This Article Abstract Full Text (PDF) All Versions of this Article: 91/3/781    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Azziz, R. Search for Related Content PubMed PubMed Citation Articles by Azziz, R. Related Collections Female Endocrinology

Diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, and Departments of Medicine and Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, California 90048

Address all correspondence and requests for reprints to: Dr. Ricardo Azziz, Department of Obstetrics and Gynecology and Center for Androgen-Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Suite 160W, Los Angeles, California 90048. E-mail: azzizr{at}cshs.org.

	Abstract

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
Context: Polycystic ovary syndrome (PCOS) is defined most commonly according to the proceedings of an expert conference sponsored by the National Institutes of Health (NIH) in April 1990, which noted the disorder as having 1) hyperandrogenism and/or hyperandrogenemia, 2) oligoovulation, and 3) exclusion of known disorders. Alternatively, another expert conference held in Rotterdam in May 2003 defined PCOS, after the exclusion of related disorders, by two of the following three features: 1) oligo- or anovulation, 2) clinical and/or biochemical signs of hyperandrogenism, or 3) polycystic ovaries. In essence, the Rotterdam 2003 expanded the NIH 1990 definition creating two new phenotypes: 1) ovulatory women with polycystic ovaries and hyperandrogenism, and 2) oligoanovulatory women with polycystic ovaries, but without hyperandrogenism.

Objective: The objective of this study was to ascertain the validity of using the Rotterdam 2003 criteria rather than the NIH 1991 criteria for the diagnosis of PCOS.

Intervention(s): Interventions included the use of the Rotterdam 2003 criteria for diagnosing PCOS and, in particular, the proposal to define two new phenotypes as PCOS.

Positions: Available data suggest that hyperandrogenic ovulatory women with polycystic ovaries tend to have mild insulin resistance and mild evidence of ovarian dysfunction, although significantly less than women with anovulatory PCOS. However, whether these women will have an increased risk of infertility or metabolic complications, such as type 2 diabetes, remains to be determined. Alternatively, the risk of insulin resistance and long-term metabolic risks of oligoovulatory women with polycystic ovaries is even less well characterized and may be nonexistent.

Conclusions: Because of the paucity of data on the two new phenotypes and their long-term implications and the potential negative impact on research, clinical practice, and patient insurability, the adoption of the Rotterdam 2003 criteria for defining PCOS should be considered premature. However, because polycystic ovaries are a frequent feature of PCOS, a modification of the NIH 1990 criteria is proposed. Additional research characterizing the phenotypes and associated morbidities of PCOS is urgently required.

	Introduction

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
IN 1935, in a seminal report, Stein and Leventhal (1) reported that polycystic ovaries, which had been initially described in 1844 by Chereau (2) and Rokitansky (3), were associated with amenorrhea. The heterogeneity of the syndrome was evident even at the initial description of seven women, with three of the women being obese, four hirsute (one obese), and one acneic. Thus began the description of a disorder that was eventually recognized as affecting as many as one in 15 reproductive-aged women (4) and to have significant reproductive, metabolic, and dermatological consequences.

	National Institutes of Health (NIH) 1990 Criteria for PCOS

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
The definition of PCOS most commonly used today arose from the proceedings of an expert conference sponsored by the NIH in April 1990 (i.e. NIH 1990 criteria). All those attending were queried regarding what they believed were diagnostic criteria of PCOS. Tabulation of the results indicated that 64%, 60%, 59%, 52%, and 48% thought that hyperandrogenemia, exclusion of other etiologies, exclusion of congenital adrenal hyperplasia (CAH), menstrual dysfunction, and clinical hyperandrogenism, respectively, were criteria that were definite or probable for the disorder (5). The proceeding then summarized these results into the following major research criteria (in order of importance): 1) hyperandrogenism and/or hyperandrogenemia, 2) oligoovulation, and 3) exclusion of known disorders, such as Cushing’s syndrome, hyperprolactinemia, and CAH (5) (Table 1). A fourth criterion, polycystic ovaries on ultrasound, was considered particularly controversial. In essence, the results of this expert conference identified PCOS as a disorder of ovarian androgen excess.

	Rotterdam 2003 Criteria for PCOS: Introducing Two New Phenotypes

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

We should note that the Rotterdam 2003 criteria did not replace the NIH 1990 criteria, because all women diagnosable by the NIH 1990 criteria would also meet the Rotterdam definition (Table 2). Rather, it expanded the definition of PCOS, adding two additional phenotypes as PCOS, including women with 1) polycystic ovaries and clinical and/or biochemical evidence of androgen excess, but without ovulatory dysfunction, and 2) polycystic ovaries and ovulatory dysfunction, but without hyperandrogenemia and/or hirsutism (i.e. no signs of androgen excess). To begin to determine whether these phenotypes truly represent PCOS, it is useful to review how syndromes are defined.

	Defining a Syndrome

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

First, we should note that PCOS is not the only disorder facing the dilemma of definition. Irritable bowel syndrome, systemic lupus erythematosus, antiphospholipid syndrome, fibromyalgia, chronic fatigue syndrome, and, more closely related to PCOS, the metabolic syndrome, are among the many disorders that are experiencing unclear and competing definitions. In fact, although the metabolic or insulin resistance syndrome was initially described in the late 1960s (9), today there are still at least six different diagnostic criteria in use (10, 11, 12, 13, 14, 15). Even the name of this syndrome has not been agreed upon. In comparison, the controversy surrounding the definition of PCOS appears almost trivial.

How are hard data used to define a syndrome and its phenotypic limits? By definition, a syndrome is of unknown etiology, at least when initially described, and this appears to be the case for PCOS. Consequently, we cannot define a syndrome as the collection of those phenotypes with a common underlying etiology. Alternatively, we can define a syndrome by its consequences or long-term impact or morbidity. For example, we define the metabolic syndrome as a symptom complex that results in an increased risk for cardiovascular disease (15). In this analysis, we should note that the features used in defining a syndrome should not also be used to determine its phenotypic limits. Consistent with this concept, in a joint statement from the American Diabetes Association and the European Association for the Study of Diabetes, Kahn et al. (15) did not consider previous publications whose focus was on the ability of the metabolic syndrome to predict type 2 diabetes mellitus (DM), because the definition of the syndrome already included glucose intolerance, a strong predictor of diabetes.

	Defining the Phenotypic Limits of the Syndrome of PCOS

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
The phenotypic limits of a syndrome can be defined by 1) identifying the specific phenotypes that may compose or be included in the syndrome, and 2) as discussed above, determining the long-term morbidity(s) that will be used as the phenotypic anchor. So, what long-term morbidity can we use to define PCOS? In a recent analysis of economic burden, we noted there is good evidence that PCOS is associated with increased risks for 1) menstrual dysfunction and abnormal uterine bleeding, 2) infertility, 3) type 2 DM, and 4) hirsutism (16). However, because hirsutism (i.e. clinical evidence of hyperandrogenism) and oligoanovulation (a strong predictor of menstrual dysfunction and infertility) are part of all current definitions of PCOS, these morbidities should probably not be considered when attempting to define the phenotypic limits and consequently the criterion for the definition. Alternatively, it may be possible to define PCOS by its increased risk for type 2 DM. It should be noted that the use of the risk of type 2 diabetes to identify the phenotypic limits of PCOS does not imply that that all women with PCOS, as defined, will develop type 2 DM, but that the phenotypic group as a whole will be at higher risk. It also is not meant to denote that this is the only or necessarily the most important of the morbidities, because these patients clearly suffer reproductive and dermatological consequences. Rather, type 2 DM is being used as a phenotypic anchor against which to measure each of the phenotypes.

How do the proposed phenotypes of PCOS relate to this morbidity? Considering the features of oligoanovulation, hirsutism and/or hyperandrogenemia, and polycystic ovaries, both the NIH 1990 and the Rotterdam 2003 criteria agree on two phenotypes (phenotypes A and B; Table 2), whereas Rotterdam 2003 defines an additional two phenotypes (phenotypes C and D; Table 2). Ample evidence is available to support the association of the two phenotypes included in both the NIH 1990 and the Rotterdam 2003 criteria (i.e. oligoanovulation, and hirsutism and/or hyperandrogenemia, with or without polycystic ovaries) with an increased risk for type 2 DM (17, 18, 19).

Alternatively, what is the evidence to support consideration of the two additional phenotypes proposed by the Rotterdam 2003 criteria (phenotypes C and D; Table 1) as PCOS? First, there is evidence that the sole presence of polycystic ovaries in women, observable in 20–30% of the population of reproductive-age women (20, 21, 22, 23, 24, 25), is associated with features reminiscent of those observed in patients with PCOS. The presence of polycystic ovaries is associated with mild elevations in circulating LH (21, 24, 26) and androgen (21, 24, 26, 27) levels and a higher prevalence of obesity and hirsutism (20, 21). Alternatively, there are conflicting data regarding the impact of polycystic ovaries on measures of insulin action (25, 27, 28, 29) and their association with impaired fertility (20, 26). Nonetheless, we should recognize that the majority of these studies were performed using older criteria for polycystic ovaries and often transabdominal ultrasonography, and the prevalence, specificity, and relevance of polycystic ovaries diagnosed by newer criteria (30) remain to be determined.

A limited number of investigators have specifically studied ovulatory women with polycystic ovaries and hyperandrogenism. Carmina and colleagues (31, 32) studied women with polycystic ovaries, clinical and/or biochemical hyperandrogenism, and normal ovulation and observed that these patients had higher circulating androgen and insulin levels and a greater 17-hydroxyprogesterone response to a long-acting GnRH analog compared with controls. However, the degrees of hyperinsulinism and hyperandrogenemia were significantly less than those observed in patients with PCOS defined by the NIH 1990 criteria. Furthermore, whether these individuals have an increased risk for developing metabolic complications, including type 2 DM, is not known.

There are even less data showing that women with polycystic ovaries and ovulatory dysfunction, but without clinical or biochemical evidence of hyperandrogenism, are at increased risk for type 2 DM, as are those patients with PCOS defined by the NIH 1990 criteria. Norman and colleagues (33) compared six women with polycystic ovaries, irregular menstrual cycles, and no hirsutism or hyperandrogenemia with 54 women with polycystic ovaries, irregular cycles, and hyperandrogenism. They did not observe significant differences between the groups in age, body mass, waist to hip ratio, total cholesterol, or integrated glucose or insulin responses to an oral glucose challenge, although this could be a reflection of the small number of subjects studied. Whether this group of patients is at risk for the development of metabolic complications, including DM, is also unknown.

Finally, we should note that many patients with ovulatory disorders other than PCOS also demonstrate polycystic ovarian morphology, including 21-hydroxylase-deficient nonclassical CAH (34, 35), bulimia and other eating disorders (36, 37), hyperprolactinemia (38), or functional hypothalamic amenorrhea (FHA) (38, 39). In addition, many adolescents transiently demonstrate polycystic-appearing ovaries (40, 41). Nonclassical CAH can be differentiated from PCOS by basal or stimulated 17-hydroxyprogesterone (42), and the medical history may be able to discern some of the patients with bulimia and other eating disorders. However, FHA is usually defined by a history of amenorrhea of at least 6-month duration; negative urinary pregnancy test; serum LH, FSH, TSH, prolactin, and androgen levels within the normal range; and LH to FSH ratio less than 2 (43). So how will FHA be differentiated from women with nonhyperandrogenic PCOS? Although it may be argued that patients with FHA and girls undergoing the pubertal transition actually demonstrate multicystic and not polycystic ovaries, comprehensive studies and distinguishing ultrasonographic criteria are generally lacking.

	Risks and Benefits of Considering the Two New Phenotypes Proposed by the Rotterdam 2003 Criteria as PCOS

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
What are the risks and benefits of accepting these two phenotypes and consequently the Rotterdam 2003 criteria as the new definition of PCOS? The negative impact of labeling the two new phenotypes proposed by the Rotterdam 2003 criteria (i.e. ovulatory women with polycystic ovaries and hyperandrogenism and, particularly, oligoanovulatory women with polycystic ovaries, but without hyperandrogenism) as PCOS can be significant. Although the proceedings of the Rotterdam 2003 conference acknowledged that the criteria were possibly not suitable for trials focusing on clinical outcomes in women with PCOS, the reality is that they are being used as such. Because these criteria increase the phenotypic heterogeneity of the disorder, their use will decrease the ability of genetic and other molecular studies to detect a common underlying abnormality. The use of these criteria also implies that we already understand the health risks of these newly proposed phenotypes far more than we do, potentially stifling future investigation. Importantly, the adoption of these criteria suggests to patients and their physicians that women with these new phenotypes are at increased risk for metabolic and cardiovascular consequences, as are patients with more classic forms of PCOS, despite the absence of data in this regard. Finally, these criteria have the potential of negatively affecting the insurability of patients who may have been prematurely labeled as having PCOS.

Alternatively, we should recognize that a finding of polycystic ovaries can predict the response to ovulation induction, because women with this ovarian morphology are more sensitive to gonadotropin stimulation than spontaneously cycling women, possibly as a result of the larger pool of small antral follicles available for recruitment (44). However, patient management need only be tailored to the ovarian morphology observed at the time of treatment and, consequently, does not require a previous diagnosis of PCOS.

	Conclusions

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 
Overall, when the available data are critically reviewed, the metabolic and possibly the reproductive implications of the two additional phenotypes proposed by the Rotterdam 2003 study are unclear and relatively poorly characterized. It should also be recognized that any differences from normal are modest at best. Finally, we should note that the numbers of studies examining these two new phenotypes and their fertility or metabolic consequence have been few and relatively small in number, and additional studies are needed to confirm these findings.

However, we recognize that emerging data indicate that patients with hyperandrogenism and polycystic ovaries, but apparently normal ovulation, demonstrate in vivo abnormalities of insulin action, albeit milder than those patients originally defined by the NIH 1990 criteria. These data suggest that this group of individuals may be at greater risk for the metabolic consequences, including type 2 DM, compared with healthy controls, although this remains to be confirmed. As such, and based on current evidence, it may be possible to expand the phenotypic limits of PCOS to include this group of women (Table 3) (45).

In conclusion, although it is clear that polycystic ovaries are a frequent feature of PCOS, the widespread adoption of the diagnostic criteria proposed in the 2003 Rotterdam meeting proceedings should be considered premature, particularly when assessing the available evidence, and may have unintended negative effects on research, clinical practice, and quality of life. However, this controversy does highlight the immediate and considerable need for additional investigation into PCOS and its associated phenotypes and morbidities. Considering that PCOS conservatively affects about one in 15 reproductive-age women and that the health care-related economic burden to the United States alone exceeds 4 billion annually (16), research in this area has been clearly insufficient. This is one priority that we can all agree on.

	Footnotes

 
First Published Online January 17, 2006

Abbreviations: CAH, Congenital adrenal hyperplasia; DM, diabetes mellitus; FHA, functional hypothalamic amenorrhea; PCOS, polycystic ovary syndrome.

This work was supported in part by National Institutes of Health Grant K24-HD-01346-01.

Received September 29, 2005.

Accepted December 23, 2005.

	References

Top Abstract Introduction National Institutes of Health... Rotterdam 2003 Criteria for... Defining a Syndrome Defining the Phenotypic Limits... Risks and Benefits of... Conclusions References

 

1. Stein IF, Leventhal ML 1935 Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 29:181–191
2. Chereau A 1844 Mémoires pour servir à l’étude des maladies des ovaires. Paris: Fortin, Masson, Cie
3. Rokitansky C 1844. A manual of pathological anatomy. Vol 2. Philadelphia: Blanchard, Lea, 1855:246 (tr. by Edward Sieveking from original German edition of 1844)
4. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO 2004 The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749[Abstract/Free Full Text]
5. Zawadzki JK, Dunaif A 1992 Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, eds. Polycystic ovary syndrome. Boston: Blackwell Scientific; 377–384
6. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25[Medline]
7. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47[Abstract/Free Full Text]
8. Crichton M 2003 Aliens Cause Global Warming. The Caltech Michelin Lecture, January 17, 2003. www.crichton-official.com/speeches/speeches_quote04.html
9. Avogaro P, Crepaldi G, Enzi G, Tiengo A 1967 Associazione di iperlidemia, diabete mellito e obesita di medio grado. Acto Diabetol Lat 4:36–41
10. World Health Organization 1999 Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO Consultation. Geneva: World Health Organization
11. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults 2001 Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497[Free Full Text]
12. Grundy SM, Brewer Jr HB, Cleeman JI, Smith Jr SC, Lenfant C, National Heart, Lung, and Blood Institute, American Heart Association 2004 Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438[Free Full Text]
13. Balkau B, Charles MA, Drivsholm T, Borch-Johnsen K, Wareham N, Yudkin JS, Morris R, Zavaroni I, van Dam R, Feskins E, Gabriel R, Diet M, Nilsson P, Hedblad B, European Group, Study of Insulin Resistance 2002 Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab 28:364–376[Medline]
14. Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, Hellman R, Jellinger PS, Kendall D, Krauss RM, Neufeld ND, Petak SM, Rodbard HW, Seibel JA, Smith DA, Wilson PW 2003 American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 9:237–252[Medline]
15. Kahn R, Buse J, Ferrannini E, Stern M 2005 The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28:2289–2304[Abstract/Free Full Text]
16. Azziz R, Marin C, Hoq L, Badamgarav E, Song P 2005 Economic burden of the polycystic ovary syndrome (PCOS) during the reproductive lifespan. J Clin Endocrinol Metab 90:4650–4658[Abstract/Free Full Text]
17. Legro RS, Kunselman AR, Dodson WC, Dunaif A 1999 Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84:165–169[Abstract/Free Full Text]
18. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J 1999 Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22:141–146[Abstract/Free Full Text]
19. Ehrmann DA, Kasza K, Azziz R, Legro RS, Ghazzi MN 2005 Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:66–71[Abstract/Free Full Text]
20. Clayton RN, Ogden V, Hodgkinson J, Worswick L, Rodin DA, Dyer S, Meade TW 1992 How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol (Oxf) 37:127–134[Medline]
21. Botsis D, Kassanos D, Pyrgiotis E, Zourlas PA 1995 Sonographic incidence of polycystic ovaries in a gynecological population. Ultrasound Obstet Gynecol 6:182–185[CrossRef][Medline]
22. Polson DW, Adams J, Wadsworth J, Franks S 1988 Polycystic ovaries–a common finding in normal women. Lancet 1:870–872[CrossRef][Medline]
23. Cresswell JL, Barker DJ, Osmond C, Egger P, Phillips DI, Fraser RB 1997 Fetal growth, length of gestation, and polycystic ovaries in adult life. Lancet 350:1131–1135[CrossRef][Medline]
24. Kousta E, White DM, Cela E, McCarthy MI, Franks S 1999 The prevalence of polycystic ovaries in women with infertility. Hum Reprod 14:2720–2723[Abstract/Free Full Text]
25. Michelmore K, Ong K, Mason S, Bennett S, Perry L, Vessey M, Balen A, Dunger D 2001 Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight. Clin Endocrinol (Oxf) 55:439–446[CrossRef][Medline]
26. Eden JA, Place J, Carter GD, Alaghband-Zadeh J, Pawson M 1989 Is the polycystic ovary a cause of infertility in the ovulatory woman? Clin Endocrinol (Oxf) 30:77–82[Medline]
27. Adams JM, Taylor AE, Crowley Jr WF, Hall JE 2004 Polycystic ovarian morphology with regular ovulatory cycles: insights into the pathophysiology of polycystic ovarian syndrome. J Clin Endocrinol Metab 89:4343–4350[Abstract/Free Full Text]
28. Legro RS, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A 2005 Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab 90:2571–2579[Abstract/Free Full Text]
29. Raskauskiene D, Jones PW, Govind A, Obhrai M, Clayton RN 2005 Do polycystic ovaries on ultrasound scan indicate decreased insulin sensitivity in sisters of women with polycystic ovary syndrome? J Clin Endocrinol Metab 90:2063–2067[Abstract/Free Full Text]
30. Jonard S, Robert Y, Dewailly D 2005 Revisiting the ovarian volume as a diagnostic criterion for polycystic ovaries. Hum Reprod 20:2893–2898[Abstract/Free Full Text]
31. Chang PL, Lindheim SR, Lowre C, Ferin M, Gonzalez F, Berglund L, Carmina E, Sauer MV, Lobo RA 2000 Normal ovulatory women with polycystic ovaries have hyperandrogenic pituitary-ovarian responses to gonadotropin-releasing hormone-agonist testing. J Clin Endocrinol Metab 85:995–1000[Abstract/Free Full Text]
32. Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA 2005 Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 90:2545–2549[Abstract/Free Full Text]
33. Norman RJ, Hague WM, Masters SC, Wang XJ 1995 Subjects with polycystic ovaries without hyperandrogenaemia exhibit similar disturbances in insulin and lipid profiles as those with polycystic ovary syndrome. Hum Reprod 10:2258–2261[Abstract/Free Full Text]
34. Dewailly D, Vantyghem-Haudiquet MC, Sainsard C, Buvat J, Cappoen JP, Ardaens K, Racadot A, Lefebvre J, Fossati P 1986 Clinical and biological phenotypes in late-onset 21-hydroxylase deficiency. J Clin Endocrinol Metab 63:418–423[Abstract]
35. Moran C, Azziz R 2003 21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender. Semin Reprod Med 21:295–300[CrossRef][Medline]
36. Jahanfar S, Eden JA, Nguyent TV 1995 Bulimia nervosa and polycystic ovary syndrome. Gynecol Endocrinol 9:113–117[Medline]
37. Morgan JF, McCluskey SE, Brunton JN, Hubert Lacey J 2002 Polycystic ovarian morphology and bulimia nervosa: a 9-year follow-up study. Fertil Steril 77:928–931[CrossRef][Medline]
38. Ardaens Y, Robert Y, Lemaitre L, Fossati P, Dewailly D 1991 Polycystic ovarian disease: contribution of vaginal endosonography and reassessment of ultrasonic diagnosis. Fertil Steril 55:1062–1068[Medline]
39. Futterweit W, Yeh HC, Mechanick JI 1988 Ultrasonographic study of ovaries of 19 women with weight loss-related hypothalamic oligo-amenorrhea. Biomed Pharmacother 42:279–283[Medline]
40. Giorlandino C, Gleicher N, Taramanni C, Vizzone A, Gentili P, Mancuso S, Forleo R 1989 Ovarian development of the female child and adolescent. I. Morphology. Int J Gynaecol Obstet 29:57–63[CrossRef][Medline]
41. Rosenfield RL, Ghai K, Ehrmann DA, Barnes RB 2000. Diagnosis of the polycystic ovary syndrome in adolescence: comparison of adolescent and adult hyperandrogenism. J Pediatr Endocrinol Metab 13(Suppl 5):1285–1289
42. Azziz R, Hincapie LA, Knochenhauer ES, Dewailly D, Fox L, Boots LR 1999 Screening for 21-hydroxylase deficient non-classic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril 72:915–925[CrossRef][Medline]
43. Berga SL, Daniels TL, Giles DE 1997 Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Fertil Steril 67:1024–1030[CrossRef][Medline]
44. Van Der Meer M, Hompes PG, De Boer JA, Schats R, Schoemaker J 1998 Cohort size rather than follicle-stimulating hormone threshold level determines ovarian sensitivity in polycystic ovary syndrome. J Clin Endocrinol Metab 83:423–426[Abstract/Free Full Text]
45. Azziz R 2005 Diagnostic criteria for polycystic ovary syndrome: a reappraisal. Fertil Steril 83:1343–1346[CrossRef][Medline]

This article has been cited by other articles:

				A. J. Cussons, G. F. Watts, V. Burke, J. E. Shaw, P. Z. Zimmet, and B. G.A. Stuckey Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome Hum. Reprod., July 16, 2008; (2008) den263v1. [Abstract] [Full Text] [PDF]

				S. K. BLANK, K. D. HELM, C. R. MCCARTNEY, and J. C. MARSHALL Polycystic Ovary Syndrome in Adolescence Ann. N.Y. Acad. Sci., June 1, 2008; 1135(1): 76 - 84. [Abstract] [Full Text] [PDF]

				S. Franks, J. Stark, and K. Hardy Follicle dynamics and anovulation in polycystic ovary syndrome Hum. Reprod. Update, May 22, 2008; (2008) dmn015v1. [Abstract] [Full Text] [PDF]

				S Cupisti, N Kajaia, R Dittrich, H Duezenli, M W Beckmann, and A Mueller Body mass index and ovarian function are associated with endocrine and metabolic abnormalities in women with hyperandrogenic syndrome Eur. J. Endocrinol., May 1, 2008; 158(5): 711 - 719. [Abstract] [Full Text] [PDF]

				N. Kajaia, H. Binder, R. Dittrich, P. G Oppelt, B. Flor, S. Cupisti, M. W Beckmann, and A. Mueller Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome Eur. J. Endocrinol., October 1, 2007; 157(4): 499 - 507. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, F. Alvarez-Blasco, J. I. Botella-Carretero, R. Sanchon, J. L. San Millan, and H. F. Escobar-Morreale Increased Body Iron Stores of Obese Women With Polycystic Ovary Syndrome Are a Consequence of Insulin Resistance and Hyperinsulinism and Are Not a Result of Reduced Menstrual Losses Diabetes Care, September 1, 2007; 30(9): 2309 - 2313. [Abstract] [Full Text] [PDF]

				E. Codner and H. F. Escobar-Morreale Hyperandrogenism and Polycystic Ovary Syndrome in Women with Type 1 Diabetes Mellitus J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1209 - 1216. [Abstract] [Full Text] [PDF]

				R. S. Legro A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome JAMA, February 7, 2007; 297(5): 509 - 519. [Abstract] [Full Text] [PDF]

				L. Ibanez, A. Jaramillo, G. Enriquez, E. Miro, A. Lopez-Bermejo, D. Dunger, and F. de Zegher Polycystic ovaries after precocious pubarche: relation to prenatal growth Hum. Reprod., February 1, 2007; 22(2): 395 - 400. [Abstract] [Full Text] [PDF]

				C. K. Welt, J. A. Gudmundsson, G. Arason, J. Adams, H. Palsdottir, G. Gudlaugsdottir, G. Ingadottir, and W. F. Crowley Characterizing Discrete Subsets of Polycystic Ovary Syndrome as Defined by the Rotterdam Criteria: The Impact of Weight on Phenotype and Metabolic Features J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4842 - 4848. [Abstract] [Full Text] [PDF]

				R. Azziz, E. Carmina, D. Dewailly, E. Diamanti-Kandarakis, H. F. Escobar-Morreale, W. Futterweit, O. E. Janssen, R. S. Legro, R. J. Norman, A. E. Taylor, et al. Criteria for Defining Polycystic Ovary Syndrome as a Predominantly Hyperandrogenic Syndrome: An Androgen Excess Society Guideline J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4237 - 4245. [Abstract] [Full Text] [PDF]

				D. Dewailly, S. Catteau-Jonard, A.-C. Reyss, M. Leroy, and P. Pigny Oligoanovulation with Polycystic Ovaries But Not Overt Hyperandrogenism J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3922 - 3927. [Abstract] [Full Text] [PDF]

				M. K. Murphy, J. E. Hall, J. M. Adams, H. Lee, and C. K. Welt Polycystic Ovarian Morphology in Normal Women Does Not Predict the Development of Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3878 - 3884. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 91/3/781    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Azziz, R. Search for Related Content PubMed PubMed Citation Articles by Azziz, R. Related Collections Female Endocrinology