Short-Term Hormone Therapy for Menopause Has No Cognitive Impact

Among postmenopausal women, the use of short-term hormone therapy for menopause does not have any cognitive effects 10 years later, according to study results published in PLOS Medicine.

The Kronos Early Estrogen Prevention Study (KEEPS; ClinicalTrials.gov Identifier: NCT00154180) and its ancillary KEEPS Cognitive and Affective Study (KEEPS-Cog) explored the link between mHT and cognition, results of which showed no cognitive benefit or harm after 48 months of mHT initiated within 3 years of the final menstrual period.

Researchers of the current analysis reported the primary results of the KEEPS Continuation Study to understand the long-term cognitive effects of mHT initiated in early postmenopause.

The researchers collected data on participants’ medical history, cognition and mood, biometrics, magnetic resonance imaging (MRI) brain scans, and positron emission tomography (PET) measurements of brain proteins.

Women enrolled in the KEEPS studies were eligible for inclusion in the KEEPS Continuation study between 2017 and 2022 at 7 sites in the US. Participants in the KEEPS trial were considered for the KEEPS Continuation study even if they did not participate in the KEEPS-Cog study or have baseline cognitive assessments.

Of note, those in the KEEPS trials had low cardiovascular disease (CVD) risk.

All participants were randomly assigned to receive 0.45 mg/day oral conjugated equine estrogens, 50 μg/day transdermal estradiol, or placebo for 48 months.

Outcomes assessed in the KEEPS Continuation study were cognition, mood, and neuroimaging for Alzheimer disease. A total of 11 cognitive tests were conducted, which included scores on verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility.

Of the 727 postmenopausal women in the KEEPS interventions, 299 were included in the KEEPS Continuation study, of whom 275 had available cognitive data in both the KEEPS and KEEPS Continuation.

Baseline characteristics, except blood pressure readings and Mini-Mental State Examination (3MSE) scores, were similar between women who continued to participate in the KEEPS Continuation vs those who did not.

In the analysis, the researchers found that participants who received mHT and those who received placebo had similar trajectories for all cognitive factors and performance in global cognition. In addition, women who received any form of mHT vs placebo had similar results in cognitive function.

The researchers noted that cognitive performance in the KEEPS trial strongly predicted cognitive performance in the KEEPS Continuation study.

In the cross-sectional comparison of cognitive outcomes, the researchers found no significant differences between the mHT and placebo group in all cognitive factors and global cognition.

Study limitations included loss of participants to follow-up and lack of generalizability to all women, such as those with other conditions or those initiating mHT later in life.

“These data provide reassurance about the long-term neurocognitive safety of mHT for symptom management in healthy, recently postmenopausal women, while also suggesting that mHT does not improve or preserve cognitive function in this population,” the researchers concluded.

One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.