New research suggests that short-term hormone therapy for menopause symptoms does not have long-term cognitive effects.
- Menopause involves distinct changes in hormone
levels and bodily function.
- Using hormone therapy can help with certain
symptoms related to menopause. Experts are interested in discovering the
full risks and benefits of using hormone replacement therapy.
- Data from a recent trial suggests that
short-term hormone therapy for menopause symptoms does not have long-term
cognitive effects, whether harmful or beneficial.
Menopause involves the
permanent stopping of menstruation.
There is a distinct drop in estrogen that occurs in menopause.
Hormone
therapy can help minimize certain menopause
symptoms like hot flashes and vaginal
dryness. Experts are interested in determining the full benefits of
menopausal hormone therapy as well as the potential drawbacks.
A paper recently published
in PLOS Medicine reported
data from the Kronos Early Estrogen Prevention Study (KEEPS) Continuation
study.
Researchers found that compared to placebo, women
who received hormonal therapy for menopause symptoms did not experience better
or worse cognitive outcomes 10 years after treatment.
The results suggest that
short-term menopausal hormone therapy is not harmful to cognitive function but
also does not appear to offer cognitive benefits.
Short-term hormone therapy and cognitive function
Researchers
wanted to learn more about the long-term effects of short-term hormone therapy.
They note that this type of therapy is used near the menopausal transition
period. The transition time before last menstruation is sometimes called perimenopause.
The research discussed in
this paper involved women who had participated in a previous study called the
Kronos Early Estrogen Prevention Study (KEEPS). This original research involved
healthy, recently postmenopausal women with low cardiovascular
disease risk who had intact uteruses.
Women in the original
research received a placebo, a transdermal patch of estradiol,
or oral conjugated equine estrogens. Participants receiving these hormonal
options also received micronized progesterone. The original study continued for
4 years.
The current paper’s results
discuss the findings from the KEEPS Continuation study, which followed up with
participants around 10 years after the original study ended. In all, 275
participants had data related to cognitive outcomes from the original study and
the KEEPS study.
For the KEEPS study,
researchers collected data on medical history, mood, and cognitive outcomes.
They also conducted several cognitive tests to examine participants’
memory, mental flexibility, and visual and auditory attention.
The KEEPS study also noted
which participants had continued or used other menopausal hormone therapy since
the end of the original study.
The results of the KEEPS
study found similar cognitive outcomes among women who had received a placebo
or hormone replacement therapy in the original trial.
Participants’ baseline data
in the original study and performance throughout the original study were better
indicators of cognitive function at long-term follow-up.
Thus, the results suggest that the use of hormone
therapy in early menopause does not affect long-term
cognitive function among women who have a low risk for cardiovascular disease.
Overall, the data helps to
increase understanding regarding the relationship between short-term menopausal
hormone therapy and cognitive function.
G. Thomas Ruiz, MD, a board certified OB-GYN
and lead OB-GYN at MemorialCare Orange Coast Medical Center in Fountain Valley,
CA, who was not involved in this study, commented on its findings to Medical News
Today:
“This study looked at cognitive effects differently
than many articles. Most studies approach the question from a standpoint that
HRT [hormone replacement therapy] improves cognitive ability. There have been
no studies that have definitively demonstrated this. But, it is good to know
that there are also no negative cognitive effects when using HRT. It should be
noted that long-term HRT is linked with a
More studies on cognitive effects of HRT needed
The data does
have some limitations. First, the follow-up study only included a fraction of
the women in the original study.
However, researchers were
able to include baseline data from these “nonparticipants” to help examine
differences between the groups. Researchers acknowledge that there may be a
risk for healthy survivor bias regarding participants who chose to participate
in both studies.
Researchers of the KEEPS
study could not fully examine all the effects of the lower number of
participants in the KEEPS study, such as the cause of death for
nonparticipants. The KEEPS study also faced struggles related to the COVID-19
pandemic.
Second, the original study
had specific inclusion criteria that limited the data’s reach. For example, it
excluded women with uncontrolled
high blood pressure or who smoked. The average age of
participants was also 52, and researchers only included women with low cardiovascular
disease risk.
In addition, most of the
study population in the KEEPS study was white. Thus, the results cannot be
generalized, and more diversity may be helpful for future research.
Some data relied on
self-reporting from participants, which is not always reliable. Researchers
used the self-report of age rather than age data from the original KEEPS trial.
In addition, they did not go into specific details about participants’ use of
hormone therapy between the end of the original study and the start of the
KEEPS study.
The data for the approximately 10-year follow-up
only involved a one-time assessment, so additional long-term follow-up may be
helpful. It may also take additional time to realize true cognitive effects.
Researchers noted that
there could be several reasons why no cognitive effects were observed. For
example, the dose and length of time of hormone therapy used in the original
research might not have been big enough to affect cognitive function.
Finally, the current paper
focuses on cognitive outcomes, but a future publication will cover the data
collected from brain scans.
Despite these limitations,
the study does point to the potential safety of short-term menopausal hormone
therapy, which could increase its use in the future.
Rikki Baldwin, DO, an
OB-GYN with Memorial Hermann, not involved in this research, told MNT:
“I hope this study helps clinicians and patients feel
more comfortable in using hormonal therapy to treat menopausal symptoms. There
should be a detailed discussion regarding timing, dosage, route, and length of
treatment. But using hormonal replacement therapy should be considered first
line therapy in appropriate patients.”
Hormone therapy: Benefits and ongoing conversations
Doctors and
other experts can offer guidance on menopausal hormone replacement therapy and
whether it is appropriate in individual situations. As researchers in this
paper note, the timing of menopausal hormone therapy is likely a critical piece
of the puzzle.
Baldwin said short-term menopausal hormone
replacement therapy has potential benefits, including reduction or resolution
of hot flashes, insomnia, and mood shifts.
“It is not FDA approved,
but it has been shown to improve bone health,” Baldwin noted. “Anecdotally,
hormone therapy was said to improve cognitive health as well. Potential risks,
as evidenced in previous studies, are worsening of cardiovascular disease, thromboembolic
events, and failure of treatment,” she added.
Ruiz noted the following
regarding the benefits of short-term menopausal hormone replacement therapy:
“Short term benefits are resolution of vasomotor symptoms and other symptoms such as insomnia, emotional lability. There may be improvements in libido. The urogenital tract functions better in the presence of estrogen, this includes the bladder and the vaginal mucosa […] Like any therapeutic, not all should use HRT because of medical contraindications to treatment. A woman should discuss HRT with her gynecologist to see if HRT is right for her."
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