The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (29 page)

Early menopause, or
primary ovarian insufficiency (POI)
(formerly termed
premature ovarian failure, POF
), is the onset of menopause before age 40. It occurs in 1 to 1.2 percent of women, affecting between 2 and 5 million women.
³⁷
While some cases of this type of ovarian failure have a genetic cause (such as
Turner’s syndrome
), or are due to chemotherapy or trauma, studies suggest that many cases may actually be due to autoimmunity.

Approximately 15 percent of women with the problem have other autoimmune endocrine diseases, most commonly thyroid disease, Addison’s disease, type 1 diabetes, and autoimmune polyglandular syndromes (as many as 15 percent of women with type 1 APS have ovarian failure). Autoantibodies
³⁸
associated with those disorders (
gonadotropin antibodies
) may also have an effect against the hormone-producing tissue of the ovaries and also react against specific steroid hormone–producing enzymes that are common to the ovary and adrenal gland.

One percent of women with rheumatoid arthritis experience autoimmune ovarian failure, and it’s also associated with vitiligo, lupus, myasthenia gravis, and Crohn’s disease.

Research conducted by Judith Luborsky, PhD, at Rush University in Chicago suggests that the cause of autoimmune ovarian failure may be immune destruction of ovarian follicles and oocytes.
³⁹
Inflammation from autoantibodies may also compromise ovarian function.
⁴⁰

In women with menstrual cycles, an inability to become pregnant may be an early sign. “We believe there is a group of women with autoimmune disease, who have autoantibodies and go through a period of infertility as they progress to a total ovarian failure,” says Dr. Luborsky. Women labeled as having “unexplained infertility” (no tubal blockages or other physical problems that prevent pregnancy) may actually have autoimmune infertility. “A significant proportion of these women have anti-ovarian autoantibodies, and this is independent of the hormones typically used to determine ovarian function,” she explains.

Blood levels of estrogen and other ovarian hormones, such as progesterone (produced by ovarian follicles after the release of a mature egg) reflect the activity of a group of follicles in the ovary. The total number of active follicles decreases with age or as a result of autoimmune disease or other trauma,
⁴¹
observes Dr. Luborsky, now an investigator in the department of biology at the Woods Hole Oceanographic Institute in Woods Hole, Massachusetts.

Autoimmune ovarian failure is not identified by the traditional tests for ovarian function, which include blood levels of
follicle stimulating hormone (FSH)
made by the pituitary gland and estrogen (made by the ovaries). As ovarian function declines with normal aging, estrogen decreases and FSH increases. To be diagnosed with premature menopause (or menopause), FSH must be above 40 International Units per liter of blood (IU/L). For a diagnosis of autoimmune ovarian failure, you need to measure autoantibodies.

“If you measure hormones in individual ovarian follicles during the declining phase, before menstruation ceases completely, you get a different picture than from measuring hormones in the blood. The follicles produce normal amounts of hormones, but because there are less of them in older women, the amount of hormones we see in the bloodstream is less,” Dr. Luborsky explains. “However, in patients with anti-ovarian autoantibodies there is more variability in the levels of hormone in the follicles. For instance, in some women with ovarian autoantibodies the follicular cells make huge amounts of progesterone, others may make very little. A lot of these women have functional follicles, but they don’t look as normal as in women who are just getting older,” she observes.

“Not all women with premature menopause will have an underlying autoimmune disease. If you are having symptoms of an early menopause, you should consider getting tested so you know what’s going on,” advises Dr. Luborsky.

A workup for autoimmune ovarian failure may include tests for anti-ovarian antibodies and other nonspecific autoimmune markers, such as an elevated
SED rate
,
antinuclear antibodies
, and
rheumatoid factor (RF)
, as well as levels of
thyroid stimulating hormone (TSH)
, elevated blood glucose, and the diagnostic tests for Addison’s disease (see
pages 225
to
226
). Accurate diagnosis can help rule out other causes of ovarian failure, such as stress (which may be reversible).

While the causes may be different, the symptoms of autoimmune and nonautoimmune ovarian failure are the same as in a normal menopause, with hot flashes, thinned and dry vaginal tissues (
atrophic vaginitis
), painful sex, infertility, bone loss, and an increased risk of cardiovascular disease caused by estrogen deprivation. As with other endocrine disorders, the treatment is replacing the lost hormones, in this case hormone therapy (HT) with estrogen and progesterone to protect the heart, bones, genital and urinary tract tissues, and the nervous system.

Many cases are diagnosed at infertility clinics. In some women with autoimmune ovarian failure, follicular function may spontaneously resume, and a pregnancy can occur. However, if a woman with this condition wants to become pregnant, aggressive treatment can be tried with hormones to stimulate ovarian follicles to produce multiple eggs, followed by
in vitro fertilization (IVF)
, but the success rate so far is low.

Testing for anti-ovarian autoantibodies may help identify women more likely to succeed with IVF. “Our studies found that women who became pregnant with IVF had a lower frequency of anti-ovarian antibodies compared to the women who did not succeed with IVF,” comments Dr. Luborsky. “Women found to have anti-ovarian antibodies may be candidates for future immune-based therapy. A few studies indicate immune suppression may result in a return of normal periods and pregnancy, although this is somewhat controversial,” she notes.

The consequences may go beyond infertility. Recent research by Dr. Luborsky has found that autoantibodies found in this type of ovarian failure also appear to be associated with ovarian cancer.
⁴²
However this research is very preliminary and does
not
indicate a cause and effect.

Symptoms associated with menopause should be cause for concern for younger women. Without estrogen therapy, atrophy of vaginal tissue can make sex uncomfortable and lead to frequent urinary tract and yeast infections. Make sure you talk to your gynecologist if you are not comfortable discussing menopausal symptoms with a rheumatologist or other specialist.

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