MS/Women ~ Issues & Concerns
Drop in Stress Hormones May Set Stage for
Arthritis/Multiple Sclerosis After Pregnancy
BETHESDA, MD -- October 30, 2001 -- A
sharp drop in stress hormones after giving birth may
predispose some women to develop certain conditions in
which the immune system attacks the body's own tissues,
according to researchers at the National Institutes of
The study was conducted by researchers at the National
Institute of Child Health and Human Development (NICHD)
and the National Institute of Arthritis,
Musculoskeletal and Kidney Diseases. The study
appeared in the October issue of The Journal
of Clinical Endocrinology and Metabolism.
"This finding has important
implications for understanding why immune disorders may
subside during pregnancy, but flare up again after birth,
" Duane Alexander, M.D., director of the NICHD.
"Understanding the immune processes involved may
provide important new therapies for each of these
Rheumatoid arthritis (RA) is a disorder
in which the immune system apparently causes pain, swelling, stiffness, and loss
of function in the joints. In multiple sclerosis, the immune system attacks the
brain and nervous system.
The immune hormones Interleukin 12
(IL-12) and tumor necrosis factor alpha TNF alpha hormones are involved in
triggering the body's immune cells to ward off disease causing invaders,
explained the study's senior investigator, George P. Chrousos, M.D., Chief of
NICHD's Pediatric and Reproductive Endocrinology Branch. Both hormones also seem
to be involved in the swelling and tissue destruction seen in rheumatoid
arthritis and multiple sclerosis. Similarly people with these conditions also
have higher-than-normal amounts of the two immune hormones.
In pregnant women who have either
multiple sclerosis or rheumatoid arthritis, symptoms may ease up or even
disappear during the third trimester of pregnancy, Dr. Chrousos said. After the
women give birth, however, their symptoms often return. Similarly, pregnant
women who do not have either disorder may develop one of them within a year of
The researchers recruited 18 women with
normal, healthy pregnancies for their study. Next, the researchers charted the
women's levels of IL-12 and TNF alpha in the third trimester of pregnancy as
well as within the weeks following the birth of their child. The investigators
found that, during the third trimester of pregnancy, the women's levels of IL-12
was about three times lower than it was after they had given birth. Similarly,
the women's TNF alpha levels were 40 percent lower during the third trimester
than it was after birth.
The researchers also found, however,
that the women's levels of the stress hormones cortisol, norepinephrine
(formerly adrenalin) and 1,25 hydroxyvitamin D3 were two to three times higher
than they were after the women had given birth. All three hormones are produced
to help the body respond to a stress. The most well known of these,
norepinephrine, is involved in the "fight or flight" response, in
which strength and reflexes are enhanced, to escape or deal with a possible
threat. Other research has shown that all three of these stress hormones serve
to hinder the production of immune system hormones.
The increase in these stress hormones
is probably caused by the master stress hormone, corticotropin releasing hormone
(CRH). This hormone is produced in the pituitary gland in response to stress,
and ultimately signals the production of cortisol, norepinephrine, and 1,25
hydroxyvitamin D3. Similarly, CRH is also produced by the placenta.
"It appears as if suppression of
IL-12 and TNF alpha results indirectly from the CRH the placenta produces,"
Dr. Chrousos said. "After birth, the supply of CRH plummets and the levels
of the two immune hormones rise sharply. This appears to result in a 'rebound'
effect that could exacerbate disorders like rheumatoid arthritis and multiple
In one earlier study, Dr. Chrousos and
his coworkers found that an abrupt drop in CRH after birth resulted in post
partum depression in some women. In a more recent study, they showed that
production of CRH by the placenta and the uterine lining played a role in
preventing the mother's immune system from rejecting the early embryo.
SOURCE: National Institutes of Health
Prevention Services Lag For American Women Disabled By
British Medical Journal (BMJ)
By Harvey McConnell
American women who are considerably disabled by multiple sclerosis are less
likely to receive appropriate preventive medical care.
"Women with impaired mobility should be considered a vulnerable population
for receipt of breast examinations, mammography, and cervical smear tests,"
declares Dr Eric Cheng and colleagues at the Department of Neurology, University
of California, Los Angeles, United States. "Studies are needed to identify
factors causing this and to evaluate interventions to reduce the variation
across mobility levels."
Clinicians point out that while people with multiple sclerosis may have impaired
mobility, their life spans are similar to age matched population controls. This
means they need standard preventive services to prevent early mortality.
Dr Cheng and colleagues collected self-reported rates of preventive care, such
as cervical smear testing, mammography, blood pressure checks, cholesterol
screening, and physician assessment of health habits for 713 women with multiple
In addition, they assessed these rates according to the patient's mobility level
--fully ambulatory, ambulatory with help, and not ambulatory-- and compared them
with (US) Healthy People 2000 recommendations.
The mean age of the women was 47 years; 86 percent were white and 40 percent had
a college degree. Overall rates for cervical smear tests, breast examinations,
and mammography exceeded Healthy People 2000 recommendations, but rates were
highest for the ambulatory group and lowest for the non-ambulatory group, the
Cervical smear testing was below Healthy People 2000 goals for the ambulatory
with help and non-ambulatory groups. In contrast, rates for general preventive
services did not differ by mobility.
Dr Cheng, using multivariable models, found that ambulatory patients had 5.32
times the odds of having a cervical smear test, 3.62 times the odds of having a
breast examination, and 3.24 times the odds of having mammography relative to
"Older age was associated with a lower rate of cervical smear tests;
however, no other variables were related to receipt of women's preventive
services, the clinicians found. Except for an increased odds of assessing eating
habits in the non-ambulatory group, mobility status did not affect the odds of
receiving general preventive services.
The researchers said that their findings "are the same as those in a
previous population based US study of women with and without mobility
impairments due to various conditions, even though women in our study had a
single chronic condition, were younger, were more educated, and all had health
insurance and a regular source of care in health systems that met broad national
Clinicians advanced several possible explanations: "Doctors may believe
that such patients do not have an adequate life expectancy to warrant women's
preventive screening. However, such attitudes would be incompatible with the
high rates of blood pressure and cholesterol checks. Alternatively, patients may
be reluctant to undergo screening services that are potentially uncomfortable or
"A third possibility is that the medical systems cannot easily accommodate
patients with mobility impairments, who may require access to specialized
equipment and extra time."
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Can Exacerbations of
MS During Pregnancy and Postpartum Be Prevented?
from Patricia K. Coyle, MD,
In general, relapses of MS actually decrease during pregnancy, particularly
during the last trimester when they are reduced to 70% below the prepregnancy
baseline. This most likely reflects the fact that pregnancy is
immunosuppressive. There are no data to show that the unusual relapses that can
occur during pregnancy are any different from those that occur prepregnancy, and
they can be treated with high-dose steroids once past the first trimester. In
the 3 months postpartum, the relapse rate increases to 70% over the prepregnancy
baseline, but then returns to the baseline level. Therefore, the several months
after giving birth are recognized as a time of high risk for MS disease attacks.
At the current time, an ongoing trial is examining whether
intravenous immune globulin (IVIG) given at the time of delivery (at 10 g or 60
g), followed by monthly IVIG (10 g) for 6 months, can prevent relapses. One
hundred women with MS are being entered into this trial. If a patient is not
going to breastfeed, disease-modifying therapy can be restarted immediately
after delivery as well. Theoretically, combination therapy with an A, B, C drug
(Avonex, Betaseron, Copaxone) plus IVIG or pulse steroids could be
given for 3-6 months postpartum.
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