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Innovations
in Hormone Replacement
Recent Findings in Cardiovascular Disease
Rogerio A. Lobo, MD
Studies have provided strong evidence that HRT protects against
osteoporosis, and there is evidence that potential benefits exist
for Alzheimer's disease, colon cancer, and depression.
One of the most encouraging connections implicated between HRT
and female health is the role that HRT may play in the prevention
of cardiovascular disease (CVD). Numerous studies have demonstrated
that HRT may convey a protective effect in this regard; however,
other findings suggest that HRT offers no such benefit.
Despite such conflicting findings, the fact remains that HRT is
an important, and often necessary, component of a woman's overall
health care. Providers of women's health care need to acknowledge
that HRT is a very individualized form of treatment. For the patient
who clearly needs HRT for relief of vasomotor symptoms and is satisfied
with treatment, there is no reason for her to discontinue HRT; she
may experience other health benefits, including the prevention of
osteoporosis, cognitive benefits, and possibly the primary prevention
of CVD.
Considering the enormous health risks posed by CVD, particularly
following menopause, and that HRT may offer some beneficial effect
in the primary prevention of CVD, it is not surprising that studies
continue to examine the effects of HRT in CVD. This supplement reviews
some of the novel and unique strategies that are being evaluated
for a new approach to HRT and its role in CVD. The research behind
these ideas were presented at the Fourth International Symposium
on Women's Health and Menopause this past May.
A WORK IN PROGRESS
Numerous studies over the past several years have analyzed the role
of HRT in CVD. Although substantial evidence strongly suggests a
cardioprotective effect of HRT, recent studies have not confirmed
this. The article "Hormone Replacement and Cardiovascular Disease"
provides an overview of the studies that have significantly influenced
the way HRT is viewed today in terms of its role in CVD. Results
from observational studies such as the Framingham Heart Study and
the Nurses' Health Study are presented, as well as findings from
two recent clinical trials, the Heart and Estrogen/progestin Replacement
Study and the Estrogen Replacement and Atherosclerosis Trial. With
this background information, the author gives us an understanding
of how different study designs and patient populations influence
final outcomes, which consequently has led to the controversy surrounding
the role of HRT in CVD. As Karen C. Johnson, MD, MPH, points out,
more long-term research is needed, and several important trials
in this area are ongoing.
Linking New Research to a New Form of HRT
Research focusing on potassium deficiency and the negative effects
associated with the hormone aldosterone has yielded intriguing results
that could have a significant influence on the development of a
different type of HRT.
The importance of potassium maintenance, particularly as it relates
to reducing the risk of CVD, is reviewed in the article "The Role
of Potassium" by Peter R. Kowey, MD. As the author explains, potassium
plays a significant role in the electrophysiologic properties of
the heart. Studies have shown that when the body's stores of potassium
are deficient, the risk of hypertension, stroke, congestive heart
failure (CHF), and cardiac arrhythmias is substantially increased.
Likewise, increased potassium intake has been linked with lowered
blood pressure, a reduced risk of mortality associated with stroke,
and a reduced risk of sudden cardiac death in patients with CHF.
The hormone aldosterone has also been implicated in the manifestation
of CVD. The role of aldosterone in the pathophysiology of CHF, and
how aldosterone-receptor inhibitors can counter its detrimental
effects, are discussed in "Aldosterone-Receptor Blocking Agents"
by Bertram Pitt, MD, FACC. This article reviews clinical trial data
on the cardioprotective effects seen with antialdosterone treatment,
focusing primarily on the aldosterone blocker spironolactone. As
the author explains, treatment with aldosterone-receptor blockers
is generally associated with an increased risk of excess potassium
retention (hyperkalemia). However, the author points out that in
a recent study, spironolactone was attributed with significantly
reducing the risk of morbidity and death in patients with severe
heart failure without leading to serious hyperkalemia.
These findings from two very different areas of research provide
important data for the treatment of CVD. Specifically, these data
are extremely important for the purpose of developing a new HRT
with a new progestin. The progestins used in current HRT formulations
can cause problems for many women. Many of the side effects associated
with HRT are attributable to the specific progestin; consequently,
women often discontinue therapy because of intolerable side effects.
Research efforts to find alternatives to standard progestins have
revealed a novel progestin with a profile almost identical to that
of natural progesterone. As described in my contribution, "Progestogens:
New Approaches," the novel progestin drospirenone is associated
with a reduction in the incidence of some adverse effects associated
with conventional progestins. Studies have shown that potassium
excretion is not affected by this new progestin; furthermore, because
it is related to spironolactone, drospirenone possesses some antialdosterone
properties. As such, this new progestin could give us the opportunity
to improve the side-effect profile of HRT as well as potentially
aid in the prevention of CVD.
On behalf of the clinicians who contributed to this supplement,
I hope you will find the articles herein both enlightening and encouraging.
I believe that the research presented in these articles has set
us on a course of better understanding the importance of potassium
balance and aldosterone antagonism in CVD and potentially achieving
certain advances in HRT.
Rogerio A. Lobo, MD, is the Willard C. Rappleye Professor of
OB/GYN and Chairman of the Department and Director, Sloane Hospital
for Women, Columbia-Presbyterian Medical Center, New York, NY.
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