Articles
Register for PCOS and Genetics
ESHRE XXV, Amsterdam
June 29 - July 1, 2009
Two studies on polycystic ovarian syndrome shed light on its causes and its
effect on brothers of women with the condition
Researchers have found evidence that chronic disease in either a mother or
father can create unfavourable conditions in the womb that are associated with
the development of polycystic ovarian syndrome (PCOS) in daughters. In another
study, researchers found that brothers of women with PCOS and insulin resistance
are themselves at greater risk of developing insulin resistance or diabetes,
suggesting that factors associated with the condition can be passed down to sons
as well as daughters.
The two studies were presented to the 25th annual meeting of the European
Society of Human Reproduction and Embryology in Amsterdam heard today (Tuesday).
Associate Professor Michael Davies told a news briefing: “We already know from
clinical studies of women with reproductive problems that foetal growth
restriction is associated with the development of PCOS symptoms in daughters,
and that problems during pregnancy and in the way the mother adapts to the
metabolic challenge of pregnancy can indicate the future cardiovascular health
of both the mother and the child. What we don’t know is whether giving birth to
a daughter who later develops PCOS is associated with increased, long term
cardiovascular disease risk in the mother. Nor do we know whether conditions
underlying chronic disease in the father increases the risk of PCOS in the
daughter.”
Prof Davies, co-director of the Research Centre for the Early Origins of Health
and Disease at the University of Adelaide (Australia), looked at records for all
female babies who were born and survived between 1973-1976 at The Queen
Elizabeth Hospital in Adelaide. He and his colleagues interviewed the daughters
to build up a picture of their health and any history of chronic disease in
their parents. So far, 998 (63%) have responded, and Prof Davies reported
preliminary data up to mid-1975 to the conference.
Sixty-two daughters (6.2% of the group) had a pre-existing diagnosis of PCOS.
Mothers of these women tended to have elevated blood pressure during pregnancy.
Daughters were nearly eight times as likely to have PCOS if their mothers had
it, and they had a slightly higher risk if their mothers smoked during
pregnancy. Mothers were 1.6 times as likely to have high blood pressure in later
life if their daughters developed PCOS. If their fathers had heart disease or
stroke, the daughters also had a higher risk of PCOS: double and three times the
risk respectively. A history of diabetes in either parent was not significant.
Prof Davies said: “These findings suggest a new pathway for the development of
PCOS. We think that factors associated with the pre-existence of cardiovascular
dysfunction in the mother or the father, and which operate during pregnancy, may
create adverse conditions for the foetus, which alter the metabolic profile of
offspring, leading to insulin resistance and reproductive consequences, such as
PCOS, for daughters. A family history of diabetes is, therefore, not essential
to observe an insulin resistance-related disease in offspring.”
He said it was still unclear exactly how the cardiovascular risk in the father
affected the daughter. “We firstly need to consider the potential role of a
common environment; for instance, that families with high levels of obesity (and
therefore cardiovascular disease) will also tend to have heavy daughters who are
thereby more likely to be affected by PCOS. However, the paternal effect that we
saw was independent of the daughter’s weight, maternal age, socioeconomic
status, maternal smoking, and country of birth, which suggests either a direct
genetic effect on the daughter, or an effect of paternal genetic factors that
are expressed during pregnancy.”
Dr Verena Mattle told the news briefing that her study was the first to show
that brothers of women who had PCOS and insulin resistance were themselves more
likely to develop insulin resistance or even diabetes or dyslipidaemia (a
disruption in the levels of lipids (or fats) in the blood).
“Until now, it was not clear whether the male relatives of women with PCOS were
at increased risk for the metabolic disorders associated with PCOS,” said Dr
Mattle, who is chief resident at the University Clinic of Gynecological
Endocrinology and Reproduction Medicine in Innsbruck (Austria).
Dr Mattle and her colleagues conducted oral glucose tolerance tests on 15
brothers of sisters with PCOS and insulin resistance (group 1). They also
performed a serum analysis to determine lipid levels. As a control, nine
brothers of sisters with PCOS but without insulin resistance were included in
the study (group 2).
The researchers found that in the first group eight brothers showed an insulin
resistance, one was diagnosed with diabetes and six had a normal glucose
tolerance test. All nine affected brothers had a body mass index (BMI) between
19-31 kg/m2 and had elevated cholesterol and triglyceride levels. The six
unaffected brothers had a BMI between 23-29, and none had high levels of
cholesterol or triglycerides. In the second group, no insulin resistance was
diagnosed. BMI was between 18-27 and two brothers had elevated cholesterol
levels. Although there was a trend towards higher BMI in the first group, Dr
Mattle said there was no statistically significant difference in BMIs between
the two groups.
Dr Mattle said: “These results mean that we should pay attention to the health
not only of women with PCOS but also to their brothers as they seem to have an
increased risk for the medical problems that make up the metabolic syndrome,
such as insulin resistance, diabetes and cardiovascular disease. Our findings
are also in accordance with the hypothesis that not only is PCOS is a heritable
disease, but that factors associated with it, such as insulin resistance, can be
passed down to the next generation of either sex.”
She said that it could not be the case that the high BMI by itself could have
caused the insulin resistance and diabetes in the affected brothers. “There must
be a correlation between PCOS and insulin resistance because we could only find
brothers with insulin resistance in the group that had sisters with PCOS and
insulin resistance, but we couldn’t find brothers with insulin resistance in the
group that had sisters with PCOS and no insulin resistance. It is known that
about 50% of women with PCOS are insulin resistant and also that lean PCOS
patients are insulin resistant. The BMI of insulin-resistant and non-resistant
brothers were not statistically different.”
Dr Mattle and her colleagues are continuing to test brothers of women with PCOS
for insulin resistance and lipid levels to collect more data from a larger
group. “At this stage we would hesitate to say that a genetic inheritance is
definitely playing a role in the increased risk of insulin resistance and other,
related conditions in these brothers. We need to explore the possible effect of
conditions in the womb and also the role of the environment. However, we think
our data strongly support the view that brothers of women with PCOS and insulin
resistance may have an increased risk of insulin resistance, diabetes and other,
adverse metabolic conditions,” she concluded
