CHAMPAIGN, Ill. --
Many women in the menopausal transition experience hot flashes:
unpredictable, sometimes disruptive, periods of intense heat in the
upper torso, neck and face. Although generations of physicians have
prescribed hormones to reduce these symptoms, very little research
has focused on the underlying causes of hot flashes.
Three new studies explore the role of
genes, obesity and alcohol consumption in contributing to -- or
lessening -- the intensity and frequency of hot flashes in midlife
women. These studies are part of a five-year research effort led by
University of Illinois
biosciences professor Jodi Flaws and colleagues at the
University of Maryland, Mercy Medical Center in Baltimore and the
School of Medicine at Johns Hopkins University.
Physicians have long
noted that some factors, such as smoking, increase the likelihood
that a woman will experience more
-- or more intense -- hot flashes than other women. Race also
appears to play a role, with African-American women at higher risk
than others. But the mechanisms that cause some women to suffer from
severe (frequent and intense) hot flashes have remained a mystery.
"Even though more than 40 million
women experience hot flashes each year," the authors wrote in their
paper published in Maturitas, "little is known about the factors
that predispose women to hot flashes."
To examine whether genetics might play
a role in hot flashes, Flaws and her colleagues conducted a
cross-sectional study involving 639 women aged 45 to 54. The
researchers looked at individual differences in the genes that code
for various hormones. An earlier study by the same team had found
that one of these genetic polymorphisms, in an estrogen-metabolizing
enzyme, cytochrome P450 1B1, was more common in women who reported
higher-than-average frequency, intensity and duration of hot
study tied the same genetic polymorphism to lower levels of an
androgen known as DHEA-S and to lower progesterone levels.
These are the first studies to find
evidence of a genetic basis for hot flashes, and the first to look
at genetic polymorphisms associated with hormone levels in healthy
women with and without hot flashes.
The progesterone finding is of
particular interest, said Flaws, because the medical community has
focused almost exclusively on the role of low estrogen levels in
bringing on hot flashes. Hormone replacement therapy, which is
sometimes offered to women to alleviate hot flashes or other
symptoms of the menopausal transition, may include one or more
estrogens alone or in combination with progesterone or an analogue,
think there should be more studies looking at the role of
progesterone in causing hot flashes," Flaws said.
The research team identified a second
polymorphism, in a gene encoding the enzyme 3-beta-hydroxysteroid
dehydrogenase, which also is associated with an increase in hot
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didn't think of hot flashes as having a genetic component," Flaws
said. "Now we have some evidence that there is at least in part some
genetics behind it."
In another paper, published in the
journal Climacteric, the researchers used the same data to analyze
the link between obesity and hot flashes. They had shown in an
earlier study that obesity is associated with more frequent and
intense hot flashes in midlife women. They now wanted to see what
might be causing this effect: Did the higher incidence of hot
flashes in obese women correlate with varying levels of specific
hormones or other factors?
When looking at blood levels of
specific hormones and related enzymes, the researchers found a
significant link between obesity and hormone levels. Higher body
mass index was significantly correlated with higher testosterone and
lower total estradiol, estrone, progesterone and sex hormone binding
globulin in midlife women.
The researchers were surprised by the
findings related to estrogen, because adipose tissue produces and
stores estradiol, the major estrogen in humans. Most people had
assumed that obese women would have higher circulating estrogen
levels because of this, Flaws said. That assumption turned out to be
incorrect, at least for women in midlife.
"It could be that estrogen levels are
higher in the fat but not circulating in the blood," she said. "It's
the blood that gets to the brain and to the thermoregulatory centers
that govern hot flashes."
A third analysis, published in the
journal Fertility and Sterility, examined the influence of alcohol
consumption on hot flashes in midlife women.
This study attempted to explain an
earlier finding that moderate alcohol consumption (up to three
drinks per month) actually reduced the severity of hot flashes by 25
percent. This effect vanished in women who consumed more than three
drinks per month.
Because alcohol consumption is known
to affect metabolism in some animals, the team thought that light
drinking might alter sex steroid hormone levels in midlife women.
But their analysis failed to turn up any significant hormonal
differences between the alcohol users and the women who never used
don't know why (moderate alcohol consumption) is reducing the risk
of hot flashes, other than it doesn't seem to be doing so by
changing hormone levels," Flaws said.
Together, these studies point to some
risk factors for hot flashes that women can change and others that
cannot be changed, Flaws said.
"Body mass index, alcohol use and
smoking are three things that can change," she said. "So probably if
women quit smoking and they lose weight, it will reduce their risk.
If they (engage in) light drinking, that might also reduce the risk
of hot flashes. And then there's the genetic piece, which we can't
[Text copied from
of Illinois news release]