What is the approach to managing hot flashes in an 83-year-old patient with mild cognitive impairment/Alzheimer's disease, who insists on taking oestradiol (estrogen) and progesterone for postmenopausal symptoms?

From the Guidelines

For an 83-year-old patient with mild cognitive impairment/Alzheimer's dementia who is adamant about taking estradiol and progesterone for hot flashes, I would strongly recommend against hormone therapy due to significant risks that outweigh potential benefits. The most recent and highest quality study, 1, suggests that the use of hormone replacement therapy (HRT) is associated with an increased risk of stroke, pulmonary embolism, and invasive breast cancer, which is particularly concerning in elderly patients with existing cognitive impairment.

Instead, I suggest starting with non-hormonal approaches such as:

• Gabapentin 100mg at bedtime, gradually increasing to 300mg if needed
• Low-dose paroxetine 7.5mg daily Environmental modifications like layered clothing, keeping the bedroom cool, and avoiding triggers (spicy foods, alcohol, caffeine) should be implemented concurrently.

If these approaches fail and the patient remains insistent on hormone therapy despite counseling, the absolute lowest effective dose should be used for the shortest possible time (e.g., estradiol 0.025mg patch with micronized progesterone 100mg daily if the uterus is intact), with close monitoring for cognitive decline, cardiovascular events, and breast cancer, as recommended by 1. This cautious approach is necessary because hormone therapy in elderly patients significantly increases risks of stroke, venous thromboembolism, and potentially worsening cognitive function, particularly in those with existing cognitive impairment.

The risk-benefit ratio is particularly unfavorable in this age group, as hot flashes typically diminish in intensity over time since menopause, and alternative treatments such as gabapentin and paroxetine have been shown to be effective in managing hot flashes, as suggested by 1. Therefore, non-hormonal approaches should be prioritized to minimize the risks associated with HRT.

From the FDA Drug Label

The WHI estrogen plus progestin substudy stratified for age showed in women 50 to 59 years of age a non-significant trend toward reducing risk of overall mortality [hazard ratio (HR) 0.69 (95 percent CI, 0.44-1. 07)]. Women’s Health Initiative Memory Study ... enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older ... to evaluate the effects of daily CE (0. 625 mg) plus MPA (2.5 mg) on the incidence of probable dementia (primary outcome) compared to placebo. After an average follow-up of 4 years, the relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21 – 3. 48).

The patient is an 83-year-old with mild cognitive impairment/Alzheimer’s dementia. The Women’s Health Initiative Memory Study found an increased risk of probable dementia in women 65 years of age and older taking estrogen plus progestin.

• The relative risk of probable dementia was 2.05 (95% CI, 1.21-3.48) compared to placebo.
• The absolute risk of probable dementia was 45 versus 22 per 10,000 women-years for estrogen plus progestin versus placebo. Given the patient's age and existing cognitive impairment, it is likely that the risks of estrogen plus progestin therapy outweigh the benefits, particularly with regards to dementia. The decision to prescribe oestradiol and progesterone should be made with caution, considering the potential increased risk of dementia and other adverse effects 2.

From the Research

Approach to Hot Flashes in an 83-Year-Old Patient

• The patient has mild cognitive impairment/Alzheimer's dementia and is adamant on taking oestradiol and progesterone for post-menopausal symptoms.
• According to 3, estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older.
• The study also found that estrogen plus progestin therapy did not prevent mild cognitive impairment in these women 3.
• Another study suggests that hormone therapy (HT) may not have a beneficial effect on cognitive status in postmenopausal women with Alzheimer's disease, and that the timing of HT initiation, type of HT, and hormone dosage used may be important factors to consider 4.
• A recent review article highlights the potential neuroprotective effects of estrogen and progesterone, including their ability to rise the expression of the brain-derived neurotrophic factor (BDNF) mRNA and degrade beta-amyloid 5.
• However, clinical research on the significance of these substances in Alzheimer's disease is fragmented, and more studies are needed to establish their role in preventing or treating the disease 5.
• In terms of managing mild cognitive impairment, lifestyle modification, such as aerobic exercise, is an approved modality to preserve cognitive ability and decrease the rate of progression to dementia 6.

Considerations for Treatment

• The patient's adamant desire to take oestradiol and progesterone for post-menopausal symptoms must be balanced with the potential risks and benefits of hormone therapy in the context of their mild cognitive impairment/Alzheimer's dementia.
• The patient's healthcare provider should carefully consider the evidence and discuss the potential risks and benefits of hormone therapy with the patient and their family 7, 3, 4.
• Alternative treatments for hot flashes, such as lifestyle modifications or non-hormonal medications, may be considered in order to minimize the risk of exacerbating the patient's cognitive impairment.