Sunday, August 05, 2007

Sensitivity to hormones linked to miscarriage

Could a heightened sensitivity to female hormones cause miscarriage? A small study found that women with recurrent miscarriage show a hypersensitivity to oestrogen and progesterone in skin tests.

The findings could lead to novel treatments for “unexplained” miscarriage, but they also call into question some current, controversial treatments for the disposition, including injecting women with progesterone.

Miscarriages often occur because the embryo has a genetic defect. But several consecutive miscarriages are unlikely to be the result of random genetic anomalies.

Instead, these can be caused by abnormalities in the uterus, unusual hormone levels, clotting disorders or lupus in the mother. “But in at least half of the cases, we can’t find the reason. It’s frustrating,” says Mark Walker at the University of Ottawa in Canada, who was not involved in the study.

Reaction time
Researchers at the Sheba Medical Center in Tel Hashomer, Israel, wanted to get to the bottom of these unexplained miscarriages. The team tested the immune reaction of women with recurrent early pregnancy loss to progesterone and oestrogen – the hormones that regulate pregnancy. Previous studies had shown a connection between miscarriage and unusual immune system responses, but none had looked at the role of these sex hormones, the researchers say.

The researchers injected the hormones into the skin of 29 women who had experienced at least three unexplained miscarriages, and 10 women who had successfully carried a baby to term and never had a miscarriage.

The injections sites, and the arm, were monitored for signs of redness and swelling. All but three of the women in the first group showed hypersensitivity to one of the two hormones, and 17 women showed hypersensitivity to both. None of the women in the control group had a reaction to the test.

“This is really novel,” says Walker. “It’s a small sample size but if the results are that profound, it definitely warrants more research.”

Killer cells
“It opens prospects as far as diagnostics and treatment,” says Alek Itsekson, who led the study. He thinks hypersensitivity to these hormones might be increasing the numbers of immune system cells called natural killer cells. These normally surround the embryo harmlessly as it grows, but an increase in their amount has been linked to early miscarriage (see Major flaw in miscarriage test).

Steroids have been tested as a possible treatment for this problem but they can have potentially dangerous side effects (see Is steroid treatment for miscarriage safe?). Knowing the mechanism behind the negative immune reaction to progesterone and oestrogen might lead to better options, the researchers say.

Itsekson’s team is looking at the same reaction in rats to try to understand exactly how the immune system is responding. They are also conducting follow-up clinical trials in humans.

The results call into question a practice sometimes used to treat recurrent miscarriage, in which injections of progesterone are given to women who have less of the hormone than normal. The usefulness of these injections is already controversial, the researchers say, and if the women are hypersensitive to progesterone the treatment may have unknown side effects.

Journal Reference: American Journal of Reproductive Immunology (vol 57, p 160)
Source: http://www.newscientist.com/article.ns?id=dn11159

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