Hormone Replacement Therapy and Cognition

Systematic Review and Meta-analysis

Author Information <http://jama.ama-assn.org/issues/v285n11/abs/#aainfo>
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


Author Information <http://jama.ama-assn.org/issues/v285n11/abs/#aainfo>
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.