The New York Times

Monday, February 1, 2000

By LAWRENCE K. ALTMAN

Estrogen Offers Hope Against H.I.V

SAN FRANCISCO, Jan. 31 -- Estrogen strongly protected against infection by the simian AIDS virus in experiments with female monkeys, offering hope that it might be used to protect against the human AIDS virus in women, researchers have reported here at a meeting on the disease.

In the study, estrogen injected into a small group of female monkeys produced a thicker layer of cells in their vaginas.

That acted as a protective barrier against infection when S.I.V., the simian AIDS virus, was squirted into the vagina to test the effectiveness of the therapy.

"The results were striking," said the head of the research team, Dr. Preston Marx of the Aaron Diamond AIDS Research Center in New York City.

Dr. Marx and public health officials cautioned that much more research was needed to prove that a topical estrogen cream applied to the vagina could protect women against H.I.V.

"We can't assume estrogen would have the same effect in women" or that topical application would be as effective as injected estrogen, Dr. Marx said in an interview today.

A reason for cautious optimism, though, is that S.I.V., which Dr. Marx has been using in work with monkeys for more than 10 years, has proved a valuable model for studying its human cousin, H.I.V.

Dr. Fred T. Valentine, an AIDS expert at New York University, said that "estrogen use might become a very important method by which women could reduce their chances of becoming infected with H.I.V. through sexual intercourse."

Dr. Valentine is one of those attending this meeting, the Seventh Conference on Retroviruses and Opportunistic Infections, where scientists said that if estrogen protected in human studies, women might be freed of having to rely on men to provide safety against H.I.V.

through use of condoms.

Further, estrogen could be particularly useful as an inexpensive method of protection in third-world countries, home to an overwhelming majority of H.I.V. cases.

In the last five years, Dr. Marx's team has used monkeys to study the role of different sex hormones in vaginal transmission of S.I.V.

In 1996, the team reported that in a similar monkey experiment, injection of progesterone had increased the risk of transmission of S.I.V. by seven times because that hormone thinned the layer of vaginal cells, making it easier for the virus to reach the body's supply of blood.

Since progesterone and estrogen usually oppose each other's effects in the body, "the obvious prediction was that if one had one effect, the other would have the opposite effect, and that estrogen should protect," Dr. Marx said in the interview.

In the estrogen experiment, conducted at a primate center at Tulane University, Dr. Marx worked with Dr. Stephen Smith, an infectious-disease specialist at St. Michael's Hospital in Newark.

The ovaries were removed from the monkeys to stop production of both estrogen and progesterone, and the researchers tested three groups of six monkeys each.

One group received no hormone replacement, and all six became infected after S.I.V. had been squirted into their vaginas.

In a group that received progesterone, five of six became infected. But in the group receiving estrogen, none became infected. These six monkeys have been repeatedly tested for S.I.V. in the year since efforts were made to infect them with the virus, and all have remained free of infection.

In the monkeys treated with estrogen, Dr. Marx said, the vaginal layer became 25 to 50 cells thick; in those that did not get estrogen, it was about 2 cells thick.

The thickness of the vaginal layer varies with the menstrual cycle and menopause status, Dr. Marx said, and premenopausal women naturally produce estrogen and progesterone. But he said he assumed that topical estrogen would increase the thickness of the layer at any given time in the menstrual cycle.