Ann Arbor, MI - A new study has shown mixed results with regard to the effects of hormone-replacement therapy (HRT) on lipids in women around the time of menopause and also shows that HRT unfavorably affects inflammatory markers [1]. Dr MaryFran Sowers (University of Michigan, Ann Arbor) and colleagues report their findings in the October 27, 2008 issue of the Archives of Internal Medicine.

"We took four groups of similarly aged women—one premenopausal, one taking [conjugated estrogens tablets] Premarin, one taking [conjugated estrogens/medroxyprogesterone acetate tablets] Prempro, and one postmenopausal—and asked the question as to whether or not either of these two hormone-therapy preparations appeared to extend the estrogenic profile that was associated with the premenopause over a period of time," Sowers explained to heartwire.

This is in reference to the timing hypothesis, which suggests that if the favorable estrogen environment of premenopause can be sustained, it may improve cardiovascular status, she says. The hypothesis speculates that HRT use should be started within six years of the menopause transition, the so-called "time window."

But these new findings cast some doubt on this, she says. "I don't think we have as good a sense as we might of what the optimal time frame might be—I think that's really to be worked out yet, and that might have tremendous ramifications based on the preexisting state of the woman's health." Any decision as to whether to use HRT "must be an individualized selection process, taking into account the existing risk factors that the woman may have for heart disease," she adds.

In the study, the researchers compared the sex steroid and cardiovascular profiles of women aged 47 to 57 years who were taking part in the Study of Women's Health Across the Nation. As described above, they were divided into four groups, and assays included a variety of sex steroids, LDL cholesterol, HDL cholesterol, triglycerides, and C-reactive protein (CRP).

The HRT users—both those taking conjugated equine estrogen alone and in conjunction with progesterone—had a more favorable ratio of HDL to LDL cholesterol than did pre- or postmenopausal women (p<0.01), but they had higher triglyceride levels (p<0.01).

HRT users also had a less favorable oxidative environment and more pronounced inflammatory response, including higher levels of CRP.

"Collectively, our findings demonstrate positive and negative aspects of conjugated-estrogen use relative to cardiovascular intermediate end points observed in women during the menopausal transition," the researchers say.

There was not as good a profile in triglycerides, and it's still a little bit ambiguous as to what the implications of this are.

Sowers added, "Our findings are in some way confirmatory. As in numerous other studies, there was a more favorable HDL/LDL ratio with HRT, but there was not as good a profile in triglycerides, and it's still a little bit ambiguous as to what the implications of this are.

"What was noteworthy, however," she continues, "was the fact that we could readily observe that markers of inflammation, such as CRP, were also elevated, and that's not considered a favorable paradigm. This adds to the greater complexity of the decisions that physicians and their patients have to undertake."

"The six-year time window is not completely and utterly without its own store of issues that must be dealt with. If women are going to be counseled to use an HRT product, this should take into account any existing risk factors that the woman may have for heart disease and the implications for what the increase in inflammatory markers might do," she concludes.