Hormone therapy in early menopause proves safe but lacks cognitive benefits

While early hormone therapy is safe for relief of menopausal symptoms, it fails to preserve cognition – what does this mean for women looking for long-term brain health solutions?

Study: Long-term cognitive effects of hormone therapy in menopause: findings from the KEEPS Continuation Study. Image credits: Neirfy / Shutterstock

This is evident from a recent study published in the journal PLOS medicinea team of researchers in the United States examined the long-term cognitive effects of menopausal hormone therapy when started early after menopause.

The study was conducted approximately ten years after initial treatment with women from the Kronos Early Estrogen Prevention Study (KEEPS) to evaluate cognitive outcomes and whether different forms of menopausal hormone therapy affect menopausal hormone therapy over time. memory and mental functions.

Hormone therapy in menopause

Many women experience cognitive problems and mood disorders during menopause, which is often treated with menopausal hormone therapy. Although menopausal hormone therapy is effective for symptom relief, its long-term effects on cognition remain unclear, especially when initiated in the early postmenopausal period.

Previous studies, such as the Women’s Health Initiative Memory Study, have shown that hormone therapy in older women in late menopause was associated with an increased risk of cognitive decline and dementia. These findings raised concerns about the safety of hormone therapy in menopause. However, subsequent studies, including the Kronos Early Estrogen Prevention Study (KEEPS), found no short-term harm when treatment was started closer to menopause.

Furthermore, findings from neuroimaging studies suggested that transdermal estradiol (tE2) may confer cognitive benefits, raising the hypothesis of a “critical window” for initiating therapy during early postmenopause. However, these theories had not yet been definitively tested in the long term.

The current study

The current study was a follow-up to the KEEPS initiative to clarify whether starting hormone therapy early in menopause affected cognitive aging or protected against age-related decline. The researchers wanted to understand the optimal timing and safety of hormone therapy in menopause, while examining cognitive outcomes approximately ten years after starting treatment.

Participants included postmenopausal women at low cardiovascular risk who participated in the original KEEPS study. The original trial divided participants into three groups: oral conjugated estrogens (oCEE), transdermal estradiol (tE2), or placebo, with all groups receiving cyclic progesterone for 48 months.

This follow-up study re-enrolled participants at seven sites and focused on cognitive assessments using a standardized battery of tests. These tests measured four cognitive domains – verbal learning, working memory, executive function and mental flexibility – along with global cognition using the modified Mini-Mental State Examination (modified MMSE). Data from the original KEEPS study and its continuation were integrated to model changes over time and assess the influence of initial exposure to menopausal hormone therapy.

The researchers used statistical methods such as latent growth models to evaluate the associations between baseline cognitive performance, changes during the trial, and cognition at follow-up. This analysis also included variables such as education, age and genetic risk for Alzheimer’s disease (APOEε4 carriage) to ensure robust findings. Additionally, the study ensured that no medications or new interventions were administered during follow-up to maintain the focus on the long-term effects of the original exposure to menopausal hormone therapy.

Important findings

The results showed that menopausal hormone therapy started early after menopause had no long-term effects – beneficial or harmful – on cognitive performance. Women treated with oCEE, tE2 or placebo in the original study showed similar cognitive results about ten years later.

The strongest predictor of cognitive performance at follow-up was participants’ baseline cognition and the changes observed during the trial period. The linear growth models confirmed that there were no significant differences in cognitive trajectories between the treatment groups for the four cognitive domains examined via the modified MMSE or in global cognition. Furthermore, the cross-sectional analyzes at follow-up also showed no benefit or harm for either menopausal hormone therapy groups compared to the placebo group.

The findings also indicated that hormone therapy in early menopause does not protect against cognitive decline, contradicting a previous hypothesis that tE2 could provide long-term benefits. Furthermore, no adverse effects associated with the treatments were observed, which also addressed safety concerns raised by previous studies in older populations.

Although this study focused on a healthy population with low cardiovascular risk, it specifically highlighted that the findings may not generalize to populations with other health characteristics, such as higher cardiovascular risk or people starting therapy later in life.

Conclusions

Overall, the study provided reassuring evidence that menopausal hormone therapy, started early after menopause, does not harm or benefit long-term cognitive function in healthy women. Although menopausal hormone therapy effectively manages menopausal symptoms, it also does not prevent cognitive decline.

These results provide valuable insights for women considering menopausal hormone therapy, highlighting its safety for symptom relief while highlighting its limitations on cognitive preservation. The researchers also underlined the need for future studies to investigate other potential long-term effects of hormone therapy in menopause, such as its impact on mood or biomarkers associated with Alzheimer’s disease.