Need for liver evaluation in polycystic ovary syndrome
2007; Elsevier BV; Volume: 47; Issue: 3 Linguagem: Inglês
10.1016/j.jhep.2007.06.009
ISSN1600-0641
Autores Tópico(s)Ovarian function and disorders
ResumoMedicine is changing and requires a more in-depth knowledge also in fields that were previously considered completely different and dedicated to other specialists. A good example of this general trend is the paper by Cerda et al. [[1]Cerda C. Pérez-Ayuso R.M. Riquelme A. Soza A. Villaseca P. Sir-Petermann T. et al.Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.J Hepatol. 2007; 47: 412-417Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar] that shows a high prevalence of nonalcoholic fatty liver disease (NAFLD) in women with Polycystic Ovary Syndrome (PCOS). The authors studied 41 young women with PCOS and found that 17 patients (41%) had NAFLD. In addition, 7 patients with NAFLD had increased aminotransferase levels raising the possibility of a transition to nonalcoholic steatohepatitis (NASH).Other reports have shown similar data recently [2Brown A.J. Tendler D.A. McMurray R.G. Setji T.L. Polycystic ovary syndrome and severe nonalcoholic steatohepatitis: beneficial effect of modest weight loss and exercise on liver biopsy findings.Endocr Pract. 2005; 11: 319-334Crossref PubMed Scopus (46) Google Scholar, 3Schwimmer J.B. Khorram O. Chiu V. Schwimmer W.B. Abnormal aminotransferase activity in women with polycystic ovary syndrome.Fertil Steril. 2005; 83: 494-497Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 4Setji T.L. Holland N.D. Sanders L.L. Pereira K.C. Diehl A.M. Brown A.J. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2006; 91: 1741-1747Crossref PubMed Scopus (178) Google Scholar, 5Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. It is time therefore that doctors caring for patients with liver diseases start to collaborate with the specialists (gynecologists, endocrinologists), who generally treat patients with PCOS and vice versa.1. PCOS: a common disorder in young womenIn the past, PCOS was considered an uncommon disorder determining infertility in some particular women who also were obese and hirsute [[6]Stein I. Leventhal M. Amenorrhoea associated with bilateral polycystic ovaries.Am J Obstet Gynecol. 1935; 29: 181-185Crossref Google Scholar]. However, after well-defined diagnostic criteria (chronic anovulation and clinical or androgen excess) were established [[7]Zawdaki J.K. Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rationale approach.in: Dunaif A. Givens J.R. Haseltine F. Merriam G.R. Polycystic Ovary Syndrome. Blackwell Scientific Publications, Boston, Mass1992: 377-384Google Scholar], it has emerged that the syndrome is very common and in all epidemiological studies its prevalence has ranged between 5 and 7% of premenopausal women [8Knochenhauer E.S. Key T.J. Kahsar-Miller W. Waggoner W. Boots L.R. Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the south-eastern USA: a prospective study.J Clin Endocrinol Metab. 1998; 83: 3078-3082Crossref PubMed Scopus (1496) Google Scholar, 9Diamanti-Kandarakis E. Kouli C.R. Bergiele A.T. Filandra A. Tsianateli T.C. Spina G.G. et al.A survey of polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.J Clin Endocrinol Metab. 1999; 84: 4006-4011Crossref PubMed Google Scholar]. New, more extensive diagnostic criteria have been adopted [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar] and PCOS may be diagnosed in patients with ovulatory cycles who have hyperandrogenism (clinical or biologic) and polycystic ovaries (ESHRE/ASRM and AES criteria) (Table 1) and in patients who have chronic anovulation, polycystic ovaries but no androgen excess (ESHRE/ASRM criteria) [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar], too. Using these new criteria, prevalence of PCOS is still higher and probably near 10% of young women [[12]Carmina E. The spectrum of androgen excess disorders.Fertil Steril. 2006; 85: 1582-1585Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar].Table 1Androgen excess society criteria for diagnosis of PCOSHyperandrogenism Clinical (hirsutism, or acne or androgenic alopecia)or Biological (increased serum testosterone or free androgen index or dehydroepiandrosterone sulfate)+Chronic anovulation (oligomenorrhea or amenorrhea or normal menses with low serum progesterone level in day 22–24 of the cycle)orPolycystic ovaries at the ultrasound (US finding of at least 12 follicles of 2–9 mm in a whole ovary and/or increased ovarian volume) Open table in a new tab 2. PCOS: an important cause of metabolic syndrome in young womenThe interest in PCOS has markedly increased after the finding that insulin resistance [[13]Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis.Endocr Rev. 1997; 18: 774-800Crossref PubMed Scopus (2250) Google Scholar] and abdominal obesity [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar] are essential features of the syndrome. Because of these characteristics, a large number of women with PCOS present with metabolic syndrome. In the USA, metabolic syndrome affects 40–50% of women with PCOS [15Glueck C.J. Papanna R. Wang P. Goldenberg N. Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome.Metabolism. 2003; 52: 908-915Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 16Apridonidze T. Essah P. Iuorno M. Nestler J.E. Prevalence and characteristics of metabolic syndrome in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2005; 90: 1929-1935Crossref PubMed Scopus (718) Google Scholar] with a prevalence that is about 7 times that of the female population of similar age. In Mediterranean countries (Italy), mostly because of differences in body weight [[17]Carmina E. Legro R.S. Stamets K. Lowell J. Lobo R.A. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet.Hum Reprod. 2003; 11: 2289-2293Crossref Scopus (148) Google Scholar], metabolic syndrome in PCOS is less common than in USA but still four times more common than in the young female population [[18]Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar]. In addition, even when metabolic syndrome is not found, a constellation of single metabolic and cardiovascular risk factors (LDL-cholesterol, HDL-cholesterol, triglycerides, C-reactive proteins, homocysteine) is found in most patients [18Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar, 19Carmina E. Longo R.A. Rini G.B. Lobo R.A. Phenotypic variation in hyperandrogenic women influences the finding of abnormal metabolic and cardiovascular risk parameters.J Clin Endocrinol Metab. 2005; 90: 2545-2549Crossref PubMed Scopus (220) Google Scholar] indicating that almost all women with PCOS present some metabolic alteration. All these data suggest that PCOS is the most common cause of metabolic syndrome and related disorders in young women.3. PCOS and liver diseasesObesity but in particular metabolic syndrome seems to be the main cause of NAFLD [20ClarK J.M. Brancati F.L. Diehl A.M. Nonalcoholic fatty liver diseases.Gastroenterology. 2002; 122: 1649-1687Abstract Full Text Full Text PDF PubMed Scopus (757) Google Scholar, 21Hamaguchi M. Kojima T. Takeda N. Nakagawa T. Taniguchi H. Fujii K. et al.The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.Ann Intern Med. 2005; 143: 722-728Crossref PubMed Scopus (836) Google Scholar]. In addition, the single components of metabolic syndrome are very common in patients with fatty liver: low HDL-cholesterol levels and/or hypertriglyceridemia are found in more than 75% of patients with NAFLD [[22]Knobler H. Schattner A. Zhomiki T. Malnick S.D. Keter D. Lurie Y. et al.Fatty liver – an additional and treatable feature.QJM. 1999; 92: 73-79Crossref PubMed Google Scholar] while hypertension is an independent predictor for NASH [[23]Dixon J.B. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.Gastroeneterology. 2001; 121: 91-100Abstract Full Text PDF PubMed Scopus (1149) Google Scholar]. Therefore, it has been suggested that NAFLD has to be considered one element of the metabolic syndrome [[24]Perlemuter G. Bigorgne A. Cassard-Doulcier A.M. Naveau S. Nonalcoholic fatty liver disease: from pathogenesis to patient care.Nat Clin Pract Endocrinol Metab. 2007; 3: 458-469Crossref PubMed Scopus (82) Google Scholar].Because of the role of PCOS in determining metabolic syndrome in young women, it is not surprising that NAFLD is very common in patients with this ovarian disorder. In this issue, Cerda et al. [[1]Cerda C. Pérez-Ayuso R.M. Riquelme A. Soza A. Villaseca P. Sir-Petermann T. et al.Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.J Hepatol. 2007; 47: 412-417Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar] report that 41% of PCOS women present NAFLD. In other studies, the prevalence of NAFLD in women with PCOS was also higher (55%) [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar].Being PCOS the most common cause of metabolic syndrome in young women, it may be hypothesized that PCOS is an important cause of NAFLD in these subjects.However, the available data are still scarce and several issues regarding the association between PCOS and liver diseases need to be clarified. In particular, we need to know whether a screening for NAFLD is needed only in PCOS patients with the full metabolic syndrome or whether it has to be performed in patients having single characters of the syndrome, too. Because increased abdominal fat is present in 30–40% of normoweight women with PCOS [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar], we need to know whether NAFLD is increased in lean PCOS patients, too. It is probable because Gambarin-Gelwan et al. reported that 39% of PCOS patients with NAFLD were lean [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. Finally, because women with PCOS present increased inflammatory factors and altered adipokines, it has to be established whether PCOS patients with NAFLD are at higher risk for NASH.Until more data are available, we suggest to assess serum aminotransferase, GGT and alkalin phosphatase levels and to search for steatosis, at least by US examination, in all PCOS women having metabolic syndrome. On the contrary, in young women with NAFLD, the existence of PCOS should be always suspected and investigated. Medicine is changing and requires a more in-depth knowledge also in fields that were previously considered completely different and dedicated to other specialists. A good example of this general trend is the paper by Cerda et al. [[1]Cerda C. Pérez-Ayuso R.M. Riquelme A. Soza A. Villaseca P. Sir-Petermann T. et al.Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.J Hepatol. 2007; 47: 412-417Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar] that shows a high prevalence of nonalcoholic fatty liver disease (NAFLD) in women with Polycystic Ovary Syndrome (PCOS). The authors studied 41 young women with PCOS and found that 17 patients (41%) had NAFLD. In addition, 7 patients with NAFLD had increased aminotransferase levels raising the possibility of a transition to nonalcoholic steatohepatitis (NASH). Other reports have shown similar data recently [2Brown A.J. Tendler D.A. McMurray R.G. Setji T.L. Polycystic ovary syndrome and severe nonalcoholic steatohepatitis: beneficial effect of modest weight loss and exercise on liver biopsy findings.Endocr Pract. 2005; 11: 319-334Crossref PubMed Scopus (46) Google Scholar, 3Schwimmer J.B. Khorram O. Chiu V. Schwimmer W.B. Abnormal aminotransferase activity in women with polycystic ovary syndrome.Fertil Steril. 2005; 83: 494-497Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 4Setji T.L. Holland N.D. Sanders L.L. Pereira K.C. Diehl A.M. Brown A.J. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2006; 91: 1741-1747Crossref PubMed Scopus (178) Google Scholar, 5Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. It is time therefore that doctors caring for patients with liver diseases start to collaborate with the specialists (gynecologists, endocrinologists), who generally treat patients with PCOS and vice versa. 1. PCOS: a common disorder in young womenIn the past, PCOS was considered an uncommon disorder determining infertility in some particular women who also were obese and hirsute [[6]Stein I. Leventhal M. Amenorrhoea associated with bilateral polycystic ovaries.Am J Obstet Gynecol. 1935; 29: 181-185Crossref Google Scholar]. However, after well-defined diagnostic criteria (chronic anovulation and clinical or androgen excess) were established [[7]Zawdaki J.K. Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rationale approach.in: Dunaif A. Givens J.R. Haseltine F. Merriam G.R. Polycystic Ovary Syndrome. Blackwell Scientific Publications, Boston, Mass1992: 377-384Google Scholar], it has emerged that the syndrome is very common and in all epidemiological studies its prevalence has ranged between 5 and 7% of premenopausal women [8Knochenhauer E.S. Key T.J. Kahsar-Miller W. Waggoner W. Boots L.R. Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the south-eastern USA: a prospective study.J Clin Endocrinol Metab. 1998; 83: 3078-3082Crossref PubMed Scopus (1496) Google Scholar, 9Diamanti-Kandarakis E. Kouli C.R. Bergiele A.T. Filandra A. Tsianateli T.C. Spina G.G. et al.A survey of polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.J Clin Endocrinol Metab. 1999; 84: 4006-4011Crossref PubMed Google Scholar]. New, more extensive diagnostic criteria have been adopted [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar] and PCOS may be diagnosed in patients with ovulatory cycles who have hyperandrogenism (clinical or biologic) and polycystic ovaries (ESHRE/ASRM and AES criteria) (Table 1) and in patients who have chronic anovulation, polycystic ovaries but no androgen excess (ESHRE/ASRM criteria) [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar], too. Using these new criteria, prevalence of PCOS is still higher and probably near 10% of young women [[12]Carmina E. The spectrum of androgen excess disorders.Fertil Steril. 2006; 85: 1582-1585Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar].Table 1Androgen excess society criteria for diagnosis of PCOSHyperandrogenism Clinical (hirsutism, or acne or androgenic alopecia)or Biological (increased serum testosterone or free androgen index or dehydroepiandrosterone sulfate)+Chronic anovulation (oligomenorrhea or amenorrhea or normal menses with low serum progesterone level in day 22–24 of the cycle)orPolycystic ovaries at the ultrasound (US finding of at least 12 follicles of 2–9 mm in a whole ovary and/or increased ovarian volume) Open table in a new tab In the past, PCOS was considered an uncommon disorder determining infertility in some particular women who also were obese and hirsute [[6]Stein I. Leventhal M. Amenorrhoea associated with bilateral polycystic ovaries.Am J Obstet Gynecol. 1935; 29: 181-185Crossref Google Scholar]. However, after well-defined diagnostic criteria (chronic anovulation and clinical or androgen excess) were established [[7]Zawdaki J.K. Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rationale approach.in: Dunaif A. Givens J.R. Haseltine F. Merriam G.R. Polycystic Ovary Syndrome. Blackwell Scientific Publications, Boston, Mass1992: 377-384Google Scholar], it has emerged that the syndrome is very common and in all epidemiological studies its prevalence has ranged between 5 and 7% of premenopausal women [8Knochenhauer E.S. Key T.J. Kahsar-Miller W. Waggoner W. Boots L.R. Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the south-eastern USA: a prospective study.J Clin Endocrinol Metab. 1998; 83: 3078-3082Crossref PubMed Scopus (1496) Google Scholar, 9Diamanti-Kandarakis E. Kouli C.R. Bergiele A.T. Filandra A. Tsianateli T.C. Spina G.G. et al.A survey of polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.J Clin Endocrinol Metab. 1999; 84: 4006-4011Crossref PubMed Google Scholar]. New, more extensive diagnostic criteria have been adopted [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar] and PCOS may be diagnosed in patients with ovulatory cycles who have hyperandrogenism (clinical or biologic) and polycystic ovaries (ESHRE/ASRM and AES criteria) (Table 1) and in patients who have chronic anovulation, polycystic ovaries but no androgen excess (ESHRE/ASRM criteria) [10Rotterdam 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.Google Scholar, 11Azziz R. Carmina E. Dewailly D. Diamanti-Kandarakis E. Escobar-Morreale H.F. Futterweit W. 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: 4237-4245Crossref PubMed Scopus (1333) Google Scholar], too. Using these new criteria, prevalence of PCOS is still higher and probably near 10% of young women [[12]Carmina E. The spectrum of androgen excess disorders.Fertil Steril. 2006; 85: 1582-1585Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar]. 2. PCOS: an important cause of metabolic syndrome in young womenThe interest in PCOS has markedly increased after the finding that insulin resistance [[13]Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis.Endocr Rev. 1997; 18: 774-800Crossref PubMed Scopus (2250) Google Scholar] and abdominal obesity [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar] are essential features of the syndrome. Because of these characteristics, a large number of women with PCOS present with metabolic syndrome. In the USA, metabolic syndrome affects 40–50% of women with PCOS [15Glueck C.J. Papanna R. Wang P. Goldenberg N. Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome.Metabolism. 2003; 52: 908-915Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 16Apridonidze T. Essah P. Iuorno M. Nestler J.E. Prevalence and characteristics of metabolic syndrome in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2005; 90: 1929-1935Crossref PubMed Scopus (718) Google Scholar] with a prevalence that is about 7 times that of the female population of similar age. In Mediterranean countries (Italy), mostly because of differences in body weight [[17]Carmina E. Legro R.S. Stamets K. Lowell J. Lobo R.A. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet.Hum Reprod. 2003; 11: 2289-2293Crossref Scopus (148) Google Scholar], metabolic syndrome in PCOS is less common than in USA but still four times more common than in the young female population [[18]Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar]. In addition, even when metabolic syndrome is not found, a constellation of single metabolic and cardiovascular risk factors (LDL-cholesterol, HDL-cholesterol, triglycerides, C-reactive proteins, homocysteine) is found in most patients [18Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar, 19Carmina E. Longo R.A. Rini G.B. Lobo R.A. Phenotypic variation in hyperandrogenic women influences the finding of abnormal metabolic and cardiovascular risk parameters.J Clin Endocrinol Metab. 2005; 90: 2545-2549Crossref PubMed Scopus (220) Google Scholar] indicating that almost all women with PCOS present some metabolic alteration. All these data suggest that PCOS is the most common cause of metabolic syndrome and related disorders in young women. The interest in PCOS has markedly increased after the finding that insulin resistance [[13]Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis.Endocr Rev. 1997; 18: 774-800Crossref PubMed Scopus (2250) Google Scholar] and abdominal obesity [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar] are essential features of the syndrome. Because of these characteristics, a large number of women with PCOS present with metabolic syndrome. In the USA, metabolic syndrome affects 40–50% of women with PCOS [15Glueck C.J. Papanna R. Wang P. Goldenberg N. Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome.Metabolism. 2003; 52: 908-915Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 16Apridonidze T. Essah P. Iuorno M. Nestler J.E. Prevalence and characteristics of metabolic syndrome in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2005; 90: 1929-1935Crossref PubMed Scopus (718) Google Scholar] with a prevalence that is about 7 times that of the female population of similar age. In Mediterranean countries (Italy), mostly because of differences in body weight [[17]Carmina E. Legro R.S. Stamets K. Lowell J. Lobo R.A. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet.Hum Reprod. 2003; 11: 2289-2293Crossref Scopus (148) Google Scholar], metabolic syndrome in PCOS is less common than in USA but still four times more common than in the young female population [[18]Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar]. In addition, even when metabolic syndrome is not found, a constellation of single metabolic and cardiovascular risk factors (LDL-cholesterol, HDL-cholesterol, triglycerides, C-reactive proteins, homocysteine) is found in most patients [18Carmina E. Napoli N. Longo R.A. Rini G.B. Lobo R.A. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS.Eur J Endocrinol. 2006; 154: 141-145Crossref PubMed Scopus (164) Google Scholar, 19Carmina E. Longo R.A. Rini G.B. Lobo R.A. Phenotypic variation in hyperandrogenic women influences the finding of abnormal metabolic and cardiovascular risk parameters.J Clin Endocrinol Metab. 2005; 90: 2545-2549Crossref PubMed Scopus (220) Google Scholar] indicating that almost all women with PCOS present some metabolic alteration. All these data suggest that PCOS is the most common cause of metabolic syndrome and related disorders in young women. 3. PCOS and liver diseasesObesity but in particular metabolic syndrome seems to be the main cause of NAFLD [20ClarK J.M. Brancati F.L. Diehl A.M. Nonalcoholic fatty liver diseases.Gastroenterology. 2002; 122: 1649-1687Abstract Full Text Full Text PDF PubMed Scopus (757) Google Scholar, 21Hamaguchi M. Kojima T. Takeda N. Nakagawa T. Taniguchi H. Fujii K. et al.The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.Ann Intern Med. 2005; 143: 722-728Crossref PubMed Scopus (836) Google Scholar]. In addition, the single components of metabolic syndrome are very common in patients with fatty liver: low HDL-cholesterol levels and/or hypertriglyceridemia are found in more than 75% of patients with NAFLD [[22]Knobler H. Schattner A. Zhomiki T. Malnick S.D. Keter D. Lurie Y. et al.Fatty liver – an additional and treatable feature.QJM. 1999; 92: 73-79Crossref PubMed Google Scholar] while hypertension is an independent predictor for NASH [[23]Dixon J.B. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.Gastroeneterology. 2001; 121: 91-100Abstract Full Text PDF PubMed Scopus (1149) Google Scholar]. Therefore, it has been suggested that NAFLD has to be considered one element of the metabolic syndrome [[24]Perlemuter G. Bigorgne A. Cassard-Doulcier A.M. Naveau S. Nonalcoholic fatty liver disease: from pathogenesis to patient care.Nat Clin Pract Endocrinol Metab. 2007; 3: 458-469Crossref PubMed Scopus (82) Google Scholar].Because of the role of PCOS in determining metabolic syndrome in young women, it is not surprising that NAFLD is very common in patients with this ovarian disorder. In this issue, Cerda et al. [[1]Cerda C. Pérez-Ayuso R.M. Riquelme A. Soza A. Villaseca P. Sir-Petermann T. et al.Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.J Hepatol. 2007; 47: 412-417Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar] report that 41% of PCOS women present NAFLD. In other studies, the prevalence of NAFLD in women with PCOS was also higher (55%) [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar].Being PCOS the most common cause of metabolic syndrome in young women, it may be hypothesized that PCOS is an important cause of NAFLD in these subjects.However, the available data are still scarce and several issues regarding the association between PCOS and liver diseases need to be clarified. In particular, we need to know whether a screening for NAFLD is needed only in PCOS patients with the full metabolic syndrome or whether it has to be performed in patients having single characters of the syndrome, too. Because increased abdominal fat is present in 30–40% of normoweight women with PCOS [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar], we need to know whether NAFLD is increased in lean PCOS patients, too. It is probable because Gambarin-Gelwan et al. reported that 39% of PCOS patients with NAFLD were lean [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. Finally, because women with PCOS present increased inflammatory factors and altered adipokines, it has to be established whether PCOS patients with NAFLD are at higher risk for NASH.Until more data are available, we suggest to assess serum aminotransferase, GGT and alkalin phosphatase levels and to search for steatosis, at least by US examination, in all PCOS women having metabolic syndrome. On the contrary, in young women with NAFLD, the existence of PCOS should be always suspected and investigated. Obesity but in particular metabolic syndrome seems to be the main cause of NAFLD [20ClarK J.M. Brancati F.L. Diehl A.M. Nonalcoholic fatty liver diseases.Gastroenterology. 2002; 122: 1649-1687Abstract Full Text Full Text PDF PubMed Scopus (757) Google Scholar, 21Hamaguchi M. Kojima T. Takeda N. Nakagawa T. Taniguchi H. Fujii K. et al.The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.Ann Intern Med. 2005; 143: 722-728Crossref PubMed Scopus (836) Google Scholar]. In addition, the single components of metabolic syndrome are very common in patients with fatty liver: low HDL-cholesterol levels and/or hypertriglyceridemia are found in more than 75% of patients with NAFLD [[22]Knobler H. Schattner A. Zhomiki T. Malnick S.D. Keter D. Lurie Y. et al.Fatty liver – an additional and treatable feature.QJM. 1999; 92: 73-79Crossref PubMed Google Scholar] while hypertension is an independent predictor for NASH [[23]Dixon J.B. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.Gastroeneterology. 2001; 121: 91-100Abstract Full Text PDF PubMed Scopus (1149) Google Scholar]. Therefore, it has been suggested that NAFLD has to be considered one element of the metabolic syndrome [[24]Perlemuter G. Bigorgne A. Cassard-Doulcier A.M. Naveau S. Nonalcoholic fatty liver disease: from pathogenesis to patient care.Nat Clin Pract Endocrinol Metab. 2007; 3: 458-469Crossref PubMed Scopus (82) Google Scholar]. Because of the role of PCOS in determining metabolic syndrome in young women, it is not surprising that NAFLD is very common in patients with this ovarian disorder. In this issue, Cerda et al. [[1]Cerda C. Pérez-Ayuso R.M. Riquelme A. Soza A. Villaseca P. Sir-Petermann T. et al.Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.J Hepatol. 2007; 47: 412-417Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar] report that 41% of PCOS women present NAFLD. In other studies, the prevalence of NAFLD in women with PCOS was also higher (55%) [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. Being PCOS the most common cause of metabolic syndrome in young women, it may be hypothesized that PCOS is an important cause of NAFLD in these subjects. However, the available data are still scarce and several issues regarding the association between PCOS and liver diseases need to be clarified. In particular, we need to know whether a screening for NAFLD is needed only in PCOS patients with the full metabolic syndrome or whether it has to be performed in patients having single characters of the syndrome, too. Because increased abdominal fat is present in 30–40% of normoweight women with PCOS [[14]Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Di Fede G, Rini GB. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab, published online 2007, April 3.Google Scholar], we need to know whether NAFLD is increased in lean PCOS patients, too. It is probable because Gambarin-Gelwan et al. reported that 39% of PCOS patients with NAFLD were lean [[5]Gambarin-Gelwan M. Kinkhabwala S.V. Schiano T.D. Bodian C. Yeh H.C. Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.Clin Gastroenterol Hepatol. 2007; 5: 496-501Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. Finally, because women with PCOS present increased inflammatory factors and altered adipokines, it has to be established whether PCOS patients with NAFLD are at higher risk for NASH. Until more data are available, we suggest to assess serum aminotransferase, GGT and alkalin phosphatase levels and to search for steatosis, at least by US examination, in all PCOS women having metabolic syndrome. On the contrary, in young women with NAFLD, the existence of PCOS should be always suspected and investigated.
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