Predicting HRT response still not a reality

OB/GYN News, Nov 15, 2001 by Kathryn DeMott

NEW ORLEANS -- Research has along way to go before physicians will be able to predict how an individual woman's circulating hormone levels will respond to a specific hormone replacement therapy regimen, Dr. Elizabeth Barrett-Connor said at the annual meeting of the North American Menopause Society.

Endogenous estrogen levels at baseline and adiposity offer some dues as to who may need estrogen. Thin women and older women tend to have low endogenous estrogen levels and are easy to identify as treatment candidates. But moving away from a one-size-fits-all approach to hormone replacement therapy (HRT) and figuring out how each woman's hormone profile will respond to a specific regimen and dosage--and having therapeutic targets to shoot for--are all still goals for researchers rather than the reality of everyday practice, said Dr. Barrett-Connor, professor and chief of the division of epidemiology at the University of California, San Diego.

In a study aimed at investigating the determinants of change in estrogen levels in response to various HRT regimens, Dr. Barrett-Connor and her colleagues examined data from 823 participants in the Postmenopausal Estrogen/Progestin Interventions trial.

All participants in Dr. Barrett-Connor's analysis had their estrone, estradiol, and bioavailable levels of estradiol measured at baseline and again 24 months after starting one of five therapies. The therapies included placebo, estrogen alone, or one of three estrogen plus progestin HRT regimens as part of the randomized controlled trial funded by the National Institutes of Health.

At baseline, factors associated with low levels of endogenous estrogen included being at least 55 years old, having a low body mass index (BMI), and smoking. Smokers had higher levels of estrone than nonsmokers.

Alcohol intake and exercise habits did not appear to affect endogenous levels of estrogen.

Women with BMI values greater than 27 tended to have higher than average levels of all three endogenous estrogens, compared with normal weight women. Those women with any history of using HRT before the study had lower levels of endogenous hormones, compared with women who had never used HRT.

Patients who had a history of hysterectomy had higher levels of estradiol than nonhysterectomized women. And as expected, oophorectomy was associated with low estrogen levels.

Once women started taking HRT, only unopposed estrogen stood out as different from the other regimens in terms of its effect on circulating hormone levels. Women who took unopposed estrogen tended to have higher than average levels of estrone.

While heavier women tended to have higher levels of endogenous estrogen at baseline, they also had smaller rises in their estrogen levels once they started taking HRT, compared with women of normal weight. Smoking also appeared to blunt the effects of HRT.

History of HRT use, hysterectomy, years since menopause, exercise, alcohol intake, and oophorectomy status did not appear to be associated with the response to HRT.

These findings won't necessarily advance the debate between endocrinologists who believe that it's helpful to know a woman's endogenous estrogen levels before starting HRT and "the rest of us who are more empirical," Dr. Barrett-Connor said.

Knowing a woman's clinical history, age, smoking status, BMI, and whether she's had a hysterectomy may turn out to be just as useful as knowing her endogenous hormone levels. But the research on both fronts just isn't developed yet.