pcos lesbos study 1999

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A Survey of the Polycystic Ovary Syndrome in the GreekIsland 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 GeneralHospital, Goudi 115 27 Athens, Greece

ABSTRACTPolycystic ovary syndrome (PCOS) is characterized by hyperan-

drogenism, chronic anovulation, and oligomenorrhea (O/M). PCOShas variable clinical phenotypes, biochemical features, and metabolicabnormalities. To determine the prevalence of PCOS in the Greekpopulation as well as the metabolic parameters, we performed across-sectional study of 192 women of reproductive age (1745 yr),living on the Greek island of Lesbos. They were divided into 4 groupsaccording to the presence of hirsutism (defined as a Ferriman-Gall-wey score 6) and O/M: group N (n 108), regular menses andabsence of hirsutism; group 1 (n 56), regular menses and hirsutism;group 2 (n 10), O/M and absence of hirsutism; and group 3 (n 18),O/M and hirsutism. Body mass index, waist to hip ratio, and meanblood pressure did not differ among the studied groups. Hormonalprofile was assessed by measuring free testosterone (FT). The prev-alence of PCOS, defined by the presence of O/M and biochemicalhyperandrogenism (FT 95th percentile of the normal women), wasestimated to be 6.77% (13 women of 192). Higher FT levels wereobservedin group3 (O/M andhirsutism)compared with groups N (P0.00001) and 1 (P 0.0001) and in groups 1 (hirsutism) and 2 (O/M)compared with group N (P 0.0001 andP 0.005, respectively). Sex

hormone-binding globulin levelswere lowerin women with PCOSandingroups 1 and 3 thanthosein group N (P 0.002, P 0.02, andP0.002, 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 toinsulin ratio (FG:I ratio). After covariance adjusted for the BMI, FIlevels were higher in group 3 and in women with PCOS than in thenormal (P 0.005 andP 0.002, respectively) and the hirsute (P 0.05 and P 0.02, respectively) women, whereas FG levels did notdiffer among the studied groups. The FG:I ratio was lower in group3, group 1, and in women with PCOS than in normal women (P 0.05). Finally, a high incidence of family history of diabetes mellitus(P 0.001) and menstrual disorders (P 0.01) was observed inwomen 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 (prevalence6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fastinghyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity. (J Clin Endocrinol Metab 84: 40064011, 1999)

POLYCYSTIC ovary syndrome (PCOS) appears to be a

common endocrine disorder of women of reproductiveage. It is characterized by chronic anovulation and hyperan-drogenism and can be clinically expressed with hirsutism,acne, or androgen-dependent alopecia (1, 2). It is clinicallyheterogeneous regarding the presence and severity of theclinical manifestations of hyperandrogenism, menstrual ir-regularities, and infertility. Additionally, PCOS seems to beassociated with obesity and metabolic abnormalities, such asinsulin resistance and dyslipidemia, factors that exaggeratethe clinical presentation, increase the morbidity, and, lastly,may play a central role in the pathogenesis of the syndrome(24). PCOS is not distinguished by other forms of hyperan-drogenism by a unique phenotype or a distinct biochemicalabnormality; this may explain the difficulty in introducing

generally accepted diagnostic criteria. The most widely ac-cepted criteria, from the 1990 NIH-NICHHD conference onPCOS, are 1) ovulatory dysfunction, 2) clinical evidence ofhyperandrogenism and/or hyperandrogenemia, and 3) ex-clusion of other known disorders, such as congenital adrenal

hyperplasia, hyperprolactinemia, or Cushings syndrome

(1). Additionally the finding of polycystic ovaries on ultra-sonography, which was originally the hallmark for the di-agnosis of the syndrome, perhaps represents a sign of a widevariety of disorders and appears to be a nonspecific findingin approximately 20% of asymptomatic women (5, 6).

The prevalence of PCOS in premenopausal women is es-timated to be about 510% (1). In the past, most prospectivestudies attempting to define the prevalence of PCOS used theultrasonographic appearance of polycystic ovaries as a pre-requisite for the diagnosis of PCOS; however, this is notincluded in the current diagnostic criteria. These studiesdemonstrated that 2123%of unselected women appear to beaffected (6 8). In a recent study, using the current criteria forthe diagnosis of PCOS, the prevalence of PCOS in a popu-lation of unselected U.S. Black and White women was re-ported to be 4% (9). However, as there are significant ethnicand racial variations in the clinical presentation of PCOS, thefrequency of obesity, insulin resistance, and the incidence ofdiabetes mellitus, it seems reasonable that the prevalence ofPCOS could differ among different populations (10, 11).

The current study was undertaken 1) to determine theprevalence of the PCOS in a sample of the population of aGreek island, 2) to identify hormonal and metabolic param-etersof women with PCOS and, in particular, among women

Received December 30, 1998. Revision received May 19, 1999. Re-revision received July 28, 1999. Accepted June 18, 1999.

Address all correspondence and requests for reprints to: E. Diamanti-Kandarakis, M.D., First Department of Medicine, Laiko General Hos-pital, 17 Agiou Thoma Street, 115 27 Athens, Greece.

0021-972X/99/$03.00/0 Vol. 84, No. 1The Journal of Clinical Endocrinology & Metabolism Printed in U.S.ACopyright 1999 by The Endocrine Society

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with clinical signs of hyperandrogenemia, and 3) to inves-tigate associations of the above-mentioned clinical manifes-tations with family history of diabetes mellitus, menstrualdisorders, cardiovascular disease, hirsutism, and premature

baldness in male relatives.

Subjects and Methods

Subjects and protocol

We studied 192 women of reproductive age who lived on the Greekisland of Lesbos and accepted our invitationof free medical examination.A large scale informational campaign took place before the study fromthe localauthorities (local TV channel, newspaper,and radiostation).Allwomen were offered a free medical examination by an endocrinologist,and no reference was made to the specific disorders being studied. Theprotocol was approved by the institutional review committee of Bostan-ion General Hospital in Lesbos. The age of the women finally enrolledin this protocol ranged between 1745 yr. None of them received oralcontraceptives or other drugs that could interferewith thehormonalandmetabolic studies. All of them were clinically healthy, none of themsuffered from chronic or acute disease, andall were euthyroidaccordingto the clinical evaluation. Postmenopausal women were excluded fromthe study.

Personal medical history was obtained from every woman according

to a customizedpreprepared questionnaire. Menstrual cycle history wascarefully detected and included a general review since menarche and adetailed recall of the last 2- to 3-yr interval. Ovulatory dysfunction wasdefined as less than eight cycles per yr, and regular menstrual cycle as2634 days in length. Emphasis was placed upon family history re-garding diabetes mellitus in the first and second degree relatives, men-strual disorders, hirsutism, and early baldness in male relatives (fatherand/or brothers). A family history of menstrualdisorders andhirsutismwas positive when oligomenorrhea and/or hirsutism existed during theyouth of the mother according to the report of the studied women.Physical examination was performed in each person by two doctors.Obesity was assessed by estimating body mass index (BMI; weight/height2, kilograms per m2), with normal ranging between 1725.9, over-weight between 26 30, and obese over 30.1. Body fat distribution wasassessed by measurements of the waist to hip girth ratio (WHR) (12). AFerriman and Gallwey score of 6 or greater (F-G, 6) was consideredhirsutism (13). Additionally, blood pressure was measured in with sub-

jects in the sitting position, and the mean blood pressure (MBP) wasestimated [MBP diastolic (systolic/3)].According to the history and the physical examination, the subjects

under study were divided into four groups. Group N consisted ofwomen with normal menstrual cycles (35 days) and absence of hir-sutism (F-G, 6), group 1 included women with hirsutism and/or acneand regular menstrual cycles, group 2 included women with oligomen-orrhea and absence of hirsutism, and, lastly, group 3 included womenpresenting with oligomenorrhea and hirsutism.

Blood samples were collected between 08000900 h and plasma freetestosterone (FT; picograms per mL), sex hormone-binding globulin(SHBG; nanomoles per L), LH (units per L), FSH (units per L), fastinginsulin (microunits per mL), and glucose (milligrams per dL) weremeasured. The fasting glucose (FG) to insulin (FI) ratio was estimated(FG:I ratio; milligrams per 104 U) and was used as an indicator ofinsulin sensitivity (14). In the cases of impaired fasting glucose (FG,110125 mg/dL), a 75-g oral glucose tolerance test was performed;subjects with overt diabetes mellitus and impaired glucose tolerancewere excluded from the above metabolic study. Additionally, serumPRL (nanograms per mL), TSH (microunits per mL), and 17-hy-droxyprogesterone (17-OHProg; nanograms per mL) levels were de-tected in blood samples of women with oligomenorrhea (groups 2 and3) to exclude other causes of menstrual disorders (15, 16).

Diagnosis of PCOS

PCOS was diagnosed in women presenting with oligomenorrhea (asdefined above) and hyperandrogenism; related disorders with similarclinical presentation wereexcluded(1990 NIH ConsensusConferenceonthe PCOS). Hyperandrogenism was defined as FT levels above the 95th

percentile of the levels detected in the group of normal cycling nonhir-sute women (group N). The polycystic ovarian morphology detected byultrasound was not considered an essential criterion for the diagnosis ofthesyndrome, asit isreportedthatapproximately 20%of normalwomencould present the above ultrasonographic appearance (6).

Assays

Plasma glucose was determined by the glucose oxidase method (glu-cose analyzer, Beckman Coulter, Inc., Palo Alto, CA). Blood sampleswere centrifuged immediately, and serum was stored at 20 C untiassayed. Serum insulin levels were measured using the RIA INSU-LIN-CT kit from CIS-Bio International (Gif-sur-Yvette, France). Dupli-cate plasma samples were analyzed for FT using the commerciallyavailable Coat-A-Count Free Testosterone kit from Diagnostic Products(Los Angeles, CA). The absolute range for FT in ovulating females wasnondetectable to 3.9 pg/mL. SHBG serum levels were measured byimmunoradiometric assay (IRMA) using the SHBG IRMA 125I (RADIMS.A., Liege, Belgium). PRL was measured using the PRL IRMA kit fromMEDGENIX DIAGNOSTICS. 17OHProg levels were measured using aRIA kit from Diagnostics Systems Laboratories, Inc. (Wesbster, TX). LHand FSH were measured using the LHsp and FSH IRMA kits fromBiosource Technologies, Inc., Europe S.A. TSH was measured using thehuman TSHIRMA kit from INCSTAR Corp. (Stillwater,MN). Theintraand interassay coefficients of variation for FT were 4.3% and 5.5%, and3.2% and 3.4% for low and high levels respectively; for SHBG, they were5.1% and 5.1%, and 5.6% and 4.6%, respectively; for insulin, they were8.2% and8.8%,and 5.4% and6.4%,respectively; for PRL, they were 4.0%and 7.1%, and 6.4% and 6.8%, respectively; for 17OHProg, they were9.3% and 9.7%, and 9.5% and 10.8, respectively; for LH, they were 6.5%and 8.8%, and 3.5% and 4.5%, respectively; for FSH, they were 2.7% and5.3%, and 1.6% and 3.6%, respectively; and for TSH, they were 3.2% and5.7%, and 3.3% and 4.9%, respectively.

Statistical analysis

Results are reported as the mean se. Multivariate analysis of covariance, using BMI as a covariant, was performed. For individuacomparisons, Tukeys test for unequal sample sizeswas used.Regardingfamilyhistory cross-tabulation of thefour studied groups, residual analysis was performed using 2 as the statistical indicator. The partitioningof the table referring to family history in women with PCOS, the normaand the hirsute groups, was performed as described by Siegel andCastellan (17). Analysis was performed using the STATISTICA/w software package (version 5.1 98).

Results

Clinical characteristics

In the studied population, 108 of 192 women had regularmenstrual cycles as defined above and no signs of hyperan-drogenism (H/A), hirsutism, and/or acne (group N). Fifty-six of 192 women (29%) demonstrated hirsutism with a F-Gscore rangingfrom 612 and regular menstrual cycles (group1). Moreover, 18 of 192 women (9.4%) presented moderate tosevere hirsutism, with a F-G score ranging from 1320, andoligomenorrhea (O/M; group 3); 10 of these 18 women pre-

sented with acne. In all cases, hirsutism had an onset inadolescence and did not progressively worsen. Additionally10 of 192 examined women (5.2%) had menstrual disorderswithout hirsutism and/or acne (F-G, 6; group 2).

The characteristics (age, BMI, and WHR) of the fourgroups of the studied population are shown in Table 1. Nostatistically significant differences existed in age (group N33.1 0.7; group 1, 31.5 1.0; group 2, 35.0 3.2; group 324.6 1.1, yr), BMI (group N, 25.9 0.6; group 1, 27.2 0.7group 2, 28.7 2.7; group 3, 28.9 1.6 kg/m2), or WHR(group N, 0.77 0.01; group 1, 0.76 0.02; group 2, 0.73

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0.01; group 3, 0.77 0.03). MBP (group N, 80.7 1.2; group

1, 79.7 1.3; group 2, 88.0 4.4; group 3, 85.7 2.9 mm Hg)did not differ even after BMI and age were used as covariates.

Hormonal profile

The data are summarized in Table 1. Although the unad-justed mean values seare displayed in Table 1 and Fig. 1,theP values are taken from the data after covariance adjust-ing for changes in the BMI. Women with hirsutism only(group 1) compared to normal women (group N) showedhigher levels of FT (2.2 0.1 vs. 1.4 0.1 pg/mL; P 0.0001).Additionally, women with oligomenorrhea (group 2)showed higher FT levels compared to group N (FT; 2.7 0.2vs.1.4 0.1 pg/mL; P 0.005). Women with hirsutism andoligomenorrhea (group 3) had higher FT levels than those in

group 1 (3.5 0.2vs. 2.2 0.1 pg/mL; P 0.0001) or groupN (3.5 0.2 vs. 1.4 0.1 pg/mL; P 0.00001); no statisticallysignificant difference wasfound in FT levels between womenof group 3 and women of group 2 (Fig. 1).

Metabolic profile

One woman of group N had diabetes mellitus and was notincluded in the metabolic studies as well as two obese women,one from group 1 (hirsutism) and the other from group 3 (hir-sutism and O/M), who showed impaired glucose tolerance.

The data are summarized in Table 1. Although the unadjusted

mean seare displayed in Table 1 and Figs. 24, the P valuesare taken from the data after covariance adjusting for changesin the BMI. FG did not differ among the four groups, whereasFI in group 3 (hirsutism and O/M) was higher than that ingroup N (42.4 9.8vs.21.9 1.5 U/mL;P 0.005) or group1 (hirsutism; 42.4 9.8vs.27.1 1.6U/mL;P 0.05; Fig. 2)The FG:I ratio was lower in group 3 compared to group N(3.21 0.25 vs. 6.2 0.4 mg/104 U;P 0.05). Additionallywomen with simple hirsutism (group 1) had a lower FG:I ratiocompared to the normal women (4.45 0.3vs.6.2 0.4 mg/104 U; P 0.05; Fig. 3). SHBG levels in women with simplehirsutism (group 1) were lower than those in group N (44.4 1.9vs.56.9 2.7 nmol/L;P 0.02). Additionally, SHBG levelsin women with hirsutism and oligomenorrhea (group 3) were

lower than those in group N (30.3 4.0vs.56.9 2.7 nmol/LP 0.002; Fig. 4). There was a noticeable trend for an increasein fasting insulin levels and a decrease in the FG:I ratio andSHBG levels from group N to group 3 (Figs. 24).

Prevalence of PCOS

Women with hirsutism and/or oligomenorrhea (groups 2and 3) who presented with hyperandrogenemia were diagnosed as having PCOS. As defined, none of the subjectssuspected of PCOS had evidence of thyroid disease, hyper-

FIG. 1. MeanFT levelsin the fourstud-iedgroups andthe PCOS women (group

N, normal women; group HIRS, hirsut-ism; group O/M, oligomenorrhea; groupHIRSO/M, oligomenorrhea and hir-sutism). *, P 0.0001 vs. N; **, P 0.005vs. N; ***, P 0.0001 vs. N andHIRS.

TABLE 1. Clinical characteristics, mean blood pressure (MBP), fasting glucose (FG) and LH to FSH ratio of the studied population (totaln 192)

N(n 108)

HIRS(1)(n 56)

O/M (2)(n 10)

HIRSO/M(3)(n 18)

Age (yr) 33.1 0.7 31.5 1.0 35.0 3.2 25.8 1.7BMI (kg/m2) 25.9 0.6 27.2 0.7 28.7 2.7 28.9 1.6WHR 0.77 0.01 0.76 0.02 0.73 0.01 0.77 0.03

MBP (mm Hg) 80.7

1.2 79.7

1.3 88.0

4.4 85.7

2.9FG (mg/dL) 101.4 1.3 102.6 1.7 104.2 4.4 107.3 6.4LH/FSH 1.7 0.15 1.8 0.2 3.6 0.4 2.10 0.3

Values are the mean SE. No significant differences were observed by analysis of covariance. Groups accordingto clinical presentation: groupN, normal; group 1, HIRS (hirsutism); group 2, O/M (oligomenorrhea); and group 3, HIRSO/M.

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prolactinemia, Cushings syndrome, or androgenic tumor.21-Hydroxylase deficiency was excluded by measuring17OHProg; none of the suspected women had an initial levelabove 2 ng/ml, effectively ruling out the disorder (15). H/Awas defined as a FT level above the 95th percentile of themean value in the normal women (group N; i.e.3.3 pg/ml).Thirteen women fulfilled the criteria, 2 from group 2 (O/M)and 11 from group 3 (O/M and hirsutism). Therefore, the

prevalence of PCOS in thepopulation under study was6.77%(13 of 192). Moreover, 6 of 56 women from group 1 (10.7%)hadH/A according to theabove definition. However, as theyreported regular menses, they were not included in the es-timation of the prevalence of the syndrome.

Anthropometric, hormonal, and metabolic parameters of the

PCOS group

The 13 women diagnosed with PCOS were compared tothe normal and hirsute groups (groups N and 1, respective-

ly). Age (24.6 1.8, yr), BMI (28.6 1.8, kg/m2), WHR(0.78 0.04), and MBP (81.8 3.6 mm Hg) of the PCOSwomen did not differ compared to those in groups N and 1PCOS women had higher FI levels (46.3 13.5 U/mLcompared with groups N and 1 (P 0.002 and P 0.02respectively), whereas FG levels (108.1 8.9 mg/dL) did nodiffer (Fig. 2 and Table 1). The FG:I ratio (3.1 0.3, mg/104

U) and SHBG level (25.7 3.6 nmol/L) were also lower in

the PCOS group compared with the normal group (P 0.05and P 0.002, respectively; Figs. 3 and 4); these findingswere independent of the BMI. Finally, the LH to FSH ratio(2.0 0.2) did not differ compared with those in the othergroups.

Family history

The observed frequencies of positive family history re-garding diabetes mellitus, menstrual disorders, hirsutismand early baldness in male relatives are shown in Table 2.

FIG. 2. Mean FI levels in the four stud-iedgroups and thePCOS women (groupN, normal women; group HIRS, hirsut-ism; group O/M, oligomenorrhea; groupHIRSO/M, oligomenorrhea and hir-sutism). *,P 0.05vs.N and HIRS; **,P 0.02vs. N and HIRS.

FIG. 3. Mean FG:I ratio in the four studied groups and the PCOSwomen (group N, normal women; group HIRS, hirsutism; group O/M,oligomenorrhea; group HIRSO/M, oligomenorrhea and hirsutism).*, P 0.05 vs. N; **, P 0.05 vs. N.

FIG. 4. Mean SHBG levels in the four studied groups and the PCOSwomen (group N, normal women; group HIRS, hirsutism; group O/Moligomenorrhea; group HIRSO/M, oligomenorrhea and hirsutism)*, P 0.02vs. N; **, P 0.002vs. N.



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Women with hirsutism and/or oligomenorrhea (groups 2and 3) showed a more frequently positive family history ofdiabetes mellitus (60% and 66.6%, respectively; P 0.006)and menstrual disorders (40% and 33.3%, respectively; P 0.00001) compared with the normal and hirsute women(groups N and 1). Women with hirsutism, regardless of thepresence of menstrual irregularities (groups 1 and 3), moreoften had a positive family history of hirsutism (21.4% and39%, respectively; P 0.0001) than nonhirsute women(groups N and 2). A family history of premature baldness inmale relatives was less often observed in group N than in therest of the groups (P 0.04).

Women with PCOS showed a high incidence of a positivefamily history of diabetes mellitus, recorded in 71% (10 of 13;P 0.001), and of menstrual disorders, recorded in 46% (6of 13; P 0.01), compared with the regular cycling women(groups N and 1). A family history of hirsutism, recorded in30% (4 of 13), and premature male balding, recorded in 7.6%(1 of 13), did not prove to be more common in the PCOSgroup (Table 2).

Discussion

The prevalence of PCOS in the studied sample ofthe Greekpopulation was 6.77% (13 of 192), in accord within the rangeof the estimated prevalence (510%) (1). This also appears to

be close to the prevalence of PCOS in a sample of the U.S.population (Whites and Blacks) reported in a recent study byKnochenhauer et al. (9). In the present study the examinedpopulation was homogeneous regarding racial and ethnicvariations. This is the first study undertaken in Europe at-tempting to determine the prevalence of PCOS using thecurrent diagnostic criteria (NIH consensus 1990). The ultra-sonographic appearance of polycystic ovaries as a diagnostic

criterion is controversial and does not seem to be either asensitive or a specific finding (6, 18, 19). Taking into accountthe bioavailability of the androgens, FT was chosen to bemeasured for hormonal analysis as the most representativeovarian androgen with minimal menstrual variation (2022).

The incidence of oligomenorrhea (14.6%; 28 of 192) in thestudied population may be overestimated because of the def-inition we used, i.e. less than 8 cycle/yr; this definition was alsoused in the recent study by Knochenhauer et al.(9). H/A wasconfirmed in 6.77% of the examined women with oligomen-orrhea or oligomenorrhea and hirsutism. The majority of the

studied women fulfilling the criteria for PCOS (11 from theoverall 13) belonged to the group characterized by the mainclinical manifestations of the syndrome (group 3). In this groupwere included 18 women with oligomenorrhea and hirsut-ism/or acne. The remaining 7 women, with the clinical man-ifestations of the syndrome but without proven hyperandro-genemia (normal FT), cannot be entirely excluded from the

diagnosis of PCOS, because another nonmeasured androgencouldhave been elevated. Therefore, theprevalence of PCOS inour sample could have been approximately 10.4% (20 of 192) ifanother elevated androgen was detected.

PCOS women appeared to have fasting hyperinsulinemia,lower FG/I ratio, and decreased SHBG levels compared withthe normal women, independently of the BMI. Insulin resis-tance in PCOS has been estimated in small groups of women

by highly sophisticated methods (i.e. ivGTT, hyperinsulinemic-euglycemic clamps) (1, 3, 23). In this study, for the first time, weused fasting hyperinsulinemia and the FG/I ratio, which have

been considered adequate and sensitive screening markers forinsulin resistance, to determine in a large sample of premeno-pausal women the presence of insulin resistance in association

with hyperandrogenic manifestations (14, 24). The gradual in-crease, a dose-dependent-like pattern, of fasting insulin levelsfrom the group of normal women to the group with the clinicaand biochemical abnormalities of the syndrome, indicates thatthe severity of fasting hyperinsulinemia is associated with theseverity of the clinical phenotype, independently of the degreeof obesity. It is noteworthy that statistical significance isachieved between the group of normal women and the groupthat presents the full-blown syndrome. The above findingsuggests that fasting hyperinsulinemia is a characteristicaccompanying feature of PCOS (3, 23). It should also be notedthat obesity, defined as a BMI above 30 kg/m2, was observedin 38% (5 of 13) of the women with PCOS, consistent with otherreports (4, 9).

Regarding the metabolic studies, in women with idio-pathic hirsutism mean FI levels were in between the levels ofnormal and PCOS women without reaching statistical sig-nificance compared to the normal group. Nevertheless, theFG/I ratio was significantly lower in the studied hirsutewomen compared to normal women. This finding raises thequestion of whether women with so-called idiopathic hir-sutism are a heterogeneous group exhibiting not only a cos-metic problem but subtle metabolic disturbances as well.

The reported incidence of idiopathic hirsutism varies from515% in Caucasian women (13, 25). However, in our study29% (56 of 192) of the examined women presented withidiopathic hirsutism. This rather impressive percentagecould be due to the ethnic variation of the Mediterranean

people. The possible role of ethnicity in the prevalence andfeatures of PCOS has been reported in other populations (i.eCaribbean-Hispanic) (26, 27). Nevertheless, it should be

borne in mind that the recruitment of women in the presentstudy was not fully randomized, and that hairiness rep-resents for many women a cosmetic problem that meritsserious consideration. The studied women with idiopathichirsutism demonstrated a statistically significant lowerSHBG level and higher FT level compared to normal womenalthough the mean FT value was within the normal range. Itshould be noted that 10.7% of the studied hirsute women

TABLE 2. The observed frequencies (percentages) of positivefamily history in the four studied groups according the clinicalpresentation and in the PCOS group compared with the normal(N) and hirsute (HIRS) groups

N HIRS(1) O/M(2) O/MHIRS(3) PCOS

Diabetes mellitus 29.6 30.4 60a 66.6a 71b

Menstrual disorders 2.8 14.3 40c 33.3c 46d

Hirsutism 5.6 21.4

e

0 39

e

30Early baldness 5.6 14.3f 30 5.6f 7.6

Probability level (P) was estimated using 2 analysis.a P 0.006vs. the other groups.b P 0.001vs. groups N and HIRS(1).c P 0.04vs. the other groups.d P 0.01vs. groups N and HIRS(1).e P 0.0001 vs. the other groups.fP 0.04vs. the other groups.

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were hyperandrogenemic, with FT levels exceeding the 95thpercentile of the normal women. Therefore, idiopathic hir-sutism is not a homogeneous clinical and biochemical entityand, instead, may include a variety of disorders in androgenmetabolism (28) as well as subclinical metabolic aberrations.

Furthermore, nonhirsute women with oligomenorrhea pre-sented higher FT levels than normal women, independently of

BMI. Moreover, two of them had H/A, as defined, and werediagnosed with PCOS. As noted by other investigators, oligo-menorrhea seems to be associated with subtle or overt eleva-tions of androgens even in the absence of hirsutism or acne andmay present a discrete form of PCOS (29, 30).

It is controversial whether women with PCOS have elevatedblood pressure. In the studied population, mean blood pres-sure, estimated by a random measurement, did not differ inwomen with PCOS and normal women. This observation is inaccordance with other studies focussed on this matter (31).

Regarding family history, we observed a high incidence offamily history of menstrual disorders in women with PCOS, inaccordance with the general view that PCOS has a strong fa-milial component (10, 32, 33). Another observation was that

hirsute women reported a strong family history of hirsutism; itseems that familiar and ethnic aspects should be taken intoconsideration. Additionally, women with PCOS reported ahigh, statistically significant incidence of family history of di-abetes mellitus compared to normal and hirsute women. Thisobservation may imply that the genetic trait of PCOS is asso-ciatedwith a diabetogene(s), and it should be further examinedin large scale studies, focussing on the prevalence of a familyhistory of diabetes mellitus in PCOS. Additionally, a familyhistory of diabetesmellituscould haveinfluenced themetabolicprofile in the studied women with PCOS. However, the onlysupporting evidence on this matter has been provided by in-sulin secretory abnormalities in women with PCOS and a fam-ily history of diabetes mellitus, assessed by sophisticated meth-

ods in a study by Erhmann et al.

(23). On the other hand, thepresence of insulin resistance, which is a distinct feature ofPCOS, seems to be independentof thefamily history of diabetesmellitus up to the third decade of life (34).

In conclusion, in the Greek population studied, PCOS isconsidered to be a common endocrine disorder, with a prev-alence of 6.77%. The metabolic abnormalities, in particularfasting hyperinsulinemia and FG:I ratio, seem to accompanythe severity of the clinical phenotype, covering the spectrumof hyperandrogenic disorders in the studied groups ofwomen, independently of obesity. These data also suggestthat women with hirsutism and regular menses constitute aheterogeneous group as far as hormonal and metabolic pa-rameters are concerned. Additionally, the incidence as well

as the role of family history of diabetes mellitus in womenwith PCOS should be considered in terms of its possibleimplication in the pathogenesis of the syndrome.

References

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