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Safer estrogen targets painful intercourse in older women 2001-05-07
By Luana Bossolo

Safer estrogen targets painful intercourse in older women

 

Researchers at Yale University's School of Medicine have designed a new form of estrogen that could improve the treatment of vaginal atrophy, commonly referred to as vaginal dryness. Experienced by many postmenopausal and other women with lost or diminished ovarian function, the condition can result in pain during sexual intercourse. The study will appear in the June 7 issue of the Journal of Medicinal Chemistry, a peer-reviewed journal of the American Chemical Society, the world's largest scientific society.

"We have synthesized the first locally active estrogen with no systemic effect [in animal studies]," said Richard Hochberg, Ph.D., the lead investigator in the study and a professor in Yale's Department of Obstetrics and Gynecology in New Haven, Conn.

Although vaginal atrophy can be effectively treated with estrogen replacement therapy, this has been associated with certain health risks, including breast cancer, endometrial cancer and stroke, leading many women to avoid this therapy altogether. Unlike the normal estrogen molecule, the new compound acts only on the tissue to which it is applied, reducing risks and providing a potentially safer alternative, the researchers say.

They suggest that the modified estrogen could be particularly helpful in treating vaginal atrophy in women for whom estrogen replacement is not advised, including those with breast or endometrial cancer.

The drug has not yet been tested in humans. If the new estrogen ultimately proves to restore some of the physical comfort of sexual intercourse in postmenopausal women while reducing health risks, it could provide an important new tool in the treatment of female sexual dysfunction in much the same way that Viagra® has helped relieve impotence in some men, predicts Hochberg.

Vaginal dyspareunia (dis-pa-ROON-ia), the medical term for vaginal atrophy, most often occurs in women after menopause. Studies have shown that more than 40 percent of postmenopausal women experience the condition, which causes thinning of the vaginal wall, dryness and itching, and leads to painful intercourse and sometimes bleeding.

In addition to oral estrogen replacement therapy, vaginal atrophy can be treated with various lubricants, but these offer only temporary relief of symptoms and do not strengthen the vaginal wall, as estrogen does. Vaginal creams containing estrogens are available and can alleviate symptoms. But such estrogen-based products are easily absorbed into the bloodstream and transported throughout the body, elevating health risks similarly to oral estrogen therapy, according to the researchers.

To reduce the risks, Hochberg and his associates created a modified version of estradiol, which is the major human estrogen. The new formulation stimulates vaginal cells but afterward is rapidly destroyed by the body's enzymes, which prevent it from circulating to other tissues and organs.

Applied directly to vaginas of mice, the drug caused significant increases in the levels of vaginal reductases - enzymes that serve as chemical markers for the stimulation of vaginal cells - an indication that the compound is capable of causing cell growth and increasing the level of vaginal lubrication, says Hochberg. In tests with rats, the estrogen showed no systemic action when injected under the skin.

The researchers are collaborating with scientists at Columbia-Presbyterian Hospital in New York City to determine whether the drug causes vaginal stimulation or systemic action in female rhesus monkeys that do not produce estrogen. Depending on the outcome of this study, human studies of the new estrogen could begin within a year or two, they say.

Another potential benefit of the Yale estrogen is treatment of wrinkles. Since the skin contains many estrogen receptors, the researchers believe that the molecule can eventually be developed into a topical cream that targets and smoothes wrinkles without affecting other tissues. Future studies are anticipated.


 
 
 
Patent Pending:   60/481641
 
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