Lower estrogen levels in the brain, a drop that occurs during menopause, could lead to weight gain in older women, new research suggests.

Scientists have long been puzzled by the excess pounds and increased appetite that occur in post-menopausal women.

Deborah Clegg, assistant professor of psychiatry at the University of Cincinnati, conducted research in which rats were found to pack on abdominal fat after estrogen receptors in the brain were blocked, simulating post-menopause.
(CBC)

To determine the effect of dwindling estrogen levels in the brain, U.S. researchers focused on two regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst.

Female rats were injected with a virus that produced the effect of a reduction in estrogen. "We put the adenovirus directly into the brains of female rats to silence the estrogen receptor in a critical brain region," Deborah Clegg, assistant professor of psychiatry at the University of Cincinnati Academic Health Center, told CBC News.

"Then we allowed the animals to continue to grow normally."

Estrogen receptors are located on cells throughout a woman's body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure.

The research found that when estrogen levels in the hypothalamus dipped, the metabolic rate and energy levels of the mice also plummeted.

"It actually put them into a form of menopause," said Clegg. 

"When we silenced the estrogen receptors that are located in this portion of the hypothalamus, the animals gained weight just like post-menopausal women do," she said.

The excess weight went straight to their middle sections, creating an increase in abdominal fat much in the same way post-menopausal women store fat.

Hormone replacement for the brain?

The findings suggested that the ER-alpha in this region of the brain plays an essential role in controlling energy balance, body fat distribution and normal body weight.

The findings were presented Monday at the 234th national meeting of the American Chemical Society.

The research may one day help scientists develop more targeted hormone replacement therapies, capable of stimulating estrogen receptors in one part of the brain or body while reducing it in the next, Clegg said.

She now plans to perform a similar experiment to deactivate ER-alpha in a different region of the hypothalamus. She anticipates that a loss of estrogen in this region may create an increase in the animals' appetites as well as their weight.

"What we would love to be able to do would be to have selective or targeted hormone replacement therapy … [for a woman to] facilitate her body fat distribution to be more like that prior to menopause, and would keep her lean even after menopause," said Clegg. 

"We believe that this would reduce her overall risk for the metabolic syndrome, diabetes and cardiovascular disease, as well as some types of cancer."