"Boning up on postmenopausal hormones"

Postmenopausal hormone supplements fight a woman’s risk of osteoporosis a potentially crippling, age-related embrittlement of the bones better than had been expected, two new studies find. A related study concludes, however, that maintaining sturdy bones beyond a woman’s childbearing years may require a troubling tradeoff: an elevated risk of breast cancer.

All three studies appear in the Nov. 6 1997.
Journal of the American Medical Asociation (JAMA).

At menopause, a woman’s ‘body dramatically
cuts its production of estrogen.
Besides launching an uncomfortable period
of physical adjustment, this change
accelerates bone loss and triggers
changes in the blood’s lipids that height-en
the risk of heart disease, The federally
funded Postmenopausal Estrogen-Progestin
Interventions (PEPl) trial was
designed to assess in nearly 900 women
age 45 to 64 how well hormone supple
ments arrest bone loss.

One group received tablets with no
active agents. The rest received estro-gens-
alone or with a progestin, another
female sex hormone, in one of three corn-mon
formulations.
Designers of PEPI hoped the 3-year
treatments would halt the rapid bone
loss that occurs early in menopause,
notes Joan McGowan of the National
Institute of Arthritis and Muscu-loskeletal
Diseases in Bethesda, Md.
‘But PEP1 showed that you more than
stabilize bone loss,” notes McGowan, a
coauthor of one of the JAMA reports.
“There is actually an increase in the
bone at the spine and the hip,” she
says-the areas most vulnerable to
debilitating fractures.
All four hormone treatments increased
bone density in the spine by 3.5 to 5 per-cent
and in the hip by 1.7 percent. Smok-ers
derived the most benefit. Untreated
smokers lost 3.5 percent of their spinal
bone, about twice as much as untreated
nonsmokers, but both smokers and non-smokers
on the hormonal therapy
gained the same amount of bone.
In a related study, physicians financed
by the Parke-Davis Pharmaceutical Re-search
Division of Warner-Lambert test-ed
various doses of an experimental
postmenopausal estrogen-progestin mix.
They found that low doses of the same
two hormones found in most oral con-traceptives
increased bone at least as
well as the available drugs used in PEPI.
However, notes study leader Leon Speroff
of the Oregon Health Sciences University
in Portland, unlike most postmenopausal
therapies, the experimental combo does
not cause menseslike bleeding in users.
He says this drug pair could be marketed
next year.

Researchers following almost 7,000
women age 65 and older as part of a frac-ture
risk study decided to look at breast
cancer incidence. In the third JAMA arti-cle,
they report that cancer risk increased
in lockstep with bone density Women
who had the most bone in hip or spine
showed 2.5 times the risk of women with
the least bone.
Though the women were not taking
supplemental hormones during the
study, the researchers worry that hor-mone
therapy might elevate breast can-cer
risk, which has been associated
with lifetime estrogen exposure (SN:
8/5/95, p. 94).
However, cautions Karl lnsogna of the
Yale University School of Medicine, coau-thor
of a commentary in JAMA, “we
should not jump to the conclusion that it
is estrogen” that links bone density and
cancer risk. Until this hypothesis is test-ed
directly, one can’t rule out other pos
sibilities, he says.
With the link between hormone thera-py
and breast cancer unproven, he told
SCIENCE NEWS, “the take home message for
women on standard hormone-replace-ment
therapy is not to quit.” J. Raloff

High Bone Mass Hints At Breast Cancer Risk 

Although long suspected, the link between high
estrogen levels and breast cancer risk has never been
proven -in part because long-term estrogen levels are
difficult to mea-sure. New data col-lected from the
Framingham Study show that
bone mineral density may be a marker for
cumulative estrogen exposure and breast can-cer
risk in postmenopausal women.

While measuring bone densities of
1,373 women (ages 47 to 80) during a four-year
period, researchers found that breast
cancer risk doubled among women with
bone mineral density levels in the highest
quartile of bone mass as compared to women
in the lowest quartile. High bone-mass den-sity
is related to high estrogen levels. Forty-four
women in the highest bone density quartile
developed breast cancer, whereas
only 12 women in the lowest quartile did.

The study did not include family his-tory
of breast cancer as a risk factor.
Women with such family histories are two
to three times more likely to develop breast
cancer than other women. Research results
are particularly significant for women with
genetic risk factors whose breast cancer risk
may increase if they take estrogen replace-ments.
Conversely, women with a family
history of osteoporosis and no breast cancer
may want to consider some form of estro-gen
replacement.