Androgens in Health and Disease.pdf - E Library

Chapter 7/Androgen Excess Disorders in Women 129
medications. Women with PCOS are at especially increased risks of ovarian hyperstimulation
syndrome, a syndrome of massive enlargement of the ovaries and transudation of
ascites into the abdominal cavity that can lead to rapid and symptomatic enlargement of
the abdomen, intravascular contraction, hypercoagulability, and systemic organ dysfunction
(13). They are also at increased risk for multiple pregnancy. There is also
emerging evidence that baseline hyperinsulinemia may contribute to the increased ovarian
hyperstimulation syndrome (OHSS) risk (14,15).
GYNECOLOGICAL CANCERS
Many gynecological cancers have been reported to be more common in women with
PCOS, including ovarian, breast, and endometrial cancer. The best case of an association
between PCOS and cancer can be made for endometrial cancer. Many risk factors for
endometrial cancer, including obesity, chronic anovulation, hypertension, and type 2
diabetes overlap with the PCOS phenotype (16). It is unknown how many induced
withdrawal bleeds/yr are necessary to provide adequate prophylaxis against the development
of uterine cancer in the PCOS population.
TYPE 2 DIABETES MELLITUS
Women with PCOS have been found to be profoundly insulin resistant at the skeletal
muscle. The mechanism is unknown. This baseline insulin resistance combined with the
worsening effect of obesity (which may affect up to 50% of the American PCOS population)
places these women at increased risk for impaired glucose tolerance and type 2
diabetes. About 30–40% of obese reproductive-age women with PCOS have been found
to have impaired glucose tolerance, and about 10% have type 2 diabetes based on a 2-h
glucose level > 200 mg/dL (17,18). Of note is that only a small fraction of women with
PCOS with either impaired glucose tolerance (IGT) or type 2 diabetes display fasting
hyperglycemia consistent with type 2 diabetes by the 1997 American Diabetes Association
criteria (fasting glucose ≥ 126 mg/dL) (19). The conversion rate to glucose intolerance
over time is uncertain, which makes recommendations for frequency of screening
for glucose intolerance difficult. The level of insulin resistance found in women with
PCOS based on dynamic measures of insulin action has, in other populations (i.e.,
children of parents with diabetes), been associated with a marked increased risk of
developing type 2 diabetes mellitus.
CARDIOVASCULAR DISEASE
Many of the studies suggesting an increased incidence of cardiovascular disease in
PCOS are inferential and are based on risk-factor models. Women with PCOS appear to
form a subset of the insulin-resistance syndrome. The insulin-resistance syndrome, which
consists of a constellation of symptoms, including insulin resistance, hypertension, and
lipid abnormalities, has been linked to increased risk for diabetes and cardiovascular
disease (20). In individuals with essential hypertension, insulin resistance results from
impairment of insulin action in peripheral tissues, primarily muscle (21). Several reasons
in addition to the abnormalities in glucose metabolism discussed here have been suggested
to account for this relationship between hyperinsulinemia and hypertension,
including sodium retention, overactivity of the sympathetic nervous system, impairment
of membrane transport, and stimulation of vascular smooth muscle cells (22).
Other effects of hyperinsulinemia and insulin resistance include the development of
an atherogenic plasma lipid profile resulting from insulin enhancement of synthesis of