7/23/18: JOHNS HOPKINS: HIGH TESTOSTERONE, LOW ESTROGEN MAY INCREASE HEART DISEASE RISK IN POSTMENOPAUSAL WOMEN: It’s the ratio between the hormones’ levels that may be significant

Estrogen Hormone Level

A recent press release by Johns Hopkins Medicine about the effect that sex-hormone levels may have on the risk of heart disease in older women caught my attention. Johns Hopkins researchers are reporting that, on the basis of one observational study of more than 2,800 postmenopausal women—it’s only one study, and the study had nothing to do with cause—they believe an increase in the ratio between testosterone and estrogen may increase the risk of cardiovascular disease.

I publish below an edited version of the May 29 press release with commentary by me in brackets.


“In an analysis of data collected from more than 2,800 women after menopause, Johns Hopkins researchers report new evidence that a higher proportion of male to female sex hormones was associated with a significant increased relative cardiovascular disease risk.

“The researchers caution that theirs was an observational study that wasn’t designed or able to show or prove cause and effect. But they say the study, described online May 28 in the Journal of the American College of Cardiology, suggests that having a more male-like hormone profile seems to increase the risk of heart disease and strokes in postmenopausal women independent of other risk factors.

[I could not obtain a copy of this study without paying for it. It is available free to journal subscribers only.]

“‘A woman’s sex hormone levels and ratios of them isn’t something that physicians regularly check,’ says Erin Michos, M.D., M.H.S., associate professor of medicine at the Johns Hopkins University School of Medicine and member of the Ciccarone Center for the Prevention of Cardiovascular Disease. ‘Because an imbalance in the proportion of testosterone (the main male sex hormone) to estrogen (the main female sex hormone) may affect heart disease risk, physicians may want to think about adding hormone tests to the toolbox of screenable risk factors, like blood pressure or cholesterol, to identify women who may be at higher risk of heart or vascular disease. But this needs further study.

[Disclosure: I have my sex hormone levels tested every year. My gynecologist wears two hats: I see her for a routine gynecological exam in her primary practice and for hormone therapy in another practice.]

“Decades of research have shown that, prior to menopause, women have lower heart disease rates than men, and because estrogen levels drop sharply after menopause, physicians once thought that replacing estrogen would reduce cardiovascular disease risk. That idea was essentially upended when results of a landmark women’s health study reported in 2002 showed that replacement female hormones weren’t necessarily protective and could possibly raise the risk of strokes, blood clots and heart disease.

[The landmark study was known as the Women’s Health Initiative (WHI). Between 1993 and 1998, the WHI enrolled 161,809 postmenopausal women between ages 50 and 70 in a set of clinical trials and an observational study at 40 clinical centers throughout the country. The trials included those for low-fat dietary pattern, calcium and vitamin D supplementation, and postmenopausal hormone use. In the hormone trials, 16,608 women who had not had hysterectomies were randomly assigned to receive either estrogen plus progestin or a placebo. The planned duration of the hormone trials (both drug and placebo) was 8 ½ years, but the estrogen-progestin trial was stopped early because researchers thought that the health risks of the hormone therapy exceeded the health benefits. Average followup of the women who took the hormones was 5.2 years.]

“Some experts have suggested that those results may have been skewed or exaggerated by the use of older forms of hormone therapy and the fact that it was given many years after menopause in the trials. Additionally, researchers had not focused on the body’s natural levels and ratios of sex hormones as an index of risk in their own right. The estrogen used in the most common hormone therapy preparation is in a different chemical form than that of the body’s natural premenopausal estrogen, estradiol.

[The most common hormone therapy preparation is Premarin®, the brand name of a conjugated estrogen, which is actually a mixture of several types of estrogens. Premarin comes from pregnant mares’ urine, hence: Pre(gnant)-mar(es’)-(ur)in(e).

[At the time that the WHI hormone trial was terminated, I was seeing a Johns Hopkins gynecologist for my routine medical care. She told me, in so many words, that the WHI hormone trial should not be used as the basis for my own eventual hormone replacement therapy decision because it involved Premarin—which she advised me to avoid—and most of the trial subjects were over 60 and had never been on hormone therapy before. She spoke highly of bioidentical hormones, which are derived from plants and more like human hormones.

[In November 2002, I attended a Women’s Journey conference, sponsored by Johns Hopkins Medicine, in Baltimore. None of the gynecologists at the conference were putting any stock in the WHI hormone trials, which were stopped primarily because of a perceived increased risk of breast cancer. While the WHI also did not find that estrogen plus progestin conferred a benefit of preventing cardiovascular disease among the trial subjects–as had long been presumed–it was the breast-cancer risk that concerned researchers.]

“For the new study, the researchers looked at data from 2,834 postmenopausal women who had participated in the federally funded Multi-Ethnic Study of Atherosclerosis (MESA). Participants were an average age of 65 at the start of the study, and 38 percent white, 28 percent African-American, 22 percent Hispanic and 12 percent Chinese-American.

“At an initial visit that took place between 2000 and 2002, researchers took blood samples and measured levels of testosterone and estradiol.

“Over 12 years of followup, the women had 283 instances of cardiovascular disease, including 171 instances of coronary heart disease and heart attacks, 88 strokes and 103 instances of heart failure as determined by medical records, hospitalizations, telephone interviews and death certificates.

“Among the postmenopausal women who were free of cardiovascular disease at the beginning, almost 5 percent developed new cardiovascular disease within five years. When the researchers compared testosterone and estradiol levels to instances of heart and cardiovascular disease, they found, in general, that higher testosterone was associated with increased risk and higher estradiol levels with lower risk. After adjusting the results to account for multiple other heart disease risk factors including age, body mass index, education, diabetes and blood pressure, they looked at the ratio of testosterone to estradiol—essentially dividing the testosterone level by the estradiol measurement. For every standardized unit increase in the ratio of testosterone to estrogen, there was a 19 percent increase in cardiovascular disease risk, a 45 percent increase in coronary heart disease risk and a 31 percent increase in heart failure risk.

“‘Although our study adds to evidence that higher estradiol relative to testosterone may have a protective effect on the cardiovascular system in older women, it is premature to advise them to take hormone therapy to reduce their risk,’ says Di Zhao, Ph.D., research associate at Johns Hopkins and the lead author of the published research results. ‘At this point, doctors may want to step up their advice to women to reduce other known risk factors after menopause,’ Dr. Zhao says.

“As to why these hormones may affect risk, Dr. Michos says there is ample evidence from other studies in women that testosterone can raise blood pressure and contribute to insulin resistance, which are harmful effects, whereas estrogen relaxes blood vessels and lowers bad cholesterol levels, which tend to be good things for the heart and vascular systems.”

[Unfortunately, testosterone also elevates a woman’s libido. A lower testosterone level may benefit your heart and arteries, but not your sex drive.]

The Johns Hopkins study was funded by the American Heart Assn. Go Red for Women Strategic Focused Research Network, the AHA, and the National Heart, Lung, and Blood Institute, among other grantors.

I would like to see further studies done on the relationship between the levels of sex hormones in postmenopausal women and their risk of heart disease. They are long overdue.

UPDATE ON MOM: My mother continues to have spectacular days when she’s alert, chatty, and eager to read and know what’s going on around her, and other days when she’s disengaged, lethargic, and doesn’t want to get out of bed. The coconut oil is not the determining variable, but I don’t know what is yet. One thought is that the more water she drinks throughout the day, the better her mind will function the next day. I also wonder about other dietary influences, but I haven’t isolated another variable, like I did with coconut oil, to test.  Social interaction does not seem to be determinative, although she definitely is more engaged when a family member is visiting and staying in the house with her. I’ll keep you posted on my clinical trials. If anyone has any thoughts and/or ideas, please share them with me at annsj@earthlink.net.  Thank you.

Ann, 7/23/18


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