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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 Health.

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 conditions."

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 giving birth.

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 sclerosis."

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

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Prevention Services Lag For American Women Disabled By Multiple Sclerosis

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 sclerosis.

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 clinicians found.

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 non-ambulatory patients.

"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 screening goals."

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 embarrassing.

"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, 11/06/01
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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