12th April 2024

Ovarian Disorders

Polycystic ovarian syndrome

Background

Polycystic ovarian syndrome (PCOS) is the commonest cause of infertility in the UK and affects up to 15% of females. The three main components of this condition are hyperinsulinaemia, excess androgens and the presence of multiple follicles. The pathogenesis involves follicular cysts in the ovary arresting during development. This leads to reduced amounts of progesterone, which normally inhibits gonadotropin-releasing hormone (GnRH). In turn, there is an increased luteinising hormone (LH) relative to follicle-stimulating hormone (FSH). There is an increased amount of androgen production in the ovaries and the adrenal gland. Both LH and high insulin levels cause excess androgens to be released.

Clinical features

This syndrome is characterised by weight gain, oligomenorrhoea, subfertility and features of hyperandrogenism (acne, hirsutism and alopecia). Insulin resistance can lead to thickening and dark discolouration of the axilla, neck and groin, known as acanthosis nigricans. PCOS is linked with cardiovascular disease, metabolic syndrome, obstructive sleep apnoea, depression and a tenfold risk of developing type 2 diabetes.

Investigations

PCOS can be diagnosed on clinical grounds; however, several investigations are useful in the workup. Biochemical tests include testosterone, prolactin, thyroid function tests, sex hormone binding globulin (SHBG), LH and FSH. Increased total testosterone and reduced level of SHBG (a protein which transports androgens) would be in keeping with PCOS. A ratio of LH/FSH ratio of >2.5:1 indicates a proportionally high amount of LH released from the follicular cysts, resulting in increased androgens. In a small proportion of patients, prolactin will be mildly increased.

Pelvic ultrasound can assess the number of cysts and ovarian volume. Patients may have impaired glucose tolerance due to insulin resistance. This can be screened with the oral glucose tolerance test and is recommended for all women with PCOS who are considering pregnancy or have risk factors, including BMI >25kg/m², >40 years of age or non-Caucasian ethnicity.

NICE guidance utilises the 2003 Rotterdam Consensus, where a diagnosis of PCOS requires two of the following, provided the other causes have been excluded.

Differential diagnosis includes thyroid dysfunction, acromegaly, hyperprolactinaemia and congenital adrenal hyperplasia.

Management

General weight reduction should be advised to all if appropriate. The management options depend on whether the patient is considering pregnancy. 

Selective oestrogen receptor modulators such as clomifene or aromatase inhibitors such as letrozole are highly effective in inducing ovulation. Clomifene has an increased risk of inducing ectopic and multiple pregnancies. The overall effectiveness of metformin concerning fertility is still contested. It may be useful in select patients with weight loss requirements and glycaemic control.

Those not considering pregnancy can take the combined oral contraceptive pill (COCP), which promotes regulation of the menstrual cycle. It has also been shown to treat hirsutism and other hyperandrogenic symptoms. Eflornithine cream can be prescribed for facial hirsutism but is only effective in a minority of cases.

References

• Adam Feather, David Randall, Mona Waterhouse, Kumar and Clark’s Clinical Medicine: (10th edition), ed. by John Booth, Kate Wiles, 10th edn (Elsevier, 19 June 2020).
• Corrine K Welt et al., Normal menstrual cycle (2023), https://www.uptodate.com/contents/normal-menstrual-cycle
• NICE, Polycystic ovary syndrome (2022) https://cks.nice.org.uk/topics/polycystic-ovary-syndrome/
• 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 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. PMID: 14711538.
• Vanessa Ngan, Abdullah Haroon, Gus Mitchell, Acanthosis nigricans (2021) <https://dermnetnz.org/topics/acanthosis-nigricans>