Regulating a hormone abundant in women approaching menopause could offer alternatives for hormone replacement therapy, Medical College of Georgia researchers say.

Follicle-stimulating hormone, released by the pituitary gland, is involved in controlling the menstrual cycle and the production of eggs by the ovaries. Researchers want to know if the hormone, which peaks after menopause, may also play a role in an inflammatory process that leads to bone loss and blood vessel damage.

The possible health effects of such high concentrations have not received much attention, says Dr. Joseph Cannon, associate dean for research and Kellett Chair in the School of Allied Health Sciences.

Most research has instead focused on the dramatic decrease in estrogen production during that time. “The loss of estrogen is often associated with health problems like osteoporosis and cardiovascular disease, but it is not the only hormone that changes at menopause,” he says.

To identify implications of high levels of FSH, Dr. Cannon and an interdisciplinary research team are studying the effect of FSH on white blood cells with a $340,000 two-year grant from the National Institutes of Health.

“It is thought that during menopause, estrogen is no longer present in sufficient amounts to inhibit the production of proteins produced by white blood cells, known as cytokines,” he says. “Cytokines are like the hormones of the immune system – the signals that white blood cells use to communicate with each other.”

Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor are important for directing the destructive power of the immune system against infectious microorganisms. However, produced in excessive amounts or at inappropriate times, they may direct white blood cells to damage the function and structure of blood vessels and bones, leading to problems like osteoporosis and cardiovascular disease.

To determine if FSH has a role in this misdirection, Dr. Cannon and his team will study 48 women ages 40-50 – the age when most are approaching menopause – and 48 women ages 20-30.

“We’ll take blood samples from pre- and peri-menopausal women, isolate the white blood cells and look at their ability to spontaneously produce cytokines,” Dr. Cannon says.

Previously published work by Dr. Cannon and colleagues indicated that when white blood cells were isolated and incubated with FSH, the cells produced more interleukin-1. This research will determine if the naturally high levels of FSH reached in peri-menopausal women have the same effect on the production of interleukin-1 as well as other cytokines.

Other studies have also found that levels of free interleukin-6 and tumor necrosis factor receptors in the blood of post-menopausal women were inversely related to their FSH levels.

“This might mean that FSH causes white blood cells to retain more receptors on their surface and therefore they remain more sensitive to the cytokines,” Dr. Cannon says. “Our current research will actually measure the receptor numbers on the white blood cells.”

To determine the clinical significance of any observed differences in FSH, cytokines and cytokine receptors, the circulating levels will be compared with each woman’s bone density – measured by a low energy X-ray technique – and with her vascular health – measured by ultrasound and other non-invasive methods.

“The implication is that a better understanding of FSH-mediated mechanisms in peri- and postmenopausal health may lead to new therapies to deal with the health issues that can develop at this stage of life,” he says.

New therapies could be aimed at regulating FSH levels to alleviate menopausal health problems without the risks implicated with steroid hormone replacement therapy.

Those can include a slightly increased risk of ovarian and breast cancer, increased breast density – making mammograms more difficult to read – and increased risk of heart attack and stroke.