Treatment options for PolyCystic Ovary Syndrome (PCOS) need to be individualized and tailored to primary features of the clinical presentation
Summary of treatment options in PCOS
- Lifestyle change (5-10 per cent weight loss + structured exercise)
- OCP (low oestrogen doses)
- Cyclic progestins (e.g. 10mg medroxyprogesterone acetate for 14 days every 2-3 months)
- Metformin (Refer to potential roles of metformin in PCOS)
Treat if the patient is concerned about hirsutism and cosmetic therapy is ineffective, inaccessible or unaffordable
- Primary therapy is the oral contraceptive pill (OCP): Monitor OGTT in those at risk of diabetes, as use of the OCP may increase insulin resistance
- Anti-androgen monotherapy should not be used without adequate contraception
- Trial therapies for ≥ six months before changing dose or medication
- Combination therapy – if ≥ six months of OCP is ineffective, add an anti-androgen to the OCP (daily spironolactone 50mg bd or cyproterone acetate 25mg/day for days 1-10 of the active OCP tablets)
- Metformin, gradually building up to 1-2g slow-release nocte (Refer to potential roles of metformin in PCOS)
- Laser recommended
- Eflornithine cream can be added and may induce a more rapid response
- If there is hyperandrogenemia, pharmacological therapy will minimise hair regrowth
- Consistent with international guidelines, women who are overweight before conception should be advised that, along with folate supplementation and smoking cessation, weight loss and optimal exercise are fundamental to pregnancy preparation, before additional interventions (Note: lifestyle change is effective, with small changes in weight having major health benefits).
- Lifestyle therapy should be first line in women with PCOS with a BMI > 30 kg/m2, for three to six months to determine whether ovulation is induced24.
- Be wary of additional age-related infertility and advise patients of this issue to optimise family planning; infertility is more marked after age 35
- Other therapies are available but again the importance of addressing lifestyle first line and aiming for at least five per cent weight loss cannot be overestimated. Pharmacological management of infertility in PCOS should be considered second line. Primary infertility therapies may include clomiphene and metformin (see table 5). Secondary therapies include gonadotrophins, laparoscopic ovarian surgery and IVF
- Australian guidelines suggest that pharmacological ovulation induction should not be recommended for first line therapy in women with PCOS who are morbidly obese (BMI > 35 kg/m2) until weight loss has occurred either through diet, exercise, bariatric surgery or other appropriate means.
- Bariatric surgery may be considered as second line therapy to improve fertility outcomes in adult women with PCOS with BMI of 35 kg/m2 who remain infertile despite an intensive structured lifestyle management program for a minimum of six months.
Metabolic syndrome, prediabetes, diabetes and cardiovascular disease risk
- Obesity independently causes metabolic complications; lifestyle and exercise are critical
- Lifestyle change with a 5 per cent weight loss reduces diabetes risk by 50-60 per cent in high-risk groups
- Metformin reduces the risk of diabetes by about 50 per cent in high-risk groups (Refer to potential roles of metformin in PCOS)
Anxiety and Depression
Addressing depression and anxiety and then lifestyle change should underpin therapy in most cases with additional therapy based on patient needs. Treatment needs to include education on both short- and long-term sequela of PCOS.
- Metformin should not be used as an alternative to lifestyle therapy in PCOS
- Data do not support a role for metformin in weight loss although, based on studies in diabetes, metformin may assist in preventing future weight gain
- Based on International Diabetes Federation recommendations for diabetes prevention, metformin may have a role in prevention of diabetes in those at high risk but in whom lifestyle therapy is not adequate, e.g. those who are overweight and have additional risk factors, including:
- Family history of type 2 diabetes in a first-degree relative
- Metabolic syndrome
- Metformin has proven efficacy in ovulation and menstrual cycle regulation and reduces hirsutism (it may be especially appropriate to consider if the OCP is contraindicated or undesired)
- The role of metformin in infertility remains controversial. Initial studies showed superiority to clomiphene in lean women, but larger recent studies suggest no benefit in overweight women. However, it is now clear that metformin takes some time to be effective ( > 4-6 months) and is less effective in very overweight women. In women with a BMI <30 kg/m2 it may be reasonable to use metformin in women who are undertaking lifestyle change, before further specific referral for fertility therapy to induce ovulation. If metformin is unsuccessful, after six months, clomiphene can be started, either alone or with metformin, after the patient comes under the care of the reproductive team. In general, however, in those undergoing specific targeted therapy for fertility, metformin should be considered after lifestyle and clomiphene therapy. In women with a BMI > 30 kg/m2 metformin is being considered as infertility treatment, clomiphene citrate should be added. Metformin should be added to clomiphene citrate in women who are clomiphene citrate resistant.
- Note: When using metformin it is better tolerated if started at 500mg slow release daily and increased over weeks to months to reach 1.5-2g daily. The potential for gastrointestinal side-effects should also be explained.
Lifestyle change is the first line in an evidence-based approach to the management of PCOS. Lifestyle change and weight loss with both reduced dietary energy intake and exercise are vital in all overweight women with PCOS, and prevention of weight gain should be emphasised in all women of normal or increased body weight with PCOS.
Weight loss of 5-10 per cent has significant clinical benefits. It improves psychological outcomes, reproductive features (menstrual cyclicity, ovulation and fertility) and metabolic outcomes (insulin resistance decreases by 30-40 per cent and risk factors for cardiovascular disease and type 2 diabetes improve). Evidence shows that lifestyle change, including the attainment of small achievable goals, results in clinical benefits, even when women remain in the overweight or obese range, despite their weight loss and lifestyle change.
Standard dietary management of obesity and related comorbidities is a nutritionally adequate, low-fat (about 30 per cent of energy; saturated fat about 10 per cent), moderate-protein (about 15 per cent) and high-carbohydrate (about 55 per cent), diet with increased fibre-rich wholegrain breads, cereals, fruits and vegetables. Fad diets are not encouraged as short-term weight loss, if achieved, is rarely sustainable.
A moderate energy-reduced diet (500-1000 kcal/day reduction) reduces body weight by 7-10 per cent over a period of 6-12 months. Specific practical tips include targeting fruit juice, soft drinks, portion sizes and high-fat foods and take only minutes to cover in consultation.
Specific dietary approaches in PCOS include high-protein, low-carbohydrate and low-glycaemic-index/glycaemic-load diets. Several small studies assessing specific dietary approaches in PCOS show similar results. No research has assessed low-glycaemic-index/glycaemic-load diets in PCOS. Current evidence suggests that a range of dietary strategies, with healthy food choices, regardless of diet composition, provided they are safe, nutritionally adequate and sustainable in the long term, will similarly improve weight and reproductive and metabolic features in PCOS.
Delivery of dietary interventions face to face with tailored dietary advice, including education, behavioural change techniques and ongoing support should be provided.
Incorporating simple moderate physical activity including structured exercise (at least 30 min. per day) and incidental exercise improves clinical outcomes in PCOS, compared with diet alone. Of this, 90 minutes per week, should be aerobic activity at moderate to high intensity (60-90 per cent of maximum heart rate). Referral to an exercise physiologist may be considered24. Insulin resistance and androgen levels fall further and ovulation improves more with exercise. There is also a trend to increased pregnancy rates with exercise versus diet in PCOS, even though there is more weight loss with diet alone.
As in the general population, goals for exercise must focus on overall health benefits and recommendations should emphasise a combination of both healthy eating and exercise (see case study).