Polycystic ovarian disease- Dilemma of modern women

        Introduction and background epidemiology

PCOS is a common disorder often complicated by chronic an ovulatory infertility and hyperandrogenism with the clinical manifestations of oligomenorrhoea, hirsutism and acne. Many women with this condition are obese and have a higher prevalence of impaired glucose tolerance, type ll diabetes and sleep apnoea than is observed in the general population . They exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome as suggested by a higher reported incidence of hypertension, dyslipidemia, visceral obesity, insulin resistance and hyperinsulinaemia. PCOS is frequently diagnosed by gynecologists and it is therefore important that there is good understanding of the long-term implication of the diagnosis on order to offer a holistic approach to the disorder.

PCOS is one of the most common endocrine disorder on women of reproductive age. Because of differences in the diagnostic criteria employed, prevalence estimates vary widely, ranging from 2.2% to as high as 26% . The prevalence of PCOS when diagnosed by the Rotterdam criteria was over twice that found when the National institute of Health (NIH) criteria were used to diagnose PCOS.

The prevalence of PCOS may be different according to ethnic background . for example, compared to Caucasians, a higher prevalence is noted among women of south Asian origin, where it presents at a younger age and has more severe symptoms . 

   Q.1 How is PCOS diagnosed ? 

  PCOS should be diagnosed according to the Rotterdam  Consensus criteria.  With two or three of the following criteria being diagnostic Of    the    condition.

• Polycystic ovaries ( either 12 or more follicles or increased ovarian volume [ >10 cm ] )
• Oligo-ovulation  or anovulation
• Clinical and / or biochemical signs of hyperandrogenism .

The recommended baseline test for hyperandrogenism os free androgen index (total testosterone divided by sex hormone binding globulin {SHBG x 100 } ). If there are signs of virilisation (e.g. deep voice , reduced breast size , increased muscle bulk , clitoral hypertrophy ), rapidly progressing hirsutism ( less than 1 year between hirsutism  being noticed and seeking medical advice) or high total testosterone levels (greater then 5 nmol/1 or more than twice the upper limit of normal reference range), androgen – secreting tumour and late onset/nonclassical congenital adrenal hyperplasia (CAH) should be excluded. 17 hydroxyprogesterone should be measured in the follicular phase and will be raised in CAH . as Ashkenazi jews or those with a family history of CAH, since the management of CAH is different than that of PCOS. If 17-hydroxyprogesterone is borderline , it will be have confirmed by an ACTH stimulation test to diagnose CAH .

Q.2   What is the risk of developing gestational diabetes in women with PCOS ?

        Clinicians may consider offering screening for gestational diabetes to women who have been diagnosed as having PCOS before pregnancy . This should be performed at 24-28 weeks of gestation , with referral to a specialist obstetric service if abnormalities are detected . the prevalence of gestational diabetes mellitus is twice as high among with PCOS compared to control women . Clinicians may consider offering a 2-hour post 75 g oral glucose tolerance test to all pregnant women with PCOS , similar as for screening in women with any other risk factors for gestational diabetes . 

Q.3 How should women with PCOS be screened for type ll diabetes.

      Women presenting with PCOS who are overweight ( body mass index [BMI] > 25KG/M) and women with PCOS who are not overweight (BMI <25KG/M ), BUT who have additional risk factors  such as advanced age (>40 years), personal history of gestational diabetes or family history of type ll diabetes , should have a 2-hour post 75 g oral glucose tolerance test performed . 

      In women with impaired fasting glucose ( fasting plasma level from 6.1 mmol/l) or ompaired glucose tolerance (plasma glucose of 7.8 mmol/l or m ore but less then 11.1 mmol/l after a 2-hour oral glucose tolerance test) an oral glucose tolerance test should be performed annually. Women of non Caucasian ethnicity ( particularly south Asian women) should have an oral glucose tolerance test regardless of their BMI, in view of their propensity towards higher insulin resistance . Fasting blood glucose level alone has been shown to be inaccurate and results in underdiagnosis of type ll diabetes in PCOS. Hence an oral glucose tolerance test is considered to be appropriate for screening women with PCOS for diabetes . 

Q.4 What is the risk of developing sleep apnoea in women with PCOS?

       Women diagnosed with PCOS should be asked (or their partners asked ) about snoring and daytime fatigue / somnolence, informed of the possible risk of sleep apnoea and offered investigation and treatment when necessary .

Q.5 What is the risk of developing cardiovascular disease (CVD) in women with PCOS ?

       Clinicians need to be aware that conventional cardiovascular risk calculator have not been validated in women with PCOS. 

       All women with PCOS should be assessed for CVD risk by assessing individual CVD risk factors (obesity, lack of physical activity, cigarette smoking, family history of type ll diabetes, dyslipidaemia, hypertension, impaired glucose tolerance, type ll diabetes) at the time of initial diagnosis.

       In clinical practice, hypertension should be treated; however, lipid-lowering treatment is not recommended routinely and should only be prescribed by a specialist. 

       The conventional cardiovascular risk calculators have not been validated in this group of women. 

       At the time of initial diagnosis women with the PCOS should be assessed for obesity with BMI and waist circumference.

      Blood pressure should be checked at the time of initial diagnosis and during oral contraceptive therapy . 

      However lipid-lowering treatment is not recommended for treating hyperandrogenaemia and should only be prescribed by a specialist. 

Q.6 What is the risk of having reduced health-related quality of life in women with PCOS ?

         They should refer the person to an appropriate professional.if    this professional is not the person’s general practitioner (GP), inform the GP of the referral. 

Q.7 What are the risk of cancer in women with PCOS and how should these women be screened ?

      It is good practice to recommend treatment with gestogens to induce withdrawal bleed at least every 3to4 months. In PCOS an endometrial thickeness of less than 7 mm is unlikely to be hyperplasia. A thickened endometrium or an endometrial polyp should prompt consideration of endometrial biopsy and/ or hysteroscopy. These does not appear to be an association with breast or ovarian cancer and no additional surveillance is required . 

     Regular  induction of a withdrawal bleed with cyclical gestogens – gestogens foe at last 12 days, oral contraceptive pills or endometrial protection gained by exposure to gestogens by device such as the Mirena^R (Bayer plc,Newbury, Break, UK) intrauterine system would be advisable in oligomenorrhoeic women with PCOS as part of good clinical practice but the most effective regimen is unclear due to a lack of randomised clinical trials.

        Found that compared with 7 mm a higher cut- off 9 mm in patient with PCOS had comparable sensitivity (100%) negative predictive value (100%) and positive predictive value (50%) but superior specificity (56%) ; for every 1 mm increase in endometrial thickness the odds ratio of hyperplasia increased by 1.48 (95% CI  I.04-2.10).

Q.8 How should women with PCOS be advised on lifestyle issues ?

        It is recommended that lifestyle changes, including diet, exercise and weight loss, are initialled as the first line of treatment for women with PCOS for improvement of long – term outcomes and should precede and/ or accompany pharmacological treatment. 

         Women who have failed to lose weight with lifestyle strategies and who have a BMI of 40 kg/m² or more or who have a BMI of 35 kg/m² or more together with a high risk obesity – related condition ( such as hypertension or type ll diabetes) should be considered for bariatric surgery .

Q.9 Is drug therapy appropriate for long-term management of women with PCOS !

        Insulin- sensitising agent have not been licensed in the UK for use in patient without diabetes. 

        Metformin has been shown to have beneficial short-term effect on insulin resistance and other cardiovascular risk markers in women with PCOS without type ll diabetes . There is evidence that metformin may modestly reduce androgen levels by around 11% in women with PCOS compared to placebo and modest reduction in body weight have been reported by some but not all studies . women with a BMI of more than 37 kg/m may not reported well to the standard dose of metformin therapy. It must be emphasised that both metformin and the thiazolidinediones are unlicensed for use in PCOS and women should be counselled before initiating therapy so that they can make an informed choice . 

        Incretin hormone-based therapies such as exenatid have been shown to reduce weight and improve insulin resistance in women with PCOS. However the clinical experience with these agents in PCOS ih limited and significant side effect may occur there for routine use of incretin-based therapies in PCOS is not recommended.Biochemical hyperandrogenaemia but without changing glucose insulin homeostasis or lipid pattern . 

Q.9 What is the prognosis following electrocautery ?

       For selected anovulatory patient especially those with a normal BMI as an alternative to ovulation induction. 

      Well as normalisation of serum androgens and SHBG up to 20 year after laparoscopy  ovarian electrocautery in over 60% of subject particularly if they have a normal BMI. Reserved for selected anovulatory patient with a normal BMI or where a laparoscopy  is required for other indication. 

Q.10 What is the prognosis following bariatric surgery ?

          Bariatric surgery may be an option for morbidly obese women with PCOS (BMI if 40 kg/m² or more or 35 kg/ m² or more with a high risk obesity related condition) if standard weight loss strategies have failed .