterranean or low GI/GL).

 General healthy eating principles should be followed for all women with PCOS across the life course, as per general population recommendations.

CCR

 To achieve weight loss in those with excess weight, an energy deficit of 30% or 500 - 750 kcal/day (1,200 to 1,500 kcal/day) could be prescribed for women, also considering individual energy requirements, body weight and physical activity levels.

CPP

 In women with PCOS, there is no or limited evidence that any specific energy equivalent diet type is better than another, or that there is any differential response to weight management intervention, compared to women without PCOS.

CPP

 Tailoring of dietary changes to food preferences, allowing for a flexible and individual approach to reducing energy intake and avoiding unduly restrictive and nutritionally unbalanced diets, are important, as per general population recommendations.

CPP

 Health professionals should encourage and advise the following for prevention of weight gain and maintenance of health:

• in adults from 18 – 64 years, a minimum of 150 min/week of moderate intensity physical activity or 75 min/week of vigorous intensities or an equivalent combination of both, including muscle strengthening activities on 2 non-consecutive days/week;

• in adolescents, at least 60 minutes of moderate to vigorous intensity physical activity/day, including those that strengthen muscle and bone at least 3 times weekly;

• activity be performed in at least 10-minute bouts or around 1000 steps, aiming to achieve at least 30 minutes daily on most days.

CCR

While evidence supports the provision of supervised vigorous aerobic exercise, which may provide greater benefits on PCOS symptoms than other types of exercise (e.g. resistance training), additional larger and longer-term studies are required to:

• Characterise optimal exercise prescription for PCOS management.

• Identify factors that improve adherence to exercise interventions.

• Identify subgroups who respond to exercise with clinical improvements.

 Health professionals should encourage and advise the following for modest weight-loss, prevention of weight-regain and greater health benefits:

• a minimum of 250 min/week of moderate intensity activities or 150 min/week of vigorous intensity or an equivalent combination of both, and muscle strengthening activities involving major muscle groups on 2 non-consecutive days/week;

• minimised sedentary, screen or sitting time.

CCR

 Physical activity includes leisure time physical activity, transportation such as walking or cycling, occupational work, household chores, games, sports or planned exercise, in the context of daily, family and community activities.

Daily, 10000 steps is ideal, including activities of daily living and 30 minutes of structured physical activity or around 3000 steps.

Structuring of recommended activities need to consider women’s and family routines as well as cultural preferences.

CPP

 Lifestyle interventions could include behavioural strategies such as goal-setting, self-monitoring, stimulus control, problem solving, assertiveness training, slower eating, reinforcing changes and relapse prevention, to optimise weight management, healthy lifestyle and emotional wellbeing in women with PCOS.

CCR

• To identify behavioural and cognitive strategies that should be targeted in women with PCOS, more observational research that characterises women’s use of self-management strategies is needed.

• To aid replication and interpretation of findings, RCTs must clearly define the theoretical frameworks and behavioural components used in intervention design.

 Comprehensive health behavioural or cognitive behavioural interventions could be considered to increase support, engagement, retention, adherence and maintenance of healthy lifestyle and improve health outcomes in women with PCOS.

CPP

 Factors such as blood glucose, weight, blood pressure, smoking, alcohol, diet, exercise, sleep and mental, emotional and sexual health need to be optimised in women with PCOS, to improve reproductive and obstetric outcomes, aligned with recommendations in the general population.

CPP

• Determine whether women with PCOS are at a higher risk of alcohol and smoking-related infertility complications (with a focus on anovulatory infertility) when compared to women without PCOS.

• Determine whether women with PCOS are at a higher risk of smoking-related CVD complications when compared to women without PCOS.

 If screening reveals CVD risk factors including obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance and lack of physical activity, women with PCOS should be considered at increased risk of CVD.

CCR

 Health professionals and women should be aware of the adverse impact of PCOS on quality of life.

CCR

• Validate QoL tools longitudinally to identify clinically meaningful differences in QoL scores.

 Health professionals should capture and consider perceptions of symptoms, impact on quality of life and personal priorities for care to improve patient outcomes.

CCR

 The PCOS quality of life tool (PCOSQ), or the modified PCOSQ, may be useful clinically to highlight PCOS features causing greatest distress, and to evaluate treatment outcomes on women’s subjective PCOS health concerns.

CPP

 Health professionals should be aware that in PCOS, there is a high prevalence of moderate to severe anxiety and depressive symptoms in adults; and a likely increased prevalence in adolescents.

CCR

• To determine accurate prevalence of psychological conditions in PCOS, more adequately powdered cross-sectional studies using structured diagnostic interviews administered by appropriately qualified professionals are required.

• Future research should consider the efficacy of different types of psychological interventions in PCOS, with a focus on how changes to mental health symptoms influence engagement with lifestyle change. In particular, the development of a PCOS specific CBT program, tailored to meet the specific mental health needs of women with PCOS is warrant.

 Anxiety and depressive symptoms should be routinely screened in all adolescents and women with PCOS at diagnosis. If the screen for these symptoms and/or other aspects of emotional wellbeing is positive, further assessment and/or referral for assessment and treatment should be completed by suitably qualified health professionals, informed by regional guidelines.

CCR

 If treatment is warranted, psychological therapy and/or pharmacological treatment should be offered in PCOS, informed by regional clinical practice guidelines.

CCR

 Factors including obesity, infertility, hirsutism need consideration along with use of hormonal medications in PCOS, as they may independently exacerbate depressive and anxiety symptoms and other aspects of emotional wellbeing.

CPP

 All health professionals should be aware of the increased prevalence of psychosexual dysfunction and should consider exploring how features of PCOS, including hirsutism and body image, impact on sex life and relationships in PCOS.

CCR

 If psychosexual dysfunction is suspected, tools such as the Female Sexual Function Index can be considered.

CCR

 Health professionals and women should be aware that features of PCOS can impact on body image.

CCR

 All health professionals and women should be aware of the increased prevalence of eating disorders and disordered eating associated with PCOS.

CCR

 If eating disorders and disordered eating are suspected, further assessment, referral and treatment, including psychological therapy, could be offered by appropriately trained health professionals, informed by regional clinical practice guidelines.

CCR

 Screening should only be considered for OSA in PCOS to identify and alleviate related symptoms, such as snoring, waking unrefreshed from sleep, daytime sleepiness, and the potential for fatigue to contribute to mood disorders. Screening should not be considered with the intention of improving cardiometabolic risk, with inadequate evidence for metabolic benefits of OSA treatment in PCOS and in general populations.

CCR

• To determine accurate prevalence of subclinical sleep disturbances in PCOS, more adequately powdered cross-sectional studies using validated subjective and objective sleep measures are required.

• While emerging evidence suggests that disturbed sleep may exacerbate IR via decreasing energy expenditure and increasing adipose tissue deposition, more research in women with PCOS is needed to confirm this hypothesis.

• Investigate effects of CBT interventions in women with PCOS who have disturbed sleep (outcomes of interest include food intake, metabolic rate, appetite hormones, weight, adherence to lifestyle changes and PCOS features).

 A simple screening questionnaire, preferably the Berlin tool [178], could be applied and if positive, referral to a specialist considered.

CCR

 A positive screen raises the likelihood of OSA, however it does not quantify symptom burden and alone does not justify treatment. If women with PCOS have OSA symptoms and a positive screen, consideration can be given to be referral to a specialist centre for further evaluation.

CPP

 Inositol (in any form) should currently be considered an experimental therapy in PCOS, with emerging evidence on efficacy highlighting the need for further research.

EBR

• To reduce heterogeneity across studies investigating supplements or herbal medicine, RCTs should focus on specific populations within PCOS (i.e. age, BMI or phenotype) and adopt more consistent approaches to formulation (i.e. limit co-supplementation), dosage, intervention duration and the type of comparator used.

• Mechanistic studies are needed to investigate herb- or nutrient-drug interactions (with common pharmacological treatments used in PCOS) and other possible interactions with the biological processes underpinning PCOS.

• Research that characterises the uptake of TCIM approaches by women with PCOS, including where they are sourcing information on this topic, will aid health professionals understanding of how to safely navigate the use of adjunct therapies in PCOS management.

 Women taking inositol and other complementary therapies are encouraged to advise their health professional.

CPP