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A scoping review presented at the Menopause Society’s annual meeting found that lisdexamfetamine and atomoxetine improved women’s self-reported executive function in three small trials, but neither improved objective cognitive test results. The evidence is preliminary, and researchers say larger, independent trials are needed before the drugs can be considered for menopause-related brain fog.
A small scoping review presented at the Menopause Society annual meeting found that lisdexamfetamine and atomoxetine improved women’s self-reported executive function in three randomized trials, but did not significantly improve their performance on objective cognitive tests. The findings suggest a possible avenue for studying menopausal brain fog, not an established treatment: researchers and an outside expert say larger trials are needed.
Pallavi Khanna, MD, of the University of Tennessee Health Science Center College of Medicine, and colleagues reviewed five studies examining links between menopause symptoms, executive function and ADHD medications. Three were crossover randomized controlled trials involving 60 women in total; the other two were cross-sectional studies drawing on data from 6,048 participants in Iceland and the United Kingdom.
In the trials, women without a prior ADHD diagnosis reported fewer executive-function difficulties while taking lisdexamfetamine, sold as Vyvanse, or the non-stimulant atomoxetine, sold as Strattera. On the Brown ADD Scales, where lower scores indicate less reported dysfunction, scores fell from 35.7 to 21.2 with lisdexamfetamine, compared with 29.8 with placebo (P<0.001). For atomoxetine, reported scores were 25.5, compared with a baseline of 38.6 and 30.1 with placebo (P=0.009).
The researchers reported that neither medication significantly improved performance on objective cognitive tests. The observational studies reported a relationship between ADHD symptom severity and menopause symptom burden. In the Icelandic study, women with an ADHD diagnosis had higher menopause symptom scores, and severe symptoms were more commonly reported among women with ADHD. These findings show an association, not that ADHD symptoms cause more severe menopause symptoms.
What the Findings Could Mean for Care
Brain fog and difficulties with attention or working memory can interfere with daily life, yet there are no FDA-approved treatments specifically for menopausal brain fog. The review raises a research question for clinicians and patients: might medication that affects attention-related brain systems ease some women’s subjective cognitive symptoms during menopause?
The distinction between self-reported improvement and unchanged objective test results matters. A person may feel better able to manage tasks without showing measurable gains on a test, and these findings do not establish how broad or lasting any benefit might be. They also do not show that ADHD medications should be prescribed for menopause symptoms. Decisions about these drugs require clinical assessment of potential benefits, risks and individual health circumstances.
Menopausal hormone therapy was not tested against either ADHD medication in the included trials. Khanna said cognitive benefits from hormone therapy have been inconsistent. The review therefore cannot establish which approach works better, or whether either treatment is appropriate for a particular patient.
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Why Researchers Examined ADHD Treatments
Khanna told MedPage Today that brain fog is a frequent concern in her menopause clinic and can resemble ADHD-related difficulties. She said the team examined whether ADHD medications might help with menopause-related symptoms and whether people with more ADHD symptoms might experience a greater menopause burden.
The biological rationale described by Khanna is that estradiol declines during the menopause transition, alongside changes in dopamine and norepinephrine; ADHD is also associated with these neurotransmitter systems. That rationale offers a basis for investigation, but it is not proof that the medications will treat menopausal cognitive symptoms.
The review searched Embase, PubMed, Scopus, PsycINFO and the Cochrane Central Register of Controlled Trials for studies combining menopause-related terms with executive function, ADHD and ADHD medication. The evidence base remained small: all three randomized trials came from one research group at one institution, and the trials excluded women with diagnosed ADHD.
“Exciting and warrant testing in larger randomized trials.”
— JoAnn E. Manson, MD, MPH, DrPH, of Harvard Medical School
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Limits of the Current Evidence
The review does not establish that ADHD medications treat menopausal brain fog. Its medication findings came from only three trials with 60 participants, all conducted by one research group, and those trials excluded women with an ADHD diagnosis. The reported benefit was on self-rated executive function; objective tests did not show significant improvement.
The review included no trials of methylphenidate, sold as Ritalin, and no direct comparison with menopausal hormone therapy. It also cannot determine how long any reported benefits last, which women might benefit, or how the drugs’ risks compare with possible gains for people seeking care for menopause-related cognitive symptoms. The observational findings linking ADHD symptoms with menopause symptom severity cannot establish cause and effect.
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Larger Independent Trials Needed
Khanna said larger, independent studies are needed to test whether these findings can be reproduced. Manson called for larger randomized trials, including comparisons with menopausal hormone therapy. Future research would need to clarify whether changes in self-reported symptoms correspond to meaningful improvements in daily functioning and how results differ among women with and without an ADHD diagnosis.
Until such studies are available, the evidence supports further investigation rather than a change in standard treatment. The review was presented at a meeting, and the source report describes it as a scoping review; details on larger follow-up trials, their timing and any results have not been reported.
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Key Questions
Did the review show that ADHD drugs improve menopausal brain fog?
It found that two medications improved women’s self-reported executive function in three small trials. Neither significantly improved objective cognitive test results, so the findings are preliminary and do not establish a treatment.
Which medications were included?
The trials examined lisdexamfetamine (Vyvanse) and atomoxetine (Strattera). The review did not include trials of methylphenidate (Ritalin).
Were the trial participants diagnosed with ADHD?
No. The three randomized trials included women without a prior ADHD diagnosis. Separate observational studies examined ADHD symptoms and menopause symptoms in larger groups.
Can these findings show that ADHD symptoms cause worse menopause symptoms?
No. The larger studies found an association between greater ADHD symptom severity and worse menopause symptoms, but observational data cannot establish that one causes the other.
What research is needed next?
Researchers called for larger, independent randomized trials, including studies that compare ADHD medications with menopausal hormone therapy and assess both self-reported symptoms and objective outcomes.
Source: rss
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