Polycystic Ovarian Syndrome

Approximately 5-10% of women suffer from PCOS, thereby making it one of the most common endocrine conditions affecting women of reproductive age. It is a difficult syndrome to define due to the multiple factors influencing its pathophysiology, however the key features include menstrual cycle changes and hyperandrogenism.

 

PCOS also cause changes in the morphology of the ovaries themselves. The main change seen is the presence of 8-10mm cysts around the edge of the ovaries, visible on an ultrasound scan. These cysts are harmless egg-containing follicles, which have improperly developed due to the hormone imbalance in PCOS. As a result, the egg from the improperly developed follicles cannot be released during ovulation and anovulation results. This is one of the main causes of subfertility.

 

Aetiology and Pathophysiology

 

The aetiology of PCOS is unknown but a few theories have been suggested:

  1. Genetics – a high number of female relatives of PCOS patients are affected
  2. Insulin resistance with/without obesity
  3. Hyperandrogenism 

 

The pathophysiology of PCOS, although still not entirely clear, is mainly due to the hormone imbalance caused by both hyperandrogenism and hyperinsulinemia, which are also effects of PCOS. They can both be described and explained by viewing the hypothalamic-pituitary-ovarian axis. 

Hypothalamic-pituitary-ovarian Axis

Hypothalamic-pituitary-ovarian Axis

[1]

 

1)    Gonadotrophin releasing hormone (GnRH) is released from the hypothalamus in a pulsatile manner, through mechanisms which are not fully understood. This pulsatile manner is extremely important to prevent desensitisation of the pituitary to GnRH, which would occur if GnRH were released continuously. In some cases of PCOS there is a rapid release rate of GnRH, causing the hypersecretion of Luteinising Hormone (LH) and ultimately the LH:FSH (Follicle stimulating hormone) hormone imbalance seen in PCOS.

 

2)    LH and FSH are released from the anterior pituitary in response to GnRH. In PCOS LH stimulates the theca interna cells of the ovaries to release androgens. FSH on the other hand normally promotes the conversion of androgens to oestrogen via aromatase activity. However due to the lower levels of FSH in PCOS, this process is not as active.

 

3)    An increase in androgen production and release causes an increase in inhibin (Inhibin B) release, which leads to an increase in the production of androgens. This vicious cycle leads to inhibin suppressing the levels of circulating FSH, thereby contributing to the increased LH:FSH ratio.

 

4)    Insulin resistance (possibly a cause or effect of PCOS) is thought to be exacerbated by the increase in androgens. Insulin resistance then causes compensatory hyperinsulinemia, which acts to increase levels of androgens, by two methods. Firstly, by lowering the circulating levels of sex hormone binding globulin (SHBG). Secondly, by acting on both insulin and IGF-1 (Insulin-like growth factor-1) receptors on the ovaries. It is also known to increase the pulse frequency of GnRH, resulting in to the contribution of the increase in LH:FSH ratio.

 

5)    The increase in LH:FSH ratio then further causes an increase in androgens through hyper-activation of LH receptors.

 

6)    Normally the levels of the ovarian steroids would negatively feedback to the hypothalamus, which in turn would reduce the pulsatile release of GnRH. But in PCOS the hypothalamus becomes increasingly insensitive to ovarian steroids and ultimately there is no negative feedback. 

 

Diagnosis – Signs and Symptoms

There are many different sets of criteria used for the diagnosis of PCOS, which can be seen here. The most commonly used suggests that the diagnosis of PCOS requires the presence of two out of the three symptoms or criterions:

 

  • Oligo-ovulation and/or anovulation;
  • Clinical and/or biochemical signs of hyperandrogenism;
  • The appearance of polycystic ovaries on an ultrasound scan.

 

One of the reasons for this type of diagnostic process is due to the fact that many women have the appearance of polycystic ovaries on an ultrasound scan but clinically they have no signs or symptoms of the syndrome. Therefore the appearance of polycystic ovaries is not a necessary criterion for the diagnosis of PCOS.

 

After these criteria have been met, it is necessary to exclude any other possible causes of these symptoms, such as:

 

  • Hypothyroidism;
  • Congenital Adrenal Hyperplasia;
  • Cushing’s Syndrome;
  • Hyperprolactinemia.

 

An accurate history is vital and symptoms such as hirsutism can be evaluated by referring to the Ferriman-Gallwey score. This can aid with estimating the circulating androgen levels. 

 

Investigations

[3]

 

Main investigations carried out to confirm PCOS:

 

  • A pelvic exam to identify any swelling or enlargement caused by the increased number of cysts on the ovary;
  • A transvaginal ultrasound to examine the ovaries for cysts;
  • A full blood count – to identify levels of androgens (mainly free testosterone), LH, FSH, Insulin, glucose, cholesterol etc.

 

Other tests such as a glucose tolerance test and a full lipid profile are also likely to be carried out to assess the many associated risks in PCOS.

 

Associated Risks

[2], [5]

 

 

These metabolic risks ultimately increase the risk of cardiovascular disease. Early markers of atherosclerosis are seen in PCOS women.

 

It is key to note that all signs of PCOS, its symptoms, and its associated risks are greater in all PCOS women compared to their weight matched controls, but are exacerbated in overweight/obese PCOS women. 

 

Management/Treatment

[4]

 

The first line therapy is through lifestyle changes. As many PCOS women are overweight or obese, they are encouraged to lose weight. It has been proven that as little as 5-10% weight loss has significant advantages by improving not only metabolic features, but also reproductive and psychological features. Regular exercise is also highly recommended, as is reducing the intake of refined carbohydrates. This is to control insulin levels. 

 

Pharmacological Options

Surgical Options

 

Laparoscopic Ovarian Drilling – this is a keyhole surgery used to destroy the testosterone producing tissue on the ovaries. Not always recommended as pharmacological treatments provide very similar effects. Used in special circumstances only.

 

Extra

 

Present data has suggested that continuing Metformin therapy during pregnancy decreases the incidence of first trimester spontaneous abortion associated with PCOS. It may also reduce the incidence of gestational diabetes. 

 

Further Reading

 

http://www.bupa.co.uk/individuals/health-information/directory/p/pcos#textBlock276306

 

http://www.gynaecologymolloy.com/polycystic-surgery.html

 

Nader, S. (2010). Infertility and pregnancy in women with polycystic ovary syndrome. Minerva Endocrinologica. 35 (4), 211-225. Link

 

Wang ET, Calderon-Margalit R. (2011). Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia.. Obstetrics & Gynecology. Link

 

References

 

[1] - Balen, A. (2004). The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Practice & Research Clinical Obstetrics & Gynaecology. 18 (5), 685-706.

 

[2] - Carmina, E and Lobo, R.A.. (1999). Polycystic Ovary Syndrome (PCOS): Arguably the Most Common Endocrinopathy Is Associated with Significant Morbidity in Women. The Journal of Clinical Endocrinology & Metabolism. 84 (6), 1897-1899.

 

[3] - Jensen, Jani R. and Ruben Alvero. "Polycystic Ovarian Syndrome." Reproductive Endocrinology and Infertility: The Requisites in Obstetrics and Gynecology. Ed. Mark Evans, MD. Philadelphia: Mosby, 2007. 65-75.

 

[4] - Polycystic Ovarian Syndrome (PCOS). Available: http://www.fcionline.com/diagnosis-treatment/polycystic-ovarian-syndrome.html. Last accessed 17/1/11.

 

[5] - Teede, H. ,Deeks, A. ,Moran, L. (2010). Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Medicine

 

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