Historically, clinical trials done in rats used mostly male rats. It was believed that female rats not only had more erratic behavior, but also an estrial cycle (the animal’s reproductive phase following ovulation) that made them less constant and more difficult to study. However, a new study published in Current Biology comes to contradict decades of scientific practice. After all, the estrous cycle has little influence on the behavior of female rats, and males act more erratically than females.
The study Mouse spontaneous behavior reflects individual variation rather than estrous state – although he is not the first to raise the hypothesis, according to the New York Times – is more robust than the previous ones. To evaluate the behavior of the rodents, motion sequencing technology was used. Several sophisticated cameras mapped the movements of 32 rats (16 of each sex) inside a large bucket for 20 minutes, 15 days in a row.
Male rats exhibited less predictable behavior than females and it was found that, from a hormonal point of view, males also have fluctuations. According to the study, male rats establish a dominance hierarchy in which alpha animals demonstrate ten times more testosterone than submissive ones.
Why might this result be important for humans?
As is the case in other species, females tend to be underrepresented in human clinical trials.
In the United States, says a 2022 study by Contemporary Clinical Trials, the main causes of death are cardiovascular disease and cancer. In the first case, 49% of patients are women, in the second the percentage is 51%. However, in clinical trials for cardiovascular disease, only 41.9% of participants are female. When we talk about trials for cancer drugs, only 41% of those tested are women.
The same study also states that, although 60% of people with psychological illnesses are women, they represent only 42% of participants in studies.
Second Rebecca Shanskyneuroscientist and co-author of Mouse spontaneous behavior reflects individual variation rather than estrous statecited by New York Timesstates that “some people assumed that using the female gender would make the data more confusing.”
This female underrepresentation is problematic because “medical products can affect men and women differently”, as explain the US drug regulatory agency (Food and Drug Association or FDA).
O 2011 study published in Acta Farmacêutica Portuguesa “Gender male vs. female: relevant factor for pharmacological responses and adverse drug effects?” indicates that the “EMEA (European Medicines Agency) guidelines recommend that women should be included in clinical trials in a way that is representative of the society where they are inserted, with due prevalence in relation to the disease for which the drug is intended”.
However, it safeguards “the importance of differences between genders to be taken into account when prescribing” and predicts that, in the future, adjustments will not be made in clinical practice based only on weight, but also on gender.
In the United States, it has only been since 1993 that the participation of women and other minorities in clinical trials has come to the fore. law from the country. The legislation “Women and minorities as a clinical research case” ensures that these people can be included in clinical trials, that trials that include them must take into account whether medicines have different effects and that monetary costs cannot be a reason for exclude women and minorities.
O United States National Institute of Healthdriving the 1993 law, from the following year onwards committed itself not to financially support any project that did not comply with the inclusion policy.
In 1977 the FDA created a guideline which advised the exclusion of all women with “potential to become pregnant” from clinical trials. The measure arose in response to the crisis caused by the thalidomide, a sedative developed by the Swiss pharmaceutical company CIBA in 1953. The drug gained fame in Europe and Canada for relieving typical pregnancy sickness. However, cases of birth defects have been reported in babies whose mothers used the medicine.