Hormone replacement therapy does not alter cognition, study suggests

Study measured the effects of hormone replacement therapy on cognition and mood in healthy women.

The use of hormone replacement therapy for up to four years in recently post-menopausal women does not improve cognition, but may provide benefits in mood, results from a recent US study indicate.

The use of hormone replacement therapy (HRT) in recently post-menopausal women does not improve cognition, but may improve mood, results from a recent US study indicate.

Millions of women use HRT to mitigate the uncomfortable symptoms of menopause, including hot flushes and a lack of acuity, despite debate about its benefits and risks since the launch of the first HRT, Premarin, in 1942. One concern about HRT is that it may increase the likelihood of dementia and Alzheimer’s disease. The Cognitive and Affective Study, a subset of the Kronos Early Estrogen Prevention Study (KEEPS), set out to measure the impact.

While the key focus of the KEEPS study was the cardiovascular impact of HRT in early menopause, the KEEPS-Cog subset concentrated on mood and cognition. In KEEPS-Cog, 431 recently postmenopausal women (mean age 52.6 years) received HRT (oral oestrogen pills and progesterone, or transdermal oestradiol patches and progesterone), with 262 getting placebo pills and patches.

The results, published in PLoS Medicine
on 2 June 2015, showed that HRT did not worsen cognitive performance over the four years measured by the Modified Mini-Mental State (3MS), an expanded version of the widely used Mini-Mental State Examination (MMSE). This supports the results of the Women’s Health Initiative Memory Study of Younger Women (WHIMSY) that was published in 2013[2]

“There has been a lot of focus on the harm of [HRT], so showing that there isn’t an increase in cognitive adverse events can be seen as reassuring,” says Haitham Hamoda, clinical lead of the menopause service at King’s College London, and member of the medical advisory council at the British Menopause Society.

At the same time, the oestrogen treatment did not improve cognitive outcomes, as some researchers had hoped. This may be because the subjects were healthy women in their early fifties or because of measures used. Anthony Mander, consultant gynaecologist at the Nuffield Manor Hospital, Oxford suggests the latter. He believes that the MMSE test is too crude, and therefore the use of MMSE-based measures could miss significant differences. He suggests the use of more sensitive computerised cognitive testing.

The study results included more positive results for the impact of HRT on mood. Treatment based on oral conjugated equine oestrogens (with or without progesterone) significantly reduced levels of tension, anxiety and depression, which can be debilitating symptoms for women undergoing menopause.

The researchers suggest that decisions about HRT should be made by a woman and her doctor, weighing the benefits and risks.


[1] Gleason CE, Dowling NM, Wharton W et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-cognitive and affective study. PLoS Medicine 2015;12(6):e1001833.

[2] Espeland MA, Shumaker SA, Leng I et al. Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Internal Medicine 2013;173:1429–1436. doi:10.1001/jamainternmed.2013.7727.

Last updated
The Pharmaceutical Journal, PJ, 27 June/4 July 2015, Vol 294, No 7868/9;294(7868):DOI:10.1211/PJ.2015.20068733

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