Prompt recognition, management, and treatment of polycystic ovary syndrome by primary care would reduce the burden of other conditions, says Dr David Haslam


P olycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women (15–20%).1 It is the cause of great anguish and distress for sufferers and is more common than diabetes and hypothyroidism—two conditions that are given far greater importance.

The prevalence of PCOS is surprising, and emphasises the lowly status that it is often granted in primary care. Guidelines for its assessment and management have been long overdue, but the handbook, 'The Polycystic Ovary Syndrome: Guidance for Diagnosis and Management'1 goes some way towards filling this void. It is a thorough, accurate, and comprehensive guide to the recognition, diagnosis, and management of the condition.

Many different specialities, including obstetrics, gynaecology, endocrinology, dermatology, dietetics, and primary care, can be involved in the treatment of PCOS. The handbook has been produced by PCOS UK, a multidisciplinary group comprising clinicians from each speciality, and is designed to encourage collaborative and coordinated management. PCOS UK is the clinical arm of Verity—a charity set up to provide support for women who suffer from the condition—which exists to increase awareness and improve management of PCOS in clinical care.

Cause and effects of PCOS

The same metabolic dysfunction is the cause of PCOS as is responsible for the more readily recognised components of 'the metabolic syndrome'—hypertension, dyslipidaemia, and impaired glucose metabolism—which lead to cardiovascular disease, stroke, and diabetes. A disorder of ovarian function, features of PCOS include symptoms and signs of androgen excess, such as hirsutism, alopecia, and acne, alongside obesity, and menstrual cycle disturbance — oligomenorrhoea or amenorrhoea.

The dysregulation of the hypothalamo-pituitary axis2 disrupts normal reproductive function, causing irregular, often anovulatory cycles; the greater the degree of obesity, the more profound the effect on ovarian function, with obesity probably now accounting for 6% of primary infertility.3 This disruption is caused by disturbances in sex hormone production, and is often accompanied by hirsutism, acne, and alopecia, signs that should alert clinicians to the presence of PCOS.2

Polycystic ovary syndrome is not linked with the traditional gynoid (pear-shaped) aspect assumed by obese women, but the classically 'apple' male morphology. Intra-abdominal adipose tissue is a dangerous, metabolically active substance, which distorts the female hormonal axis by peripheral conversion of sex hormones under the influence of adipocyte aromatase, together with a fall in the plasma sex steroid hormone-binding globulin levels.4

Although the term 'metabolic syndrome' has been useful in highlighting the clustering of cardiometabolic conditions because of the common aetiological pathways centring on insulin resistance, this classification is now too restrictive. The 'main' co-morbidities it includes are in danger of eclipsing Cinderella conditions such as PCOS and non-alcoholic steatohepatitis (NASH). These two conditions often occur in the same individual, and their diagnosis, assessment, and management run a parallel course.5 Box 1 gives the indicative signs, symptoms, and pathology for NASH. The course of PCOS and NASH can be influenced by weight loss and pharmaceutical management, making them ideal conditions for screening.

Box 1: Non-alcoholic steatohepatitis

NASH is often codiagnosed in individuals found to have PCOS

  • Early symptoms of NASH include fatigue, weight loss, and weakness, leading eventually to symptoms such as fluid retention, muscle wasting, and gastrointestinal bleeding
  • Obesity and diabetes are causative factors6
  • It can progress from non-alcoholic fatty liver to fibrosis, cirrhosis, liver failure, and, sometimes, hepatocellular carcinoma, and death6
  • NASH is set to become the leading cause of liver failure in the developed world7
  • The condition can be detected by screening for abnormal LFTs, although the gold standard investigations are ultrasound and liver biopsy.8
 
NASH=non-alcoholic steatohepatitis; PCOS=polycystic ovary syndrome; LFT=liver function test

Primary care management

Although complex cases are seen in specialist clinics and infertility centres, most patients with PCOS will be dealt with in primary care, which is ideally suited to its management, and is where the guideline will have most influence. Individuals may present with a wide range of symptoms across a number of disciplines:

  • obesity—affects almost a quarter of the female population9
  • acne—affects an estimated 15% of women10
  • hirsutism—affects approximately 12% of women10
  • alopecia1
  • oligomenorrhoea1
  • infertility.1

Practice nurses and GPs have a wide range of expertise and treatment to offer patients, yet PCOS still goes unrecognised and undiagnosed in surgeries, and its management is not incentivised by the GMS contract. The first role of primary care in the treatment of PCOS is to be aware of the condition when a woman presents at the surgery with any of these symptoms.

Abdominal obesity is a physical sign of serious underlying pathology; raising the possibility not only of overt PCOS, but also a risk of intercurrent diabetes and cardiovascular disease. Nearly 40% of women with PCOS have been identified as having impaired glucose tolerance or overt type 2 diabetes.11

Raised levels of low density lipoprotein cholesterol and reduced levels of high density lipoprotein cholesterol are associated with PCOS, and also possibly hypertension.11 Echocardiographic studies in women with PCOS reveal evidence of abnormal myocardial function,12 and other techniques have shown increased arterial stiffness, endothelial dysfunction, and atherosclerosis.12

A significant improvement in symptoms, such as hirsutism, menstrual irregularity, and even infertility, can be achieved by a weight loss of even 5%.

Treatment of PCOS symptoms

The correct treatment of PCOS will not only lessen the burden of gynaecological disorders, infertility, and dermatological conditions, but will also reduce the later incidence of diabetes, coronary heart disease, and stroke. In turn, this will reduce the demands on primary care and already scarce resources.

Recommended treatment of the varied symptoms of PCOS is as follows (although some of these therapies, such as those for infertility or hirsutism, may require onward referral to secondary care):1

  • obesity—increased physical activity (60–90 minutes per day to achieve or sustain weight loss); the anti-obesity drugs orlistat and sibutramine have been shown to be effective; diet with reduced saturated fat and refined carbohydrates, and as many fruit, vegetables, and whole grains as possible
  • menstrual irregularity—a low-dose 'lipid friendly' combined contraceptive (as women with PCOS are thought to be at increased risk of cardiovascular disease), or a progestogen are effective in restoring regularity
  • infertility—tamoxifen or clomiphene citrate (clomiphene has a 40% pregnancy rate, 10% rate of multiple pregnancy). Where there is resistance to anti-oestrogens, therapy with parenteral gonadotrophin (very low doses to avoid multiple pregnancy and risk of ovarian hyperstimulation syndrome), or laparascopic ovarian diathermy, which avoids the risks of multiple pregnancy, and is as effective as gonadotrophin
  • hirsutism—anti-androgen therapy will stop progress of hair growth and regrowth; non-hormonal therapy with vaniqa (eflornithine) for facial hirsutism
  • acne—topical retinoids or topical antimicrobials (benzoyl peroxide/antibiotics), alone or in combination with anti-androgen therapy
  • metformin is probably the most promising treatment at the present time. It can improve hyperandrogenism, fertility, insulin sensitivity, and lipid profile.

Indications for referral

The following symptoms can be indicative of more serious pathology and should be referred for further investigation:

  • serum testosterone >5 nmol/l (for investigation of other possible causes of raised androgen levels, such as tumours, late-onset congenital adrenal hyperplasia, Cushing's syndrome)
  • infertility
  • rapid-onset hirsutism (to eliminate the presence of androgen-secreting tumours)
  • amenorrhoea of more than 6 months (for pelvic ultrasound scan to exclude endometrial hyperplasia)
  • refractory symptoms.

PCOS and the GMS contract

If primary care takes up the gauntlet of improved recognition and management of PCOS (as well as NASH and other conditions), the workload will once again be increased. As PCOS and NASH sit neatly alongside those other components of the metabolic syndrome, there is a case to be made for its inclusion in the GMS contract QOF targets.13 Sufferers are at increased risk of serious co-morbid conditions so it would be advantageous for primary care to identify and intervene earlier rather than later. With the advent of the recent Rotterdam consensus in 2004,14 the diagnosis of PCOS has been greatly simplified and is now easier to screen for; the presence of two out of the following three criteria being diagnostic:14

  • oligo-ovulation or anovulation
  • hyperandrogenism, (clinical and/or biochemical)
  • polycystic ovaries, and the exclusion of other aetiologies.

Furthermore, the expansion of the obesity category itself in the GMS contract needs urgent and thorough reappraisal; the production of an obesity register is of no clinical benefit whatsoever without a programme of screening to identify high risk individuals. Screening for clinical evidence of oligomenorrhoea, for hyperandrogenism, and for liver function tests (LFTs) for a diagnosis of NASH could feasibly become part of this process (notwithstanding the fact that not all PCOS sufferers are obese). Alternatively, PCOS could be given recognition in the GMS contract as a disease domain in its own right; it is more common than hypothyroidism and diabetes, which already have separate categories.

Conclusions

The purpose of including a disease entity in the QOF targets is to identify and manage a particular condition, with a view to improving the health of sufferers, and preventing harmful sequelae. These criteria are fulfilled by both PCOS and NASH, which are treatable, and the course and progression can be altered, primarily by achieving weight loss, but also by specific pharmacotherapy. The guideline will raise the profile of PCOS,1 and improve its management, which will be to the benefit of patients with this condition.

 

  • PCOS is a common condition that does not usually require specialist treatment
  • A local guideline for diagnosis and treatment (based on the PCOS national handbook) could save money on referrals to various hospital outpatient departments
  • Effective treatment of PCOS is likely to reduce long-term costs against the indicative budget by helping to prevent complications (e.g. NASH, sub-fertility, and diabetes)
  • Key tariff prices:1
      • general medical outpatient = £200 (new), £94 (follow-up)
      • hepatology outpatient = £267 (new), £86 (follow-up)
      • gynaecology outpatient = £138 (new), £76 (follow-up)
      • dermatology outpatient = £118 (new), £88 (follow-up)
  1. Polycystic Ovary Syndrome UK. The Polycystic Ovary Syndrome: Guidance for Diagnosis and Management. PCOS UK, 2006.
  2. Haslam D, James W. Obesity. Lancet 2005; 366 (9492):1197–1209.
  3. Green B, Weiss N, Daling J. Risk of ovulatory infertility in relation to body weight. Fertil Steril 1988; 50 (5): 721–726.
  4. Franks S, Kiddy D, Sharp P et al. Obesity and polycystic ovarian syndrome. Ann N Y Acad Sci 1991; 626: 201–206.
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  9. Department of Health. Health Survey for England 2004. London: DH, 2005.
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  13. Meyer C, McGrath B, Teede H. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. J Clin Endocrinol Metab 2005; 90 (10): 5711–5716.
  14. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81 (1): 19–25.G