Estrogen Replacement Therapy Appears Not To Harm Primate Brain Cells

Researchers at The University of Arizona in Tucson report good news for the millions of women currently receiving hormone replacement therapy.

They have found that continuous estrogen replacement therapy in primates does not seem to damage the cells of the brain that produce beta-endorphins and several other important chemicals. Ty Abel, a doctoral student in the UA neuroscience program, and Naomi Rance, UA associate professor of pathology, presented their results yesterday at the 28th Annual Society for Neuroscience Meeting in Los Angeles.

According to Abel, studies in rodents have long documented damage to some brain regions from certain types of continual, rather than cyclical, estrogen supplementation. "One idea," explained Abel, "was that in rats, this naturally occurring substance was aging the brain over time."

The estrogen-induced damage in rodent brains appeared to be specific to cells in the hypothalamus that produce a large molecule called proopiomelanocortin, or POMC. This large molecule is broken down into several products such as beta-endorphin, which is involved in mood, pain perception and memory, and alpha-MSH, which has anti-inflammatory properties and may be involved in the regulation of body weight. The phenomenon of estrogen-induced damage in rodents has been termed "estrogen toxicity".

"This really hasn't been looked at in primates," said Abel, "and the possibility of estrogen toxicity has become important as more and more women are choosing to take continuous, rather than cyclical, hormone replacement therapy to reduce break-through bleeding or to avoid menstruation."

In order to assess the effects of estrogen toxicity in primates, Abel and Rance examined the donated brains from monkeys that had been enrolled in a hormone replacement study at the Comparative Medicine Clinical Research Center and the Department of Comparative Medicine at the Wake Forest School of Medicine. The hormone replacement regimen was designed to mimic that of post-menopausal women receiving continuous estrogen replacement therapy.

Because estrogen-toxicity effects in rodents are found in a region of the brain called the hypothalamus, Abel and Rance studied three different areas of the hypothalamus from the donated monkey tissue. The hypothalamus is responsible for the production of many different neurohormones.

The researchers were able to determine, by examining expression of POMC RNA, that there was no difference in the number of these cells in animals that had undergone hormone replacement therapy for thirty months after the removal of the ovaries, compared to animals that had not had the therapy after ovary removal. The researchers also found that there was no change in the shape of POMC cells from monkeys with hormone replacement therapy, indicating that the cells were probably not dying.

Large numbers of reactive microglia, the brain's immune cells, can indicate damage to neural tissues. When the relative numbers of microglia were compared in the hypothalami of monkeys with and without hormone replacement therapy, again, Abel and Rance found no differences between the two groups of monkeys.

"I think,"says Abel, "that the fact that we looked at so many parameters of POMC neurons makes a pretty strong case that these monkeys are not suffering from damage to their Beta-endorphin systems."

"If estrogen-toxicity is a built-in mechanism of aging in rodents, there appear to be differences in the aging mechanisms of rodents and primates. There are a lot of compelling reasons for women to undergo estrogen-replacement therapy, and this finding that things appear to be different in the primate is encouraging."

U.S. women are now living one-third of their lives after menopause, and, according to an article in the American Journal of Public Health (Rosenberg, 1993), estrogen and progesterone supplements are currently among the most commonly prescribed drugs in the United States.

This study on the effects of continual estrogen replacement in primates was funded by the National Institutes of Health, and Abel was supported by a Predoctoral Fellowship from the Robert S. Flinn Biomedical Research Initiative.