Selective estrogen receptor modulators (
SERMs) are structurally different compounds that interact with intracellular
estrogen receptors in target organs as
estrogen receptor agonists and antagonists. These drugs have been intensively studied over the past decade and have proven to be a highly versatile group for the treatment of different conditions associated with aging, including
hormone-responsive
cancer and
osteoporosis.
Tamoxifen and
toremifene are currently used to treat advanced
breast cancer and also have beneficial effects on bone mineral density and serum
lipids in postmenopausal women.
Raloxifene is the only
SERM approved worldwide for the prevention and treatment of
postmenopausal osteoporosis and vertebral fractures. However, although these
SERMs have many benefits, they may also be responsible for some potentially very serious adverse effects, such as thromboembolic disorders and, in the case of
tamoxifen,
uterine cancer. These adverse effects represent a major concern given that long-term
therapy is required to prevent
osteoporosis. Moreover, both preclinical and clinical reports suggest that
tamoxifen,
toremifene and
raloxifene are considerably less potent than
estrogen. The search for the 'ideal'
SERM, which would have
estrogenic effects on bone and serum
lipids, neutral effects on the uterus, and antiestrogenic effects on breast tissue, but none of the adverse effects associated with current
therapies, is currently under way.
Ospemifene,
lasofoxifene,
bazedoxifene and
arzoxifene, which are new
SERM molecules with potential greater efficacy and potency than previous
SERMs, are currently under investigation for use in the treatment and prevention of
osteoporosis. These drugs have been shown to be comparably effective to conventional
hormone replacement therapy in animal models of
osteoporosis, with potential indications for an improved safety profile. Clinical efficacy data from ongoing phase III trials are awaited so that a true understanding of the therapeutic potential of these compounds can be obtained.