Register for SERMs offer safer alternative than HRT
MenopauseJanuary 22, 2003
As scientific evidence mounts linking hormone replacement therapy (HRT) to breast cancer and other illnesses, a class of drugs called selective estrogen receptor modulators (SERMs) is emerging as a safer and more versatile alternative to prevent and treat the symptoms and complications of menopause.
Findings indicate that SERMs may be the preferred choice to HRT by mitigating the risk of breast cancer but maintaining many of the therapeutic benefits. SERMs act at the level of the estrogen receptor but appear to have either estrogenic or antiestrogenic effects depending on the tissue.
Because of this tissue specific activity, SERMs are potentially a versatile drug class that offers the prospect of developing individualized, targeted treatments, according to the study published in the January 1, 2003, issue of Cancer.
SERMs, the authors declared, "may ultimately provide women and their physicians with the ability to make safe and confident selections from a repertoire of medications that promise to expand life span and improve quality of life for women after menopause."
For decades now HRT in estrogen-alone or combined estrogen-progesterone forms has been used by millions of women to alleviate the unwanted symptoms associated with menopause, such as flushing, mood swings, and night sweats. HRT also prevents such postmenopausal complications as urogenital atrophy, osteoporosis, and osteoporotic fractures; it prolongs life expectancy and protects women from colorectal cancer, neurocognitive dysfunction, and Alzheimer disease. However, HRT has been linked to a significant and growing number of adverse effects.
The observed risk of breast cancer with HRT has long alarmed patients and physicians and dissuaded many from using or prescribing HRT. With new revelations from the Women's Health Initiative (WHI) trial about the increased risk of coronary artery disease and strokes, many women have stopped using HRT altogether. This has left scientists searching for a safer alternative.
Diamanti-Kandarakis et al. reviewed the literature to investigate the risks and benefits of HRT and SERMs. The authors also examined their respective clinical and cellular effects on breast tissue to assess the potential of selective modulation of estrogen receptors to treat postmenopausal women.
HRT's proven efficacy to prevent osteoporosis, osteoporotic fractures, and specific cancers and alleviate the vasomotor and central nervous system disturbances of menopause are its greatest benefit. However, recent studies have also proved its substantial risks. Meta-analyses of clinical data to date have demonstrated that there is a significant increased risk of breast cancer by 2.3% per year of use. WHI demonstrated a more substantial 26% increased risk of breast cancer after 5 years of HRT.
Other studies have demonstrated that progesterone in combined HRT forms likely increases the risk of breast cancer even further. In contrast SERMs are actually protective against breast cancer. Tamoxifen has long been used to treat estrogen-receptor-positive breast cancer and shown to be protective in women at high risk for breast cancer. Raloxifene has also been shown to be protective against breast cancer.
SERMs' potential as the next generation in menopausal treatment is that it exhibits different effects depending on the tissue; this is likely due to the way the SERM interacts with estrogen receptor (ER) a and ERb subtypes and the ER subtype distribution.
Studies have found, for example, that the SERM tamoxifen exhibits antiestrogenic effects in the breast thus inhibiting growth of breast tumor cells that have estrogen-receptors. In the uterus tamoxifen is estrogenic and stimulatory, thereby increasing the risk of endometrial cancer. Raloxifene, another SERM, has been shown to increase bone mineral density in postmenopausal women but has antiestrogenic effects on both breast tissue and endometrial tissue. Both SERMs have estrogenic effects on serum lipoproteins and coagulation.
Raloxifene has been recently shown to reduce cardiovascular events but increase the incidence of thromboembolic events, such as strokes. SERMs exacerbate vasomotor instability such as hot flashes but have unknown effects on the central nervous system.
"The demonstration that SERMs act in an estrogen agonistic or antagonistic manner, depending on the target tissue, suggests that this class of drugs may be invaluable in the prevention and/or treatment of menopausal morbidities," wrote the authors.
The value in SERM versatility is that there is now potential "to create an arsenal of SERMs with individual combinations of tissue specificities, because this may enable the individualization of patient treatment according to a particular woman's risk factor and/or disease profile for each menopause-associated morbidity."
The authors concluded, "a major goal of pharmacologic research is the discovery of novel SERMs that can retain estrogenic effects on bones, lipids, and the central nervous system while acting as antiestrogens at the breast and endometrium." This article was prepared by Cancer Weekly editors from staff and other reports.
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