With a recent study in the BMJ suggesting an increased risk of dementia in those using hormone replacement therapy (HRT), should women now peel off their patches? Rod Tucker investigates, in the first in a Review series of articles for the Pharmacist.

The menopause represents a normal physiological change that occurs on average in women age 50. Though not strictly an illness, the low levels of oestrogen associated with the menopause classically give rise to vasomotor symptoms such as hot flushes and night sweats. Hormone replacement therapy (HRT) and which is recommended by NICE, helps to alleviate these menopausal symptoms and users can now obtain a prescription prepayment certificate which covers 12 months’ worth of treatment. In addition, there has been a recent increase in the use of HRT which has been attributed to what has become known as the ‘ Davina effect’, following a television documentary on the menopause by Davina McCall.

But HRT has had a somewhat checkered history. Many of the earliest observational studies were positive. It seemed that HRT provided a cardiovascular benefit and was even able to prolong life when compared with non-users. Nevertheless, these purported advantages paled into insignificance and women took fright, abandoning HRT, following the publication of the Women’s Health Initiative study in 2002, which identified an elevated risk of coronary heart disease and breast cancer in those taking oral, combined hormonal therapy.

HRT and dementia

In addition to the purported cardiovascular and longevity benefits, as early as 1998, a literature review concluded how observational studies suggested a 29% reduced risk of developing dementia among oestrogen users. However, observational studies merely indicate an association and not causation. In other words, just because two factors are statistically associated, it doesn’t necessarily mean that one causes the other or vice versa. A randomised, placebo-controlled trial provides the best level of evidence. Unfortunately, one such trial with combination HRT in 2003, concluded that treatment actually increased the risk for probable dementia in postmenopausal women aged 65 years and older. Nevertheless, a later re-analysis of the trial found that among women aged between 50 and 55, there was no overall sustained benefit or risk to cognitive function from using HRT.

Has the recent study changed anything?

In a recent study in the BMJ, Danish researchers set out to examine the relationship between HRT use and the development of dementia. The team used national registry data between 2000 and 2018 and looked at the incidence of dementia among women aged 50 to 60 years who used HRT. such as co-morbidities, levels of education, the researchers adjusted for these in their analysis. The findings were both clear and consistent: when compared to non-users, the use of combined HRT was associated with a 24% higher risk of developing dementia. This elevated risk was apparent even in women who had used HRT for less than a year and much higher, at 71%, for those using HRT for more than 12 years. Interestingly, a small point almost buried within the paper, was how among women who used progestin or oestrogen only HRT, the risk of developing dementia was not significant.

Finally, it is important to realise that this was an observational study and therefore unable to prove a causative link. The authors acknowledged this and wrote how ‘further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk.’ Furthermore, elevated risk only applied to oral combined HRT.

So, should women stop taking HRT based on these findings? Probably not. First, because these findings are not definitive and second, HRT is often prescribed as transdermal patches which were not included in the study. Finally, unless women don’t feel a benefit from their treatment, stopping HRT is likely to cause a rebound of the bothersome menopausal symptoms that led to its use in the first place.

Rod Tucker BPharm, PhD is a clinical writer