Menopausal Hormone Therapy and Dementia

Menopause, a natural stage of aging in a woman's life, is an area of health that has seen calls for more scientific research. Women typically enter the menopausal transition between 45 and 55-years old, however this can vary. From a biological perspective, menopause occurs when the levels of reproductive hormones produced start to decline. This can be a natural byproduct of aging, or it might be the result of surgery or a treatment, such as chemotherapy.

Some individuals are fortunate to experience minimal symptoms during the menopausal transition. For others, symptoms such as menstrual changes, hot flashes, changes in mood and/or memory, issues with sleep and bladder control, can prove debilitating. The decision of whether to treat such symptoms pharmacologically is different for each individual and is based on a number of different factors. For women that do wish to undergo treatment, menopausal hormone therapy (MHT) – also known as hormone replacement therapy – is commonly prescribed.

Some of the neurological symptoms associated with menopause are similar to early signs of dementia. The ability of MHT to alleviate such symptoms in some women has led scientists to question whether a link exists between specific hormone levels and dementia. If so, could MHT be effective at preventing age-related brain decline?

That was the focus of a new research study at the University of Nottingham, led by Dr. Yana Vinogradova. The researchers conducted large-scale analyses of two primary care databases in the UK, QResearch and the Clinical Practise Research Datalink (CPRD). They compared 118,501 women with a primary diagnosis of dementia to 497,416 controls to explore the risk of developing dementia and Alzheimer's disease specifically in women that were prescribed different types of MHT. Their comprehensive study, published in the British Medical Journal, found that the use of MHT is not linked to an increased risk of developing dementia.

The potential impact that menopause and its treatment can have on a woman's quality of life calls for research studies like this. That's why Technology Networks interviewed Vinogradova, to learn more about menopause research, how the study was conducted and what women need to know about MHT.

Molly Campbell (MC): For our readers that may be unacquainted with MHT, please can you outline what the different types are and why it is prescribed for women during menopause?

Yana Vinogradova (YV): When a woman naturally stops being fertile, we say she enters her menopause. During this time, her hormone levels may fluctuate before eventually settling down at lower levels. The period of fluctuating levels may come with a variety of unpleasant symptoms, such as hot flushes, memory or concentration loss, insomnia, mood swings or depression. In a few women these symptoms can be very severe. To ease symptoms, MHT can be prescribed, which counteracts the fluctuations. As with any medication, however, an MHT treatment has side effects, so doctors try to identify the hormonal preparation that will best suit the patient. The key component of all MHT treatments is an oestrogen, but oestrogen on its own can cause damage to the womb. So, oestrogen-only treatments are normally prescribed only to women who have undergone a procedure which has involved removal of the uterus. All other women are normally prescribed a "combined" treatment of an oestrogen and a progestogen, because the progestogen has a protective effect on the womb lining.

MC: MHT has been the focus of extensive research exploring potential risks and side effects. Why did you decide to focus on a potential association between MHT prescriptions and the risk of developing dementia?

YV: Some of the symptoms of menopause are similar to early signs of dementia, so there was a hypothesis that, because MHT eased these symptoms, it might also have a preventive effect on the development of dementia. Existing evidence, however, has been rather inconsistent. Small studies, based on brain research, have suggested possible beneficial consequences from using MHT, while larger trials and observational studies have suggested that some MHT treatments might actually cause additional harm to the aging brain. Most previous studies have also either been small, lacked sufficient data over the long period of follow up required or had some design weaknesses. So, using rich primary care data sets linked to secondary care and other data sources, and covering a large sample from the general population over a long period, we set out to clarify and more robustly estimate the magnitudes of possible risks or benefits.

MC: Can you describe your key study methods and why they were adopted?

YV: We used all information supplied by general practices to two of the largest primary care databases in the UK – QResearch and the Clinical Practice Research Datalink (CPRD). All women diagnosed with dementia at the age of 55 or older (cases) were matched to women from the same practice and of the same age (controls). We then compared the use of MHT in both groups and considered all available clinical information, such as other relevant diseases and drugs, family histories of dementia, patient ethnicity and smoking and drinking habits. Our analyses investigated the details of different MHT treatments – types, individual hormones used, durations of treatments and dosages. We also separately examined outcomes of Alzheimer’s disease because of specific earlier findings of additional risk relating to this form of dementia.

MC: Your key finding was that there is no overall associations between the use of MHT and the risk of developing dementia, regardless of the type of treatment and/or application method. How can this result be translated to the clinical space?

YV: The study showed that MHT is not linked to the development of dementia, either as a cause or prevention. This will increase the confidence of doctors when prescribing the therapy. However, it should also deter women from considering that hormone replacement therapy treatments may help to prevent the development of dementia. This is also positive, because MHT treatments – like all medications – potentially have serious (although rare) side effects, such as increased risks of breast cancer and blood clots, and women should use them only after a discussion with their doctor.

MC: Did you encounter any challenges in this research project? If so, how did you overcome them?

YV: We used routinely collected data but, for a lot of women, precise information about the symptoms of menopause they had experienced was not consistently recorded. This meant that, in some cases, it was difficult to separate out symptoms of the menopause from those associated with development of dementia. In particular, this was a problem in our analysis for Alzheimer’s disease, which is a slowly developing form of dementia and where we did find a small cumulative association with long-term use of combined MHT treatments (measurable only after five years of use). The menopausal symptoms requiring long-term use in these women might have been signs of the already developing disease so – to try to overcome this – we disregarded prescriptions for MHT treatments for cases and controls in the last three years before the case diagnosis. We also included in the analysis information about mental health problems and prescribing of antidepressants and antipsychotics, but we were still unable to be certain that we had fully disentangled the data.

MC: Are there other potential associations between MHT use and disease risk that you would like to study?

YV: There is obviously a lot of interest in MHT treatments and some remaining polarization within the community about potential risks and benefits. So, we may continue our studies in this area to look in detail at outcomes within the general population of potential benefits – such as osteoporosis – and risks – such as cardiovascular disease.

MC: What "take home" message would you provide our readers based on this study and what we know about MHT?  

YV: Our discussions with individual women and evidence from other sources show that symptoms of the menopause for some women require treatment in order to maintain a reasonable quality of life. MHT treatments are known to be effective and have been shown – particularly in more recent studies investigating the claims of earlier studies – to be safe for most women if properly prescribed. All drug treatments, however, have side effects, occasionally potentially serious, and MHT treatments should be discussed by a patient and her doctor. Some women may have specifically increased risks, but all women need to take risks into account to ensure their future good health. It should also be noted that our study covers a wide range of treatments, but not all. Women considering other MHT treatments should seek evidence from other sources about their safety (preferably from peer-reviewed academic studies) and should discuss safe usage with their doctors.

Dr. Yana Vinogradova was speaking to Molly Campbell, Science Writer for Technology Networks.