New study promises safer hormone replacement therapy

October 24, 2002

LITTLE ROCK, Arkansas - Scientists in Arkansas have identified a synthetic estrogen-like compound that reverses bone loss in mice without affecting the reproductive system, as does conventional hormone replacement therapy. The finding, reported in the Oct. 25 edition of Science, could lead to new therapies to prevent osteoporosis for millions of women and men, and enable safer alternatives to existing hormone treatments, shown earlier this year to pose more serious risks than previously thought.

"We are developing a new class of pharmaceutical agents with the potential for bone-building, sex-neutral hormone replacement therapy," said lead investigator Stavros C. Manolagas, MD, PhD, an endocrinologist with the Central Arkansas Veterans Health Care System and the University of Arkansas for Medical Sciences. He also directs the Osteoporosis and Metabolic Bone Diseases Center in Little Rock, a research laboratory established jointly by VA and UAMS.

Manolagas' team reported last year in the journal Cell that sex hormones exert their bone-protecting and reproductive effects through separate cellular mechanisms--one fast-acting and non-sex-specific, the other long-term and sex-specific. The researchers also identified a synthetic estrogen-like hormone--"estren"--to work in one pathway but not the other. This earlier study, conducted with mouse bone cells, suggested the possibility of gender-neutral hormone replacements that could produce benefits to the bone without reproductive side effects.

The new study is the first time scientists have demonstrated in animals how synthetic hormones can build bone without affecting reproductive organs.

Manolagas and colleagues tested the effects of estren, compared to conventional estrogen and testosterone, in male and female mice. Some of the mice had their ovaries or testis removed, to halt the production of their natural sex hormones. These mice showed a 6-percent loss in bone density, a 23-percent loss in bone strength, and, in the female mice, a 71-percent loss in the weight of the uterus.

The researchers then gave back a naturally occurring form of estrogen, for females, or testosterone, for males, to one group of sex-organ-deficient mice. Another group received the synthetic hormone estren, regardless of sex.

Remarkably, estren was even more effective than estrogen for females, and just as effective as testosterone for males, in helping bone. In fact, while estrogen only prevented bone loss, the estren actually increased bone density and strength, even to levels above those of the female mice with their ovaries intact. Most important, the estren--unlike the estrogen or testosterone--had no effect on the weight of the uterus or seminal vesicle. Moreover, the estren, unlike estrogen, did not trigger the growth of breast-cancer cells in a Petri dish. While estrogen preserves the mass and function of female sex organs, it has also been shown to cause tumors with prolonged use as a therapy.

Manolagas said the results of the study show that synthetic hormones such as estren may provide a safe form of hormone replacement therapy that preserves and even builds bone, without affecting the reproductive system. He added that estren may even provide other anti-aging benefits, such as protecting blood vessels and nerve cells, since these tissues appear to respond to sex steroids through the same mechanism as does bone tissue--without involvement of the reproductive organs.

Hormone replacement therapy (HRT), using estrogen and progestin, was the treatment of choice until very recently for millions of menopausal women seeking to halt the bone loss that causes osteoporosis, and to help with other symptoms, such as hot flashes and mood swings. The therapy was also thought to cut the risk of heart disease. The therapy was associated with a small increase in the risk for uterine and breast cancer, but the benefits were thought to outweigh the risks.

This belief was challenged in July when the National Heart, Lung and Blood Institute stopped a major clinical trial after finding significantly increased rates of breast cancer and cardiovascular disease in women taking HRT, compared to women on placebo. Soon after, a report in the British journal The Lancet showed an increased risk of breast cancer, stroke and blood clots for women on HRT.

Osteoporosis is a debilitating disease in which bones become weak and brittle and more likely to break. Fractures of the hip, spine, wrist and ribs are most common. Of the 10 million Americans estimated to have osteoporosis, 80 percent are women. The sex hormones--namely estrogen in women, and testosterone in men--help build and preserve bone throughout early and middle adulthood; as their levels decrease with age, the risk of osteoporosis increases. In fact, in the five to seven years following menopause, women can lose up to 20 percent of their bone mass.
Funding for Manolagas' study was provided by the Department of Veterans Affairs and the National Institutes of Health.

Veterans Affairs Research Communications

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to