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PCOS Lesbos Study 1999

PCOS Lesbos Study 1999

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Polycystic Ovarian Syndrome - a research study on the island of Lesbos, Greece
Polycystic Ovarian Syndrome - a research study on the island of Lesbos, Greece

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00/0 The Journal of Clinical Endocrinology & Metabolism Copyright © 1999 by The Endocrine Society

Vol. 84, No. 11 Printed in U.S.A.

A Survey of the Polycystic Ovary Syndrome in the Greek Island of Lesbos: Hormonal and Metabolic Profile
EVANTHIA DIAMANTI-KANDARAKIS, CHRYSSA R. KOULI, ANGELIKI T. BERGIELE, FANNY A. FILANDRA, THOMAIS C. TSIANATELI, GIOVANNA G. SPINA, EVANGELIA D. ZAPANTI, AND MICHAEL I. BARTZIS
Endocrine Section, First Department of Medicine, University of Athens Medical School, Laiko General Hospital, Goudi 115 27 Athens, Greece
ABSTRACT Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17– 45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score Ն6) and O/M: group N (n ϭ 108), regular menses and absence of hirsutism; group 1 (n ϭ 56), regular menses and hirsutism; group 2 (n ϭ 10), O/M and absence of hirsutism; and group 3 (n ϭ 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT Ն95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P Ͻ 0.00001) and 1 (P Ͻ 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P Ͻ 0.0001 and P Ͻ 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P Ͻ 0.002, P Ͻ 0.02, and P Ͻ 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P Ͻ 0.005 and P Ͻ 0.002, respectively) and the hirsute (P Ͻ 0.05 and P Ͻ 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P Ͻ 0.05). Finally, a high incidence of family history of diabetes mellitus (P ϭ 0.001) and menstrual disorders (P ϭ 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity. (J Clin Endocrinol Metab 84: 4006 – 4011, 1999)

OLYCYSTIC ovary syndrome (PCOS) appears to be a common endocrine disorder of women of reproductive age. It is characterized by chronic anovulation and hyperandrogenism and can be clinically expressed with hirsutism, acne, or androgen-dependent alopecia (1, 2). It is clinically heterogeneous regarding the presence and severity of the clinical manifestations of hyperandrogenism, menstrual irregularities, and infertility. Additionally, PCOS seems to be associated with obesity and metabolic abnormalities, such as insulin resistance and dyslipidemia, factors that exaggerate the clinical presentation, increase the morbidity, and, lastly, may play a central role in the pathogenesis of the syndrome (2– 4). PCOS is not distinguished by other forms of hyperandrogenism by a unique phenotype or a distinct biochemical abnormality; this may explain the difficulty in introducing generally accepted diagnostic criteria. The most widely accepted criteria, from the 1990 NIH-NICHHD conference on PCOS, are 1) ovulatory dysfunction, 2) clinical evidence of hyperandrogenism and/or hyperandrogenemia, and 3) exclusion of other known disorders, such as congenital adrenal
Received December 30, 1998. Revision received May 19, 1999. Rerevision received July 28, 1999. Accepted June 18, 1999. Address all correspondence and requests for reprints to: E. DiamantiKandarakis, M.D., First Department of Medicine, Laiko General Hospital, 17 Agiou Thoma Street, 115 27 Athens, Greece.

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hyperplasia, hyperprolactinemia, or Cushing’s syndrome (1). Additionally the finding of polycystic ovaries on ultrasonography, which was originally the hallmark for the diagnosis of the syndrome, perhaps represents a sign of a wide variety of disorders and appears to be a nonspecific finding in approximately 20% of asymptomatic women (5, 6). The prevalence of PCOS in premenopausal women is estimated to be about 5–10% (1). In the past, most prospective studies attempting to define the prevalence of PCOS used the ultrasonographic appearance of polycystic ovaries as a prerequisite for the diagnosis of PCOS; however, this is not included in the current diagnostic criteria. These studies demonstrated that 21–23% of unselected women appear to be affected (6 – 8). In a recent study, using the current criteria for the diagnosis of PCOS, the prevalence of PCOS in a population of unselected U.S. Black and White women was reported to be 4% (9). However, as there are significant ethnic and racial variations in the clinical presentation of PCOS, the frequency of obesity, insulin resistance, and the incidence of diabetes mellitus, it seems reasonable that the prevalence of PCOS could differ among different populations (10, 11). The current study was undertaken 1) to determine the prevalence of the PCOS in a sample of the population of a Greek island, 2) to identify hormonal and metabolic parameters of women with PCOS and, in particular, among women

4006

FSH (units per L). Multivariate analysis of covariance. SHBG serum levels were measured by immunoradiometric assay (IRMA) using the SHBG IRMA 125I (RADIM S. 16). TSH was measured using the human TSH IRMA kit from INCSTAR Corp.6%. they were 9. France). (Wesbster. respectively. According to the history and the physical examination. a 75-g oral glucose tolerance test was performed.8%.1% and 5.77 Ϯ 0. they were 4.6% and 3. Body fat distribution was assessed by measurements of the waist to hip girth ratio (WHR) (12). and 3. they were 3.6.5%.7 Ϯ 2. related disorders with similar clinical presentation were excluded (1990 NIH Consensus Conference on the PCOS). Menstrual cycle history was carefully detected and included a general review since menarche and a detailed recall of the last 2. hirsutism. group 2 included women with oligomenorrhea and absence of hirsutism. Inc.3% and 4.4% for low and high levels respectively.5 Ϯ 1. 18 of 192 women (9. weight/ height2. and radio station). nanomoles per L).4%) presented moderate to severe hirsutism. overweight between 26 –30. Inc.3%. they were 6. 17OHProg levels were measured using a RIA kit from Diagnostics Systems Laboratories.A. respectively. PRL was measured using the PRL IRMA kit from MEDGENIX DIAGNOSTICS. Fiftysix of 192 women (29%) demonstrated hirsutism with a F-G score ranging from 6 –12 and regular menstrual cycles (group 1). group 1. and 3) to investigate associations of the above-mentioned clinical manifestations with family history of diabetes mellitus. All women were offered a free medical examination by an endocrinologist. lastly. Group N consisted of women with normal menstrual cycles (Ͻ35 days) and absence of hirsutism (F-G. for LH. hirsutism had an onset in adolescence and did not progressively worsen.1%. group 3). menstrual disorders. Serum insulin levels were measured using the RIA INSULIN-CT kit from CIS-Bio International (Gif-sur-Yvette. and 6.7. TSH (microunits per mL).9. All of them were clinically healthy.7. Personal medical history was obtained from every woman according to a customized preprepared questionnaire.5%. kilograms per m2).8. and 3.9 Ϯ 0. Additionally. respectively. as it is reported that approximately 20% of normal women could present the above ultrasonographic appearance (6).6 Ϯ 1. 28. Ͻ6). Analysis was performed using the STATISTICA/w software package (version 5. group 2. 0. the subjects under study were divided into four groups. for FSH. for 17OHProg. Additionally. Belgium).7%. newspaper.9%. picograms per mL). the normal and the hirsute groups. None of them received oral contraceptives or other drugs that could interfere with the hormonal and metabolic studies.3% and 9. group 1.0 Ϯ 3. respectively. The intraand interassay coefficients of variation for FT were 4. and the mean blood pressure (MBP) was estimated [MBP ϭ diastolic ϩ (systolic/3)].8%. was performed as described by Siegel and Castellan (17). and 9. 108 of 192 women had regular menstrual cycles as defined above and no signs of hyperandrogenism (H/A). was performed. The polycystic ovarian morphology detected by ultrasound was not considered an essential criterion for the diagnosis of the syndrome. Postmenopausal women were excluded from the study. milligrams per 10Ϫ4 U) and was used as an indicator of insulin sensitivity (14). and premature baldness in male relatives. Beckman Coulter. group 2. percentile of the levels detected in the group of normal cycling nonhirsute women (group N). and serum was stored at Ϫ20 C until assayed.SURVEY OF PCOS: METABOLIC PROFILE 4007 with clinical signs of hyperandrogenemia. for insulin. A Ferriman and Gallwey score of 6 or greater (F-G. and glucose (milligrams per dL) were measured. Results Clinical characteristics Diagnosis of PCOS PCOS was diagnosed in women presenting with oligomenorrhea (as defined above) and hyperandrogenism. yr).7. LH and FSH were measured using the LHsp and FSH IRMA kits from Biosource Technologies.6% and 4. In the cases of impaired fasting glucose (FG.01. and obese over 30. menstrual disorders.9 Ϯ 1. residual analysis was performed using ␹2 as the statistical indicator. nanograms per mL) levels were detected in blood samples of women with oligomenorrhea (groups 2 and 3) to exclude other causes of menstrual disorders (15. Europe S. and WHR) of the four groups of the studied population are shown in Table 1. 28. Lie ` ge. they were 2.5% and 10. No statistically significant differences existed in age (group N. Moreover.2% and 5. and 17-hydroxyprogesterone (17-OHProg. The characteristics (age.4% and 6. Obesity was assessed by estimating body mass index (BMI. and 5.2% and 8. A family history of menstrual disorders and hirsutism was positive when oligomenorrhea and/or hirsutism existed during the youth of the mother according to the report of the studied women. 10 of 192 examined women (5.. and for TSH. hirsutism.3% and 5. Physical examination was performed in each person by two doctors. 0. The fasting glucose (FG) to insulin (FI) ratio was estimated (FG:I ratio. Duplicate plasma samples were analyzed for FT using the commercially available Coat-A-Count Free Testosterone kit from Diagnostic Products (Los Angeles. with a F-G score ranging from 13–20.1%. 110 –125 mg/dL).6 kg/m2). TX). serum PRL (nanograms per mL). Hyperandrogenism was defined as FT levels above the 95th In the studied population. and/or acne (group N). 33. In all cases.4%. group 3. Subjects and Methods Subjects and protocol We studied 192 women of reproductive age who lived on the Greek island of Lesbos and accepted our invitation of free medical examination. group 1 included women with hirsutism and/or acne and regular menstrual cycles.1Ј 98).1 Ϯ 0.to 3-yr interval.2 Ϯ 0. CA).5% and 8. The absolute range for FT in ovulating females was nondetectable to 3. and 5. 24.8%. Ն6) was considered hirsutism (13).5% and 4. respectively.0.2%) had menstrual disorders without hirsutism and/or acne (F-G..A.0% and 7.. 31. blood pressure was measured in with subjects in the sitting position. 10 of these 18 women presented with acne. 0. none of them suffered from chronic or acute disease. CA). BMI. for SHBG. Statistical analysis Results are reported as the mean Ϯ se. Emphasis was placed upon family history regarding diabetes mellitus in the first and second degree relatives. they were 5. group 1.2. BMI (group N. respectively. 27. for PRL. 35. Assays Plasma glucose was determined by the glucose oxidase method (glucose analyzer.76 Ϯ 0. sex hormone-binding globulin (SHBG. and oligomenorrhea (O/M. 25.73 Ϯ . group 2. and 1. LH (units per L). Additionally. Blood samples were collected between 0800 – 0900 h and plasma free testosterone (FT. MN). Inc. A large scale informational campaign took place before the study from the local authorities (local TV channel. The age of the women finally enrolled in this protocol ranged between 17– 45 yr. Ovulatory dysfunction was defined as less than eight cycles per yr. hirsutism.1. (Stillwater. and. The protocol was approved by the institutional review committee of Bostanion General Hospital in Lesbos.9 pg/mL.4% and 6. group 3.6%. Tukey’s test for unequal sample sizes was used. and regular menstrual cycle as 26 –34 days in length. group 3 included women presenting with oligomenorrhea and hirsutism. and 3. and early baldness in male relatives (father and/or brothers). Palo Alto. with normal ranging between 17–25.1. using BMI as a covariant.2% and 3.7% and 5. group 2). The partitioning of the table referring to family history in women with PCOS. For individual comparisons.7%. and no reference was made to the specific disorders being studied. subjects with overt diabetes mellitus and impaired glucose tolerance were excluded from the above metabolic study. cardiovascular disease. fasting insulin (microunits per mL). or WHR (group N. Blood samples were centrifuged immediately. Ͻ6. they were 8.02. and all were euthyroid according to the clinical evaluation. Regarding family history cross-tabulation of the four studied groups. respectively.

1. *. FIG. 85. 1.2 Ϯ 0. P Ͻ 0.4.4 mg/10Ϫ4 U. P Ͻ 0.4 mg/ 10Ϫ4 U.4 Ϯ 0.7 Ϯ 0.03).15 31. P Ͻ 0.10 Ϯ 0.7 Ϯ 1.21 Ϯ 0.7 nmol/L.1 pg/mL.2 vs. group HIRSϩO/M.3 Values are the mean Ϯ SE. 1.005 vs. P Ͻ 0.9 Ϯ 0.77 Ϯ 0. Fig.4 Ϯ 1. normal. Although the unadjusted mean values Ϯ se are displayed in Table 1 and Fig.1 vs. 3). Additionally.05.005). N. none of the subjects suspected of PCOS had evidence of thyroid disease. 6.9 Ϯ 2. Groups according to clinical presentation: group N. group 1.2 Ϯ 0.0001 vs. P Ͻ 0.7 Ϯ 0. Prevalence of PCOS One woman of group N had diabetes mellitus and was not included in the metabolic studies as well as two obese women.7 Ϯ 1. P Ͻ 0. HIRSϩO/M. no statistically significant difference was found in FT levels between women of group 3 and women of group 2 (Fig. 1.005) or group 1 (hirsutism.0 27. P Ͻ 0.76 Ϯ 0. 2.3 1.0 Ϯ 4. whereas FI in group 3 (hirsutism and O/M) was higher than that in group N (42.2 Ϯ 4. **.7 Ϯ 2.9 Ϯ 1.2 Ϯ 0. 1. oligomenorrhea. Additionally. 56.02 79. 1). 2).77 Ϯ 0.02). the P values are taken from the data after covariance adjusting for changes in the BMI. group 1.5 Ϯ 0. group O/M.01.9 Ϯ 2.3 Ϯ 4. Women with hirsutism and oligomenorrhea (group 3) had higher FT levels than those in group 1 (3. women with oligomenorrhea (group 2) showed higher FT levels compared to group N (FT. and group 3.0001).9 vs. The FG:I ratio was lower in group 3 compared to group N (3. group 2.03 85.4 Ϯ 9. Women with hirsutism and/or oligomenorrhea (groups 2 and 3) who presented with hyperandrogenemia were diagnosed as having PCOS. group HIRS. MBP (group N.2 vs. Although the unadjusted mean Ϯ se are displayed in Table 1 and Figs.4008 DIAMANTI-KANDARAKIS ET AL. There was a noticeable trend for an increase in fasting insulin levels and a decrease in the FG:I ratio and SHBG levels from group N to group 3 (Figs.00001).6 0.4 Ϯ 0. group 2. oligomenorrhea and hirsutism). 56. 4).1 Ϯ 0.2 vs.7 0.4 104. SHBG levels in women with simple hirsutism (group 1) were lower than those in group N (44.8 vs. 6. Hormonal profile The data are summarized in Table 1.01 88.77 Ϯ 0. N and HIRS.3 Ϯ 6.7 25. hyper- .6 0.0001 vs. No significant differences were observed by analysis of covariance.3 102. group 3. Metabolic profile The data are summarized in Table 1. Mean FT levels in the four studied groups and the PCOS women (group N. Fig.4 25.8 Ϯ 0.05).7 Ϯ 2. Fig. P Ͻ 0. 27.3 vs. P Ͻ 0.1 Ϯ 1.5 ␮U/mL.4 2. O/M (oligomenorrhea).45 Ϯ 0. the P values are taken from the data after covariance adjusting for changes in the BMI.5 Ϯ 1. ***. 80.0 Ϯ 4.0 vs. Additionally. 42.7 Ϯ 1.4 Ϯ 9.2 101. 79.6 ␮U/mL. 2–4). group 3.2 28.9 Ϯ 1.01 80. normal women.5 Ϯ 0. P Ͻ 0.8 vs.7 0.7 28. P Ͻ 0.6 Ϯ 0.9 107.1 pg/mL.25 vs. 0. HIRS (hirsutism). Clinical characteristics.0001) or group N (3. hirsutism.05. women with simple hirsutism (group 1) had a lower FG:I ratio compared to the normal women (4.3.002.7 nmol/L.7 Ϯ 1.6 Ϯ 1. 2. who showed impaired glucose tolerance.0 Ϯ 3.2 35.2 Ϯ 0. one from group 1 (hirsutism) and the other from group 3 (hirsutism and O/M).73 Ϯ 0. mean blood pressure (MBP). 2–4. JCE & M • 1999 Vol 84 • No 11 TABLE 1. Women with hirsutism only (group 1) compared to normal women (group N) showed higher levels of FT (2. 21. P Ͻ 0. As defined.1 pg/mL. N. 0.2.7 1.4 Ϯ 1. SHBG levels in women with hirsutism and oligomenorrhea (group 3) were lower than those in group N (30.8 Ϯ 1. P Ͻ 0.9 mm Hg) did not differ even after BMI and age were used as covariates.4 Ϯ 0.4 3. 88. FG did not differ among the four groups.1 pg/mL.7 Ϯ 2. fasting glucose (FG) and LH to FSH ratio of the studied population (total n ϭ 192) N (n ϭ 108) HIRS(1) (n ϭ 56) O/M (2) (n ϭ 10) HIRSϩO/M(3) (n ϭ 18) Age (yr) BMI (kg/m2) WHR MBP (mm Hg) FG (mg/dL) LH/FSH 33.2 Ϯ 0.

6 Ϯ 1. WHR (0. BMI (28. P Ͻ 0. 6 of 56 women from group 1 (10. Moreover. Mean FG:I ratio in the four studied groups and the PCOS women (group N. *. N.3 pg/ml). oligomenorrhea and hirsutism).6 mm Hg) of the PCOS women did not differ compared to those in groups N and 1. 2. group O/M. i.e. Mean SHBG levels in the four studied groups and the PCOS women (group N. P Ͻ 0. The FG:I ratio (3. group O/M.02 vs.0 Ϯ 0. *. yr). . none of the suspected women had an initial level above 2 ng/ml. *. and early baldness in male relatives are shown in Table 2. group O/M.002 vs. oligomenorrhea.05 vs.05 vs.6 nmol/L) were also lower in the PCOS group compared with the normal group (P Ͻ 0. Cushing’s syndrome.1 Ϯ 0.6 Ϯ 1. oligomenorrhea and hirsutism). FIG. hirsutism. these findings were independent of the BMI. P Ͻ 0. oligomenorrhea and hirsutism). or androgenic tumor. **. respectively).8. group HIRSϩO/M.02 vs. P Ͻ 0. hirsutism.8. group HIRSϩO/M. group HIRS. respective- The observed frequencies of positive family history regarding diabetes mellitus. normal women. oligomenorrhea. **. Finally. as they reported regular menses. Ͼ3. respectively. normal women. hormonal. 21-Hydroxylase deficiency was excluded by measuring 17OHProg. group HIRS. 2 from group 2 (O/M) and 11 from group 3 (O/M and hirsutism). Figs.02. whereas FG levels (108.002 and P Ͻ 0. and metabolic parameters of the PCOS group ly). and MBP (81.2) did not differ compared with those in the other groups.SURVEY OF PCOS: METABOLIC PROFILE 4009 FIG. **. N and HIRS. oligomenorrhea.04). Age (24. N.05 and P Ͻ 0. 3. N. P Ͻ 0. group HIRSϩO/M.77% (13 of 192).7%) had H/A according to the above definition. Anthropometric.9 mg/dL) did not differ (Fig. effectively ruling out the disorder (15).05 vs. menstrual disorders. mg/10Ϫ4 U) and SHBG level (25. Family history The 13 women diagnosed with PCOS were compared to the normal and hirsute groups (groups N and 1. Therefore.5 ␮U/mL) compared with groups N and 1 (P Ͻ 0. kg/m2). the LH to FSH ratio (2. 2 and Table 1). Thirteen women fulfilled the criteria.78 Ϯ 0.8 Ϯ 3. hirsutism. 4. the prevalence of PCOS in the population under study was 6.1 Ϯ 8. normal women. PCOS women had higher FI levels (46. Mean FI levels in the four studied groups and the PCOS women (group N. However.7 Ϯ 3. H/A was defined as a FT level above the 95th percentile of the mean value in the normal women (group N. prolactinemia.002. group HIRS. P Ͻ 0. 3 and 4). N and HIRS. FIG. they were not included in the estimation of the prevalence of the syndrome. N. hirsutism.3.3 Ϯ 13.

e.3 21. did not prove to be more common in the PCOS group (Table 2).04 vs. Women with hirsutism and/or oligomenorrhea (groups 2 and 3) showed a more frequently positive family history of diabetes mellitus (60% and 66. lower FG/I ratio. the other groups.7% of the studied hirsute women . the other groups. b P ϭ 0. groups N and HIRS(1). less than 8 cycle/yr. and of menstrual disorders.6 Probability level (P) was estimated using ␹2 analysis.4% and 39%. Discussion The prevalence of PCOS in the studied sample of the Greek population was 6. e P ϭ 0. The observed frequencies (percentages) of positive family history in the four studied groups according the clinical presentation and in the PCOS group compared with the normal (N) and hirsute (HIRS) groups N HIRS(1) O/M(2) O/MϩHIRS(3) PCOS Diabetes mellitus Menstrual disorders Hirsutism Early baldness 29. population (Whites and Blacks) reported in a recent study by Knochenhauer et al. 24).3%. was observed in 38% (5 of 13) of the women with PCOS. The above finding suggests that fasting hyperinsulinemia is a characteristic accompanying feature of PCOS (3.001 vs. the FG/I ratio was significantly lower in the studied hirsute women compared to normal women. recorded in 71% (10 of 13.6% (1 of 13).4 14. In the present study the examined population was homogeneous regarding racial and ethnic variations. Women with hirsutism. P ϭ 0. and that “hairiness” represents for many women a cosmetic problem that merits serious consideration. c P ϭ 0. groups N and HIRS(1).77% of the examined women with oligomenorrhea or oligomenorrhea and hirsutism. The gradual increase. It is noteworthy that statistical significance is achieved between the group of normal women and the group that presents the full-blown syndrome. more often had a positive family history of hirsutism (21.6 2.3c 39e 5. A family history of hirsutism. Taking into account the bioavailability of the androgens. The majority of the studied women fulfilling the criteria for PCOS (11 from the overall 13) belonged to the group characterized by the main clinical manifestations of the syndrome (group 3). because another nonmeasured androgen could have been elevated. The possible role of ethnicity in the prevalence and features of PCOS has been reported in other populations (i. this definition was also used in the recent study by Knochenhauer et al. Therefore. which have been considered adequate and sensitive screening markers for insulin resistance. recorded in 30% (4 of 13). respectively. However. The incidence of oligomenorrhea (14. with the clinical manifestations of the syndrome but without proven hyperandrogenemia (normal FT). independently of the degree of obesity.006) and menstrual disorders (40% and 33. recorded in 46% (6 of 13.e. a P ϭ 0.04 vs. respectively. compared with the regular cycling women (groups N and 1). f P ϭ 0. Nevertheless. FT was chosen to be measured for hormonal analysis as the most representative ovarian androgen with minimal menstrual variation (20 –22).6 5. The studied women with idiopathic hirsutism demonstrated a statistically significant lower SHBG level and higher FT level compared to normal women. 9). It should also be noted that obesity. Women with PCOS showed a high incidence of a positive family history of diabetes mellitus. although the mean FT value was within the normal range. the other groups. in women with idiopathic hirsutism mean FI levels were in between the levels of normal and PCOS women without reaching statistical significance compared to the normal group. P ϭ 0. in accord within the range of the estimated prevalence (5–10%) (1). defined as a BMI above 30 kg/m2.01 vs.4% (20 of 192) if another elevated androgen was detected. cannot be entirely excluded from the diagnosis of PCOS. consistent with other reports (4. A family history of premature baldness in male relatives was less often observed in group N than in the rest of the groups (P ϭ 0.001). (9). and decreased SHBG levels compared with the normal women. the other groups.6%. we used fasting hyperinsulinemia and the FG/I ratio. it should be borne in mind that the recruitment of women in the present study was not fully randomized. In this group were included 18 women with oligomenorrhea and hirsutism/or acne.6%. hyperinsulinemiceuglycemic clamps) (1.S.006 vs. This rather impressive percentage could be due to the ethnic variation of the Mediterranean people. respectively. 3. H/A was confirmed in 6. 27). recorded in 7. 23). This finding raises the question of whether women with so-called idiopathic hirsutism are a heterogeneous group exhibiting not only a cosmetic problem but subtle metabolic disturbances as well.77% (13 of 192).3f 60 40c 0 30 a 66. This also appears to be close to the prevalence of PCOS in a sample of the U. Caribbean-Hispanic) (26. for the first time.0001 vs. It should be noted that 10. The reported incidence of idiopathic hirsutism varies from 5–15% in Caucasian women (13. Insulin resistance in PCOS has been estimated in small groups of women by highly sophisticated methods (i.4010 DIAMANTI-KANDARAKIS ET AL. 18. PCOS women appeared to have fasting hyperinsulinemia. of fasting insulin levels from the group of normal women to the group with the clinical and biochemical abnormalities of the syndrome.6 30. a dose-dependent-like pattern. (9).8 5. The ultrasonographic appearance of polycystic ovaries as a diagnostic criterion is controversial and does not seem to be either a sensitive or a specific finding (6. In this study. P ϭ 0. 25). P ϭ 0.01). independently of the BMI. d P ϭ 0. 19). 28 of 192) in the studied population may be overestimated because of the definition we used.0001) than nonhirsute women (groups N and 2). ivGTT. Nevertheless. in our study 29% (56 of 192) of the examined women presented with idiopathic hirsutism. i.04).6f a 71b 46d 30 7.6 33. regardless of the presence of menstrual irregularities (groups 1 and 3). JCE & M • 1999 Vol 84 • No 11 TABLE 2.00001) compared with the normal and hirsute women (groups N and 1). 23). indicates that the severity of fasting hyperinsulinemia is associated with the severity of the clinical phenotype. and premature male balding. Regarding the metabolic studies. to determine in a large sample of premenopausal women the presence of insulin resistance in association with hyperandrogenic manifestations (14. This is the first study undertaken in Europe attempting to determine the prevalence of PCOS using the current diagnostic criteria (NIH consensus 1990). The remaining 7 women. the prevalence of PCOS in our sample could have been approximately 10.4e 14. P ϭ 0.e.

Sauerbrei EE. fat distribution and family history of diabetes mellitus. 12. Dunaif A. Aust NZ Obstet Gynaecol. 32. J Clin Endocrinol Metab. 1997 Consensus Development Conference on Insulin Resistance. Clin Endocrinol (Oxf). 67:569 –572. 1992 Elucidating the genetics of polycystic ovary syndrome. Diabetes Care. estimated by a random measurement. J Clin Ultrasound. On the other hand. Clin Endocrinol (Oxf). Rosenfield RL. Adams J. Additionally. 1998. 1995 Insulin secretory defects in polycystic ovary syndrome. 98:9S–16S. J Clin Endocrinol Metab. J Clin Endocrinol Metab.SURVEY OF PCOS: METABOLIC PROFILE 4011 were hyperandrogenemic. statistically significant incidence of family history of diabetes mellitus compared to normal and hirsute women. In: Dunaif A. Dunaif A. Dunaif A. Jacobs HS. Waggoner W. two of them had H/A. 20. Oka K. and were diagnosed with PCOS. New york: McGraw-Hill. 69:577–584. independently of obesity. Lancet. Venturoli S. Murray R. J Clin Endocrinol Metab. as determined by liquid chromatography. Another observation was that hirsute women reported a strong family history of hirsutism. 1998 Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. 1984 Polycystic ovaries: a sign. 11. 1964 The prevalence of “hirsutism” in young women. 1976 Obesity and oligomenorrhea are associated with hyperandrogenism independent of hirsutism. Clin Endocrinol (Oxf). Insulin resistance and hyperandrogenemia in the polycystic ovary syndrome: Influence of obesity. Haseltine FP. Bovicelli L. Lorusso R. References 1. Dunaif A. As noted by other investigators. 1998 A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. 33. 1996 New perspectives in polycystic ovary syndrome. Trends Endocrinol Metab. This observation may imply that the genetic trait of PCOS is associated with a diabetogene(s). focussing on the prevalence of a family history of diabetes mellitus in PCOS. 96:520 –527. Boston: Blackwell. 1981 Medical implications of ultrasonocally detected polycystic ovaries. 75:508 –513. Peto TE. Givens JR. 42:765–769. 33). Phillips RA. Hirano T. Sharp PS. 1988 Polycystic ovaries: a common finding in normal women. Proc of the 4th Eur Congr of Endocrinol. 1993 Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in Caribbean-Hispanic women. Ferriman D. 1985 Ultrasonic findings in polycystic ovarian disease. Potter HD. Merriam GR. in polycystic ovary syndrome. Azziz R. 21:1440 –1445. 1982 Plasma free and protein-bound testosterone in hirsutism. J Clin Invest. Polycystic ovary syndrome. Norman RJ. Gallwey J. Mahabeer S. 21:310 –319. 1989 Profound peripheral insulin resistance. Therefore. 42:1462–1468. J Clin Endocrinol Metab. 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Boston: Blackwell. 2:271–280. in accordance with the general view that PCOS has a strong familial component (10. independently of BMI. Zacur HA. Pardridge WM. Ogden V. idiopathic hirsutism is not a homogeneous clinical and biochemical entity and. with FT levels exceeding the 95th percentile of the normal women. Rosenfield RL. Dunaif A. 1995 The genetics of polycystic ovary syndrome. Lancet. 19. Additionally. Allen SE. Boots LR. ADA. 1961 Clinical assessment of body hair growth in women. 3. oligomenorrhea seems to be associated with subtle or overt elevations of androgens even in the absence of hirsutism or acne and may present a discrete form of PCOS (29. Semin Reprod Endocrinol. 34:67–72. Azziz R. 10. 1967 Testosterone and androstenedione blood production rates in normal women and women with idiopathic hirsutism or polycystic ovaries. Futterweit W. 4. 17. Paradisi R. France JT. Dunaif A. nonhirsute women with oligomenorrhea presented higher FT levels than normal women. In the studied population. Fertil Steril. Wadsworth J.77%. Wu CH. may include a variety of disorders in androgen metabolism (28) as well as subclinical metabolic aberrations. Farquhar CM. Givens JR. Dunaif A. Karrison T. 2nd ed. Orsini LF. 31. et al. 16. the incidence as well as the role of family history of diabetes mellitus in women with PCOS should be considered in terms of its possible implication in the pathogenesis of the syndrome. Polson DW. 83:2694 –2698. Delson R. Key TJ. et al. 1992 Current issues in endocrinology and metabolism: polycystic ovary syndrome. Dobrjansky A. as defined. Azziz R. Givens JR. 1986 Serum Bioavailability of sex steroid hormones. Kiddy DS. not a diagnosis. Clin Res. 32. 30. the presence of insulin resistance. 1992 How common are polycystic ovaries in normal women and what is their significance for the fertility of the population. Legro RS. 1989 21-Hydroxylase deficiency in female hyperandrogenism: screening and diagnosis. 60:188 –194. eds. which is a distinct feature of PCOS. However. Noguchi M. Fertil Steril. Vydelingum N. Diamanti-Kandarakis E. 1997 Prevalence of hyperandrogenemia among nonhirsute oligo-ovulatory women. Weiss DJ. McKnight E. 18. and it should be further examined in large scale studies.118. mean blood pressure. p. 38:1165–1174. 29. Hague WM. 7:267–271. 27. 6. 26. 34:557–560. Haseltine FP. Kissebah A. Cooperberg PL. J Clin Endocrinol Metab. did not differ in women with PCOS and normal women. Mitchell JM. 23. Kahsar-Miller M. Diabetes. 13. 63:58 – 62. et al. J Clin Invest. 35:796A. Boston: Blackwell. (23). 9. Polycystic ovary syndrome. 30). 34. 7. White DM. Adams J. Richards C. 1988 Nonparametric statistics for the behavioral sciences. with a prevalence of 6. Dunaif A. . Clin Chem. 1987 Increased prevalence of polycystic ovarian disease in Hispanic women [Abstract]. covering the spectrum of hyperandrogenic disorders in the studied groups of women. Kouli C. 46:891–902. assessed by sophisticated methods in a study by Erhmann et al. The metabolic abnormalities. 28. Haseltine FP. P3–35. Knochenhauer ES. Masters S. Tsianateli T. Kim MH. Hosseinian AH. 24. Sorbara L. Green G. Regarding family history. 2. 21. et al. Givens JR. Legro RS. 1994 The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. et al. 1990 Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases. 32:213–220. Polonsky KS. Merriam GR. we observed a high incidence of family history of menstrual disorders in women with PCOS. Merriam GR. Swanson M. it seems that familiar and ethnic aspects should be taken into consideration. 1995 Ethnic differences in insulin and glucose response to glucose between white and Indian women with polycystic ovary syndrome. women with PCOS reported a high. 1992 Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach.

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