Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is typically first identified during the early reproductive years. The PCOS diagnosis is made if two of the three following criteria are presented: a) hyperandrogenism (either clinical or biochemical); b) ovulatory dysfunction and c) the presence of polycystic ovaries and if other disorders that mimic the clinical features of PCOS are excluded¹. These include: thyroid disease, hyperprolactinemia and non-classic congenital adrenal hyperplasia (21-hydroxylase deficiency)². Other disorders, such as  hyperinsulinemia, metabolic syndrome and obesity, are common features of this syndrome^3-5.

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PCOS is the most common endocrine disorder in women. Based on the National Institute of Health criteria, the prevalence of PCOS is between 6 and 10%. However, when the broader Rotterdam criteria are applied², prevalence can be as high as 15%.

PCOS is a low-grade chronic inflammation condition with cytokines such as TNF-a and polymerase chain reaction (PCR)are increased in this population⁶.  In patients with PCOS, several inflammatory markers are overproduced and are strongly associated with insulin resistance (IR)^6-9. Although, its aetiology remains obscure², IR with accompanying compensatory hyperinsulinemia seems to play a pathophysiological role in the development of this syndrome¹⁰.

Typically, the ovaries in patients with PCOS are two to five times the normal size. A cross-section of the surface of the ovary  shows a white, thickened cortex with multiple cysts that are typically less than a centimetre in diameter. The superficial cortex is fibrotic and hypocellular and may contain prominent blood vessels¹¹.

Ultrasonography is fundamental to make a diagnose of ovarian polycystic ovary (PCO). According to Rotterdam criteria¹, the PCO morphology is defined by the presence of 12 or more follicles measuring 2–9 mm in diameter in each ovary and/or increased ovarian volume (>10 mL).

Usually, a polycystic ovary is described as an enlarged ovary with many antral follicles (≥12) distributed under the cortex and with a central stromal echogenicity¹². Increased ovarian blood flow (reduced pulsatility index and reduced resistance index) is another representative characteristic of the PCO¹³.

However, other ultrasound features can be helpful to recognized an polycystic ovary^14,15 including number of antral follicle >25, stromal index and stromal to ovarian area ratio (S/A).

Recently, Lujan et al¹⁴ revisited the Rotterdam ultrasonographic criteria for PCOS. They concluded that a threshold follicle count throughout the entire ovary of 26 follicles had the best compromise between sensitivity (85%) and specificity (94%) when discriminating between controls and PCOS.

The relative proportion between the stroma and the ovarian surface area in the median section (S/A ratio) was first described by Fulghesu¹⁵ as a sensitive ultrasound marker for PCO.  The author reported that PCOS patients had significantly higher ovarian area, stroma and mean S/A ratio when compared to those with  multi-follicular features and control groups. Cut-off values had been defined for area (7.00 cm²), stroma (1.95 cm²) and S/A ratio (0.34). The sensitivity for PCOS diagnosis was 4%, 62% and 100% respectively. They concluded that the evaluation of the S/A ratio could differentiate between PCOS and control or multi-follicular women with both a sensitivity and a specificity of 100%.

These ultrasound characteristics of PCO have been related to clinical and biochemical parameters frequently associated to PCOS. Follicle counts and small follicles (3–4 mm) were positively associated with androgens, stromal echogenicity was positively associated with free testosterone and ovarian volume was positively related to systolic blood pressure and insulina^12,13. Blood flow was positively associated with testosterone^13,16 and S/A (cut-off=0.32) was positively related with androstenedione and testosterone¹⁷.

These findings suggest that ultrasound features may predict clinical features in PCOS patients.

Almost 70 % of the symptomatic patients report hirsutism and acne caused by excessive ovarian production of androstenedione and testosterone. Hirsutism is evaluated using the Ferriman-Gallwey map scoring system¹⁸. Clinical acne is defined by a history of persistent acne (presence of acne on most days for at least 3 years) and presence of more than 10 inflammatory acne lesions¹⁹. Most of the patients report irregular menstrual cycles, in particular oligomenorrhea, which is defined by <8 spontaneous menstrual cycles per year for at least 3 years²⁰.

Other clinical features, such as obesity, hyperinsulinemia, non-alcoholic fatty liver disease (NAFLD) are also often presented in this population.

PCOS patients present a risk to develop IR and non-alcoholic fatty liver disease. Therefore,all women with PCOS diagnosis should perform an oral glucose tolerance test (OGTT; 75 g of glucose)²¹ in order to evaluate and treat the patients with hyperinsulinemia. Moreover, a liver ultrasound scan should be considered for all hyperinsulinemic overweight women, who have a high risk to develop a NAFLD²².

1. 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;81:19–25.

2. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012;97:28–38.

3. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011;7:219–31.

4. Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998;83:2694–2698.

5. Hudecova M, Holte J, Olovsson M, Larsson A, Berne C, Sundstrom- Poromaa I. Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up. Fertil Steril 2011;96:1271–1274.

6. Repaci A, Gambineri A, Pasquali R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 2011;335:30–41.

7. Miele L, Vallone S, Cefalo C, La Torre G, Di Stasi C, Vecchio FM, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:778–786.

8. Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 2002;106:24–30.

9. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793–1801.

10. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165–1174.

11. Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition, New Delhi, Wolter Kluwer, 2012 pp1075 to 1090.

12. Christ JP, Vanden Brink H, Brooks ED, Pierson RA, Chizen DR, Lujan ME . Ultrasound features of polycystic ovaries relate to degree of reproductive and metabolic disturbance in polycystic ovary syndrome. Fertil Steril 2015;103:787-794

13. Carmina E, Orio F, Palomba S, Longo RA, Lombardi G, Lobo RA. Ovarian size and blood flow in women with polycystic ovary syndrome (PCOS) and their correlations with some endocrine parameters. Fertil Steril 2005;84:413-419.

14. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, Haider E, Pierson RA, Chizen DR. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013; 28:1361-1368.

15. Fulghesu AM, Ciampelli M, Belosi C, Apa R, Pavone V, Lanzone A. A new ultrasound criterion for the diagnosis of polycystic ovary syndrome: the ovarian stroma/total area ratio. Fertil Steril 2001;76:326-231.

16. Carmina E, Campagna AM, Fruzzetti F, Lobo RA. AMH measurement versus ovarian ultrasound in the diagnosis of polycystic ovary syndrome (PCOS) in different phenotypes. Endocr Pratic 2016;22:287-293.

17. Fulghesu AM, Angioni S, Frau E, Belosi C, Apa R, Mioni R, Xamin N, Capobianco GP, Dessole S, Fruzzetti F, Lazzarini V, Minerba L, Melis GB, Lanzone A. Ultrasound in polycystic ovary syndrome—the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study. Hum Repord 2007;22:2501-2508.

18. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440–1447.

19. Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol 2005;141:333–338.

20. Moro F, De Simone C, Morciano A, Tropea A, Sagnella F, Palla C, Scarinci E, Teti A, Caldarola G, D’Agostino M, Mancuso S, Lanzone A, Apa R. Psoriatic patients have an increased risk of polycystic ovary syndrome: results of a cross-sectional analysis. Fertil Steril 2013;99:936–942.

21. Ciampelli M, Leoni F, Cucinelli F, Mancuso S, Panunzi S, De Gaetano A, et al. Assessment of insulin sensitivity from measurements in the fasting state and during an oral glucose tolerance test in polycystic ovary syndrome and menopausal patients. J Clin Endocrinol Metab 2005;90:1398–1406.

22. Gangale MF, Miele L, Lanzone A, Sagnella F, Martinez D, Tropea A, Moro F, Morciano A, Ciardulli A, Palla C, Pompili M, Cefalo C, Grieco A, Apa R. Long-term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome. Clin Endocrinol (Oxf) 2011;75:520–527.

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