A new study published in the journal Genomic Psychiatry points to an important possibility: a drug administered through the nose may be absorbed and reach the head and brain region differently in women and men — and in women, its availability may also vary depending on the stage of the hormonal cycle.

The study focused on Davunetide , an experimental drug being studied for its potential to protect nerve cells and the tiny structures inside them. The findings don't prove the drug is effective against Alzheimer's, but they raise a broader question: Could clinical trials that mix women and men miss an effect that only exists in some patients?

What did they investigate?

Devontide, also known as NAP, is a small fragment of the protein ADNP, which participates in protecting nerve cells and maintaining microtubules — tiny “tracks” in nerve cells that are used to transport substances and maintain the cell’s structure.

The researchers labeled the drug with a fluorescent substance and administered it to mice and rats via nasal spray. They then used imaging to track the distribution of the drug in the head and the rest of the body.

The mice were also tested at different stages of the estrous cycle, which in some ways parallels the menstrual cycle in women, to see whether changing levels of estrogen affect drug absorption.

They also analyzed data from a previous human study in which six healthy women and two healthy men were given devontide nasally. The researchers compared the levels of the drug in the blood and the length of time it remained in the body.

What did they find?

In the mice, the drug was found to be more available in the head region than in the males, especially during periods when estrogen levels were high. When estrogen levels dropped, the difference between males and females was greatly reduced.

Even when another group of five males and five females were tested, without sorting the females by menstrual phase, higher availability was found in the females in the head region relative to the rest of the body.

A similar trend was observed in human data: in women, the peak concentration of the drug in the blood was higher, sometimes more than double that measured in men. In men, however, the drug remained in the body for a longer time.

The findings indicate that the same dose and route of administration do not necessarily ensure the same exposure to the drug in women and men.

What are the conclusions?

Researchers suggest that biological sex, sex hormones, age, the structure of the nasal cavity, blood vessels, and the blood-brain barrier may affect the way a drug intended for the brain is absorbed and distributed in the body.

They say such differences may explain why previous trials of devonate have sometimes seen better responses in women. It is possible that when the results for women and men are analyzed together, the differences between them “disappear” into the overall average—so that a drug that may help one group may appear ineffective.

The study reinforces the need to design clinical trials taking into account biological sex, age, and hormonal status, and not assume that drugs work the same way for everyone.

However, it is important to highlight the limitations of the study: the number of animals in each comparison was small, and the human study only involved eight people. In addition, the study examined the drug's availability in the body—not its effectiveness in treating Alzheimer's or dementia.

What are the recommendations for the public?

There is no recommendation for the use of devonate at this time. It is an experimental drug that is not currently approved as a treatment for Alzheimer's, dementia, or other tau diseases.

The practical significance of the study is mainly for researchers and drug developers: women and men should be tested separately, the effect of hormones and age should be examined, and whether different doses or administration routes are needed for different groups.

It is important for the public to know that “personalized medicine” is not just about genetics. Biological sex, age, and hormonal changes may also affect how the body absorbs and responds to medications.

The main message from the study:

The same drug, at the same dose and route of administration, may reach the brain differently in women and men. The study shows that in females, the availability of devontide through the nose was higher when estrogen levels increased—reinforcing the need to consider gender and hormones as a central part of brain drug development.

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The full article:

• Link:
  https://www.neurology.org/doi/10.1212/WNL0000000000214916

• Reference:

Blatt, J., Guz, LS, Shabat, D., & Gozes, I. (2026). Intranasal bioavailability is estrous-cycle regulated: Davunetide as a case study. Genomic Psychiatry, 2(3), 112–120. https://doi.org/10.61373/gp026r.0039