HRT’s bone benefit lingers for years after use

Women who took hormone replacement therapy for 2-3 years as part of Danish clinical trials had denser bones than untreated subjects 5-15 years later, researchers reported at the 10th World Congress on the Menopause. What you have gained, you have gained forever. The impact of that is enormous said by a professor at the Center for Clinical and Basic Research in Ballerup, Denmark. A total of 263 postmenopausal women included in the PERF study had been enrolled in one of four randomized, placebo-controlled trials of estrogen in combination with progestin that ran from 1983 to 1996 as said by senior research physician at the center. When the studies were concluded, women treated with HRT had 5.4 percent higher bone mineral density (BMD) at the forearm and 7.2 percent higher BMD at the femoral neck than women taking placebo. And when their BMD was re-assessed 5, 11, or 15 years later, women who had taken active HRD still had BMD that was 4.3 percent greater at the forearm and 6.7 percent greater at the spine than women who had been assigned to placebo.

One doctor, who submitted the study for publication in a major peer-reviewed journal, declined to comment on his data concerning fracture rates in the women. The results of the PERF study drew considerable attention at the meeting, which was sponsored by the International Menopause Society. The meeting was marked by a far rosier endorsement of HRT than has characterized recent US meetings. From the first plenary session onward, HRT was generally hailed as good medicine for healthy women in early menopause, with randomized, placebo-controlled studies from around the world documenting its positive impact on bone, vasomotor symptoms, sleep quality, abdominal fat, and lipids (other than triglycerides). Pilot results of the Women’s Hormone Intervention Secondary Prevention (WHISP) study from London even provided cautious reassurance about low dose estrogen (1 mg/day of 17B estradiol) with norethisterone acetate in women with cardiovascular disease – the very group that drew the most concern in the 1998 Heart and Estrogen/Progestin Replacement Study (HERS).

The WHISP study, with 100 subjects enrolled following a recent myocardial infarction or acute cardiac syndrome, was not powered to assess whether HRD might prevent future cardiac events, and it was hampered by a high, 12-month drop-out rate among women assigned to HRT. But the study showed no increased incidence of death, MI, stroke, or cardiovascular disease among women taking HRD rather than placebo. There was also some suggestion of improved CVD markers at three and six months.

The news was well received among menopause specialists from Europe, South and Central America, Australia, and the Far East, many of whom seemed ready to give HRT the benefit of the doubt with regard to its potential benefit for most women, at least until they learn the results of the US-based Women’s Health Initiative in 2006. That much anticipated study may clear up many mysteries about HRT, which at one time was seen as a virtual "cure-all" for women at menopause and beyond, but has come under sobering scrutiny in light of recent trials questioning its role in heart disease, Alzheimer’s disease, urinary incontinence, and breast cancer.

A recent international position paper on women’s health and menopause co-sponsored by the National Institutes of Health cast doubt on HRT’s preeminence in treating or preventing most significant health problems affecting postmenopausal women. But at the Berlin meeting – reflective, perhaps, of clinical practice throughout the world – the blush had barely faded from HRT’s decades-long reputation as a valuable symptom reliever and disease prevention agent. The opening plenary session included a lecture on interpretations of epidemiology by a professor of endocrinology and ob-gynecology at Oregon Health Science University in Portland.

It is not wise to turn your back on the vast amount of biologic data and observational data that indicate hormone therapy offers primary protection against coronary heart disease. The suggestion that older women with heart disease may not benefit from HRT really only justifies the belief that HRT should be used early in menopause and for a long period of time. It may be that "it takes a healthy endothelium to respond to estrogen," just as it may take a healthy neuron to respond to estrogen and protect against Alzheimer’s disease.

To discuss prescribing HRT until randomized, clinical trial prove it protect against heart disease, bone fractures, and Alzheimer’s disease would be like awaiting randomized, placebo- controlled trials to advise patients to quit smoking. Results of the PERF study offered HRT advocates encouragement about its effect on bone when used early in women who are undergoing natural menopause. The mean age of the study participants today is 25. Upon follow-up 5-15 years after discontinuing HRT, the women’s BMD remained higher than that of women in historic placebo groups. This contradicts suggestions from a small US study published decades ago that bone protection from HRT was fleeting.

Bone loss in the HRT group after withdrawal of treatment was completely parallel to the rate of bone loss in the placebo group. In other words, women who had been taking HRT started off with denser ones. Both groups lost bone at about the same rate (1.3 percent a year in the former HRT group and 1.2 percent a year in the placebo group an – an insignificant difference), so that the women with a history of taking HRT ended up with a net advantage. None of the subjects were taking estrogen or other medications known to influence bone metabolism during the follow-up period.

A professor of medicine at the Mayo Clinic in Rochester, Minn., called the findings "important". If you lose all of the effect of estrogen after a period of time, that means you have to take it forever.