Mothers of women with a
common endocrine disorder -- polycystic ovary syndrome (PCOS) -- provide
evidence that menstrual irregularity and unhealthy metabolic traits
associated with PCOS are inherited and persist with age, according to a new
study published today in the Proceedings of the National Academy of
Sciences (www.pnas).
"There have been few studies looking at the long-term consequences of
PCOS," said senior author Andrea Dunaif, M.D., President of The Endocrine
Society and Chief of Endocrinology, Metabolism and Molecular Medicine of
the Feinberg School of Medicine at Northwestern University in Chicago. "The
results of our study strongly suggest that metabolic problems will continue
as women with PCOS age, putting them at a high risk for cardiovascular
disease and type 2 diabetes."
PCOS is a common problem affecting about 7% young adult women. Women
with this disorder have irregular menstrual cycles and elevated levels of
male hormones, or androgens, which may result in excessive facial hair
growth and acne. PCOS is frequently also associated with insulin resistance
and the syndrome is a leading cause of type 2 diabetes in adolescent and
young adult women. Women with PCOS also have elevations of low-density
lipoprotein (LDL, or "bad") cholesterol and a markedly increased prevalence
of a condition called metabolic syndrome. Another negative health feature
of PCOS is abnormal lipid levels, but the reasons are controversial.
Insulin resistance, type 2 diabetes, increased LDL levels and metabolic
syndrome all increase risk for cardiovascular disease.
Studies of women with PCOS, by definition, have been limited to women
in their reproductive years; therefore, little is known about their health
as they age. The long-term health consequences of PCOS are of considerable
importance because many of these women have risk factors that confer
substantially increased risk for developing cardiovascular disease and
other problems. It is well documented that PCOS runs in families. Though
limited, past studies of mothers of women with PCOS have shown increased
androgen levels, insulin resistance, and glucose intolerance, suggesting
that these traits are inherited.
Armed with this information, Dr. Dunaif and colleagues, Susan Sam, M.D.
and Richard S. Legro, M.D., of Pennsylvania State University College of
Medicine, in Hershey, Pa., wanted to test their hypothesis that abnormal
lipid levels are an inherited trait in families of women with PCOS as well
as look at the impact of age on reproductive and metabolic characteristics.
They studied 215 non-Hispanic white mothers of women with PCOS and 62
control women of comparable age, weight, and ethnicity, drawn from the
National Health and Nutrition Examination Survey III (NHANES III). The
study group was limited to non-Hispanic white women because of the
potential confounding effects of ethnicity on insulin sensitivity and lipid
levels. All participants were asked to complete a questionnaire on their
reproductive history, exercise habits, tobacco use, and alcohol intake.
In investigating lipid levels, the researchers found that mothers of
women with PCOS had elevated total and LDL cholesterol but triglycerides
and high- density lipoprotein (HDL, or "good") cholesterol did not differ
between the groups. The mothers had markers of insulin resistance. They
also had an increased prevalence of metabolic syndrome compared to
nationwide prevalence in normal women of similar age. The strongest
predictor of LDL levels in mothers was their daughters' LDL levels. The
researchers had previously found that elevated LDL levels are the
predominant lipid abnormality in women with PCOS, a finding that was
mirrored in the mothers' group.
Thirty-one percent of mothers reported a history of irregular menses.
There were no differences in age or body mass index between these mothers
and those with a history of regular menses. Mothers with menstrual issues
also had higher levels of androgens, glucose, and LDL compared with mothers
with a history of regular menses, suggesting, say researchers, that these
mothers may have had PCOS. Total testosterone and unbound testosterone
levels were higher in mothers with a history of irregular menses than in
the controls. The prevalence of hyperandrogenemia was likely underestimated
in this study because of a general decline in ovarian function with age,
which leads to lower circulating androgen levels.
"Our study shows that menstrual history is an accurate marker for PCOS
in both epidemiologic and genetic studies," said Dr. Legro.
Forty-seven percent of mothers had metabolic syndrome compared with 32
percent of the control group. There was a significant increase in the
prevalence of metabolic syndrome in obese mothers compared with the general
population represented by the women in NHANES III. Moreover, the
researchers believe that the prevalence of metabolic syndrome in mothers is
underestimated because mothers receiving medications for hypertension,
diabetes, or hyperlipidemia were excluded. Overall, these findings suggest
that mothers of women with PCOS should be screened for cardiovascular
disease risk factors.
This study was supported by grants from the National Institutes of
Health National Institute of Child Health and Human Development and Office
of Research on Women's Health.
Founded in 1916, The Endocrine Society is the world's oldest, largest,
and most active organization devoted to research on hormones, and the
clinical practice of endocrinology. Endocrinologists are specially trained
doctors who diagnose, treat and conduct basic and clinical research on
complex hormonal disorders such as diabetes, thyroid disease, osteoporosis,
obesity, hypertension, cholesterol and reproductive disorders. Today, The
Endocrine Society's membership consists of over 13,000 scientists,
physicians, educators, nurses and students, in more than 80 countries.
Together, these members represent all basic, applied, and clinical
interests in endocrinology. The Endocrine Society is based in Chevy Chase,
Maryland. To learn more about the Society, and the field of endocrinology,
visit the Society's web site at www.endo-society
The Endocrine Society
www.endo-society
www.pnas
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