Preventing Heart Disease with Estrogens

Cardiovascular disease is the leading cause of death in women. However, prior to the age of 60-65 cardiovascular disease rarely occurs in women. It’s been proposed that the decline in estrogen following menopause may be a contributing factor to this sudden increase in cardiovascular disease. Furthermore, when researchers look at data from women who used hormone replacement and those who didn’t they almost always see a decrease in cardiovascular disease in the those using hormone replacement.    

So, if there is good reason to believe estrogens protect the cardiovascular system, shouldn’t all women be prescribed hormone replacement therapy after menopause? Not so long ago, if you posed this question to your doctor they would have most likely answered, “yes, most women should be prescribed hormone replacement therapy after menopause.” However, nowadays, the answer to this question isn’t as uniform amongst doctors. Your probably wondering, what happened and what does it mean for my health? 

In 2002, a large clinical trial entitled the Women’s Health Initiative (WHI) surprised the world with conclusions from the authors that hormone replacement increases the risk of cardiovascular disease and that the risks associated with hormone replacement therapy out ways any benefit. This went against a large body of epidemiological and observational trial results showing hormone replacement largely decreases the risk of cardiovascular disease in postmenopausal women. With this new information at their clinical decision-making disposal,  providers rapidly discontinuing their patient’s hormone replacement under the impression that doing so would save lives. The consequences of this decision: postmenopausal women were left with no treatment options for symptoms such as hot flashes, uncertainty regarding the risks of past hormone use, and having to stomach the attitude that the menopause increases risk of cardiovascular disease and there’s not much that can be done.

Fortunately, in the years to follow, results from this trial and others were reevaluated and reinterpreted leading to the emergence of several treatment paradigms on how to manage the care of postmenopausal women in the context of cardiovascular disease prevention. One of the more common interpretations of all available evidence is the “Timing Hypothesis.” Its states that started early after menopause, hormone replacement provides cardiovascular disease protection in a manner which the benefits out ways the risks. The timing hypothesis holds that once cardiovascular disease is established, hormone replacement may be harmful. However, taken before cardiovascular disease develops it may significantly decrease the risk of its development and progression.

There are two others widely held strategies to maximize the safety of hormone replacement. Firstly, use estrogens identical to the body’s estrogens. The term “bioidentical hormone replacement” was coined to identify naturally occurring hormones like estradiol, estriol, and estrone, as opposed to the estrogen in Prempro – conjugated equine estrogen (the estrogen used in the WHI trial). A large body of preclinical evidence suggests the pharmacology is different between bioidentical hormones and Prempro. It can be anticipated the effects in humans will be different as well. Bottom line - use “bioidentical” estrogens never conjugated equine estrogens. Secondly, use topically applied formulations. Oral estrogens are inflammatory, while topically applied estrogens are not. Clinical trials have demonstrated difference between oral and transdermal estrogens showing the topically applied formulations are not inflammatory while the oral formulations are in fact inflammatory. The use of an oral estrogen in the WHI may have contributed to the observed increase in cardiovascular disease.

All in all, considering hormone replacement for cardiovascular disease prevention must be handled on a patient-by-patient basis. There is certainly enough information in the medical literature for a conversation to be had between you and your provider, and an informed decision to be made on whether or not to start treatment. In fact, many women may benefit from hormone replacement. Your age, time since menopause, type of estrogens used, and route of administration of estrogens are all important factors for maximizing safety and deciding whether hormone replacement is right for you.  

Written by

Angelo Maida, PharmD

Compounding Pharmacist at Maida Pharmacy Compounding and Wellness