- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00784615
Evaluation of Endocrine and Metabolic Parameters in the New Diagnostic Phenotypes of Polycystic Ovary Syndrome
Descriptive, Transversal Study of Evaluation of Cardiovascular Risks Factors and Prevalence of Metabolic Syndrome in the Different Phenotypes of Women With Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is a very frequent endocrine disease of women in reproductive age, with an estimated prevalence of 5 to 10 % according to the studied population. In 2003 a committee of experts joined in Rotterdam under the auspice of the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology, defined diagnostic criteria. It should include unless two of the following: menstrual irregularities; excess of male hormones (clinic or biochemical) and polycystic ovaries under ultrasound examination; giving rise to four subgroups or phenotypes:
1- Women with polycystic ovaries, hyperandrogenism and oligoamenorrhea . 2. Women with normal ovaries, hyperandrogenism and oligoamenorrhea. 3- Women with polycystic ovaries, oligoamenorrhea without hyperandrogenism. 4- Women with polycystic ovaries, hyperandrogenism with normal menses. PCOS shares components of Metabolic Syndrome for the high prevalence of insulin resistance (abdominal obesity, impaired glucose tolerance, type 2 diabetes, hypertension, endothelial dysfunction, impaired lipid profile and probably cardiovascular disease). All these findings lead us to assume that women with PCOS could have an increased risk of developing cardiovascular disease. Nevertheless it is premature to assume that every PCOS phenotype has the same cardiac and metabolic risk factors. So, it is important to evaluate the endocrine and metabolic characteristic in different phenotypes of PCOS to prevent the co morbidities that predispose to cardiovascular disease. And of course to avoid unnecessary measures in groups that could not show increased risk.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Polycystic ovary syndrome (PCOS) is a very frequent endocrine disease of women in reproductive age, with an estimated prevalence of 5 to 10 % according to the studied population.
Its cause remains not fully understood. PCOS is characterized by hyperandrogenism, chronic anovulation and / or polycystic ovaries. Patients, in a high percentage of cases show obesity, hirsutism, acne, menstrual irregularities and infertility. Clinically and biologically PCOS is a heterogeneous disorder with a not yet clear pathogenesis. Therefore, discussions on its definition and diagnosis still subsist. Seventy years ago Stein and Leventhal published their findings in 7 women with amenorrhea, hirsutism, acne, obesity and polycystic appearance of their ovaries. Since then, diagnostic criteria for PCOS suffered multiple modifications.
In 1990 a group of experts under the auspices of the National Institutes of Health (NIH) considered affected by PCOS every woman with hyperandrogenism and chronic anovulation; after having excluded other specific diseases that mimic that clinic like Cushing's syndrome, androgen secreting tumors and congenital adrenal hyperplasia (NIH criteria). The presence of polycystic ovaries under ultrasound exploration was considered controversial criteria and was not included for diagnosis. In May 2003 a new committee of experts joined in Rotterdam under the auspice of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE), included polycystic ovaries by ultrasound to the physiologic abnormalities for diagnosis. Thus, diagnosis should include unless two of the following: oligo or anovulation; hyperandrogenism (clinic or biochemical) and polycystic ovaries under ultrasound examination.
Rotterdam consensus widened the definition already proposed by NIH in 1990 giving rise to four subgroups or phenotypes:
1- Women with polycystic ovaries, hyperandrogenism and oligoamenorrhea. 2. Women with normal ovaries, hyperandrogenism and oligoamenorrhea. 3- Women with polycystic ovaries, oligoamenorrhea without hyperandrogenism. 4- Women with polycystic ovaries, hyperandrogenism with normal menses. This new criteria increase de prevalence, diversity and also controversy about PCOS. Some authors like Franks accept that the new consensus gave significant advances in the etiological knowledge of the syndrome. Others, like Azziz, proposed that is premature to include ovulating women and the ones with no clear evidence of androgens excess. In the last subgroups is no clear if they have an increased risk of cardiovascular and / or metabolic diseases.
The clinical heterogeneity of the syndrome is the product of a multifaceted process; where converge genetic and environmental influences. Many hypotheses try to explain the primary defect; but insulin resistance (IR) seems the most suitable according to most of studies. IR is present in 60 to 70 % of patients independently of obesity. Compensatory hyperinsulinism has a fundamental role in the pathology of PCOS. In vitro insulin stimulates androgen synthesis in ovary theca cells, acting on its own receptor and inhibits hepatic synthesis of sex hormone binding globulin (SHBG), increasing free testosterone. It also leads to the amplification of LH induced expression of cytochrome P450c 17 alfa (a limiting enzyme in androgen synthesis).
PCOS shares components of Metabolic Syndrome for the high prevalence of IR (abdominal obesity, impaired glucose tolerance, type 2 diabetes, hypertension, endothelial dysfunction, impaired lipid profile and probably cardiovascular disease). Dunaif and Sam using NIH criteria for PCOS diagnosis suggested a sole entity called XX syndrome. Central adiposity seems to play an important role in the development of this metabolic phenotype trough the production of many cytokines and adipocytes derived proteins, known as "adipocytokines". Failures on its regulation could contribute to the development of IR. The late one for itself or trough metabolic disturbances is associated with endothelial dysfunction and atherosclerosis.
Adiponectin is exclusively secreted in adipose tissue and could inhibit the expression of vascular endothelial adhesion molecules induced by TNF-alfa. So, it could be an anti atherogenic effect of adiponectin. In obese subjects and those with type 2 diabetes and IR (whom has a high incidence of coronary atherosclerosis) it was found low plasma levels of adiponectin. Recent studies propose low serum levels of adiponectin as an early marker for metabolic risk in women with PCOS.
C Reactive Protein (CRP), a low grade inflammation marker, has been suggested as an independent predictor of cardiovascular event in women; even more relevant than LDL cholesterol. Those facts have been reassured in the recent publication of Reynolds risk score which adds to the classical ATP III´s Framingham score; the usage of CRP in women, increasing its prognostic value. Higher levels of CRP have been described in women with PCOS compared with normal controls.
All these findings lead us to assume that women with PCOS have an increased risk of developing cardiovascular disease. As there is no universally accepted definition for PCOS, studies that show an association between PCOS and cardiovascular disease are of relative value. Legro stated that "It is premature to assume that every PCOS phenotype has the same cardiac and metabolic risk factors".
So, it is important to evaluate the endocrine and metabolic characteristic in different phenotypes of PCOS to prevent the co morbidities that predispose to cardiovascular disease. And of course to avoid unnecessary measures in groups that could not show increased risk.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
-
-
-
Cordoba, Argentina, X5000
- Recruiting
- Hospital Universitario de Maternidad y Neonatología
-
Contact:
- Paula S Mereshian, MD
- Phone Number: 54 351 433 1053
- Email: paula.mereshian@gmail.com
-
Principal Investigator:
- Carolina Fux Otta, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Two of the following
- Ovulatory Dysfunction: Clinically defined by oligomenorrhea (menstrual cycles lasting more than 35 days) or amenorrhea (lacking of menstruations in the last 90 days). In patients with menstrual cycles between 25 and 35 days, a serum level of progesterone drawn during days 21 to 23 of cycle < a 4 ng/ml.
- Clinical hyperandrogenism defined for the presence of hirsutism, acne, androgenic alopecia) and or biochemical (increases in total testosterone, bioavailable testosterone or free androgen index).
- Polycystic Ovaries: Defined by the presence, in as less one ovary, of 12 or more follicles (measuring 2 to 9 mm in diameter) and or increased ovarian volume > 10 mL).
Exclusion Criteria:
- Hyperprolactinemia
- Hypothyroidism
- Other causes of hyperandrogenism like Cushing's Syndrome, congenital adrenal hyperplasia, androgens secreting tumors
- Drug therapy used three months previous to enrollment in the study
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
1
Women with polycystic ovaries, oligo or anovulation and hyperandrogenism.
|
Total testosterone, bioavailable testosterone, Free androgen index, Total cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein
|
2
Women with polycystic ovaries and oligo or anovulation without hyperandrogenism
|
Total testosterone, bioavailable testosterone, Free androgen index, Total cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein
|
3
Women with normal ovaries, oligo or anovulation and hyperandrogenism
|
Total testosterone, bioavailable testosterone, Free androgen index, Total cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein
|
4
Women with normal ovaries, oligo or anovulation and hyperandrogenism
|
Total testosterone, bioavailable testosterone, Free androgen index, Total cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein
|
5
Women with out polycystic ovary syndrome
|
Total testosterone, bioavailable testosterone, Free androgen index, Total cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Serum levels: Total, bioavailable testosterone, Free androgen index. Total, LDL and HDL Cholesterol, Triglycerides, insulinemia, OGTT, HOMA index, Adiponectin, C Reactive Protein. Transvaginal Ultrasound:Number,size of ovary follicles and ovary volume
Time Frame: At the begining of the study
|
At the begining of the study
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Carolina Fux Otta, MD, Hospital Universitario de Maternidad y Neonatología. Universidad Nacional de Córdoba
- Study Director: Marta Fiol de Cuneo, MD, Catedra de Fisiología Humana. Universidad Nacional de Córdoba
Publications and helpful links
General Publications
- 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 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.
- Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. doi: 10.1056/NEJMra041536. No abstract available.
- Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65. doi: 10.1056/NEJMoa021993.
- Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003 Jan 28;107(3):391-7. doi: 10.1161/01.cir.0000055014.62083.05.
- Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.
- Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8. doi: 10.1210/jcem.85.7.6682.
- Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006-11. doi: 10.1210/jcem.84.11.6148.
- Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. doi: 10.1210/edrv.18.6.0318.
- Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
- Barbieri RL, Makris A, Randall RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986 May;62(5):904-10. doi: 10.1210/jcem-62-5-904.
- Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1991 Jan;72(1):83-9. doi: 10.1210/jcem-72-1-83.
- Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.
- Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun;88(6):2562-8. doi: 10.1210/jc.2003-030334.
- Wild RA. Long-term health consequences of PCOS. Hum Reprod Update. 2002 May-Jun;8(3):231-41. doi: 10.1093/humupd/8.3.231.
- Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand. 1992 Dec;71(8):599-604. doi: 10.3109/00016349209006227.
- Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg RA. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol. 1998 May;51(5):415-22. doi: 10.1016/s0895-4356(98)00010-9.
- Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001 Mar 13;103(10):1410-5. doi: 10.1161/01.cir.103.10.1410.
- Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003 Oct;14(8):365-70. doi: 10.1016/j.tem.2003.08.002.
- Norman RJ, Homan G, Moran L, Noakes M. Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome. Endocrine. 2006 Aug;30(1):35-43. doi: 10.1385/ENDO:30:1:35.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
- Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999 Dec 21-28;100(25):2473-6. doi: 10.1161/01.cir.100.25.2473.
- Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab. 2006 Mar;91(3):781-5. doi: 10.1210/jc.2005-2153. Epub 2006 Jan 17.
- Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999 Jan;22(1):141-6. doi: 10.2337/diacare.22.1.141.
- Bloomgarden ZT. American Association of Clinical Endocrinologists (AACE) consensus conference on the insulin resistance syndrome: 25-26 August 2002, Washington, DC. Diabetes Care. 2003 Apr;26(4):1297-303. doi: 10.2337/diacare.26.4.1297. No abstract available.
- Boulman N, Levy Y, Leiba R, Shachar S, Linn R, Zinder O, Blumenfeld Z. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J Clin Endocrinol Metab. 2004 May;89(5):2160-5. doi: 10.1210/jc.2003-031096.
- FERRIMAN D, GALLWEY JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961 Nov;21:1440-7. doi: 10.1210/jcem-21-11-1440. No abstract available.
- Franks S. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria. J Clin Endocrinol Metab. 2006 Mar;91(3):786-9. doi: 10.1210/jc.2005-2501. Epub 2006 Jan 17.
- Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, McCarthy M. The genetic basis of polycystic ovary syndrome. Hum Reprod. 1997 Dec;12(12):2641-8. doi: 10.1093/humrep/12.12.2641.
- Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2001 Jun;86(6):2453-5. doi: 10.1210/jcem.86.6.7580.
- Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004 Jun;89(6):2548-56. doi: 10.1210/jc.2004-0395.
- Legro RS. The genetics of polycystic ovary syndrome. Am J Med. 1995 Jan 16;98(1A):9S-16S. doi: 10.1016/s0002-9343(99)80053-9.
- Legro RS. Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rev. 2003 Jun;24(3):302-12. doi: 10.1210/er.2003-0004.
- Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med. 2001 Dec 1;111(8):607-13. doi: 10.1016/s0002-9343(01)00948-2.
- Ludwig E. Androgenetic alopecia. Arch Dermatol. 1977 Jan;113(1):109. doi: 10.1001/archderm.1977.01640010111023. No abstract available.
- Orio F Jr, Palomba S, Cascella T, Milan G, Mioni R, Pagano C, Zullo F, Colao A, Lombardi G, Vettor R. Adiponectin levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun;88(6):2619-23. doi: 10.1210/jc.2002-022033.
- Robinson S, Henderson AD, Gelding SV, Kiddy D, Niththyananthan R, Bush A, Richmond W, Johnston DG, Franks S. Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries. Clin Endocrinol (Oxf). 1996 Mar;44(3):277-84. doi: 10.1046/j.1365-2265.1996.674495.x.
- Sir-Petermann T, Maliqueo M, Codner E, Echiburu B, Crisosto N, Perez V, Perez-Bravo F, Cassorla F. Early metabolic derangements in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Dec;92(12):4637-42. doi: 10.1210/jc.2007-1036. Epub 2007 Sep 11.
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Fux-2
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Polycystic Ovary Syndrome
-
Cairo UniversityCompleted
-
Alexandria UniversityRecruitingPolycystic Ovary Syndrome (PCOS)Egypt
-
Saudi German Hospital - MadinahCompletedPolycystic Ovary Syndrome (PCOS)Saudi Arabia
-
University of CopenhagenCompletedPolycystic Ovary Syndrome (PCOS)Denmark
-
Odense University HospitalCompleted
-
Poznan University of Medical SciencesUniversity of California, DavisUnknownPolycystic Ovary Syndrome (PCOS)Poland
-
Assaf-Harofeh Medical CenterUnknownInfertility | Polycystic OvariesIsrael
-
Riphah International UniversityCompleted
-
Dexa Medica GroupCompletedPolycystic Ovary Syndrome (PCOS)Indonesia
-
Virginia Commonwealth UniversityEunice Kennedy Shriver National Institute of Child Health and Human Development...TerminatedPolycystic Ovary Syndrome (PCOS)United States
Clinical Trials on Blood samples, transvaginal ultrasound
-
ART Fertility Clinics LLCNot yet recruitingMiscarriage, Recurrent | Miscarriage | Infertility, Female | IVFUnited Arab Emirates
-
ART Fertility Clinics LLCNot yet recruitingInfertility, Female | IVF | Premature Ovarian FailureUnited Arab Emirates
-
University Hospital MuensterCompleted
-
Washington University School of MedicineNational Cancer Institute (NCI)Completed
-
University of AarhusCompleted
-
Aljazeera HospitalKasr El Aini HospitalUnknown
-
ART Fertility Clinics LLCCompletedEndometrial DiseasesUnited Arab Emirates
-
Intermountain Women and Children's ResearchUnknownCervical InsufficiencyUnited States
-
Semmelweis UniversityCharles University, Czech Republic; Jagiellonian University; St John of God Hospital...Not yet recruitingEndometriosis | Radiculopathy | Nerve Sheath TumorHungary
-
ChaingMai UniversityWithdrawnPreterm Delivery Within 7 Day After AdmissionThailand