Does HRT Cause Dementia?

I’ve said it before, and I’ll say it again. There is a veritable cottage industry out there hell-bent on scaring women, whether it be about hormones or hair dye. The most recent stories about hormones and dementia are no exception. Nonetheless, it is worthwhile to take a minute to delve into what’s behind the recent headline “Hormones linked to Dementia.”

Dr. Sharon Malone Unpacks the Latest Headlines on HRT and Dementia

The study, published in the June 2023 issue of the British Medical Journal, by Nelsan Pourhadi, et. al., examined the records of 5589 Danish women diagnosed with dementia between 2000 and 2018 and matched them with 55,890 women without dementia. This is what is called a retrospective case-cohort study–essentially a look back into the medical histories of these two groups to see how they differed not just in the presence or absence of dementia but also to see whether the risk of dementia was associated with the use of menopausal hormones. 

What did they find? They found that compared to never users, the women who took estrogen and progestin therapy had a 24% higher incidence of dementia. I know that sounds scary, but I need you to stay with me.

The hormones used by women in this study were estradiol (90% oral) and non-bioidentical progestins. Women who used estrogen only (those with hysterectomies) were NOT included in this analysis. Information on age at menopause or the doses of estrogen-progestin therapy were not included. The median age for starting hormone replacement therapy (HRT) was 53. The median duration of hormone usage was only 3.8 years, and two-thirds of the women in the study had stopped their hormones over eight years prior to their diagnosis of dementia. 68% of the women diagnosed with dementia had never used hormones.

Is There a Link Between Estrogen and Dementia?

The numbers are the numbers, and I take no issue with them, but the bigger question is why is there a higher incidence of dementia in estrogen and progestin users? Is it the hormone use or something else that distinguishes these two groups? Funny you should ask. Okay, you didn’t ask, but I’m going to tell you anyway. 

The women diagnosed with dementia differed from the control group in the following ways–they had lower levels of education, lower household incomes, were more likely to live alone, and had significantly higher rates of hypertension, diabetes, and thyroid disease. It is also quite possible that the estrogen-progestin group had a higher incidence of vasomotor symptoms, which in and of themselves, are associated with a higher incidence of dementia. 

All of these risk factors are known to be independently or in combination positively associated with dementia. Retrospective studies are not able to ferret out any direct causal effects. And as we all know, association does not equal causation.

Dr. JoAnn Manson, one of the principal investigators of the Women’s Health Initiative, wrote a rebuttal to this article that was published in the same issue of the BMJ. Bet you didn’t hear about that, did you? Her editorial comments were entitled “Menopausal hormone therapy and dementia–A causal link remains unlikely.” Need I say more? 

It is worth noting that the WHI, a randomized control study, did not find an increased dementia risk in younger women who took hormone replacement therapy even with almost twenty years of follow-up. But to be fair, the data is confusing. What we have been able to glean from a review of the studies about hormones and dementia is that timing of initiation of menopausal hormone therapy matters (early is better than later), the route of administration may matter (oral vs. transdermal), and the type of progestin (bioidentical vs. synthetic) may play a role as well.

The bottom line is this, to quote Dr. Manson, “A causal link remains unlikely.” There are viable alternative explanations as to why these two groups differed (users vs. nonusers) that may have little or nothing to do with hormone use alone. Retrospective studies do not have the ability to answer the question of ‘why.’ They can only describe the ‘what.’ 

This gets me back to a point that I will make again and again. Why are two out of every three patients with dementia female? Why are there not more research dollars devoted to answering some of these questions about mid-life women’s health, particularly something as important as brain health? But let me step down from my soapbox and get back to the issue at hand. 

Should you be concerned about the use of estrogen and progestin and an increased risk of dementia? Probably not. The consensus still remains that for women who initiate hormone therapy before age 60 or within ten years of menopause, the benefits outweigh the risks. We also know that the lifetime risk of dementia for women who have early or premature menopause is increased by up to 70%. The use of menopausal therapy in these patients is recommended at least until the average age of menopause. 

I’m going to let Dr. Manson have the last word–”These findings (of the study above) cannot inform shared decision-making about use of hormone therapy for menopausal symptoms.”

If you’re interested in learning more about HRT, browse Alloy’s menopausal solutions to learn more.