Alzheimer's disease and HRT

Last edited 04/2019

The Women's Health Initiative Memory study (1,2) has revealed that:
  • in postmenopausal women >= 65 years of age, hormone replacement therapy (HRT), increased the risk of probable dementia

Further evidence relating to the use of conjugated equine oestrogens revealed that (3,4):

  • ostrogen therapy alone did not reduce dementia or mild cognitive impairment incidence and increased the risk for both dementia and mild cognitive impairment (3)
  • pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both dementia and mild cognitive impairment (3)
  • for women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment (4)
  • the authors conclude that use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended

This evidence contrasts with, and supersedes, that seen in previous observational studies (5):

  • a meta-analysis of twenty-nine studies suggest that HRT users may have a lower risk of dementia (5).The same review reported that, in women with menopausal symptoms but not in asymptomatic women, HRT may have a beneficial effect on verbal memory, vigilance, reasoning and motor speed

A Cochrane systematic review (6) notes that:

  • women over 65 years of age who were relatively healthy and taking continuous combined HRT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000) - this is based on the Women's Health Initiative Memory study (1,2)
  • concluded that HRT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women (6)

A case-control study has shown (7):

  • use of systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer's disease
    • risk of the disease did not differ significantly between users of estradiol only (odds ratio 1.09, 95% confidence interval 1.05 to 1.14) and those of oestrogen-progestogen (1.17, 1.13 to 1.21)
    • risk increases in users of oestrogen-progestogen therapy were not related to different progestogens (norethisterone acetate, medroxyprogesterone acetate, or other progestogens); but in women younger than 60 at hormone therapy initiation, these risk increases were associated with hormone therapy exposure over 10 years
    • exclusive use of vaginal estradiol did not affect the risk of the disease (0.99, 0.96 to 1.01).

NICE state with respect to HRT and dementia (8):

  • Explain to menopausal women that the likelihood of HRT affecting their risk of dementia is unknown

Reference:

  1. Shumaker SA et al. Estrogen plus progestin and incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289:2651-62.
  2. Rapp SR et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289:2663-72.
  3. Shumaker SA et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291:2947-58.
  4. Espeland MA et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291:2959-68.
  5. Le Blanc et al.Hormone replacement therapy and cognition systematic review and meta-analysis. JAMA 2001;285:1489-99
  6. Marjoribanks J et al. Long-term hormone therapy for perimenopausal and postmenopausal women.Cochrane Database Syst Rev. 2017 Jan 17;1:CD004143.
  7. Savolainen-Peltonen H et al. Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study. BMJ. 2019 Mar 6;364:l665
  8. NICE (November 2015). Menopause: diagnosis and management