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Subject 101: Polycystic ovarium syndrome (PCOS)

Polycystic ovarium syndrome (PCOS)

PCOS is the most common endocrine disorders in women of child-bearing age and is an important cause of menstrual irregularity, infertility and androgen excess in women.1 PCOS means literally that there are several (poly) cysts in the ovarium1. But polycystic ovary appearance on ultrasonography is not sufficient to diagnose PCOS and is present in 20-30% of otherwise healthy women as well.2 PCOS is often misunderstood and wrongly diagnosed. Therefore I would like to dedicate this subject 101 to PCOS.

(Mis)Diagnosis and Rotterdam criteria

PCOS is a heterogeneous disorder which is associated with clinical, endocrine and ultrasonographic features that also could be present in several other diseases.3 The overall prevalence of PCOS is between 6-10%.4 With the term PCOS the confusion that only a polycystic ovary appearance on ultrasound is enough to make the diagnosis which could lead to under- and overestimation of symptoms. The diagnosis PCOS can be made if at least two of the following three criteria are present: Oligo- or anovulation, clinical/biochemical signs of hyperandrogenism and polycystic ovary (PCO) appearance on ultrasonography.4 The clinical image can be diverse and symptoms intensity can vary.5 The symptoms of PCOS could also be present in a range of other disorders such as thyroid disorders, states of prolactin excess and congenital adrenal hyperplasia.3 The overall consensus is that PCOS remains a diagnosis of exclusion.6

Pathophysiology of PCOS

The pathophysiology of PCOS is multifactorial and polygenic and the cause of PCOS is not all clear.7 Insulin resistance,  which manifests the most in obese or overweight women but often also in lean PCOS women, is one of the key of this complex disorder.8 Hyperinsulinemia has a causal association to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne and hirsutism.8 Another key observation is that women with PCOS have elevated levels of LH due to increased amplitude or frequency of LH pulses.7 The shorter pulses of GnRH result in promoting LH while FSH secretion is the same or even decreased.9 Androgen production in the ovary is by the theca interna layer of the ovarian follicles, whereas the granulose cells in ovary’s have receptors for FSH.9 The result is that the follicles are failing to develop and high levels of androgens appear.

Infertility affects 40% of women with PCOS.2 That means that 60% of women with PCOS are not affected with infertility. Even if there is a diminished ovulation rate in most women with PCOS, every ovulation could result in a pregnancy. Therefore, it remains important for women with PCOS and without an active childwish to use contraceptives even if the chance of a pregnancy is smaller than in the healthy population.

Consequences

There are several shortterm and longterm consequences for women with PCOS.10 Women with PCOS have a prevalence of 50-70% of insulin resistance leading to a number of comorbidities including the metabolic syndrome.6 Lifestyle changes such as weight loss can improve the metabolic syndrome by lowering androgen levels and improve PCOS as well.6 Mental health disorders including depression, anxiety and bipolar disorders and binge eating disorder also occur more frequently in women with PCOS.6  Besides that, women with PCOS have an increased risk of endometrial hyperplasia and carcinoma due to chronic anovulation that is associated with PCOS.2 This could be prevented by using progesterone to prevent endometrial hyperplasia.

Conclusion

In conclusion,  PCOS is an important endocrine disorder in women which is strongly correlated to insulin dysfunction. PCOS remains a diagnosis of exclusion, other endocrine disorders should be excluded before the diagnosis of PCOS can be made. Women with PCOS must be aware of the short term and long term consequences of the disorder and PCOS does not mean an infertility problem per se.

M. Kok & F. Dusseldorp

Department of gynaecology, Academic Medical Centre, Amsterdam, The Netherlands

References

  1. Diagnostic evaluation of polycystic ovary syndrome in adolescents. Uptodata. Online available here
  2. Sirmans SM, Kristen AP. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2014; 6: 1-13
  3. Kyritsi E.M., Diitriadis G.K., Kyrou L, Kaltas G, Randeva H.S. PCOS remains a diagnosis of exclusion: a concise review of key endocrinopathies to exclude. Clinical endocrinology. 2016 sep. 24 (only published at pubmed yet)
  4. Bozdag G, Mumusoglu S., Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction; 2016 sep 22 (only published at pubmed yet)
  5. Bachanek M, Abdalla N., Cendrowski K, Sawicki W. Value of ultrasonography in the diagnosis of polycystic ovary syndrome. Journal of clinical endocrinology and metabolism. 2015 dec; (15(63) 410-22
  6. Azziz R, Carmina E, Dewailly D, Diamanti-Kandaraki E, Escobar-Morreale HF, Futterweit W, janssen OE, Legro RS, Norman RJ, Tayler AE, Witchel SF. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen excess society guideline. J Clin Endocrin Metab 2006 nov; 91(11):4237-45
  7. Balen A. The pathophysiology of polycycstic ovary syndrome: trying to understand PCOS and its endocrinology. Best practice & research clinical obstetrics and gynaecology. Vol 18, no. 5. Pp 685-706, 2004.
  8. De Leo V, La Marca A, Felice P. Insulin-Lowering Agents in the management of polycystic ovary syndrome. Endocr Rev. 2003;24:633-67
  9. Cheung A, Cog F. Polycystic Ovary Syndrome: A contemporary view. J Obstet Gynaecol Can. 2010 May; 3(5):423-5, 426-8
  10. Heineman MJ, Evers JLH, Massuger LFAG, Steegers EAP (2007). Obstetrie en Gynaecologie. De voortplanting van de mens. (6e druk) Amsterdam; Reed Business

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