Effect of Timing of Postmenopausal Estrogen Therapy on Bone Density

Source: Schneider DL, et al. JAMA 1997;277:543-547.

Schneider et al from the university of california, San Diego report the results of a cross-sectional study from a middle-class retirement community in Rancho Bernardo, California, that assessed estrogen use with information obtained by a questionnaire administered to 740 women who participated in a study of osteoporosis with bone density measurements. Postmenopausal hormone therapy was divided into the following groups: never users, early users (started before age 60 with no current use), past late users (started at age 60 or older with no current use), current late users (started at age 60 or older with current use), and current continuous users (started before age 60 persisting with current use). A variety of estrogen preparations were used and only one-third of the current users were taking a combination of estrogen and progestin. The highest bone density levels were measured in current users who had started at menopause, but among current users there was no difference in bone density levels in those who had started at menopause and those who had started after age 60 with at least nine years of use. Thus, the authors concluded that estrogen therapy begun after age 60 with continuous use was nearly as good as starting at the age of menopause.

Comment by Leon Speroff, MD

It is becoming increasingly apparent that maximal benefit against osteoporosis is associated with long-term use of postmenopausal estrogen therapy. Prior to this report, the most useful data came from the Framingham Study that concluded that even seven years of estrogen therapy after menopause had little effect in women older than 75 (N Engl J Med 1993;329:1141). There is a growing belief among the bone people that the most effective bone density screening for osteoporosis would be in women in their late 60s. High-risk women could then be selected for treatment. This study supports that contention.

In this study, women who were in their 70s and stopped estrogen therapy after an average of 10 years after menopause had only slightly better bone densities than the never-users. A previous report indicated that starting estrogen at menopause and continuing it until late in life was very effective in maintaining a high bone density (Cauley JA, et al. Ann Intern Med 1995;122:9). Cauley et al found greater protection against fractures in women who started estrogen at the time of menopause and continued until late in life. The data in the current study suggest that there is little difference in bone density, comparing women who start estrogen in their late 60s to those who start at the time of menopause. This cross-sectional study suffers from the problem that women who elected to start estrogen late in life were different than women who chose to start estrogen earlier and to continue on it. Thus, there is the possibility that the women who started later in life had a better bone density level before they even began estrogen therapy. Whichever way you look at these reports, one message is clear. Short-term use for symptoms at the time of menopause has little impact on fractures late in life.

These data are consistent with the new observation that estrogen therapy does not simply halt the loss of bone but actually increases bone mass. In long-term follow-up studies (20 years or more) in Europe, bone density has demonstrated a steady increase over the years, not just a short-term increase followed by a plateau and then a slower decline. This would be consistent with a major benefit to be achieved in women who start estrogen therapy late in life. In my view, this strengthens the contention of bone experts who believe that it would be cost-effective to measure bone density in women in their late 60s and to be aggressive with treatment of those with abnormally low results.

Of course, these thoughts are focused on the problem of osteoporosis, and we should never forget that postmenopausal hormone therapy is associated with a broad spectrum of benefits, including protection against cardiovascular disease, genitourinary atrophy, stress incontinence, and probably Alzheimer's disease. It is likely that the message is a straightforward one: as long as a women wants these benefits, she must be a current user of estrogen therapy.