Understanding the interplay of menopausal hormone therapy and dementia

In the area of women’s health, the question of whether menopausal hormone therapy (MHT) increases the risk of dementia is a topic of substantial concern and debate. Understanding the evidence related to this topic will help pharmacists assist patients in making informed decisions.Let’s explore a case involving a 52-year-old woman, Mrs. Kim. She presents to your pharmacy seeking guidance on managing her menopausal symptoms, which include frequent hot flashes that negatively impact her daily life. Mrs. Kim is in good health overall, with no significant medical history aside from her recent diagnosis of vasomotor menopausal symptoms (VMS).As a pharmacist, you initiate a conversation with Mrs. Kim about the available options for managing VMS. You discuss lifestyle modifications, nonhormonal therapies, and the potential benefits and risks of MHT. Given her overall good health and the bothersome nature of her symptoms, Mrs. Kim expresses interest in MHT; however, she is concerned about the risk of dementia with MHT based on a blog post she recently saw online.MHT for vasomotor symptomsIn patients experiencing moderate to severe hot flashes, MHT can reduce VMS by up to 90%, as well as improve sleep and mood-related symptoms.1 Both the Society of Obstetricians and Gynaecologists of Canada and the North American Menopause Society provide strong recommendations that the benefit-risk ratio is favourable for treatment of bothersome VMS with MHT in women ≤ 60 years of age or who are within 10 years of menopause onset (defined as 1 year of amenorrhea caused by declining ovarian reserve or at the onset of VMS in women with iatrogenic amenorrhea) and have no contraindications.1-3 However, for women who initiate therapy more than 10 years from menopause onset or who are older than 60 years, the benefit-risk ratio is less favourable due to the greater absolute risks of coronary heart disease, venous thromboembolism and dementia.2,3MHT and dementia: the evidenceSeveral studies have sought to answer Mrs. Kim’s question regarding the dementia risk of MHT. The Women’s Health Initiative Memory Study (WHIMS) published in 2003 reported that use of estrogen and progestin MHT in women ≥ 65 years of age may increase the risk of dementia.4 Prolonged use (> 5 years) of combined estrogen and progestogen MHT may increase the risk of developing Alzheimer’s disease based on weak observational data.5 More recently, a nested-case control study published in 2023, reported an association between MHT and dementia, in patients aged 55 years or younger; however, this association is contrasted by the findings of three previous randomized controlled trials that did not find an association between MHT use and dementia in early menopausal patients.6,7The KEEPS-Cog study, for example, suggested that for recently postmenopausal women (up to 3 years since their last menstrual period) combined estrogen and progesterone MHT did not alter cognition.8 Furthermore, the Women’s Heath Initiative Memory Study of Younger Women (WHIMSY), which focused on postmenopausal women aged 50–55, found that MHT did not affect overall cognitive function.9 Additionally, randomized controlled trial evidence supports that conjugated equine estrogens alone do not affect cognition regardless of being started within six years of menopause or > 10 years after menopause.10,11Your recommendationConsidering the current evidence, you explain to Mrs. Kim that MHT can provide substantial relief from VMS. Additionally, you also provide her with an up-to-date summary of the risks, including those related to dementia, and indicate that given her age and overall health status the benefits of MHT likely outweigh the risks. By engaging in this open dialogue with Mrs. Kim, you empower her to make an informed decision that aligns with her values and health goals.SummaryFor women under the age of 65 years, especially those under the age of 55 years, there appears to be no increased risk of dementia with MHT.7 However, for women ≥ 65 years, continued use of estrogen plus progestogen MHT may increase the risk of dementia.7 By fostering open communication and staying informed of current evidence, pharmacists can help to ensure that each woman receives the most appropriate and safe care for her menopausal symptoms.Katelyn Halpape is a clinical pharmacist at the Dube Centre for Mental Health in Saskatoon, SK, and an Associate Professor in the College of Pharmacy and Nutrition at the University of Saskatchewan.References: Lega IC, Fine A, Antoniades ML, et al. A pragmatic approach to the management of menopause. Can Med Assoc J 2023;195(19):E677-82.Yuksel N, Evaniuk D, Huang L, et al. SOGC Clinical Practice Guideline. Guideline No. 422a: Menopause: vasomotor symptoms, prescription therapeutic agents, complementary and alternative medicine, nutrition, and lifestyle. J Obstet Gynaecol Can 2021;43(10):1188-1204.e1. (accessed January 31, 2024.North American Menopause Society (NAMS) 2023 Nonhormone Therapy Position Statement Advisory Panel. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023;30(6):573-590. (accessed January 31, 2024).Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289(20):2651-62.Vinogradova Y, Dening T, Hippisley-Cox J, et al. Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases. BMJ 2021;374:n2182.Pourhadi N, Mørch LS, Holm EA, et al. Menopausal hormone therapy and dementia: nationwide, nested case-control study. BMJ 2023;381:e072770.RxFiles. Menopause Newsletter. October 2023.Gleason CE, Dowling NM, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS–Cognitive and Affective Study. PLoS Med 2015;12(6):e1001833.Espeland MA, Shumaker SA, Leng I, et al. Long term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50–55 years. JAMA Intern Med 2013;173(15):10.1001/jamainternmed.2013.7727.Henderson VW, St. John JA, Hodis HN, et al. Cognitive effects of estradiol after menopause. Neurology 2016;87(7):699-708.Crandall CJ, Mehta JM, Manson JE. Management of menopausal symptoms: a review. JAMA 2023;329(5):405-20.

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Understanding the interplay of menopausal hormone therapy and dementia

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Katelyn Halpape

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