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Examining the Evidence


Does cognitive function decline during the menopausal transition?

July 2009 · Vol. 21, No. 07

These important findings from SWAN confirm the memory problems reported by many women during the menopausal transition. They also build on the findings of clinical trials of HT in younger menopausal women, which explored the effect of HT on cardiovascular health, to underscore the critical role that timing of such therapy can play.1,2

Other cohort studies of middle-aged women in the United States have found the menopausal transition to be associated with undesirable changes in mood3,4; some experts have described the endocrine shifts that accompany menopause as “hormonal chaos.”5

Details of the study

Participants were 42 to 52 years old and had an intact uterus and at least one ovary at entry. They were followed for 4 years, with delineation of the menopausal stage (i.e., premenopause, early and late perimenopause, and menopause) and assessment of hormone use prior to the final menstrual period and after menopause. The outcome was longitudinal performance in three cognitive domains:

  • processing speed—assessed using the Symbol Digit Modalities Test. Premenopausal, early perimenopausal, and postmenopausal women improved with repeated administration of this test, but late perimenopausal women did not. Prior use of HT improved the score, whereas late use of HT reduced it.
  • verbal memory—evaluated via the East Boston Memory Test. Test scores increased during premenopause and postmenopause but not during early or late perimenopause. Prior use of HT improved the test score, but late use reduced the score.
  • working memory—assessed using the Digit Span Backward test. This domain did not vary by stage of menopause.

Participants who initiated menopausal HT or oral contraceptives prior to the last menstrual period were excluded from the analysis during use of HT. They were allowed to reenter the study, however, once HT or oral contraceptives were discontinued.

As the cognitive component of SWAN began, the mean age of participants was 50 years, and 8% were premenopausal, 49% were early perimenopausal, 12% were late perimenopausal, and 27% were postmenopausal. In addition, 4% were both postmenopausal and current users of HT.

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Because perimenopausal HT should include a dosage of progestin adequate to suppress ovulation in order to prevent iatrogenic irregular uterine bleeding, women who are healthy, lean, nonsmoking, and still having menstrual periods can safely use a conventional oral contraceptive. Options for other symptomatic perimenopausal women include a continuous oral menopausal regimen formulated with 5 μg of ethinyl estradiol and 1 mg of norethindrone acetate (Femhrt 1/5) or 1 mg of estradiol and 0.5 mg of norethindrone acetate (Activella 1/0.5 or generic).—ANDREW M. KAUNITZ, MD

References

1. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477.

2. Manson JE, Allison MA, Rossouw JE, et al. For the WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356:2591-2602.

3. Freeman EW, Sammel MD, Lin H, et al. Symptoms associated with the menopausal transition and reproductive hormones in midlife women. Obstet Gynecol. 2007;110(2 Pt 1):230-240.

4. Woods NF, Smith-DiJulio K, Percival DB, Tao EY, Mariella A, Mitchell S. Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women’s Health Study. Menopause. 2008;15:223-232.

5. Berga SL. Disordered folliculogenesis during the menopausal transition: explaining chaos. Menopause. 2009;16:11-12.

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