ACSH Statement on HRT

Recent reports in the medical literature have profoundly shaken the popular and medical wisdom which held that estrogen-progestin combination therapy enhances life and health for women in the post-menopausal years. Women are relatively free from heart disease, bone loss, vaginal dryness and hot flashes prior to menopause, but manifest increased risk for such ailments after menopause. Therefore, it seemed intuitively obvious that a replenishing of the naturally diminished supply of estrogen and progesterone would restore women to their earlier, lower risk profile.

The evidence, however, contradicts the intuitive: a new, large, randomized study shows that women taking a combination of estrogen and progestin (at a dosage equivalent to the Wyeth drug Prempro) for four or more years face a slightly increased risk of heart disease, breast cancer or stroke. The increased risk for an individual woman is quite small. The same study is also evaluating women using estrogen-only preparations (such as Premarin). This has not been completed yet, and the interim data analysis has not demonstrated a trend toward net harm, as the combination therapy study did.

In light of these findings, what is a woman to do?

ACSH's answer is this: in conjunction with her physician, a woman evaluating postmenopausal hormone therapy must define

a)what individual goals she is seeking to achieve; and

b) what her unique risks might be.

For example, both estrogen and estrogen/progestin combinations do prevent osteoporosis, a common condition which develops after menopause, leaving women susceptible to bone less and fractures. But the estrogen/progestin replacements are not the only preparations that do so.

Thus, if osteoporosis is the primary risk concern, medication such as raloxifene (Evista), a selective estrogen receptor modulator or "designer estrogen," might be considered to reduce risk. At this point, side-effects of raloxifene are limited to occasional leg cramping and a slightly increased risk of blood clots in the legs. Based upon studies which have shown an improvement in blood cholesterol levels in users, there has been speculation that raloxifene may reduce heart disease risk--but there are not data now to support that claim. There is some evidence that raloxifene reduces the risk of breast cancer.

There are other medications effective against osteoporosis, such as bisphosphonates (Didronel, Fosamax), which have shown both safety and efficacy over the years.

Similarly, if the primary concern for the postmenopausal woman is elevation of the risk of coronary heart disease, various other medical interventions which favorably affect lipid profiles primarily statins -- should be seriously considered instead.

Smoking cessation, it should be pointed out, will also substantially lower a woman's risk of heart and bone disease, without medication.

There is accumulating evidence to support combination estrogen/progestin therapy as a means of reducing a woman's risk of colon cancer. But there are other therapies that may well have the same or better risk reduction, including taking daily aspirin or use of other nonsteroidal anti-inflammatory agents (including Vioxx and Celebrex). This area is currently under active investigation; the final word is not yet in.

Estrogen and combination therapies are particularly efficacious in addressing uncomfortable even disabling symptoms of menopause, especially hot flashes, and including vaginal atrophy and dryness. For local symptoms, local applications of non-systemic estrogens may offer substantial relief (Estring and estrogen creams). For hot flashes, at this time there appears to be no other alternative to estrogen therapy, either alone or in combination. Given that

a) hot flashes often remit after a few years; and

b) the increased risk for estrogen replacement sets in primarily after several years of use

a woman might discuss with her physician using ERT for a limited period of time to specifically address hot flashes. Attempts to taper and discontinue the medication should also be done regularly, since the duration of these episodes is unpredictable.

There is certainly no evidence to support the continued use of hormone therapy to prevent or retard the development of heart or vascular disease. Despite the apparent logic of this approach, the new study results confirm several other recent studies which refute the efficacy of hormone therapy against heart disease. But that is no reason to throw the baby out with the bath water: hormone therapy which includes estrogen still has an important, although now somewhat more limited, role to play in women's health.