The 2017 Hormone Therapy Position Statement of The North American Menopause Society

The North American Menopause Society 2017 Hormone Therapy Position Statement Advisory Panel

Disclosures

The North American Menopause Society (NAMS). 2018;24(7):728-753. 

In This Article

Mood, Depression, and Cognition

For postmenopausal women without clinical depression, evidence is mixed concerning the effects of HT on mood, with small, short-term trials suggesting that HT improves mood, whereas others showed no change. Postmenopausal women with a history of perimenopause-related depression responsive to HT may experience a recurrence of depressive symptoms after estradiol withdrawal.[154]

Small clinical trials support the use of ET for cognitive benefits when initiated immediately after surgical menopause.[155,156] Three large RCTs demonstrate neutral effects of HT on cognitive function when used early in the postmenopause period versus initiating treatment in women aged older than 65 years.[7,157,158]

Two hypotheses—the critical window hypothesis[159,160] and the healthy cell bias hypothesis[161] —provide a framework for understanding the scientific literature on HT and cognition, but neither has been definitively supported in RCTs of postmenopausal women.

Later Initiation of Hormone Therapy

Several large clinical trials indicate that HT does not improve memory or other cognitive abilities and that CEE + MPA may be harmful for memory when initiated in women aged older than 65 years.[162–164]

Alzheimer Disease

Four observational studies provide support for the view that timing of HT initiation is a significant determinant of Alzheimer disease risk, with early initiation lowering risk and later initiation associated with increased risk.

Dementia

In the WHI Memory Study, CEE + MPA doubled the risk of all-cause dementia (23 cases per 10,000 women) when initiated in women aged older than 65 years,[164] whereas CEE alone did not significantly increase the risk of dementia.[169] The effect of HT may be modified by baseline cognitive function, with more favorable effects in women with normal cognitive function before HT initiation.[170,171]

Key Points

  • In the absence of more definitive findings, HT cannot be recommended at any age to prevent or treat a decline in cognitive function or dementia.

  • On the basis of the WHI Memory Study, caution should be taken in initiating continuous-combined daily CEE + MPA in women aged older than 65 years, given the relatively small or infrequent increase in risk for dementia of an extra 23 cases per 10,000 person-years seen in the WHI.

  • Estrogen therapy may have positive cognitive benefits when initiated immediately after early surgical menopause, but HT in the early natural postmenopause period has neutral effects on current cognitive function.

  • Only limited support (observational studies) is available for a critical window hypothesis of HT in Alzheimer disease prevention.

  • The effect of HT may be modified by baseline cognitive function, with more favorable effects in women with normal cognitive function before HT initiation.

  • Evidence is insufficient to support HT use in the treatment of clinical depression. In small RCTs, ET was effective in improving clinical depression in perimenopausal but not postmenopausal women.

  • Progestins may contribute to mood disturbance.

  • Women whose depression improves with HT are likely to experience a worsening of mood after estrogen withdrawal.

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