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Polycystic Ovarian Syndrome (PCOS) is
the most common endocrine abnormality in reproductive-aged
women affecting approximately 5-10% of this population.
The classic triad of this syndrome consists of chronic
ovulation dysfunction, hirsutism (male pattern hair
growth) and obesity. The exciting news recently involves
understanding the contribution of insulin resistance
to the etiology and treatment of PCOS as well as the
recent addition of ultrasound as a diagnostic tool.
PCOS involves a "vicious cycle"
of hormonal imbalance that may begin with a hypersensitivity
of the pituitary to GnRH. The pituitary responds with
an increase in LH secretion resulting in increased ovarian
androgen production by the ovarian thecal cells. Consequently,
FSH production is inhibited thereby further preventing
follicle development and ovulation. Additionally, estrone
proliferates the endometrium unopposed and increases
the risk of endometrial hyperplasia and possibly cancer.
To summarize, PCOS is perpetuated by tonic elevations
of LH resulting in hyperandrogenemia and chronic anovulation.
PCOS is usually diagnosed clinically in
women who present with oligomenorrhea (menstrual intervals
>35 days), hyperandrogenism (elevated testosterone
or hirsutism/acne) and obesity, after excluding other
hormonal disorders. However, most women with PCOS do
not exhibit all of these features and there is a considerable
controversy about the definition and required criteria
for the diagnosis. The new criteria include two of the
following three signs: ovulation dysfunction; excessive
hair growth and/or acne; and polycystic appearing ovaries
on ultrasound.
The clinical presentation and medical
consequences of PCOS include: infertility; abnormal
uterine bleeding with the risk of endometrial hyperplasia
(a precancerous change to the uterine lining); hyperandrogenism;
obesity; insulin resistance with the risk of impaired
glucose tolerance and diabetes. Insulin resistance is
a key finding in the "metabolic syndrome"
along with elevated cholesterol, triglycerides, blood
pressure, and waist circumference.
Polycystic ovary syndrome is primarily a clinical diagnosis,
and laboratory findings should only be used to support
the clinical testing and rule out other serious disorders.
Evaluation should include measurement of thyroid-stimulating
hormone (TSH),
prolactin, and in some cases, morning 17alpha hydroxyprogesterone
to rule
out late-onset adrenal hyperplasia. Patients, regardless
of age, with a greater than 3 month menstrual interval
and/or an endometrial thickness of >= 7mm on ultrasound
should undergo an endometrial biopsy to assess the risk
of hyperplasia. Insulin resistance can best be evaluated
by a 2-hour glucose tolerance test (GTT).
Weight reduction, diet and exercise
are recommended for all women with PCOS. Some studies
have also shown a 5-10% loss in body weight may result
in a return of
ovulatory cycles and a higher spontaneous pregnancy
rate.
Monthly progestin therapy can be used
to prevent abnormal endometrial proliferation by
inducing withdrawal bleeding. Another option for these
women is to use low dose oral contraceptive pills (OCP)
to regulate the menstrual cycle and provide contraception.
Antiandrogens may be combined with oral contraceptive
pills for the treatment of hirsutism and acne.
In patients desiring pregnancy, ovulation
induction is often required usually with clomiphene
citrate. Approximately 80% of women with PCOS ovulate
in response to
clomiphene, but only about 40% of them become pregnant.
Most recently, an enzyme inhibitor of aromatase, letrozole,
has been shown to have equal success as clomiphene with
ovulation but less of a negative impact on endometrial
proliferation. (Of note, this is a non -FDA approved
use of letrozole and recently the drug manufacturer
has advised against its use in women pursuing pregnancy.)
Insulin resistance has been implicated
in the reproductive consequences of PCOS, namely infertility,
miscarriage, and gestational diabetes. Multiple studies
have supported the use of metformin to ameliorate these
problems. The dose and duration of metformin has not
been determined and there has been no definitive evidence
for birth defects.
Ovarian surgery has been an effective
therapy for patients resistant to clomiphene citrate
and/or letrozole. Laparoscopy with bilateral ovarian
diathermy involves "drilling" holes in the
ovary utilizing electrocautery or laser providing an
approximate 84% ovulation induction rate and 56% pregnancy
rate with maintenance of ovulation demonstrated for
up to 20 years in the majority of patients.
PCOS is a chronic condition that can be successfully
managed with close surveillance. Approaches are directed
at preventing potential long-term consequences of chronic
anovulation (abnormal uterine bleeding and endometrial
hyperplasia), the metabolic abnormalities associated
with the syndrome (insulin resistance and diabetes),
treating infertility, as well as improving the external
manifestations of hyperandrogenism (hirsutism and acne).
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Sam
Thatcher MD, Ph.D.
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Shahab
S. Minassian, M.D.,
Drexel Fertility and Reproductive Endocrinology
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