PCOS

Notes

Introduction

PCOS is a common condition, with prevalence estimated anywhere between 2% and 30% depending on the criteria used.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. There is a wide clinical spectrum, with some women experiencing relatively mild symptoms whilst others suffer from debilitating effects.

Clinical features are those of hyperandrogenism (acne, oligomenorrhoea and hirsutism) and anovulatory infertility.

Epidemiology

PCOS is a common endocrine/metabolic condition affecting women of reproductive age.

The estimated prevalence of PCOS varies depending on the studied population and the diagnostic criteria used. A meta-analysis by Bozdag et al found that based on the Rotterdam criteria (as advised by the RCOG guidelines), prevalence is estimated to be 10% (8-13%).

Pathogenesis

The aetiology of PCOS remains poorly understood.

Genetics: It is known that PCOS has a strong genetic component. A Dutch twin study by Vink et al indicated a correlation of 0.71 for monozygotic twin sisters and 0.38 for dizygotic twin sisters and other sisters. Genome-wide association studies (GWAS) have gone on to identify a number of loci that may be involved in the development of PCOS. Many of these regions are related to hormone production and insulin resistance.

Increased LH: Changes to luteinising hormone (LH) are commonly seen. Serum levels are elevated in around 40% of women and its pulse frequency and amplitude can be increased. In addition to these changes, increased expression of LH receptors may be seen in the thecal and granulosa cells of the ovary. These changes result in an increased LH to FSH ratio which leads to excess androgens production by theca cells (in the ovary).

Insulin resistance: Insulin resistance is common in patients with PCOS. The underlying cause of the insulin resistance is still not completely understood but it results in hyperinsulinaemia secondary to increased pancreatic production of insulin. This leads to theca cells secreting more androgens and a reduction in sex hormone-binding globulin (SHBG), leading to increased biologically active free androgens.

Clinical features

The features of PCOS are those of androgen excess and menstrual irregularity.

The clinical manifestations of PCOS can vary significantly between patients. Menstrual abnormalities are common and consist of oligomenorrhoea (infrequent menstruation) or amenorrhoea (absent menstruation). Ovulation is less frequent in women with PCOS meaning sub-fertility and infertility are common.

There is an increased frequency of pregnancy complications in patients with PCOS. The risk of spontaneous abortion is 20-40% higher than the general population, this is thought to be related to a multitude of factors including insulin resistance, excess androgens and increased BMI. Other pregnancy-related complications that are seen with increased frequency in PCOS include gestational diabetes and pre-term labour.

Androgen excess or hyperandrogenism manifests itself with acne and hirsutism (terminal hair in male pattern distribution). Obesity is common in PCOS and metabolic complications include an increased risk of T2DM and non-alcoholic fatty liver disease.

Symptoms

  • Oligo/amenorrhoea
  • Infertility/sub-fertility
  • Acne
  • Hirsutism
  • Obesity
  • Sleep apnea
  • Anxiety/depression

Signs

  • Hirsutism
  • Obesity
  • Male pattern baldness
  • Acanthosis nigricans (dry, thickened, 'velvety' skin with a grey/brown pigmentation most commonly seen in the axilla, neck and groin)

Differential diagnosis

It is essential to exclude other causes of similar symptoms.

  • Cushing’s syndrome
  • Primary hypothyroidism
  • Androgen-secreting tumour
  • Non-classic congenital adrenal hyperplasia
  • Premature ovarian failure

Diagnosis

The RCOG advise the Rotterdam criteria be used to make a diagnosis of PCOS.

PCOS is indicated by the presence of two of the following three points:

  1. Polycystic ovaries (12 or more follicles (2-9mm) on one ovary or increased ovarian volume (>10cm3))
  2. Oligo-anovulation or anovulation
  3. Clinical and/or biochemical signs of hyperandrogenism

Management

Management of PCOS is complex and may require ongoing long-term care.

Counselling

PCOS is a chronic condition with long-term implications for a women’s health.Each patient should receive counselling from a medical professional. The nature of PCOS and potential implications on fertility and cardiovascular health should be explained.

Essentially, the importance of optimising modifiable risk factors such as weight and diet should be highlighted. Though women should be aware PCOS itself may make weight loss challenging.

Support groups exist and may be a source of comfort and information. See further reading section below for more information.

Managing clinical features of PCOS

1. Oligo/amenorrhoea

In adult patients with oligo/amenorrhoea for 3 months or longer NICE CKS advise a cyclical progestogen to induce a withdrawal bleed and referral for a TV USS (any abnormalities will require further investigation).

Induction of regular withdrawal bleeds (at least every 3-4 months) and prevention of endometrial thickening is advised. Options include cyclical progestogen, combined oral contraceptive and levonorgestrel-releasing intrauterine system.

Some patients may be unwilling to take any hormonal therapy. Ensure they are aware of the potential health risk, refer to specialist care and organise regular TV USS.

In adolescent patients consider the combined oral contraceptive to manage hyperandrogenism symptoms and menstrual irregularity.

2. Hirsutism

Weight loss (if overweight) may help reduce hyperandrogenism - though this can be challenging. The combined oral contraceptive may be of benefit.

If the women wants to consider hair removal techniques these should be discussed.

3. Acne

The combined oral contraceptive should be considered first-line therapy if there are no contraindications. Weight loss should be encouraged if relevant.

Consider other therapies as part of normal acne management. For more see our notes on Acne vulgaris.

4. Infertility

Advise on weight loss (if overweight) and smoking cessation should be given. Other causes of infertility should be excluded.

Lifestyle

A healthy lifestyle is recommended. In patients who are overweight, support and advice to lose weight should be given.

A healthy diet and regular exercise should be advised. Referral to dietician can be considered.

Psychological health

Anxiety and depression are common and should be screened for. Other issues such as psychosexual difficulties and eating disorders may occur and require specialist referral.

Pregnancy

Women planning pregnancy should have an oral glucose tolerance test. If already pregnant it should be conducted prior to 20 weeks.

Pregnant women should have an oral glucose tolerance test again at 24-28 weeks.

In particular metformin should be avoided in pregnancy.

Cancer and PCOS

There appears to be an increased risk of endometrial cancer in patients with PCOS.

The combination of oligo/amenorrhoea and pre-menopausal oestrogen levels are thought to lead to endometrial hyperplasia and endometrial carcinoma.

It is recommended that in patients with oligo/amenorrhoea, withdrawal bleed is induced every 3-4 months. TV USS is considered in patients with abnormal uterine bleeding or absent withdrawal bleeds.

Complicatons

PCOS may result in a number of complications that should be anticipated or screened for.

  • T2DM
  • Gestational diabetes
  • Cardiovascular disease
  • Sleep apnea
  • Depression/anxiety

Further reading

  • RCOG: Long-term Consequences of Polycystic Ovary Syndrome, Green-top Guideline No. 33, Nov 2014.
  • Verity: A UK based charity that provides support to those with PCOS.

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