Hormone Replacement Therapy and Cognition
Systematic Review and Meta-analysis
Erin S. LeBlanc, MD, MPH; Jeri Janowsky, PhD;
Benjamin K. S. Chan, MS; Heidi D. Nelson, MD, MPH
Context Some observational data suggest that hormone replacement therapy
(HRT) may reduce the risk of cognitive decline and dementia but results have
been conflicting.
Objective To review and evaluate studies of HRT for preventing cognitive
decline and dementia in healthy postmenopausal women.
Data Sources Studies with English-language abstracts identified in MEDLINE
(1966-August 2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000);
Cochrane Library databases; and articles listed in reference lists of key
articles.
Study Selection Randomized controlled trials and cohort studies were reviewed for
the effects of HRT on cognitive decline; cohort and case-control studies were
reviewed for dementia risk. No randomized controlled trials regarding dementia
risk were identified.
Data Extraction Twenty-nine studies met inclusion criteria and were rated. Two
reviewers rated study quality independently and 100% agreement was reached on
Jadad scores and 80% agreement was reached on US Preventive Services Task Force
quality scores. A final score was reached through consensus if reviewers
disagreed.
Data Synthesis Studies of cognition were not combined quantitatively because of
heterogeneous study design. Women symptomatic from menopause had improvements
in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of
other cognitive functions. Generally, no benefits were observed in asymptomatic
women. A meta-analysis of observational studies suggested that HRT was
associated with a decreased risk of dementia (summary odds ratio, 0.66; 95%
confidence interval, 0.53-0.82). However, possible biases and lack of control
for potential confounders limit interpretation of these studies. Studies did
not contain enough information to assess adequately the effects of progestin
use, various estrogen preparations or doses, or duration of therapy.
Conclusions In women with menopausal symptoms, HRT may have specific cognitive
effects, and future studies should target these effects. The meta-analysis found
a decreased risk of dementia in HRT users but most studies had important
methodological limitations.
JAMA. 2001;285:1489-1499
Estrogen Replacement Therapy and Ovarian Cancer Mortality in
a Large Prospective Study of US Women
Carmen Rodriguez, MD, MPH; Alpa V. Patel, MPH;
Eugenia E. Calle, PhD; Eric J. Jacob, PhD; Michael J. Thun, MD, MS
Context Postmenopausal estrogen use is associated with increased risk of
endometrial and breast cancer, 2 hormone-related cancers. The effect of
postmenopausal estrogen use on ovarian cancer is not established.
Objectives To examine the association between postmenopausal estrogen use and
ovarian cancer mortality and to determine whether the association differs
according to duration and recency of use.
Design and Setting The American Cancer Society's Cancer Prevention Study II, a
prospective US cohort study with mortality follow-up from 1982 to 1996.
Participants A total of 211 581 postmenopausal women who completed a
baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or
ovarian surgery at enrollment.
Main Outcome
Measure Ovarian cancer mortality,
compared among never users, users at baseline, and former users as well as by
total years of use of estrogen replacement therapy (ERT).
Results A total of 944 ovarian cancer deaths were recorded in 14 years of
follow-up. Women who were using ERT at baseline had higher death rates from
ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval
[CI], 1.16-1.96). Risk was slightly but not significantly increased among
former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was
associated with increased risk in both baseline and former users. Baseline
users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while
former users with 10 or more years of use had an RR of 1.59 (95% CI,
1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000
women were 64.4 for baseline users with 10 or more years of use, 38.3 for
former users with 10 or more years of use, and 26.4 for never users. Among
former users with 10 or more years of use, risk decreased with time since last
use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI,
1.29-3.25; RR for last use 15 years ago, 1.31; 95%
CI, 0.79-2.17).
Conclusions In this population, postmenopausal estrogen use for 10 or more
years was associated with increased risk of ovarian cancer mortality that
persisted up to 29 years after cessation of use.
JAMA. 2001;285:1460-1465
Edward
E. Rylander,M.D.
D.A.B.F.P. AND D.A.B.P.M.