By Leanna Coy, FNP-BC
KEY TAKEAWAYS:
- The timing for starting HRT may matter more than the decision itself
- Late initiation carries added risks
- The science is still evolving
The history of hormone therapy for menopause symptoms is fraught with confusing and contradictory information. This leads many women to delay hormone replacement therapy (HRT) as they weigh the benefits against the risks to their health. Estrogen loss affects the whole body, including the brain. Many women notice this as they begin to experience brain fog and memory issues during the midlife menopause transition.
With more women in the workforce and serving as unpaid caregivers for both older and younger family members, maintaining memory and cognitive function is essential. Women also make up more than two-thirds of people living with Alzheimer’s disease. These concerns make HRT worth early consideration for managing brain health.
The confusing history of HRT and brain health
Research on HRT for brain health goes back to the Women’s Health Initiative Memory Study (WHIMS) in 1995. The study looked at how hormone therapy affected dementia and changes in thinking over time in women aged 65 and older. The results showed a 49% increased risk of dementia when conjugated equine estrogen (CEE) was used. The dementia risk jumped to 79% when the HRT was a combination of estrogen and medroxyprogesterone.
For clarification, the brand Premarin is the most commonly used CEE. It is made from the urine of pregnant mares, which is where the name comes from (PREgnant MARe urine). It’s used as an oral pill, vaginal cream, or injection. By contrast, estradiol is a bioidentical hormone, meaning its chemical makeup is identical to the primary estrogen the human body naturally produces. It’s prescribed as an oral pill, transdermal patch, gel, spray, vaginal ring, and vaginal cream.
What happens to women’s brains
During the menopause transition, women gradually lose hormones, especially estrogen. Estradiol is the primary form of estrogen that works on the brain and declines over time. As estradiol declines, memory function and performance are affected, leading to brain fog. For some women, the menopause transition begins in their 40s. This means a woman’s brain begins aging in midlife, much earlier than what men experience.
There is considerable variation in women’s physiology during this stage. This is due to the wide age range in which women begin the menopause transition – from their late 30s to mid-60s. With this wide age span, you’re going to have women who are at different baseline levels of cognitive and overall health. For example, women who live with chronic health issues, such as diabetes or high blood pressure, have an even greater risk for cognitive changes. The variations are part of the treatment challenges because, as women know, one size doesn’t fit all.
What is the critical window hypothesis
There is a theory about starting HRT early. This theory suggests a window of time during the menopause transition and shortly after entering menopause when estrogen treatments are most effective. This comes from research on women who experience surgical menopause following a hysterectomy or the removal of their ovaries. Surgical menopause is linked to an increased risk of cognitive problems and dementia.
What the science shows
For years, many follow-up studies focused on women over age 60, with mixed results. More recent research is looking at younger women and addressing those variables. Studies have shown that starting HRT prior to having a hysterectomy or removal of the ovaries reduces the cognitive decline that women typically experience after a hysterectomy. This suggests that starting HRT earlier may be more beneficial.
One study published last year found that when women started HRT within 5 years of entering menopause, had a 32% lower risk of Alzheimer’s disease than those who went untreated. It also found that starting HRT at age 65 or older increased the risk for Alzheimer’s disease by 38%.
Another study focused on women with the APOE4 gene, which can greatly increase someone’s risk for dementia. The study found that HRT improves thinking and brain size in APOE4 gene carries. The best improvement was seen in women who started HRT at a younger age.
More studies are needed to clarify key aspects of HRT for preventing cognitive decline. Researchers need to determine the best timing for starting treatment, the recommended doses, and the treatment duration. They also need to include women who aren’t in perfect health, such as those with diabetes or hypertension.
What this means for menopausal people
Cognitive decline is more than just concerns about dementia or Alzheimer’s disease. Some decline is a normal part of aging, but too much too soon can begin to affect someone’s quality of life. If you are considering HRT, talk with your primary care provider or gynecologist to get a good understanding of your overall health and risk for dementia. With you, the provider can weigh the risks and benefits of starting HRT against your health and dementia risks, so you can decide whether it makes sense for you.
In the meantime, take steps on your own to help maintain brain health. Socialize regularly and do activities that challenge your brain. Stay physically active and eat a healthy diet, such as the Mediterranean diet, to support your brain health. If you aren’t doing these things, don’t feel like you have to make many changes all at once. Make gradual changes that can still make a difference.
