Testosterone, not estrogen, is the more likely driver of the gender gap in anesthetic sensitivity. In a new study, higher testosterone levels were associated with higher anesthetic responses. That sits beside a long-known gap. Females are more likely to have chronic pain and to respond poorly to treatment than males.
This study sheds new light on an old topic. It found new mechanisms behind the gap. That may one day help doctors better treat chronic pain in women.
It is no secret that females are prone to mood and emotional disorders. They are also more likely to have chronic pain. One proposed reason for higher pain sensitivity in females is estrogen. Testosterone has gotten far less attention.
But what if females feel more pain because they have less testosterone than males? This new study, at least, seems to suggest that.
Of course, pain sensitivity also differs because brain structure differs between the sexes. But hormones also have a lot to do with it.
One more thing is worth knowing. Females do have testosterone in their bodies, but at levels several times lower than males.
And the problem is not only that females feel more pain. They also respond less to certain painkillers.
Do women need more anesthesia than men?
Researchers at the University of Pennsylvania, Philadelphia, did this new study in mice. They tested the mice for sensitivity to anesthetics like isoflurane, sevoflurane, halothane, and desflurane.
They had many findings, some of them unexpected. For example, females needed almost 25% more isoflurane to be put under. Females also woke up much faster after the anesthesia than males. In fact, many females woke up at a dose that would knock out male mice. So, yes, the gap between the sexes is huge. It shows that females are less sensitive to anesthetics. The same effect showed up with all the four drugs in the test.
Females did not only wake up faster. They also became alert much faster. Researchers stuck small stickers on the snouts of the mice. Female mice started pulling the sticker off after 242 seconds on average. Male mice took 483 seconds. Again, the gap is huge.
Still, these findings alone do not show whether estrogen or testosterone causes the gap.
So, in the next phase, researchers castrated male mice. With less testosterone, the male mice became more resistant to anesthetics. But removing the ovaries from female mice had no such effect. This confirms that testosterone, not estrogen, strongly shapes sensitivity to anesthetics.
Researchers also noticed that a standard EEG (a test of brain waves) does not explain these differences. So they also used full brain scans to see why the differences exist. The female hypothalamus had fewer active neurons in the region that brings on sleep.
Researchers also ran a small study on 30 people. Men were slower than women to regain full attention after anesthesia.
The Bottom Line
This study did add something new to what we know. It has long been known that females are less sensitive to anesthetics and painkillers. This study confirmed that the cause is testosterone levels. Other differences between males and females also play a part. But those differences come from hormone differences between the sexes. The study also showed that full brain scans beat regular EEGs for seeing these differences. If you are dealing with chronic pain, you may visit Padda Institute for an expert consult and a treatment plan built for you.
Frequently asked questions
Does testosterone affect anesthesia?
Yes. In this study, higher testosterone meant a stronger response to anesthesia. Researchers castrated male mice, and their testosterone fell. Those males became more resistant to anesthetics. Removing the ovaries from female mice changed nothing. That points to testosterone, not estrogen, as the hormone that sets how strongly the brain responds to an anesthetic.
Do women wake up from anesthesia faster than men?
In the mouse tests, yes. Many female mice woke up at a dose that would have kept males under. They also became alert sooner. Females started pulling a sticker off their snouts after 242 seconds on average, males after 483 seconds. A small study of 30 people found the same trend. Men were slower to regain full attention after anesthesia.
Why do women feel more pain than men?
Females are more likely to live with chronic pain. They respond less well to treatment and less to certain painkillers. Brain structure plays a part, but hormones matter too. Estrogen has long taken the blame. This study suggests the bigger factor may be testosterone. Women carry it at levels several times lower than men.
Why can’t a standard EEG show the difference?
The researchers found that a standard EEG did not explain why females and males responded differently. Full brain scans did. They showed fewer active neurons in the sleep region of the female hypothalamus. That is why the study concludes full brain imaging tells doctors more than a regular EEG about sex differences in anesthesia.
Source:
Wasilczuk, A. Z., Rinehart, C., Aggarwal, A., Stone, M. E., Mashour, G. A., Avidan, M. S., Kelz, M. B., & Proekt, A. (2024). Hormonal basis of sex differences in anesthetic sensitivity. Proceedings of the National Academy of Sciences of the United States of America, 121(3), e2312913120. https://doi.org/10.1073/pnas.2312913120
Dr. Gurpreet Singh Padda, MD, MBA, MHP
