SEPTEMBER: PCOS Awareness Month

Polycystic ovary syndrome (PCOS) represents one of the most common female endocrinological disorders. World Health Organization (WHO) has estimated that PCOS affected 116 million women (3.4%) worldwide in 2012.

 Globally, prevalence estimates of PCOS are highly variable, ranging from 2.2% to as high as 26%. The prevalence of PCOS depends on the choice of diagnostic criteria.

The difficulty in agreeing on the diagnostic criteria of PCOS is related to the intrinsic characteristics of the syndrome: heterogeneity of symptoms, the variability of these in the different age groups, lack of overlapping biochemical parameters and cut-offs shared, useful in the clinical practice.

PCOS is, in fact, a very complex dysfunction involving the hypothalamus, the pituitary gland, ovaries, adrenal gland and peripheral adipose tissue all contribute creating an imbalance generally associated with three characteristic symptoms: oligo-anovulation, hirsutism and infertility.

Unfortunately, since the onset of PCOS is the result of a complex series of alterations of physiological mechanisms, we do not always see its full expression, that is, not necessarily all the symptoms and clinical signs of the pathology as described by Stein and Leventhal in 1935.

 DIAGNOSIS CRITERIA

In 1990 in Bethesda, following the National Institute of Health / National Conference Institute of Child and Human Development (NIH / NICHD), were established the criteria for the diagnosis of PCOS:

  • anovulation;
  • hyperandrogenism confirmed by clinical signs or laboratory evidence;
  • exclusion of other causes of hyperandrogenism.

For the researchers the diagnosis of PCOS can largely be considered a diagnosis of exclusion: they must, in fact, all those disorders characterized by an excess of androgens are excluded o ovulatory disorders with clearly defined causes: 21-hydroxylase deficiency which is observed in non-classical adrenal hyperplasia (NCAH) and which affects 1-10% shaggy women; Cushing’s syndrome with hyperandrogenic features adrenal carcinomas; ovarian and other adrenal androgenic neoplasms secreting, present in 1: 300-1000 androgenized women; exogenous anabolic drugs, the prevalence of which is unknown, but which generally falls only within the minor androgenization.

Many authors also exclude disorders that can lead to ovulatory dysfunction such as thyroid dysfunction and hyperprolactinemia or hypothalamic amenorrhea, the prevalence of which is of the order of 1-3%.
Other characteristics present in women with PCOS, such as obesity (found in 30-60% of patients, depending on ethnic differences), insulin resistance and hyperinsulinemia (present in 50-70%), and the LH / FSH ratio> 2 or 3 (frequency of 30-50%).

However, these last two characteristics were not included in the diagnostic criteria proposed, as both are present in other types of disorders.

In 2003 in Rotterdam the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) drawn up a consensus document which establishes universally applicable criteria for a diagnostic process standard of Polycystic Ovary Syndrome.

According to Rotterdam criteria, the diagnosis of PCOS can be done in patients who have at least 2 of the following 3 criteria:

  • Oligo-anovulation;
  • Hyperandrogenism (clinical or biochemical);
  • Presence of 12 or more follicles with a diameter of 2 ± 9 mm in each ovary, and/or increase in ovarian volume (> 10 ml).

Also, in this case, all those disorders characterized by excess must be excluded from androgenic or ovulatory disorders with clearly recognized causes.

Based on these criteria it is possible to identify four main phenotypes of PCOS:

  1. Classic PCOS phenotype I: Hyperandrogenism, chronic anovulation, polycystic ovaries
  2. Classical PCOS phenotype II: Hyperandrogenism, chronic anovulation and morphologically normal ovaries;
  3. Ovulatory PCOS phenotype III; Hyperandrogenism, polycystic ovaries, presence of ovulatory cycles
  4. PCOS normoandrogenic phenotype IV: Chronic anovulation, polycystic ovaries, no signs of hyperandrogenism.

In 2004, the Expert Committee of Androgen Excess PCOS Society (EPCOS) found it would be more correct to include only the first three phenotypes thus implying necessity the presence of hyperandrogenism for the definition of PCOS.

PCOS AND INSULIN RESISTANCE

Insulin resistance is another metabolic characteristic frequently associated with PCOS.

In PCOS there is often an excess of insulin production by the pancreas, excess which is a serious risk factor for the onset of non-insulin diabetes dependent (NIDDM). Hyperinsulinemia would provide a significant contribution to the premature arrest of the growth of the follicle, a characteristic event of PCOS anovulation. The last evidence showed that ovary never becomes insulin-resistance, it means that it continues responding to insulin and this hyper response worsts the ovarian functionality.

Insulin resistance occurs in PCOS with higher prevalence in overweight and obese women (80%) but can affect also lean PCOS women (40%). In this case, the therapeutical approach needs to control insulin response before to work on the ovarian dysfunction.

SYMPTOMS AND AGE

More and more evidence demonstrated that PCOS involves the woman’s “whole life”: it begins in intrauterine life in subjects genetically predisposed, it manifests at the time of puberty and lasts into the fertile age and exposes, especially after menopause, to a higher risk of developing carcinoma endometrial, cardiovascular diseases, hypertension, type 2 diabetes mellitus.

For these reasons it is clear that a correct and early diagnosis of this syndrome is fundamental, as it allows to carry out the most suitable treatments and controls thus reducing the risk of developing all related complications.

In October 2010, the PCOS Consensus Workshop Group met in Amsterdam to make a point on today’s knowledge of the syndrome and the studies needed to clarify the points still unresolved. The peculiar feature of the work carried out was the new approach diagnosis based on a different identification of symptoms in function of the woman’s age.

PCOS AWARENESS MONTH

PCOS Awareness Month is a federally designated event. The aim of PCOS Awareness Month is to help improve the lives of those affected by PCOS and to help them to overcome their symptoms as well as prevent and reduce their risks for life-threatening related diseases such as diabetes, cardiovascular disease, nonalcoholic fatty liver disease and cancer.

Lo.Li.Pharma group has always been involved in PCOS diagnosis research and to offer these women a better therapeutic solution.

Today we want to invite you to join with us to support PCOS awareness.

REFERENCES

  1. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-191.
  2. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach.
    In: Dunaif A, Givens JR, Haseltine F, Merriam GR, eds. Polycystic ovary syndrome. Boston: Blackwell Scientific 1992; pp. 377-384.
  3. 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.
  4. Azziz R, Carmina E, Dewailly D, et al. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab 2006; 91: 4237-4245. Sample WF, Lippe BM, Gyepes
  5. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774-800.
  6. Nestler JE. Insulin regulation of human ovarian androgens. Human Reprod 1997; Suppl. 1: 53-62.
  7. Papaleo E, Unfer V, Baillargeon J P, Chiu TT. Contribution of myo-inositol to reproduction. Eur J Obstet Gynecol Reprod Biol. 2009; 147(2): 120-123.
  8. Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012; 27(1): 14-24.
  9. Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol 2010; 203: 201-205.
  10. Puurunen J, Piltonen T, Morin-Papunen L, Perheentupa A, Järvelä I, Ruokonen A, Tapanainen JS. Unfavorable hormonal, metabolic, and inflammatory alterations persist after menopause in women with PCOS. J Clin Endocrinol Metab. 2011; 96(6): 1827-1834.
  11. Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U. Insulin action and age. European Group for the Study of Insulin Resistance (EGIR). Diabetes. 1996; 45(7): 947-953.