Neuroscientists Agnès Lacreuse, Luke Remage-Healey and their graduate students at UMass Amherst, collaborator Jessica Mong at the University of Maryland and first author Nicole Gervais worked together on this research. Gervais, who conducted the experiments as a postdoctoral researcher at UMass Amherst, is now at the University of Toronto. The authors studied alittle group of aged male and feminine marmosets, non-human primates whose brains are very similar to humans’ and which exhibit “complex behavior,” senior author Lacreuse explains.

She adds, “This drug is given to stop recurrent carcinoma in humans and it does save lives, but tons of times, patients aren't compliant due to unpleasant side effects that affect quality of life.” Their study, showing changes within the animals according to a number of the human complaints, allowed the researchers to assess cognitive behavior, thermal regulation and neuronal changes in drug-treated vs. control groups. Their findings appear within the week in the Journal of Neuroscience.

As Gervais explains, studies in humans are hampered by confounders. “The patients have had cancer, so it’s hard to disentangle the strain of their disease and treatment from the drug effects.” She adds, “We wanted to understand if the symptoms while using the aromatase inhibitors are often reproduced in an animal model, and further explore the mechanisms to know how they work and find alternative treatments.”

In this work supported by the NIH’s National Institute on Aging and National Institute of Neurological Disorders and Stroke, the researchers administered the estrogen-inhibiting drug orally “the way it’s given to humans and at an identical dose,” visit Gervais explains, for one month, and observed that it did indeed suppress estrogen production within the body. They then compared changes in behavior, memory, electrophysiology, and thermoregulation within the treated and control groups

Gervais says, “Sure enough, we found deficits in some aspects of memory and that we also saw the foremost striking leads to thermal regulation, a deficit within the ability to manage blood heat when the ambient temperature increases, but only in females. It doesn’t match hot flashes exactly but it’s according to what we all know about the regulation of hot flashes by estrogens in women. Females on the drug couldn't regulate their temperature also as control females.”

It was within the investigation of neurons that the researchers saw something quite surprising, says Remage-Healey. “In the hippocampus, which is assumed to be critical for learning and memory functions, rather than reduced estrogen levels we found that the drug caused a paradoxical increase in estrogen levels.”