A Sept. 20 Health section article on testosterone suggested a study had found that the Intrinsa patch slightly improved sexual function in pre-menopausal women. That study involved a medicated cream, not Intrinsa. (Published 9/22/2005)

If you could follow gynecologist Jessica Berger-Weiss around in her Silver Spring office for a day, you might be surprised by what you hear. Four to five times a day, every day, women in their thirties, forties and fifties emotionally tell Berger-Weiss about a problem they think is uniquely theirs: "Doctor, I just don't have any interest in sex."

Women in midlife are inundated with emotional and physical reasons why they can't experience a fulfilling sex life. Who hasn't heard the jokes about couples saying so long to sex once they have children? Add in typical midlife events such as stress, illness, depression, medications, relationship problems and plain old boredom, and it's no wonder some middle-aged women have little interest in intimate relations. "Though loss of sex drive is unfortunate, it is common -- almost universal," said Andrew Goldstein, co-director of the Sexual Wellness Center in Annapolis.

"Libido is very important for a relationship," said Goldstein. "If a woman has no desire, the responsibility [for initiating sex] always falls to her partner. Of course, partners become very unhappy. They take it personally. They feel rejected."

Although many factors contribute to low sexual desire in women, Goldstein said that for some there is an underlying biological mechanism at work. Goldstein is an investigator in a study of Intrinsa, a Procter & Gamble (P&G) testosterone patch that the company hopes will provide a medical solution for women's diminished desire. He and many of his colleagues believe that testosterone can restore sex drive in some women.

Like all hormones, testosterone works by stimulating an area of the brain, in this case the area associated with sexual desire. Usually thought of as a male hormone, testosterone is produced by women as well, albeit in small amounts, beginning at puberty. Women produce testosterone primarily in their ovaries with a small amount produced by the adrenal glands. Between the ages of 30 and 50, a woman's ovaries gradually shut down in the process leading up to menopause. By the time a woman is 40, her testosterone level has declined by up to 50 percent. After menopause, it drops even further.

Goldstein, Berger-Weiss and dozens of other physicians in the Washington area offer testosterone therapy to women seeking to improve their sex lives. Although the Food and Drug Administration (FDA) has not approved a testosterone-only product for women, citing the lack of long-term safety data, some physicians prescribe methyltestosterone, an estrogen-testosterone combination designed to treat symptoms of menopause. Some, like Berger-Weiss, refer patients to compounding pharmacies, which make customized testosterone products.

But is it normal, or even desirable, for a middle-aged woman to have the testosterone level of someone much younger?

"It's not natural for it [testosterone] to be there [after a certain age]," said James Simon, a clinical professor at George Washington University Medical School. However, he said, "only in the last 100 years have women lived long enough to need hormone therapy. In every other species, females die when their reproductive ability goes away. Historically, we don't know what 'normal' is," said Simon, who is also involved in the P&G research.

A Fact of Life?

Low libido is the most common sexual disorder in women, according to the 1994 National Health and Social Life Survey, in which one in three female respondents said they were uninterested in sex. Hypoactive sexual desire disorder (HSDD) -- defined as "persistently or recurrently deficient (or absent) sexual fantasies and desire for sexual activity" -- has been listed in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) since 1987.

"Women are raising the issue with their physicians as frequently if not more so than men," according to Berger-Weiss.

Numerous studies over the past 20 years have established the therapeutic value of testosterone for restoring women's libido. A review of the research published in the journal Menopause last year concluded that "certain types of testosterone therapy were associated with higher frequency of sexual activity . . . desire, thoughts and fantasies, arousal, responsiveness, and pleasure."

In 2000, the New England Journal of Medicine published the results of some of the first studies of the P&G patch, which showed that testosterone markedly improved sexual function in women whose ovaries had been surgically removed. In the past year, several more published studies have shown significant improvement in the libidos of surgically menopausal women who used the patch. So far, there have been no published studies of women who have gone through menopause naturally, although P&G is funding research on that group.

Last year, the journal published an article showing the patch prompted substantial improvement in low-libido women who had gone through natural menopause. Most recently, Intrinsa was found to slightly improve sexual function in pre-menopausal women, as published in the journal Menopause.

Hormones play a critical role in all aspects of reproductive health, according to Judith Reichman, "Today" show medical correspondent and author of "I'm Not in the Mood" (William Morrow & Co., 1998). Women need estrogen for lubrication and comfort during sex. But they need testosterone to feel desire in the first place. With diminished testosterone, Reichman said, women don't just lose desire for their partners, they lose desire for any partner.

Some women's health advocates oppose the use of pharmaceuticals to stimulate sex drive. According to Leonore Tiefer, associate professor at New York University Medical School, "There are no norms in terms of sexual desire, nor could there ever be any." Treating lack of libido with a drug "causes a lack of attention to real sexual problems and their sources. Just because a chemical produces a response is no reason to think the situation prior was a medical condition," she says.

What's the Problem?

For some women, lack of desire is not a problem. Like the late writer Hunter S. Thompson, they are glad to finally dismount the "wild stallion" they've been riding most of their adult lives and settle down to other pursuits. But many who no longer enjoy sexual satisfaction miss it -- a lot.

Jean Atkins, 53, of suburban Maryland, said she lost interest in sex completely after a hysterectomy and removal of her ovaries three years ago. Until that time, sexual desire was a normal part of her life. After the surgery, she said, "it was the furthest thing from my mind."

Atkins mourned the loss of what had been an important part of her relationship with her husband. "He was very understanding," she said. "But we were both just kind of disappointed." When a friend told her that P&G's testosterone patch was being tested in a clinical trial, Atkins jumped at the chance to enroll in it.

Now she is welcoming sex back into her life.

"I notice a difference. I think about sex more than I have in years," Atkins said. After completing her part in the study, she learned that she had received Intrinsa, not the placebo against which it was being compared. Although she experienced some of the common side effects of testosterone, such as an extra facial hair or two, she plans to continue taking testosterone.

How Much Is Enough?

Blood testosterone levels in women have not been shown to correspond with libido. According to Simon, "In men there is a correspondence -- the more testosterone, the more erections and sexual thoughts." But while men may be more creatures of their hormones, said Simon, "women are very complex" in their sexual responses.

Further confounding the issue is that measurements of testosterone are not reliable in women. Because women produce so little of the hormone, testosterone tests, which were developed for men, are not sensitive enough to provide an accurate measurement.

In a study published in the July 6 issue of the Journal of the American Medical Association, researchers in Australia (one of whom receives funding from P&G) found no association between low libido and low blood testosterone levels. They wrote, "The measurement of serum testosterone . . . in individuals with low sexual function is not informative and levels of these hormones should not be used for the purpose of diagnosing (testosterone) insufficiency in women."

In other words, said Simon, with female sexual function, "Treat the symptom, not the blood test."

The Hormone of Desire

The 1990s saw several books about the benefits of testosterone for loss of sexual desire. "The Hormone of Desire" by Susan Rako (Harmony Books, 1994) decried the "patronizing, dismissive and irresponsibly uninformed" attitude of medical establishment toward the female sex drive.

Reichman created a stir when she appeared on Oprah Winfrey's television show with her book "I'm Too Young to Get Old: Health Care for Women Over Forty" (Times Books, 1996), and touted testosterone for increasing libido. Demand for the product spiked after that broadcast, according to compounding pharmacists.

That was nearly a decade ago. At the time, Reichman declared a "revolution" in testosterone use. But revolutions can be a long time in the making, and they seldom come without a battle.

Perceiving a potentially huge market, P&G developed Intrinsa, the first in a new class of drugs designed specifically for women's sexual problems. The product has been in clinical trials throughout the United States, Australia and Europe for more than six years.

Last December, the FDA denied approval of Intrinsa. Testimony from Tiefer and others persuaded an advisory panel that there were not enough long-term data to prove the product is safe.

In addition, Tiefer says, off-label use of Intrinsa was likely, meaning physicians would prescribe it in wider populations, such as pre-menopausal women and post-menopausal women who still had their ovaries. There are no studies of Intrinsa's safety in these women, Tiefer said.

Jan Shifren, director of the Vincent Menopause Program at Massachusetts General Hospital, is investigating the use of Intrinsa in women who have gone through natural menopause. All the women in Shifren's study expressed dissatisfaction with their sex lives. Her data show that the testosterone patch restored their desire. She presented this research at a meeting of the North American Menopause Society last year.

Both the women receiving testosterone and those receiving a placebo reported an increase in frequency of intercourse and sexual pleasure. Researchers can only speculate as to why this placebo effect occurred -- the desire of participants to have a better sex life, for example, or improved communication with their partners.

"We could never assume that this treatment would be suitable for everyone. If we see a pre-menopausal woman with low sexual desire, we treat the other causes first," says Shifren. "It's not a tablet you take an hour before you have sexual relations. It's a hormone designed for long-term use."

And that's precisely what bothers critics like Tiefer. "It was tested against a placebo for only six months," Tiefer said in a written statement. "This is grossly inadequate to evaluate long-term cardiovascular risk and rule out worries about breast cancer."

P&G issued a statement in December saying it hopes to work with the FDA to provide additional safety data. Until that time, many physicians like Berger-Weiss are comfortable prescribing compounded testosterone and combination testosterone-estrogen therapies.

Women Do Care

After more than six years of taking testosterone she obtains from a compounding pharmacy, Fran Way, 72, a retired nurse practitioner in Fort Meyers, Fla., feels better about her whole life. Not only did the testosterone cream she applies each day restore her desire for intimacy, she said, "for me, it even caused the return of sexual dreams and fantasies."

Way wishes more women were aware of testosterone. "We seem to think that women are just bored or dissatisfied with their relationships. I watch some of our friends who have been in relationships for a long time. There is no seductiveness. It seems they have just settled."

Simon has made a similar observation. "Some in our profession think that women don't care [about sex]. We would never say that about a man. Women do care more than we think. Women are entitled to a healthy sex life."

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Freelance writer Lynn Crawford Cook last wrote for Health about parents who quit or rearrange their jobs to spend time at home with their teenage children. To respond to this article, send e-mail to health@washpost.com, or send a letter to the address on Page F2.

SLUG: HE/testost-1 DATE: 09/14/05 PHOTOGRAPHER: Katherine Frey Neg. #freyk 172435 Location: Holy Cross Hospital, Silver Spring, MD Summary: Gynecologist Jessica Berger-Weiss caption: Gynecologist Jessica Berger-Weiss offers testosterone therapy to women seeking to improve their sex lives. StaffPhoto imported to Merlin on Wed Sep 14 17:16:03 2005Silver Spring gynecologist Jessica Berger-Weiss prescribes testosterone to women with low libido. Intrinsa, a Procter & Gamble (P&G) testosterone patch, has boosted sexual function in women in some studies. So far, though, no published studies have shown a benefit for women who have gone through menopause naturally.