Women, Hormones and the Heart
Heart Disease in Women is a very important, unique and exciting topic. This article is a part of a
series that focuses on the special problems of Heart Disease in Women. You can find the others in
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This week, the topic is ....
WOMEN, HORMONES AND THE HEART
A lot has been written about the role hormones play in causing or preventing heart disease and
stroke in women. In this article, we will take a look at the still controversial issue of the role of
hormones in heart disease in women.
The two major endogenous hormones (that is, hormones produeced in the body itself) in women
are estrogen and progesterone. Each has a specific physiologic role in growth and development,
pregnancy, lactation and other functions. Levels of both hormones alter at different stages of growth
- pre-pubertal, reproductive age and after menopause. The varying levels cause different changes in
the organ systems including the heart and blood vessels, some of which may increase or decrease
the risks of disease.
In addition, hormones may be exogenous (administered in medication). The most common source
of exogenous hormones in women is in oral contraceptive pills.
We will discuss first the impact birth control pills have had on the epidemiology of heart disease and
later the effect of hormone replacement therapy in post-menopausal women.
Oral Contraceptives and Heart Disease
Ever since birth control pills were introduces in 1960, there have been reports suggesting an
increased risk of heart attacks and stroke. The earlier pills contained high doses - around 150
micrograms - of estradiol (In contrast, pills in 1988 contain only 35 micrograms). Also, addition of
progesterone derivatives further altered the effects of the pill. Recently, the addition of
third-generation progesterones like desogestrel and gestodene lowers LDL cholesterol levels and
raises HDL cholesterol - changes that reduce heart disease risk. For more on cholesterol effects,
read my earlier article on heart disease prevention.
Prescribing patterns have also changed, following recognition that oral contraceptives raise blood
pressure and pose additional risk in older women who smoke cigarettes. These changes in
products and their use would be expected to reduce the cardiovascular risks associated with oral
A study carried out by the World Health Organization reported the association between current use
of oral contraceptives and heart attack in more than 300 cases. The study suggested that the pill
might be responsible for an increased risk of heart attacks. However, the absolute risk in
nonsmoking women younger than 35 years was low. The risk was dramatically increased in older
women who smoked, and in women with known hypertension whose blood pressure was not
checked before prescription. Risk was not associated with dose or duration of use of estrogen and
did not persist after oral contraceptives were discontinued.
In summary, new oral contraceptives carry a greatly reduced risk of cardiovascular complications
compared with other high-dose preparations, but third-generation progestins appear to greatly
increase risk of venous blood clots in the leg veins. Overall, the risk/benefit ratio is excellent except
for women who smoke.
Post-menopausal Estrogen Therapy
Several reviews have provided evidence that a remarkably consistent reduced risk of coronary
heart disease (CHD) and a somewhat less consistent reduced risk of stroke is seen in women using
postmenopausal estrogen in the United States and Europe.
Because the risk of CHD exceeds the risk of all other estrogen-associated conditions combined in
the United States, and because estrogen use has been associated with reduced mortality from all
causes combined, post-menopausal estrogen has been proposed as the standard of care in
countries where heart disease is the leading cause of death and a major cause of morbidity in
women. An analysis of many studies carried out earlier, most from the US, it has been shown that
post-menopausal estrogen reduces the risk of CHD by 35% to 50%. This means that on the basis
of a calculation of overall risks and benefits, a healthy woman at no particular increased risk for
heart disease, cancer, or osteoporosis would gain on average one additional year of life !
How does estrogen protect against Coronary Heart Disease ?
Multiple mechanisms may be involved. These include:
including favorable changes in lipids
altered lipoprotein profile
changes in fibrinogen and PAI-1
effects on blood vessel reactivity
Are these findings biased ?
It has been postulated that the striking differences noticed with post-menopausal estrogen therapy
may be an artifact produced by pre-selecting low-risk patients. Estrogen replacement therapy is
more likely to be prescribed to higher income, highly educated groups, who for different reasons
are more likely to have fewer risk factors for heart disease.
Recently this "healthy woman selection bias" has been strikingly documented by the Healthy
Women's Study, which followed 355 premenopausal women through menopause. Women who
later elected to take hormones were, when premenopausal, significantly more educated and had
significantly more favorable levels of HDL cholesterol, blood pressure, fasting insulin, body weight,
alcohol intake, and physical activity. Thus, the amount of protection attributed to estrogen may be
Two major US trials have been designed to quantitate the cardioprotective effect of
postmenopausal estrogen unconfounded by healthy woman selection bias.
HERS is a 5-year randomized placebo-controlled secondary prevention trial of conjugated
equine estrogen plus medroxyprogesterone acetate (a form of progesterone) in women who
already have CHD. This study of 2673 postmenopausal women is planned to end in 1998.
Unopposed estrogen is not being evaluated.
The Women's Health Initiative (WHI), a placebo-controlled primary prevention trial in
27,500 postmenopausal women, is scheduled to complete randomization in 1998. The three
major outcomes are CVD, osteoporosis, and breast cancer. Active treatments are
conjugated equine estrogen alone for women without a uterus or conjugated equine estrogen
plus continuous medroxyprogesterone acetate for women with an intact uterus, as compared
with placebo. The WHI is planned to end in 2006. This trial will be the first to provide
disease data in ethnic minority women on hormone therapy.
In summary, ongoing research suggests that estrogen replacement therapy reduces risk of
CVD but may increase the risk of other diseases, including breast cancer and venous blood clots.
The potential benefits and risks need to be confirmed in clinical trials such as those now in progress.
Until more definitive data are available, clinicians should individualize therapy based on a woman's
baseline risk for CVD and should weigh the potential net benefit on overall health.
Emerging data suggest selective estrogen receptive modulators, also known as "designer"
estrogens, may have beneficial effects on the cardiovascular system as well as bone without
untoward effects on breast or uterus. However, the clinical effectiveness of newer hormonal agents
for disease prevention remains to be established.