“How does hormone supplementation affect the heart?” This is a question that our pharmacists hear regularly. Much like the poor, maligned egg in the cardio-healthy diet, hormones have fallen in and out of favor with regard to their effect on the cardiovascular system over the years.

Although a number of studies examine hormonal effects on the cardiovascular system, these studies rarely distinguish between bioidentical and synthetic hormones. However, one study by Dr. Ferdinand Roefsena, Rebecca J. Yang, and Dr. Johannes Veldhuis looked specifically at the bioidentical hormones, estradiol, and progesterone, publishing their results in the Journal of the Endocrine Society. Let’s see what they found!

How Was the Study Designed?

Forty healthy postmenopausal women, ages 50-80, participated in the study. The women were divided into four treatment groups:

1. Bioidentical estradiol (injection) and bioidentical progesterone (by mouth)
2. Bioidentical estradiol (injection) and no bioidentical progesterone
3. Bioidentical progesterone (by mouth) and no bioidentical estradiol
4. No bioidentical estradiol and no bioidentical progesterone

After 23 days of using these therapies, the women’s blood was drawn and the researchers measured various markers.

What Did the Study Look At?

Because the study was only 23 days long, Dr. Roefsena et al. were unable to evaluate primary endpoints, such as heart attacks or strokes. Instead, they looked at various markers in the blood that have been associated with physical outcomes such as heart disease, stroke, and diabetes. The researchers looked at many significant markers, including:

1. Total cholesterol
2. Low-density lipoprotein cholesterol (LDL-C) (referred to as “bad” cholesterol by the American Heart Association)
3. High-density lipoprotein cholesterol (HDL-C) (referred to as “good” cholesterol by the American Heart Association)
4. Apolipoprotein B (Apo B)
5. High sensitivity C-reactive protein (hsCRP)
6. Adiponectin

With the exception of HDL-C and adiponectin, for which higher levels appear beneficial, decreased levels of the other markers listed above are generally considered favorable, according to the American Heart Association.

What Did the Study Find?

When compared to women who weren’t using any hormone therapies:

1. Women who used bioidentical estradiol alone had lower levels of total cholesterol, LDL-C, and Apo B. They also had higher levels of HDL-C, which are considered beneficial differences. The researchers had expected this result, based on previous studies as described in the article The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? by Dr. Kent Holtorf.
2. Women who used bioidentical progesterone alone had decreased adiponectin, but they were still well within the average reference range (below which would indicate risk).
3. Women who used bioidentical estradiol and bioidentical progesterone together had lower levels of total cholesterol, LDL-C, Apo B, and HDL-C. While the reduced HDL-C levels are not considered beneficial, other studies, as discussed in Dr. Holtorf’s article, indicate that when synthetic progestins are used instead of bioidentical progesterone, the cholesterol and LDL-C-lowering effect of bioidentical estradiol is also blocked. Bioidentical progesterone did not block this effect!
4. hsCRP levels were higher in women using bioidentical estradiol and bioidentical progesterone, but still well below the value above which indicates increased risk.

How Do Hormones Affect the Heart?

As the researchers expected, the women using bioidentical estradiol exhibited improved cholesterol levels (including decreased LDL-C and increased HDL-C). Even though the bioidentical progesterone was associated with reduced HDL-C levels, it allowed the positive effects of bioidentical estradiol on the other cholesterol levels to remain. Synthetic progestins have been seen to reduce the positive effects of bioidentical estradiol on cholesterol levels, as evidenced by the studies discussed in Holtorf’s article. These findings suggest that bioidentical hormones may be preferable to synthetic.

This study is not without its flaws, such as its short length and small group size. Its short length made it necessary to evaluate markers rather than primary endpoints, and the data was further limited by comparing the groups to each rather than evaluating the differences between the beginning and ending measurements. The patients in the bioidentical estradiol groups were treated with injectable bioidentical estradiol—a form which is rarely used in clinical practice—and used two doses ten days apart as opposed to the usual two- to four-week intervals.

Despite this study’s shortcomings, when we combine its results with information obtained in other studies, we see that bioidentical progesterone doesn’t appear to interfere with the positive effects estrogen has on cholesterol levels. By contrast, other studies have suggested that synthetic progestins do negate these effects. And this makes perfect sense! Why would we assume that a molecule that is similar, but not identical to what the body makes, should have the same effect in the body as a molecule that is identical to what the body makes?

Due to our differences as individuals, no study is perfect. Therefore, the question of whether hormones are good for your heart may never be answered definitively because the answer may differ from person to person. Through studies like that by Dr. Roefsena et al. and others, however, one thing is becoming clear: the difference between bioidentical and synthetic hormones may prove a significant factor in whether hormones are beneficial to the heart.