Hormone Therapy Linked to Improved Cognition in Postmenopausal Women

Extended estrogen exposure and longer-term hormone therapy (HT) was shown to benefit cognitive function among postmenopausal women, according to a study published in the journal Menopause, the journal of the North American Menopause Society (NAMS).

Researchers sought to examine the effect of estrogen on cognitive decline among older women. As women comprise two-thirds of the 5.5 million cases of Alzheimer disease in the United States, the authors noted that this may be attributed to declining estrogen levels. Estrogen is known to have a significant role in overall brain health and cognitive function, which is why a longer exposure to hormones could prove beneficial.

The study authors analyzed the impact of longer reproductive windows complemented with hormone therapy in 2114 postmenopausal women (mean age = 74.94 years) in a 12-year population-based study in Cache County, Utah. The study cohort completed a women’s health questionnaire that asked questions regarding reproductive history and HT usage and additionally were analyzed based on their endogenous estrogen exposure (EEE), which was calculated based on the reproductive window of age at puberty and age at menopause, adjusted for pregnancy and breastfeeding:

• HT variables included duration of use, HT type (none; unopposed [estrogen alone]; opposed [estrogen compounds including progesterone]), and time of HT initiation
• Cognitive status assessed by a modified version of the Mini-Mental State Examination (3MS) administered at 4 triennial waves
• Linear mixed-effects models examined the relationship between estrogen exposure and 3MS score over time

Study results revealed a significant positive association between EEE and cognitive status (β = 0.03, P = .054), with an additional positive association found between longer duration of HT use and cognition (β = 0.02, P = .046) that was found to have a chief impact on age based on a greater benefit exhibited among older women compared with younger women. Timing of HT initiation was significantly associated with 3MS (β = 0.55, P = .048), in which higher cognitive scores were shown for those who initiated HT within 5 years of menopause as opposed to those who initiated HT 6 or more years later.

The study represented a stark relation between higher cognitive function later in life and extended estrogen exposure through EEE and HT use, especially in older women, noted the authors.

While the study represents beneficial evidence from HT usage, there have been conflicting studies that have associated its use with increased risk of mortality and heightened breast cancer incidence. Stephanie Faubion, MD, NAMS medical director, provided insight into the most up-to-date information on hormone therapy found in a study by the Women’s Health Initiative (WHI) and the risk-to-benefit balance for HT.

“One caveat to the analysis of risks and benefits in the WHI is that these are not the most commonly used formulations of HT used now, which are mostly transdermal preparations of estradiol and oral micronized progesterone. Thus, we are making some assumptions about this balance of risk and benefit of HT based on different types/formulations/routes of administration from what is used today,” said Faubion.

Utilizing information from the WHI and other studies, Faubion provided a recommendation to women based on variables such as the time of menopause, HT benefit, and those experiencing vasomotor symptoms.

“We recommend HT for management of menopausal symptoms in women who are under the age of 60 and within 10 years of their last menstrual cycle and in whom the benefits typically outweigh the risks. It is about 90% to 95% effective in relieving hot flashes and night sweats. Hormone therapy also protects bone, and is probably beneficial for the heart in women who are in their 50s. The risk/benefit ratio is less favorable in women in their 60s, and it may even be harmful when started in women in their 70s,” said Faubion.

Reference

Matyi JM, Rattinger GB, Schwartz S, et al. Lifetime estrogen exposure and cognition in late life. [published online October 16, 2019]. Menopause. doi: 10.1097/GME.0000000000001405.