Hormones and autoimmune disease

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Volume 19 - No. 1 (2001)By Celia MilneRaging Hormones

Until recently, the link between hormones and autoimmune disease was merely a medical curiosity. Now evidence is mounting to make the connection inescapable and worth studying.

Hanna Little, 34, has had rheumatoid arthritis ebbing and flowing in her body since she was in her early-20s. The best she has felt during those years was in 1995 when she was pregnant; a remarkable state of affairs considering that she was carrying triplets! While she was expecting, Little’s chronic arthritis pain eased up. 'It was the best I'd felt in seven years,” she recalls. “I could walk longer and faster, and be on my feet more.”

But two days after , and Molly were born, the arthritis returned with a vengeance. The Oshawa, Ontario, mother was left with terrible pain in her joints and three tiny babies to care for. “It felt like someone had taken a sledgehammer to my feet,” said Little, who is affected in her feet, both ankles, right elbow, both hands and her shoulders.

Rheumatoid arthritis (RA) is an autoimmune disease, meaning a disease in which the body’s immune system turns against itself. Other common autoimmune diseases include lupus, which destroys the joints and possibly other organs, and multiple sclerosis (MS), which damages the myelin coating of nerves in the brain and spinal cord. Pointing to the importance of hormones, all of these diseases are far more prevalent in women than men. The ratio of women to men who have RA is 4:1, for lupus it’s 9:1, and for MS it’s 2:1.

Seventy percent of women with RA find that their disease becomes less severe while pregnant. As well, studies have shown about a twofold higher risk of RA in women who have not had children. This could either mean that not having children is a risk factor for RA, or that women destined to develop RA have reduced fertility even before their arthritis shows up.

Not every autoimmune disease eases during pregnancy. “Some women with lupus got better during pregnancy, some had no difference in disease during pregnancy, and some had horrendous flaring to the point where they had to terminate their pregnancy or they might have died,” reports Dr. Kirk Osterland, the director of clinical immunology at Royal Hospital in Montreal and a professor of medicine at McGill University.

PMS and your disease

In women with lupus, RA or MS, the disease often flares just before their menstrual period, when estrogen and progesterone are at low levels. Marliese Polley from Port , Ontario, says that she has noticed a link between the severity of her RA and her menstrual cycle. “I do find that before my period I feel more achy and sore. It must be hormone-related,” she says.

Polley developed RA 12 years ago, just two weeks after her second child was born. RA following pregnancy is not atypical. “Since he was born, it has gotten worse and worse. It affects all my joints,” says Polley, 40. Even though she’s enjoying some relief through an experimental medication, her joints have been badly damaged by the disease. She has had one knee replaced and her neck fused. She needs surgery on both feet and her left shoulder, procedures she’s putting off because it would make caring for her two children too difficult.

For years, Little has also noticed that the severity of her disease is linked to her menstrual cycle. “I do get tired the first two days of my period — stiff, sore and exhausted,” she says. “There’s probably a hormonal link.”

Estrogen and your immune system

“There is no question that hormones play a role,” says Dr. Keystone, director of advanced therapeutics in arthritis at Mount Sinai Hospital and a professor of medicine at the University of Toronto. “Estrogen turns on the immune system, testosterone turns it down. We don’t know why, but we are moving forward with work on the mechanism and therapy.”

A woman’s immune system is different from a man’s in two major ways. First, a woman’s immune system is more active than a man’s. Women produce stronger responses to immune-system challenges; for example, they produce more antibodies to fight infectious diseases such as the common cold. As well, women reject skin grafts more quickly. “By extension, perhaps when the immune system misfires, it misfires harder,” says Dr. Barbara Giesser, an associate professor of clinical neurology at the Arizona Health Sciences Center in Tucson.

The second way in which a woman’s immune system differs is that a woman’s immune system has the innate ability to become suppressed during pregnancy. This enables a woman to carry a child in her womb without provoking an immune attack on what, technically, is a foreign body. “When women are pregnant their bodies are in an immuno-depressed state. This is built in to propagate the species,” explains Dr. Giesser, who is also an MS researcher.

The ability of a woman’s body to suppress the immune system during pregnancy may be why RA is also suppressed during pregnancy. It stands to follow, then, that it might be possible to create a therapy that mimics the hormonal changes that occur in pregnancy.

“Why can’t they fool my body into thinking it’s pregnant?” asks Little. “That would be heaven — just to get rid of the pain.”

A question comes of age

For years, Dr. Rhonda Voskuhl, a neurologist and assistant professor in the department of neurology at the University of California, Los Angeles, has been fascinated by why females are so much more susceptible to autoimmune diseases, and why these diseases can change so dramatically during pregnancy. “A few years ago, we would ask why and scientists would say we don’t know, it’s too complicated,” she says. “There were other questions they were pursuing.” The subject, she says, has “come of age” in the last year.

Dr. Voskuhl has been studying the effect of the hormone estriol, which females produce late in pregnancy, on patients with MS. This hormone can be made synthetically from soybeans. In a recent trial, she fed the hormone to mice who had a mouse-version of MS, and their MS symptoms became less severe.

Recently, she completed tests of estriol in women with MS, monitoring the progression of their disease using monthly MRIs. The treatment phase of the trial is complete but the results have yet to be tabulated. “This is the first time a pregnancy hormone has been given to treat autoimmune disease,” exclaimed Dr. Voskuhl. “The implications are big. If it helps in MS, then the RA people will be on it immediately.

“The patients say they are doing well, but we need to see it on MRI,” said Dr. Voskuhl. Her study is tiny — only 12 patients are enrolled because of the huge expense of MRIs — but if the treatment works it will lead to a larger trial. Then maybe in a few years, it will lead to a new, inexpensive, oral treatment for MS and RA, she said.

Early science in laboratories may seem like cold comfort to women on the front lines of diseases such as RA. But where there’s progress, there’s hope, say Polley and Little. Both are optimistic that research will lead to a better chance to suppress the disease that waxes and wanes in mysterious ways throughout their bodies.

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