Figure 2: Summary of a targeted approach to therapy.

(Teede et al, The Royal Australian College of General Practitioners.  CHECK Program: Polycystic ovary syndrome, 2008. Reproduced with permission.) 

Table 4: Summary of treatment options in PCOS

Oligomenorrhoea/amenorrhoea

• Lifestyle change (5-10 per cent weight loss + structured exercise)*
• OCP (low oestrogen doses, e.g. 20μg may be preferable)
• Cyclic progestins (e.g. 10mg medroxyprogesterone acetate for 14 days every 2-3 months)
• Metformin (off-label prescribing: See table 5)

Hirsutism treatment recommendations

• Treat if the patient is concerned about hirsutism and cosmetic therapy is ineffective, inaccessible or unaffordable

        - Pharmacological therapy

• 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 (off-label prescribing, yet clear evidence of benefit: See table 5)

         - Cosmetic therapy

• Laser recommended
• Eflornithine cream can be added and may induce a more rapid response
• If there is hyperandrogenaemia, pharmacological therapy will minimise hair regrowth

Infertility

• 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 means²⁴.

• 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 anintensive structured lifestyle management program for a minimum of six months²⁴.

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 (see table 5)

† Metformin and the OCP are not currently approved for use in PCOS by the TGA – The OCP is primarily indicated for contraception, and metformin for diabetes. However, their use is recommended by international and national endocrine societies and is evidence based. In future, applications to the TGA for these indications are needed.

Table 5: Summary of potential roles of metformin in 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 
   - IGT
• 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 resistant²⁴.

  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.