tionnaire regarding symptoms of PCOS among their immediate family, metabolically.
metabolically. The aim of this study was to investigate the metabolic,
aunts and female cousins. The diagnosis of PCOS was based on hormonal
evidence of hyperandrogenism, anovulation, and exclusion of other causes
of androgen excess. Forty-eight patients with a history of regular ovulatory
menses without hirsutism or infertility served as controls. Analysis was
performed with SPSS using chi-squared.
Results: In relatives of PCOS when compared to controls: A) Hirsutism
was significantly more common in mothers (25%), sisters (22%), aunts
(18%) and cousins (16%)(p 0.05). No hirsutism was reported among
controls; B) Anovulation was more common in mothers (30% vs. 4%, p
0.01), aunts (18% vs. 0%, p 0.01) and cousins (11% vs. 0%, p 0.05)
but not sisters; C) Infertility was statistically increased (p 0.05) in sisters
(13%) and aunts (20%) but not in mothers or cousins; D) The prevalence of
premature balding was not increase among fathers (p 0.225) and brothers
(p 0.122).
Conclusions: 1) Hirsutism is more common among female relatives of
PCOS, while anovulation and infertility may occur with increased fre-
quency in select subsets of relatives. These data subscribe to the hereditary
nature of PCOS. 2) Mothers of PCOS patients report increased hirsutism
which is consistent with the disorder. Unexpectedly, infertility was not more
common among this generation. 3) Premature balding was not found to be
more common among male relatives of PCOS patients and therefore, may
not be a marker for the male phenotype.
P-315
The pubertal presentation of polycystic ovary syndrome (PCOS). Song
L. Nguyen, Michael H. Dahan, Iroso Abu, Richard Y. Yoo, Ketan S. Patel,
R. Jeffrey Chang. Univ of CA, San Diego, San Diego, CA; Univ of CA,
Davis, Davis, CA.
Objective: The adolescent presentation of PCOS is poorly understood
with reports indicating earlier development of certain pubertal symptoms.
The purpose of this pilot study is to determine clinical manifestations of
adolescent PCOS.
Design: A closed and open ended questionnaire directed at PCOS and
normal control patients regarding the onset of puberty.
Materials/Methods: Sixty-seven adult PCOS patients from the PCOS
Association and UCSD clinics responded to the questionnaire. Inclusion
criteria for PCOS patients: clinical and hormonal evidence of hyperandro-
genism, anovulation, and exclusion of other causes of androgen excess.
Forty-eight patients with regular ovulatory menses and without hyperan-
drogenism, hirsutism or infertility served as controls. Analysis was per-
formed with SPSS using chi-squared and Student t test.
Results: In PCOS thelarche, 10.8 1.8 yrs vs. 11.8 1.5 yrs (p 0.002)
and menarche, 12.3 1.7 yrs vs. 13.0 1.4 yrs (p 0.01) occurred at an
earlier age than controls. In a chi-squared analysis, 15% of PCOS patients
reported pubic hair growth before age 8 as opposed to 0% in the control
group (p 0.005). In 33% of PCOS regular menses occurred at a later age
than controls, 16.7 8.4 yrs vs. 14.2 2.6 yrs (p 0.04). Thirty-three
percent of PCOS patients reported being obese as a child as compared to
only 8% of the control (p 0.002), childhood acanthosis nigricans was
more prevalent in the PCOS group, 16% vs. 4% (p 0.03), and 47% of
PCOS patients tended to become sleepy after meals as children as compared
to only 8% of the control group (p 0.0001).
Conclusions: 1) A minority of PCOS patients reported a history of
premature pubarche. 2) Thelarche and menarche occurred earlier in PCOS
patients compared to controls. 3) These pubertal events may have been the
result of hyperandrogenism or increased body mass index. 4) Clinical
symptoms in PCOS at puberty suggest increased frequency of insulin
resistance.
P-316
The clinical, metabolic and endocrinologic effects of metformin treat-
ment in polycystic ovarian syndrome. Gurkan Uncu, Turkan Atakan,
Osman Develioglu, Mehpare Tufekci. Uludag Univ, Faculty of Medicine,
Bursa, Turkey.
Objective: Polycystic ovarian syndrome (PCOS) is a heterogeneous dis-
ease characterized with oligomenorrheic or amenorrheic cycles, hirsutism,
acne, obesity. . .clinically, elevated LH/FSH ratio, high serum androgens
levels. . .hormonally and hyperinsulinism, carbonhydrate intolerance. . .
FERTILITY & STERILITY
hormonal, and clinical effects of metformin, insulin sensitizing treatment, in
all PCOS cases.
Design: Prospective, open, uncontrolled.
Materials/Methods: The study was performed with 32 PCOS patients
diagnosed with clinical and hormonal parameters in Uludag University,
Faculty of Medicine, Department of Obstetrics and Gynecology, Reproduc-
tive Endocrinology and Infertility Unit between March 2000 and August
2001. Clinical parameters (body mass index, Ferriman Gallway score. . .), 3
day serum hormone levels (LH, FSH, androgens. . .) were determined and
75g oral glucose tolerance test was performed concomitantly with serum
insulin and C-peptide levels. Metformin, 850mg bid, were given to all
patients and at the 6 month of treatment, all parameters were re-evaluated.
Results: Twenty-five of 32 patients were re-evaluated at the 6 month of
treatment. Oligomenorrhea and amenorrhea turned to regular cycles in 19 of
25 patients (76%) and these patients were called as responders. In respond-
ers (n:19); the mean body mass index decreased significantly from 24.1
5.4 to 23.5 4.81. The mean total and free testosterone levels decreased
significantly at the end of treatment (total testosterone; ng/ml,137.3 45.1
to 90.0 51.6, free testosterone; pq/ml, 3.0 1.9 to 2.1 1.3). The
fasting, 30 minutes, 90 minutes and 120 minutes serum insulin levels
decreased in responders. The mean glucose/insulin ratio was 4.9 2.0
before treatment, and 8.5 3.8 after treatment. Zero, 30, 90, and 120
minutes insulin/C-peptide ratio dcreased significantly in responders. In
non-responders (n:6); Hormonal parameters did not change statistically.
Although the mean serum insulin level at 0 and 30 minutes decreased
significantly, the mean glucose/insulin and insulin/C-peptide level did not
change at the end of treatment. There was no statistically significant differ-
ence between responders and non-responders regarding to hormonal, clin-
ical and metabolic parameters prior to therapy except serum androstenedion
levels. The mean androstenedion level was higher in non responders (2.0
0.8) than responders ( 1.4 0.4), prior to treatment.
Conclusions: Since the serum androgen levels decreased significantly in
responders, it can be easily said that hyperandrogenism is secondary to
hyperinsulinism. Metformin is an highly effective drug in the treatment of
PCOS and can be used without any limitation regarding to insulin resistance
since there was no diference in clinical, metabolic and hormonal parameters
between responders and non-responders prior to treatment. We need the
studies to reveal which patients are responders, in the future.
Supported by: The study was not suppported.
P-317
Association of thrombophilias in women with unexplained recurrent
pregnancy loss (RPL). Trine N. Bagous, Leslie Norman, Raymond Ke,
William H. Kutteh. Univ of Tennessee, Memphis, TN.
Objective: Recurrent pregnancy loss (RPL) affects 2% to 5% of couples
and represents a major concern for reproductive medicine specialists. De-
spite extensive chromosomal, endocrine, anatomic and microbiologic eval-
uation 30% to 40% of cases remain unexplained. Certain coagulation
disorders, such as anticardiolipin antibodies (ACA) and lupus anticoagulant
(LAC), may predispose women to placental thrombosis and have been
associated with RPL. Other abnormalities leading to hypercoagulable states
include mutations such as Factor V Leiden (G1691A), Factor II-prothrom-
bin (G20210A) and hyperhomocysteinemia (thermolabile MTHFR C677T)
as well as deficiencies of Protein C, Protein S and Antithrombin III. We
explored the possible association of these markers of thrombophilia with
unexplained RPL.
Design: Single-center, prospective thrombophilic evaluation of women
who were found to have unexplained RPL.
Materials/Methods: Patients were included if they had at least two con-
secutive pregnancy losses and agreed to participate in the study. All women
had a complete evaluation for RPL including karyotypes on both partners,
hysterosalpingogram or hysteroscopy, endocrine tests (midluteal progester-
one, TSH, prolactin, fasting insulin and glucose), and cervical cultures for
chlamydia and mycoplasma. The thrombophilic workup included the fol-
lowing: ACA, LAC, activated prothrombin time (APTT), thrombin time
(TT), Protein C, Protein S, Antithrombin III, Factor V Leiden, and homo-
cysteine. Anticardiolipin antibodies were detected in serum by ELISA.
LAC, APTT, and TT were detected by in vitro coagulation tests. Factor V
Leiden was detected by polymerase chain reaction. Protein C, Protein S, and
antithrombin III were quantitated from citrated platelet-poor plasma. Ho-
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