Polycystic Ovary Syndrome: what diabetes educators need to know

The common features of PCOS are extensive and include:^{3, 4}

• reproductive features: hyperandrogenism, anovulation and infertility
• metabolic features: insulin resistance, impaired glucose tolerance (IGT), gestational diabetes (GDM), type 2 diabetes (T2D) and adverse cardiovascular risk profiles
• psychological features: increased anxiety and depression and reduced quality of life

Women with PCOS are also more likely to be overweight or obese, and carrying excess weight worsens metabolic and reproductive features.^{5, 6}

Diagnosis is usually made using the 2002 Rotterdam criteria which require the presence of two out of three of the following (with the exclusion of other aetiologies such as congenital adrenal hyperplasia, androgen-secreting tumours and Cushing’s syndrome):

• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism (elevated male hormone levels)
• Polycystic ovaries on ultrasound

The cause of PCOS remains unknown but is likely to result from a combination of genetic,  environmental (including the in-utero environment) and lifestyle factors.⁷

 Evidence-based guidelines for diagnosing and managing PCOS

In 2018 the first international evidence-based guideline for the diagnosis and management of polycystic ovary syndrome (PCOS) was developed.⁸  The development process involved an Australian-led international and multidisciplinary collaboration of health professionals and consumers. The guideline is approved by the National Health and Medical Research Council (NHMRC) and aims to support both health professionals and women with PCOS in improving care, health outcomes and quality of life.  The recommendations from the guideline will be discussed throughout the remainder of this article.

PCOS and diabetes

Women with PCOS have a higher prevalence of IGT, GDM and T2D, as a result of underlying insulin resistance.  A 2018 meta-analysis of 40 studies found a 3.3-fold increased prevalence of IGT and 2.9-fold increased prevalence of T2D.⁹   The prevalence varied by ethnicity, with women of Asian background more likely to be affected, and was higher in women who were overweight or obese.⁹  The risk of developing GDM during pregnancy has been found to be increased around 3-fold in women with PCOS.¹⁰

The 2018 International evidence-based guideline for the assessment and management of polycystic ovary syndrome recommends regular screening for diabetes, as follows:¹¹

• Glycaemic status should be assessed at baseline in all with PCOS and thereafter, every one to three years, based on presence of other diabetes risk factors.
• In high risk women with PCOS (including a BMI > 25kg/m² or in Asians > 23kg/m², history of abnormal glucose tolerance or family history of diabetes, hypertension or high-risk ethnicity) an oral glucose tolerance test (OGTT) is recommended. Otherwise a fasting glucose or HbA1c should be performed.
• An OGTT should be offered in all women with PCOS when planning pregnancy or seeking fertility treatment.
• If not performed preconception, an OGTT should be offered at < 20 weeks gestation, and all women with PCOS should be offered the test at 24-28 weeks gestation.

While traditionally associated with insulin resistance and T2D, there is also evidence to suggest a higher prevalence of PCOS in women with type 1 diabetes (T1D). In fact, a 2016 systematic review and meta-analysis found a pooled prevalence of 24% in adolescent and adult women with T1D, significantly higher than in women without diabetes.¹²  The mechanisms are still unclear but it has been hypothesised that exogenous hyperinsulinism, resulting from the administration of large doses of subcutaneous insulin needed to reach the portal circulation in T1D, may lead to increased androgen production.¹² Further research is needed to identify the pathophysiological mechanisms underlying PCOS and to address the long-term consequences of PCOS in women with T1D.¹²

PCOS and weight

Women with PCOS are more likely to be overweight or obese, particularly in regard to central obesity, and there is evidence that rates of weight gain are greater than in the general population.^{6, 13}  Excess weight worsens reproductive, metabolic and psychological features of the condition.⁵ It is also a significant concern for women themselves.

While women with PCOS often report difficulties losing weight, a recent systematic review of weight loss interventions found no differences in weight loss between women with or without PCOS.¹⁴  This is an important message, as a recent US study found that women with PCOS had a greater perceived susceptibility for disease and weight gain and poorer perceived control over these health outcomes.¹⁵ They were also less likely to agree that a healthy diet or physical activity could reduce risk of weight gain compared to women without PCOS.¹⁵ Helping women to understand the benefits of lifestyle modification, even with quite modest weight loss (5-10% of weight), may increase their self-efficacy and motivation to make lifestyle changes.

Management of PCOS

Management of PCOS aims to:

• Normalise hyperandrogenaemia and its associated symptoms such as hirsutism and acne.
• Improve menstrual cyclicity and reproductive function.
• Reduce the risk of associated chronic health problems including T2DM and CVD.

Lifestyle modification, including diet, exercise and weight management, is recommended as the first line of treatment and has been shown to improve body composition, hyperandrogenism and insulin resistance and reduce metabolic risk factors.^{11, 16–18}  While some women may also require pharmacological treatments, these are recommended to be prescribed alongside lifestyle changes.⁸

Nutrition recommendations for PCOS

Despite the important role of diet, long-term, well controlled studies investigating different dietary approaches in women with PCOS are lacking.⁸  While dietary interventions resulting in weight loss have shown benefits, there is currently insufficient evidence to support one specific type of diet over another for women with PCOS.⁸  For this reason, general healthy eating recommendations should be encouraged, focused on weight loss in those who are overweight and on prevention of weight gain in those who are of a healthy weight.⁸  Similar to recommendations for people with diabetes, dietary changes should be tailored to food preferences, allowing for a flexible and individual approach to reducing energy intake and avoiding unduly restrictive and nutritionally unbalanced diets.

Several studies have reported a higher prevalence of body image concerns and disordered eating in women with PCOS and a recent meta-analysis of seven studies found that women with PCOS have more than three times the odds of having abnormal eating disorder scores or an eating disorder diagnosis¹⁹.  These findings highlight the importance of screening women with PCOS for disordered eating before recommending weight management interventions.  The international guideline emphasises the importance of health professionals being aware of the increased prevalence of body image dissatisfaction and disordered eating in these women and recommend screening for these conditions where suspected.⁸  Further assessment, referral and treatment, including psychological therapy, should be offered where indicated. The guideline provides initial questions to screen for body image dissatisfaction and disordered eating.

Referring women with PCOS to an Accredited Practising Dietitian (APD) for individualised dietary advice is recommended.

Physical activity recommendations for PCOS

Alongside diet, physical activity plays an important role in the management of PCOS.  Regular exercise has been found to improve anthropometric and metabolic outcomes in women with PCOS although the impact on reproductive outcomes is unclear.²⁰  Similar to diet, there is limited evidence for the benefits of specific types of exercise for women with PCOS, and recommendations are the same as those of the general population.⁸  This includes incorporating regular moderate-to-vigorous exercise, including muscle strengthening exercises, with the amount dependent on whether the goal is general health and prevention of weight gain, or weight loss and prevention of weight regain. Women are also encouraged to aim for at least 10000 steps per day, including activities of daily living, and to minimise sedentary, screen and sitting time.

Referral to an Accredited Exercise Physiologist (AEP) for individualised exercise advice is recommended.

Metformin

Metformin is commonly being used in women with PCOS although its prescription for this purpose in Australia is off-label on a private prescription.  In combination with lifestyle modification, metformin has been found to improve body mass index, menstrual cyclicity, androgen levels and metabolic features.⁸

The international guideline recommends the use of metformin in women with PCOS who have IGT or T2D and those from high risk ethnic backgrounds.⁸  They also suggest considering metformin for women who are overweight (BMI > 25kg/m²), regardless of metabolic status to help with managing weight and metabolic outcomes where lifestyle modification hasn’t addressed metabolic features. However, it is recommended as an addition to lifestyle intervention, not as a substitute, and women  should be informed of the evidence for its use, the side effects and considerations with long-term use, including vitamin B12 deficiency.⁸

For women who are trying to conceive, the guideline recommends that metformin could be used alone in women with PCOS, with anovulatory infertility and no other infertility factors, to improve ovulation, pregnancy and live birth rates, although women should be informed that there are more effective ovulation induction agents.⁸

Other pharmacological agents

Other medications that may be used in women with PCOS, depending on their symptoms and goals of treatment, include the combined oral contraceptive pill (COCP; to help address menstrual cycle regularity and hyperandrogenism), anti-androgens (to help with hyperandrogenism if the COCP hasn’t been effective on its own) and anti-obesity medications, if appropriate.⁸  For women having difficulties conceiving, medications to induce ovulation may be used, including letrozole, clomiphene citrate (alone or in combination with metformin) and gonadotrophins.⁸  Where ovulation induction isn’t successful in achieving a pregnancy, laparoscopic ovarian drilling and in-vitro fertilisation (IVF) may be considered.⁸