Harper's Bazaar

Sex Drugs For Women?

Viagra was designed strictly for men. Then researchers learned that Sexual dysfunction is an even bigger problem for women, and the race to Create a female tonic was on. Steve Fishman charts the progress. Photographed by Frederik Lieberath

One day, Maria thought, To hell with it, excuse the language. There had been fights with her husband, whom she adored, but just now she was occupied. The accounting job, and she had a young child. And the new house. It had lovely elm trees in the yards, front and back. The place looked beautiful.

"How about me?" her husband would ask. "What's the point?" she would answer him offhandedly. Maria had reddish-brown hair, a sunset shade, and dreamy eyes-that's how she thinks of them. She touched her hair as she said, "I don't think about sex."

Really, though, she did. She might not want sex, but how could she avoid the thought? On TV, in the movies, there were always women having sex, and looking as if they loved it-though she'd decided those scenes must be unrealistic, since she'd never experienced anything remotely like it.

Maria is 36 and exercises two or three times a week, She has strong, beautiful legs, which her husband says are her best feature, though he likes her smile, too. It shows her bright teeth, though not too much, and makes her cheeks plump a little. Smiling, she'd look in the mirror, and think, I don't look like I've aged a bit since 25. In fact, she'd add, I feel better now about myself than I did when I was 25. So why hadn't her sex life blossomed with everything else?

She'd consulted half a dozen gynecologists. She'd been to counseling. She'd bought books and pornographic movies. She'd masturbated, or tried to. She'd blamed her husband, wondering, at separate times, about his technique and her emotions. Maybe she wasn't wildly in love any longer. "I was on a search" , she confessed, without smiling.

A slice of the medical community has recently signed on to that same search for the female orgasm. Since Viagra, Pfizer's billion-dollar-a-year pill, rebooted the sex lives of men two years ago, drug companies seem to be waking up and saying, "What about women?" Last February, researchers at the University of Chicago publicized survey data showing that sexual dysfunction-the inability to have an orgasm or enjoy sex-is a bigger problem for women than for men. Forty-three percent of women ages 18 to 59 experience some trouble, while only 31 percent of men do. Before that, there was almost no work being done on women. Now, it's a big race. The pace of research has accelerated to the point where it looks entirely possible that women will have their own tested version-or versions-of Viagra in the works within the next couple of years. Already, new findings in many laboratories show that Viagra-or at least its main ingredient, sildenafil-does work for women (despite some reports to the contrary last year). Many other sex-enhancing substances designed for men appear likely to work for women too.

The promise of these hectic new efforts isn't only for those, like Maria, who have never had an orgasm. Ultimately, the promise is that any woman who wants an improved sex life might soon be able to take a pill or apply a cream.

"Something women could take," says one impatient doctor in New York, who's already had a pharmacist mix up a couple of what he hopes are orgasm-promoting concoctions, "whenever they want to have sex."

Rx FOR BETTER SEX: New York Urologist Jed C. Kaminetsky, M.D., has concocted his own treatment for female sexual dysfunction. Dr. K's Dream Cream is a topical medication designed to increase blood flow to the vagina and clitoris.

Sex Researchers Discover Women

"We"re 20 years behind where men are," says Irwin Goldstein, M.D., at Boston University School of Medicine, one of the most energetic presences in the science of female sexual response. Last fall, he organized what he says was the largest ever conference on the subject at BU, drawing more that 400 physicians, sex therapists, and psychologists. Spend a little time with him and you get the impression of someone in a rush-as if he might be trying by his quick step to pace the field itself. "Someone has to keep this ball rolling," he says.

In 1998, Goldstein authored a key paper showing that Viagra-conceived as a mere angina drug, which had the unwanted side effect of producing erections-was a safe and effective treatment for what was then commonly called impotence. (Now the preferred, snazzier term is "erectile dysfunction.") By the time Viagra appeared, Goldstein says, "we thought we had everything done in the male world."

Yet in the female world, sexual dysfunction remained, as a paper to be published this month reports, "an under-researched and poorly understood area." There were only a few-perhaps three-labs working on the problem.

The anatomy and physiology of female genitalia wasn't even well under stood. "In the textbooks, you'd see 25 pages on male genitalia and two on female," says Jennifer Berman, M.D. When Berman finished her urologic training at the University of Maryland in 1998, she was advised to get serious-cut her hair, wear glasses, and not tell anyone she was interested in female sexual dysfunction. Why? Because it was not a real medical problem.

If a woman had a sex-related complaint, she usually got shipped off to a therapist. Sex, of course, does have a lot to do with psychology. Give women a placebo and, in the short term at least, it improves the sex lives of one third. But therapists couldn't do a thing for many women. So there had to be problems outside the patient's head. Sexual malfunction might be easier to observe in men-an unresponsive penis is unmistakable-but why couldn't women have physiological malfunctions, too? "You're allowed to have a toe problem and an eye problem," says Goldstein. "Why not a clitoris problem?"

Viagra seemed likely to help. The drug promotes blood flow to the penis, which results in erection. Everyone knows that, during sex, the clitoris and labia swell with blood. Wouldn't Viagra boost that kind of blood flow too?

Pentech's Uprima, another sex drug for men (expected to get government approval within a few months) works not on the circulatory system but on the brain. Researchers have theorized that apomorphine, Uprima's active ingredient, might be especially good for women because it could affect both sensitivity and desire for sex. So far this much is known: In men, apomorphine initiates erections; in female rabbits, it promotes blood flow to the clitoris and vagina.

And what about prostaglandin, a natural fatty acid that, when injected into the penis, has produced such reliable erections? Or testosterone, "the hormone of desire," as one doctor labels it? When added to postmenopausal women's hormone-replacement therapy, testosterone seems to boost their interest in sex.

Another promising agent is the amino acid L-arginine-a nutrient, not a medicine (and therefore not FDA regulated)-which dilates blood vessels. When ArginMax, a supplement containing L-arginine, was given to a small group of women, two thirds reported increased clitoral sensitivity.

Now this once underfunded field seems inundated with drug company money. Goldstein has started clinical trials on Uprima and Viagra. In Texas, Cindy Meston, Ph.D., a clinical psychologist who's been studying female sexual response for nine years, says, "I'm turning down offers."

Berman never did cut her hair or buy glasses. She was too busy in the lab. She prescribed Viagra to three female patients in 1998-was possibly the first doctor to do so. When all three reported an increase in sexual satisfaction, she did a small study. She gave Viagra, along with a questionnaire, to 13 women. Seven said their sexual experiences were better.

Things might have stopped there, except Berman went to work with Goldstein at Boston University. Soon, the two of them would co-author one of the first papers to show a physiological cause for impaired sexual functioning in women-diminished blood flow.

Berman wanted to work with patients, too. Others might have hesitated. A female-sexual-dysfunction clinic didn't seem an entirely respectable (or for that matter, moneymaking) part of a big-time urology department. But Goldstein helped shuttle it through the bureaucracy.

As soon as she got the go-ahead, Berman phoned her sister, Laura, a sex therapist, who happened to be looking to relocate. "We'd always fantasized that we'd open a clinic together," Laura says. (Their father, a surgeon, had long made a joke of it around the family dinner table.). In July 1998, they opened the Women's Sexual Health Clinic in the Urology Department of Boston University, the first comprehensive research and treatment program in the country.

The clinic is open just one day a week-and booked two months in advance. You walk in through a door marked Urology/Continence, then follow a beat-up pink rug, patched here and there with silver duct tape. In the waiting room sit impotent males. They're the ones with coats in their laps; the diagnostic medication they're given often produces erections, which they tend to hide.

Once called the Viagra twins, the Bermans share one office with one desk. Both answer the phone, "Dr. Berman."

Last year, the Boston University team reported on 48 women with sexual dysfunction. In virtually all of them, after taking Viagra, "physiologic measurements significantly increased" - and so did sexual satisfaction.

Jennifer's plaques are on one wall: Laura's are on another. A snapshot of the two of them, arm in arm, is on a third. The desk tends to get littered with samples from the orgasm promoters-creams, pills, dietary supplements-though, as Laura complains, "people steal things all the time." There's also a clitoral vacuum-like device called EROS CTD, which the Bermans, are testing on some of their patients.

A Visit To The Viagra Twins

Some women come to the clinic complaining that they just don't feel much like having sex, which bolsters the Chicago study's finding that women's most common "dysfunction" is a lack of desire. But Paula, a recent patient, didn't buy it. A Rhode Islander with a Ph.D., green eyes, and auburn hair, Paula is a self-possessed, successful teacher and administrator and, until recently, had a great sex life with her husband. Then, two years ago, she had surgery for cancer. Surgeons took out her uterus and both ovaries. "It's bizarre," Paula told Jennifer. "Now there's a lack of sensation. I can feel me clitoris, but I have no sexual sensation. It's like I'm touching the tip of my little finger.

When surgeons remove a man's prostate, they use magnifying loupes and carefully dissect around the nerves that are responsible for erections. When women get hysterectomies, their surgeons are oblivious to nerve pathways. Jennifer Berman has seen the operation. Perhaps that was the cause of Paula's lack of sensation. Or else the loss of her ovaries, producers of estrogen and testosterone, deprived her of hormones that feed desire, lubrication, and sensitivity.

Paula was referred for diagnostic tests-some of which are just now being developed. Until recently, the only objective measure of sexual excitement in women was a cumbersome 25-year-old laboratory technique called photoplethysmography, which indirectly measures vaginal blood flow. A small tampon-shaped instrument, inserted in the vagina, emits a light and measures how much light is reflected back. The greater the blood flow, the less light. It seems a rough measure, especially now that women are accustomed to such exquisitely detailed medical images as pregnancy ultrasounds, CT scans, and MRIs.

Recently, these sophisticated technologies have been used to measure arousal. (In France, a couple had sex inside an MRI machine, producing detailed pictures.) And now, Jennifer Berman is experimenting with measuring blood flow to the genital area with ultrasound.

Paula dressed in a hospital gown and slipped on a video headset. She'd selected an erotic video-"This one usually works," a nurse had said. She settled in with a vibrator in an exam room amid jars of Q-tips and cotton balls, and 15 minutes later, a medical team rushed in to read the ultrasound.

It turns out that the physiological changes a woman experiences during sexual stimulation are as striking in their way as a man's erection. During what's called the arousal phase, the vagina lengthens and widens, acidity lowers, sensitivity increases, and the clitoris, labia, and walls of the vagina become engorged with blood. You can see the blood flow on the ultrasound image.

Yet the oddest, and most confounding, aspect of treating female sexual dysfunction may be that even when a woman's genitals register excitement-even when you can see it on ultrasound-the woman will shrug and say, "I don't feel aroused." Berman theorizes that for some of these women, using Viagra to get an extraordinarily large flow of blood to the genitals will boost their sense of excitement.

An hour before her next visit to the clinic, Paula took 100mg. Of Viagra. Her face flushed, but more important, she was aroused. She said, "I could hear my blood pumping on the ultrasound."

Early last year, the first report on Viagra in women gloomily suggested that women were beyond the reach of medications-three in four failed to report a benefit. But that study turned out to have been flawed. Last year, Goldstein and the Berman sisters reported on 48 women who'd gone through the same routine as Paula. Overall, after taking Viagra, physiologic measurements significantly increased,-and so did subjective satisfaction.

Paula was prescribed a small dose of hormones (estrogen and testosterone) and , when she wanted to have sex, 50 mg. of Viagra. Suddenly, she says, "it was like it used to be."

In women as in men, Viagra pills have side effects such as headache and sinus congestion. So last fall, New York urologist Jed C. Kaminetsky, M.D., came up with a new strategy: He asked a pharmacist to grind up some Viagra and put it into an absorbable solution that a woman could apply directly inside her vagina.

Some scientists were skeptical that Viagra would be absorbed. "It's hard to get a drug through the skin," says Jennifer Berman. Kaminetsky couldn't offer decisive proof, but at a recent conference, he presented a small, preliminary survey of some of his female patients who'd used the Viagra cream. Fifteen of 23 women said they felt more sensation or more aroused, says Kaminetsky.

Then he got an idea for another concoction. Kaminetsky had the pharmacist make a cream with L-arginine and some other vasodilators (agents that make blood vessels expand). I started playing around with it and changing the dosages," he says. His pharmacist packaged some of the white cream in a red applicator with a blue stopper. A local TV reporter dubbed his invention "dream cream," and Kaminetsky kind of liked that. He stuck a label on the side of the applicator: DR. K'S DREAM CREAM.

Who knows how this might shake out if government safety and efficacy studies are ever done? But clearly, Kaminetsky tapped into something. What his experience indicated, beyond doubt, was the extent of the interest. Some colleagues gave him a smirk (Goldstein and the Bermans are withholding judgment until the cream is fully tested), but thousands of women dialed up his Website. They flew in from California and Florida. Almost a dozen sent blank checks-"Send the stuff at any price," they said. (Venture capitalists called to see if he wanted to go into business.)

Maria, the 36-year-old woman who had everything but a sex life, found her way to Kaminetsky's office. She told him she'd almost given up on having an orgasm when she saw the TV report on the dream cream. She figured, what did she have to lose? She paid her $350 (there's no insurance coverage) and took in the remarkable view of the Empire State Building from his window.

The first time she tried it, she says, her husband got worried. She hadn't told him she was doing anything different. What was going on? He wondered. She was into sex in a way she usually wasn't. "The first time I had an orgasm, it was amazing," says Maria. "I said to myself, Look what I've been missing. Feeling spread all over my body."

Even though many drugs, like Viagra, don't work on the brain's centers of desire, clearly there's a feedback loop. Perhaps some women who tell researchers their desire is off are actually experiencing diminished sensation. "now I think about sex," Maria says, "I think about the feeling and it makes me more motivated to do it."

Maria has bought 25 applicators at $25 a shot. "Now I can't do without it," she says. She doesn't have an orgasm every time. She's had three in a couple of months-she counts them. But there's more pleasure each time.

Of course, Dr. K's Dream Cream is only one little homemade remedy. The FDA has yet to approve any sex drug for use by women. (A drug company can't legally market a medicine for an unapproved use-such as for female sexual dysfunction-though an eager doctor can prescribe one.) Goldstein says it will be years before "a woman will be able to walk into a specialist's office and walk away with a safe and effective agent to facilitate her sexual response."

But the main cause for delay is the nine to 12 months it could take to move new treatments through the FDA-approval process. New pills and potions will exist much sooner. "In the next year we'll know something about Viagra," says Julia Heiman, a professor of psychiatry and behavioral science at the University of Washington, in Seattle. Jennifer Berman and others are also testing apomorphine (Pentech's Uprima). Perhaps someday, Viagra will be prescribed for some women, apomorphine for others.

Some researchers worry that the new treatments will distort attitudes toward sex. Is it really pathological to have a low sex drive? Will new medicines create unrealistic standards? "It could set up Olympic expectations of sexual activity," says Meston, "where a single orgasm isn't enough."

Maybe that will be a problem with men and Viagra first. Doctors acknowledge that a large share of the prescriptions are being written for men whose sexual machinery already works just fine. But the story is likely to be a little different with women, given that nearly half of them (43 percent) fit the definition of sexually dysfunctional. It's probably not going overboard to expect-or hope-that new medicines will help them experience any orgasms at all.