It is generally assumed, in health-related research, that males and females of a given species respond to a specific drug in much the same way. This is why preclinical studies in animals often analyze the effects of therapies only in one sex – typically the male. But when it comes to diseases in which hormones play a role, like diabetes, should these results continue to be read as universal?
Two researchers at the Institut de Recherches Cliniques de Montréal (IRCM), Jennifer Estall, PhD, and her student, Aurèle Besse-Patin, are now trying to answer this question.
“Studying both male and female populations was seen as doubling a study’s costs and duration,” Dr. Estall, IRCM’s director of Molecular Mechanisms of Diabetes unit, said in a press release. “In most cases, males have been preferred to avoid the potential influence of female hormonal fluctuations on the data.”
Younger females can also be harder for investgators to turn into animals models of diseases like diabetes or obesity, because they tend to resist sudden diet changes — like high-sugar or high-fat foods — that serve as triggers for these disease models.
“However, this mindset is changing,” said Besse-Patin. “The research community is realizing that perhaps some of these studies provide us with only one side of the coin.”
Medical researchers already know that men and women develop metabolic disease differently, with women tending to be naturally protected until menopause. This difference could also influence how these diseases are treated.
“In the past, drugs tested only in males might have been abandoned because they did not work as well as we wanted them to,” Dr. Estall said. “However, females could have responded better or, conversely, may respond less or in a different way, and this was not regularly evaluated for newly emerging treatments.”
She and her assistant are planning to tackle exactly this knowledge gap. “Our team wants to provide a more comprehensive picture of the effect of sex on how drugs work before they are tested in people. By doing so, we hope to draw attention to treatments that could otherwise fall under the radar.”
The researchers will study how female mice respond to a hormone thought to be of considerable benefit in cardiovascular, liver, and fat metabolism: the fibroblast growth factor 21 (FGF21). The administration of FGF21 has been shown to improve metabolism and the effectiveness of insulin, as well as reduce triglycerides in the blood and increase levels of the so-called ‘good’ fat. All of these effects could make it a promising treatment for metabolic diseases like diabetes.
“Our results will share insightful information about how male and female respectively respond to FGF21,” said Besse-Patin. “For example, we could see whether it works more significantly in female populations, or if it shows distinctive beneficial effects in one sex over another.”
Previous work with FGF21 was almost exclusively done in male animals. And in human trials, where both sexes were represented, comparisons were not made between men and women, with potential differences left unstudied.
“All in all, by characterizing FGF21 action in females, we will provide a better framework as to whether it is an effective drug to treat metabolic disease in both men and women,” Dr. Estall said. “We hope to shed light on an approach still emergent in our field, and that our results will encourage our research community to do the same.”
