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A scoping review of five studies found that lisdexamfetamine and atomoxetine improved women’s self-reported executive function in three small trials, but not their performance on objective cognitive tests. Researchers say the findings are preliminary and call for larger, independent trials; the review does not establish these drugs as treatment for menopausal brain fog.
A small scoping review presented at the Menopause Society annual meeting suggests that lisdexamfetamine and atomoxetine may improve women’s self-reported executive function during menopause, but neither drug significantly improved performance on objective cognitive tests. The findings are preliminary and do not establish either ADHD medication as a treatment for menopausal brain fog.
The review, led by Pallavi Khanna, MD, of the University of Tennessee Health Science Center College of Medicine, included five studies. Three were randomized crossover trials involving a total of 60 women without a prior ADHD diagnosis. Those trials assessed executive function with the Brown ADD Scales, where lower scores indicate fewer difficulties, as well as with objective cognitive tests.
In the lisdexamfetamine trial, participants’ Brown ADD Scale scores fell from a baseline average of 35.7 to 21.2, compared with a score of 29.8 for participants taking placebo (P<0.001). In the atomoxetine trial, scores fell from 38.6 to 25.5, compared with 30.1 for placebo (P=0.009). The researchers reported that neither medication significantly improved objective cognitive test results.
The other two studies were cross-sectional analyses of 6,048 women in Iceland and the U.K. They examined ADHD symptoms and menopause symptom scores, rather than testing medication. In the Icelandic study, women with an ADHD diagnosis had higher menopause symptom scores than women without one, and severe menopause symptoms were more commonly reported in the ADHD group. In the U.K. study, diagnosis itself was not associated with symptom burden, but higher ADHD symptom scores were linked to worse menopause symptoms.
What Self-Reported Gains Could Mean
Brain fog and difficulties with memory, attention, or planning can affect work and everyday tasks. The review raises a possible avenue for studying these complaints, but the difference between subjective improvement and unchanged objective test performance matters: the trials suggest participants felt their executive function improved, not that the tested cognitive abilities demonstrably improved.
There are currently no FDA-approved treatments specifically for menopausal brain fog, according to the report. The review does not show that ADHD drugs should be prescribed for this purpose, and it does not establish their safety or effectiveness for menopausal symptoms. Its findings support further research into who might benefit and whether any perceived gains translate into measurable or lasting changes.
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Why Researchers Examined ADHD Drugs
Khanna and colleagues searched five research databases for studies connecting menopause, executive function, ADHD, and ADHD medications. Their rationale drew on the possibility that changes in estradiol during the menopause transition may coincide with changes in dopamine and norepinephrine, neurotransmitters also associated with ADHD. This biological rationale prompted the researchers to examine whether ADHD medications might affect menopause-related cognitive complaints; it is not proof that the medications treat those complaints.
The review also looked at whether ADHD symptoms were associated with menopause symptom severity. In the Icelandic data, 54.2% of women with ADHD reported severe menopause symptoms, compared with 30.1% of women without ADHD; among women with more severe ADHD, the figure was 72.8%, compared with 28.9% in the comparison group. These observational findings show an association, not that ADHD causes more severe menopause symptoms. The report notes that hormone therapy’s cognitive benefits have been inconsistent, and the review did not compare it directly with either ADHD medication.
“This study is purely hypothesis-generating and needs to be replicated.”
— JoAnn E. Manson, MD, MPH, DrPH, Harvard Medical School and former Menopause Society president; not involved in the study
Limits of the Current Evidence
The medication evidence comes from just 60 participants across three crossover trials, all conducted by one research group at a single institution. The trials excluded women with diagnosed ADHD, so the results do not answer whether women who already have ADHD experience the same effects during menopause. The two larger studies were observational and cannot show that ADHD symptoms cause menopause symptoms or that treating ADHD changes them.
The review included no studies of methylphenidate, commonly known by the brand name Ritalin, and no direct comparison of ADHD medication with hormone therapy. It also does not establish the medications’ long-term effects, which patients might benefit, or whether changes in self-rated executive function improve daily functioning. The findings were presented as a scoping review and conference poster, and require replication.
Larger Trials Are the Next Test
Khanna said larger, independent trials are needed. Manson also called for the findings to be replicated and for future randomized research to compare ADHD medications with menopausal hormone therapy. Until those studies are done, the review supports further investigation, not a clinical recommendation to use ADHD drugs for menopause-related brain fog.
Future research would need to test both self-reported symptoms and objective cognitive outcomes, and clarify who is eligible and whether any effects persist. The source report did not provide a timetable for new trials. For now, the effectiveness of these drugs for menopausal brain fog remains uncertain.
Key Questions
Did the review show that ADHD drugs treat menopausal brain fog?
No. It found preliminary evidence of improved self-reported executive function in small trials, but no significant improvement on objective cognitive tests. The review does not establish either drug as a treatment for menopausal brain fog.
Which medications were studied?
The three randomized crossover trials examined lisdexamfetamine and atomoxetine. The review found no studies testing methylphenidate for this purpose.
How large was the medication evidence base?
The medication trials included 60 women in total and came from one research group at a single institution. The review also included two observational studies of 6,048 women, but those studies did not test medication.
Does having ADHD mean someone will have worse menopause symptoms?
The observational studies found associations between higher ADHD symptoms and worse menopause symptoms, but their results differed on the role of a formal diagnosis. They cannot establish that ADHD causes more severe menopause symptoms.
What research is needed next?
Researchers called for larger, independent randomized trials, including comparisons with menopausal hormone therapy. Studies would need to assess both participants’ reported symptoms and objective cognitive test results.
Source: rss
