Hormone
replacement
therapy
(HRT)
was
tied
to
a
lower
risk
of
dementia
in
a
prospective
study
of
nearly
185,000
postmenopausal
women
in
the
U.K.
Biobank.

Over
13
years
of
follow-up,
HRT
use
was
associated
with
a
lower
risk
of
all-cause
dementia
(HR
0.90,
95%
CI
0.84-0.96),
according
to
Anne-Marie
Minihane,
PhD,
of
the
University
of
East
Anglia
in
Norwich,
England,
and
colleagues.

Starting
HRT
between
ages
46
and
56
yielded
the
greatest
benefit,
Minihane
and
co-authors
reported
in


Alzheimer’s
&
Dementia.
For
all
postmenopausal
women
starting
HRT
at
ages
46
to
50,
the
HR
was
0.87
(95%
CI
0.80-0.95,

P=0.002);
for
those
starting
at
ages
51
to
56,
the
HR
was
0.77
(95%
CI
0.70-0.86,

P<0.001).

Associations
emerged
for
women
who
had
surgical
menopause
(HR
0.74,
95%
CI
0.65-0.84),
those
who
carried
an

APOE4
gene
(HR
0.87,
95%
CI
0.80-0.95)
and
women
with
lower
endogenous
estrogen
exposure
(HR
0.84,
95%
CI
0.77-0.93).

The
study
is
the
largest
of
its
kind,
the
researchers
noted.
The
findings
supported
those
of
a
recent

retrospective
study
that
showed
women
who
used
estrogen-only
menopause
hormone
therapy
had
a
reduced
risk
of
Alzheimer’s
disease.

Women
account
for
nearly
two-thirds
of
cases
of
Alzheimer’s
disease,
the
main
form
of
dementia,
Minihane
observed.
“In
addition
to
living
longer,
the
reason
behind
the
higher
female
prevalence
is
thought
to
be
related
to
the
effects
of
menopause
on
brain
metabolism
and
the
impact
of
the
main
genetic
risk
factor

APOE4
being
greater
in
women,”
she
said
in
a
statement.

Earlier
research
suggested
that
HRT
might
protect
against
Alzheimer’s
and
cardiovascular
disease,
but
in
2003,
the

Women’s
Health
Initiative
Memory
Study
(WHIMS)
reported
that
estrogen-plus-progestin
formulations
increased
probable
dementia
risk
in
women
ages
65
or
older.
The
Women’s
Health
Initiative
trial
also
linked
combined
estrogen
and
progestin
to
higher
breast
cancer
and
heart
disease
risks,
leading
to
black-box
warnings
which
the

FDA
removed
in
2026.

In
the
U.S.,

HRT
use
declined
among
postmenopausal
women
from
26.9%
in
1999
to
4.7%
in
2020.
The
treatment
continues
to
be

controversial.

The
novelty
of
the
U.K.
Biobank
research
is
the
timing
of
HRT
initiation,
said
Aimee
Spector,
PhD,
of
University
College
London
(UCL),
who
wasn’t
involved
with
the
study.

“This
supports
the
‘window
of
opportunity’
hypothesis,
suggesting
that
HRT
use
during
the
menopause
transition
phase,
where
symptoms
are
typically
more
problematic,
is
important,”
Spector
wrote
on
the

U.K.
Science
Media
Center
website.

“We
need
very
large
studies
with
long-term
follow-up
to
understand
whether
what
happens
around
menopause
relates
to
brain
health
later
in
life,”
added
UCL’s
Sarah
James,
PhD,
who
also
wasn’t
involved
with
the
research.

“The
results
around
surgical
menopause
and
earlier
HRT
initiation
are
particularly
interesting
and
provide
compelling
evidence
that
timing
and
individual
circumstances
matter
for
the
observed
relationship
with
dementia
risk,”
James
wrote
on
the
Science
Media
Center
site.

“The
next
step
is
to
build
on
this
work:
we
need
to
see
these
findings
replicated
in
more
representative
populations
and
with
better
information
about
HRT
formulation,
dose,
route,
duration,
and
timing,”
she
stated.

The

U.K.
Biobank
study
followed
183,450
postmenopausal
women
for
an
average
of
13.3
years,
analyzing
relationships
between
women
who
used
HRT
for
at
least
1
year
and
long-term
dementia
outcomes.
Age
at
menopause
and
HRT
use
were
self-reported.

Women
with
dementia
had
a
mean
baseline
age
of
65;
those
without
dementia
were
60
at
baseline.
In
both
groups,
most
women
had
natural
menopause
at
a
mean
age
of
50.

Overall,
3,948
dementia
cases
were
identified.
Of
these,
1,993
were
Alzheimer’s
disease
and
1,955
were
either
“dementia,
unspecified”
or
a
non-Alzheimer’s
form
of
dementia.
Findings
were
adjusted
for
covariates
known
to
influence
dementia
risk
or
HRT
use.

HRT
was
associated
with
a
lower
risk
of
Alzheimer’s
(HR
0.84,
95%
CI
0.77-0.92,

P<0.001),
but
not
with
non-Alzheimer’s
dementia
(HR
0.95,
95%
CI
0.87-1.04,

P=0.28),
the
researchers
said.

The
U.K.
Biobank
contains
generic
HRT
information,
they
acknowledged.
Future
work
should
examine
how
dementia
risk
may
differ
by
hormone
therapy
composition,
dose,
and
administration
(oral,
topical,
or
vaginal),
they
noted.

The
findings
point
to
varying
responses
in
subgroups
of
women,
highlighting
the
need
for
randomized
controlled
trials
to
guide
HRT
prescriptions
aimed
at
lowering
dementia
risk,
they
added.

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