Testosterone found to be responsible for sensitivity to general anesthesia
American scientists conducted a series of experiments on mice and humans, and found that sensitivity to general anesthesia is modulated by testosterone: castration of male mice increased resistance to anesthesia, and its introduction increased sensitivity to anesthesia by conversion into estradiol. The cortical activity was independent of sex in both humans and mice. The study was published in the journal Proceedings of the National Academy of Sciences.
It is known that general anesthetics activate neurons in the nuclei that promote sleep, and inhibit neurons that promote wakefulness. Many of these nuclei are located in the hypothalamus, which is responsible for neuroendocrine regulation in the body, causing its function to be affected by sex and sex hormones. Therefore, some scientists suggest that the effects of anesthetics may depend on gender.
It is already known that women are three times more likely to regain consciousness under general anesthesia. However, there are not yet any theories that can explain this observation, because experiments on mice that study the effects of anesthetics ignore the influence of the sex of the mice. Therefore, causality in this area has not yet been established.
A team of scientists led by Alex Proekt (Alex Proekt) from the University of Pennsylvania tested the effects of sex and sex hormones on sensitivity to volatile anesthetics in mice. They used isoflurane and assessed how quickly males and females would remove the duct tape from their muzzle. The mean value of the half-maximal effective concentration for induction of anesthesia was significantly higher in females, female mice took longer to induce anesthesia, and they came out of anesthesia faster (p = 0.008). A duct tape study showed that females coped faster than males (p = 0.019) after identical exposure to isoflurane. This suggests that female mice are more tolerant to isoflurane than males. Similar results were observed with different anesthetics and different tests.
A human clinical trial in which 12 healthy women and 18 healthy men between the ages of 22 and 40 were given isoflurane showed that women regained the ability to follow auditory cues that signify coming out of anesthesia faster than men. The psychomotor vigilance test, which indicates preserved cognitive function, was also handled faster by women.
Further experiments on mice showed that castration of males leads to a significant increase in resistance to general anesthesia. At the same time, the removal of the ovaries had no effect on sensitivity to anesthesia. Scientists suggested that sex differences in sensitivity to anesthetics are primarily due to the presence of testosterone. And indeed - the introduction of the hormone to mice dramatically increased their sensitivity to anesthetics.
It is noteworthy that the scientists explained this effect by the conversion of testosterone aromatase into estradiol in the nuclei of the hypothalamus. In this case, the activity of the cerebral cortex does not change in any way on the electroencephalograms of both sexes of both species. But brain mapping of mice showed that sexually dimorphic patterns of activity of hypothalamic structures that promote sleep consistently correlate with sensitivity to anesthetics.
This study shows for the first time an organic basis for sex differences in sensitivity to general anesthetics. Further studies should focus on the specific mechanisms of hormone action on the activity of hypothalamic nuclei.