Postmenopausal Hormone Therapy Does Not Enhance Cognition

WEST CHESTER, Pa., Sept. 24 -- Hormone therapy had no significant effects on the cognitive performance of women shortly after menopause, according to investigators here.
Among 180 recently postmenopausal women with memory or concentration complaints, those randomized to hormone therapy for four months had significantly increased sexual desire and thoughts, but no difference in cognition, reported Michael J. Gast, M.D., Ph.D., of Wyeth Pharmaceuticals, and colleagues, in the Sept. 25 issue of Neurology.
The pilot study, called the Cognitive Complaints in Early Menopause Trial (COGENT), was terminated before the final expected enrollment of 275 patients, following the release of findings from the Women's Health Initiative linking hormone replacement to breast cancer, Dr. Gast and colleagues noted.
Even during the short duration, the authors saw evidence of modest but non-significant negative effects on long- and short-term verbal memory among women on hormonal therapy.
On the plus side, women with vasomotors symptoms who took hormones reported a reduction in symptoms and subjective improvement in quality of life, but these measures, too, were not significantly different from placebo.
The decline in enrollment coinciding with the publication of the WHI study effectively sealed the fate of the COGENT study, the authors noted.
"Although this is the largest randomized trial to date of hormonal therapy and cognition in recently menopausal women, the lower than expected participation likely rendered this study underpowered to decisively distinguish between hormonal therapy effects versus placebo (effect size <0.45)," they wrote.
COGENT was a randomized, double-blind, placebo-controlled study of healthy women from the ages of 45 to 55. The women had intact uteruses and were one to three years past their last menstrual period.
All participants had reported one or more cognitive complaints on the Self-Reported Cognitive Function Questionnaire, a brief, subjective survey of memory and concentration. Women with neurologic, systemic, or psychiatric diseases that could influence cognition were excluded.
The women were randomly assigned to conjugated equine estrogen at 0.625 mg/medroxyprogesterone acetate 2.5 mg (Prempro), or placebo, for four months.
Study endpoints included memory, subjective cognition, quality of life, sexuality, and sleep. Change in cognition from baseline was measured using validated instruments, including the California Verbal Learning Test, Memory Function Questionnaire, and Brief Test of Attention.
Of the 180 women who were randomized, 158 completed the study. The authors found that there were no differences between the hormone and placebo groups on any cognitive function or quality-of-life measures, with the exception of a significant increase among women on hormones in sexual interest and thoughts, two of six subscales on the McCoy Female Sexuality Scale Questionnaire. Analysis was by intention to treat.
Women who received hormones had an increase from baseline scores on the level of interest in sex subscale (P<0.05), and this difference was significantly greater at four months compared with placebo (P<0.001).
Women in the hormone therapy group also had higher reported levels of sexual thoughts than those in the placebo group at both one and four months (P<0.05). There were no differences between the treatment groups in the remaining four subscales on the questionnaire, however.
Women in the hormone therapy group also had modest but non-significant decline in short-delay free verbal recall subscores (P=0.054) and long-delay free recall (P=0.066).
"Women with baseline vasomotor symptoms showed a decrease in vasomotor symptoms and an improvement in general quality-of-life, but no cognitive benefit versus placebo," the authors wrote.
They noted that two larger studies looking at the effects of the daily conjugated equine estrogen/medroxyprogesterone acetate therapy on cognitive test performance in older women showed trends toward negative effects on verbal memory (P=0.06, in the Heart and Estrogen/progestin Replacement Study, or HERS) and modest decreases in in three measures of verbal learning and memory on an abbreviated version of the California Verbal Learning Test in the Women's Health Initiative Study of Cognitive Aging.
"Our finding of near-significant, modest negative effects of combined estrogen and progestin therapy on verbal memory contrasts with previous clinical trials using estrogen alone," they wrote, "which reported improvements in verbal memory in small samples of recently menopausal women, and neutral effects in large samples of older postmenopausal women. This raises the possibility that progestins might modulate the effects of estrogen on verbal memory."
The study was funded Wyeth, maker of Prempro. Dr. Gast and two of his four co-authors are current or former employees of the company, and the remaining two co-authors have received grants in excess of $10,000 and honoraria from the company. Primary source: NeurologySource reference: Maki PM et al. "Hormone therapy in menopausal women with cognitive complaints: A randomized, double-blind trial." Neurology 2007; 69: 1322-1330.