How
does hormone therapy affect heart and metabolic health?
- Research presented at the 2024 Annual Meeting of
The Menopause Society in Chicago has aimed to uncover the impact of
hormone replacement therapy on various aspects of health.
- One study reports that extended use of some
hormone therapies can improve markers of cardiovascular health at
menopause.
- A large meta-analysis further found that hormone
therapy can help improve insulin sensitivity by restoring estrogen levels.
Hormone replacement
therapy (HRT) is a widespread treatment for a range of
menopause symptoms, such as hot flashes, night sweats, and vaginal dryness.
It works by restoring levels of different hormones in
the body — typically, but not always, estrogen —
as these tend to decrease with age, a process often responsible for many of the
symptoms associated with menopause.
HRTs for menopause can
include estrogen, progesterone,
or sometimes testosterone therapies, depending on what
an individual needs.
Debates abound about which types of HRT are safe and
which are not and what impact the prolonged use of HRT could have on health.
Some of these questions were recently addressed by
researchers presenting new studies at the 2024 Annual Meeting of The Menopause
Society, held in Chicago from September 10 to 14.
One study presented at the meeting, whose
findings are yet to appear in a peer-reviewed journal, found that estrogen-based
hormone therapy appeared to have a positive long-term effect on almost all
markers of cardiovascular health.
The study — led by researchers from Penn State Hershey
Medical Center — used data from the Women’s Health Initiative (WHI),
and compared cardiovascular health biomarker values in participants who were
taking certain estrogen-based hormone therapies versus a placebo.
Specifically, they looked at participants who were
either on conjugated equine estrogens —
a commonly prescribed oral HRT — or taking conjugated equine estrogens
alongside medroxyprogesterone acetate,
which doctors sometimes prescribe for the management of menopause symptoms like hot flashes.
The
researchers found that those who took conjugated equine estrogens for at least
1 year saw a 13% increase in high-density
lipoprotein cholesterol (HDL-C), also known as “good
cholesterol.” Those taking conjugated equine estrogens plus medroxyprogesterone
acetate saw a 7% increase in HDL-C measures.
So-called bad cholesterol — low-density lipoprotein
cholesterol (LDL-C) — decreased by approximately 11% in both HRT groups. In
particular, Lipoprotein(a)
or Lp(a) — a form of
LDL-C strongly associated with a range of cardiovascular problems — decreased
by 15% in those taking conjugated equine estrogens alone.
For those taking plus medroxyprogesterone acetate, the
decrease in Lp(a) level was even greater—at 20%.
Finally, the researchers also found that markers of
insulin resistance were also lower in those on HRTs, decreasing by 14% in
participants taking conjugated equine estrogens only and by 8% in those taking
conjugated equine estrogens with medroxyprogesterone acetate.
The only marker of cardiovascular health that showed
no improvement with HRT was triglyceride levels.
How does
menopause affect the risk of heart disease?
Due to the various
hormonal changes that take place when a person enters menopause, their risk of heart disease and
cardiovascular problems increases, as research has
shown.
“Once a woman goes into menopause, estrogen levels
become nonexistent, which negatively affects the cardiovascular system,” Sheryl A. Ross, MD, a
board certified OB/GYN and women’s health expert at Providence Saint John’s
Health Center in Santa Monica, CA, who was not involved in the research
presented at the annual meeting, explained for Medical News Today.
Cheng-Han Chen, MD, a board certified
interventional cardiologist and medical director of the Structural Heart
Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, also not
involved in this research, told us that:
“This [drop in estrogen
levels] then leads to changes, such as increased artery plaque buildup,
increased cholesterol, and increased
blood pressure, that can all increase someone’s risk of heart
disease.”
That is because “estrogen production helps maintain
the elasticity in the blood vessels, reduces LDL or the ‘bad’ cholesterol and
promotes HDL or the ‘good’ cholesterol production,” Ross further detailed.
These mechanisms could explain why the long-term
estrogen supplementation in the Penn State Hershey Medical Center study led to
improvements in biomarkers of cardiovascular health.
“Taking estrogen replacement therapy can help by
bringing back the benefits of elasticity in blood vessels, reducing LDL levels
and promoting HDL levels, which support heart health,” Ross also told us.
“It is suggested to start estrogen replacement therapy
as you enter menopause for optimal cardiovascular benefits,” she advised.
Researchers from Reading Hospital Tower Health, Drexel
University College of Medicine in Pennsylvania, and other institutions
presented further findings suggesting
that HRT was associated with lower insulin resistance in women at postmenopause.
This research team conducted a review and
meta-analyses of 17 randomized controlled trials, with a total of 29,287
participants. Of these participants, 15,350 were on an HRT of either estrogen
or estrogen plus progestogen, and 13,937 received a placebo.
The participants’ mean ages ranged from 47 to 75, and
their treatment duration was between 8 weeks and 2 years.
The review and
meta-analysis, whose results have yet to appear in a peer-reviewed journal, found
that all the HRT studies—whether administered orally or transdermally—were
associated with improved insulin
sensitivity at postmenopause.
Insulin sensitivity tends to decrease at menopause,
which can lead to dangerously high blood
sugar levels, which in turn increases a person’s risk of
developing type 2 diabetes.
Thus, the improvement in insulin sensitivity that
comes with HRT is good news, as it could have a protective effect against
diabetes.
“Hormone replacement therapy, including estrogen and
progesterone medication, […] improves metabolic health by regulating insulin
production, maintaining body weight and fat distribution, and reducing the risk
of type 2 diabetes,” explained Ross. “These benefits support and improve
hormonal balance and metabolic health.”
Who should
and who should not take HRT?
Even with these positive
findings about HRT, doctors caution that some of these therapies may affect
different individuals in different ways and could come with their own sets of
side effects.
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 the research presented at the annual meeting, told MNT that:
“[Oral] preparations [of]
HRT tend to be metabolized in the liver, and may have an increased risk of
increasing platelet
aggregation, which leads to
increase clotting in small [blood] vessels. On the other hand, most [bio]identical
hormone replacement therapy is absorbed across the skin, [and
thus] avoids being metabolized in the liver, and tends to have less of a
platelet aggregation effect. [Bio]identical hormones also have the benefit of
being identical to the type of estrogen that was made by the ovary during the
menstruating life.”
Ruiz thus advised that when looking for the most
appropriate HRT, an individual, and their doctor may want to consider the type
of treatment that resolves the symptoms that most concern them with the lowest
medication dosage.
“For most women, the initial goal is to treat the
vasal-motor symptoms associated with menopause, [such as] hot flashes,
insomnia, […] joint pains, […] mild depression. Some women will also see
changes in their vaginal tissue, which can make sexual activity more
uncomfortable due to vaginal dryness,” he said.
“The best hormone replacement therapy is the lowest
dose which resolves their symptoms,” Ruiz suggested. “Each woman should be
treated individually and given what she needs to help manage symptoms.”
Ross also
emphasized that HRT can play a crucial role in reducing the risk of osteoporosis,
which is another concern around menopause. “HRT, especially for women at risk
for osteoporosis, has also been shown to prevent bone loss and bone fractures,”
she told us.
Nevertheless, she cautioned that:
“Those women with increased
risk of venous thromboembolism/blood clots, stroke,
ischemic heart disease, and breast cancer may
not be a candidate for HRT. Women with a strong family history of breast cancer
involving a first degree relative-mother or sister, especially if they carry
the BRCA gene, may not be
candidates for HRT.”
HRT: What
questions remain unanswered?
According to Ross, some
questions about the long-term health impact of HRT for menopause symptoms
remain to be answered.
These include:
- whether a person should stop HRT after the age of
60 to avoid increasing their risk of
breast cancer, as high estrogen levels have been associated
with breast cancer risk
- whether a person should take HRT preventively for
heart health support even when they do not have disruptive menopause
symptoms
- whether they should take HRT for brain health, to lower their dementia risk
- and whether they can use HRT in pellet form or
compounded HRT safely in the case that they do have disruptive menopause
symptoms.
From his
perspective, Chen also noted that doctors “remain concerned that long-term HRT
treatment can increase an individual’s risk for blood clots, stroke, and breast
cancer.”
Ross said that for now, what is most important is to
get specialized medical advice that considers the person’s individual
situation.
“Discuss any questions or concerns you have regarding
HRT with your healthcare provider […], so you can make the best decision for
your personal health,” she emphasized.