The Chemistry of Desire

By MICHAEL D. LEMONICK

Eight years ago, after she had a hysterectomy at age 42, Roslyn Washington was left with an unexpected side effect. Her doctors, who had recommended removing her ovaries as well as her uterus because of fibroid tumors and an ovarian cyst, had warned her about a lengthy recovery period. But, she says, "I was not aware of the fact that there would be a decrease in my sexual life." That's something of an understatement. Washington, an office manager from Silver Spring, Md., who is married and has a teenage daughter, says that after the surgery she felt no sexual desire whatsoever. "I didn't think about it," she says. "I didn't get that urge from a glance or a look or a touch." It was a profound loss. "Without that connection, without the sexual aspects, you feel in some instances like you're really less than a woman," she says.

Then several years later Washington heard a radio ad seeking women like her for a study of testosterone patches. People usually think of testosterone as a male hormone, but women have plenty in their systems too, and researchers have reason to believe that the hormone is involved in the female sex drive. About half of women's testosterone is produced in the ovaries, so the patches were an attempt to replace what had been lost through surgery. Washington signed up and was one of 75 women accepted for the study out of 50,000 who applied; clearly she was not alone in her misery. Twice a week for the next year she affixed a thin, clear patch onto her abdomen, alternating sites over where her right and left ovaries used to be.

Washington didn't know whether she was receiving transdermal testosterone or a placebo. She did know that things were very different. "I hadn't felt like that in years," she says. "I felt stimulated. It was like, 'Oh, yeah, I'd forgotten that's what it feels like.' It was good." Alas, when the trial ended, her desire ebbed.

It's tempting to conclude that Procter & Gamble, manufacturer of the testosterone patch, had found the elusive chemical key to female desire. The study, published in 2000 in the New England Journal of Medicine, reported that many of the women who, like Washington, were on real testosterone had more sexual fantasies and more sex and masturbated more than they had before. But so, albeit to a lesser extent, did women who wore patches with no testosterone at all. For women suffering from lost libido, the placebo effect was almost as strong as that of the hormone. In short, the mere belief that the treatment would rekindle sexual desire was often enough to turn up the heat.

This finding illustrates the promise and the perplexity of research into the biology of human sexuality, where mind, body and experience are endlessly intermingled. People find themselves turned on in obvious situations--slow-dancing together, seeing someone with a sexy body, finding a member of the opposite or same gender to be excitingly sharp-witted or funny. But carnal longings strike at surprising times too--in the wake of a victory by your favorite team (for men, anyway) or at times of fear or even after a tragedy, like the death of a parent.

No matter how lust is triggered, though, sex, like eating or sleeping, is ultimately biochemical, governed by hormones, neurotransmitters and other substances that interact in complicated ways to create the familiar sensations of desire, arousal, orgasm. By understanding how that happens, scientists should in principle be able to help people like Washington for whom sex just isn't working. And indeed, over the past decade or two, scientists have identified many of the pieces of this complex puzzle. It clearly involves testosterone, along with other hormones, including estrogen and oxytocin, and brain chemicals such as dopamine, serotonin and norepinephrine. And there are numerous other bodily chemicals that turn us on, ranging from the commonplace, nitric oxide, to the obscure, vasoactive intestinal polypeptide.

Scientists have also learned that the old notion that 90% of sex is in the mind is literally true: the parts of the brain involved in sexual response include, at the very least, the sensory vagus nerves, the midbrain reticular formation, the basal ganglia, the anterior insula cortex, the amygdala, the cerebellum and the hypothalamus.

If all this sounds complicated, it is. Researchers are still struggling to understand how these pieces fit together and how they might be different for men and women. It's not clear which chemicals of desire are unleashed and under which circumstances, because setting and mood, as women know better than men, can make all the difference between arousal and annoyance.

Nevertheless, scientists are light-years ahead of where they were in the 1920s and '30s, when estrogen and testosterone were first identified, and they know a great deal more than they did in the 1940s, when Alfred Kinsey, followed by the research team of William Masters and Virginia Johnson in the 1960s, published some of the first scholarly studies of human sexuality. Those studies concluded that sexual response proceeds in distinct stages, beginning with excitement--erection in men, engorgement of vaginal and clitoral tissue in women--proceeding to orgasm and finally to "resolution," in which tissues return to their normal state.

They didn't delve into biochemistry, though, and it turns out they probably didn't get the stages right either. In the 1970s psychiatrist Helen Singer Kaplan, who founded the Human Sexuality Program at New York Weill Cornell Medical Center, pointed out that before you get physically aroused, you have to feel sexual desire--a statement that seems pretty obvious. It's also pretty obvious to anyone who has been in a heterosexual relationship that men and women tend to experience sexuality somewhat differently. So where Masters and Johnson saw sexual arousal as a linear progression toward orgasm, researchers like Dr. Rosemary Basson of the University of British Columbia argued in 1999 that women, at least, operate in a more circular pattern. Desire can precede stimulation or be triggered by it. Satisfaction is possible at any of the stages. And orgasm isn't necessarily the ultimate goal.

Stimulation, moreover, can take all sorts of forms. Says Dr. Jennifer Berman, a urologist and director of the Female Sexual Medicine Center at UCLA: "Women experience desire as a result of context--how they feel about themselves and their partner, how safe they feel, their closeness and their attachment." Men, says Berman, "tend to be more visually directed and stimulated than women are." Thus Playboy and Hooters and the estimated $10 billion-a-year mainly male-oriented pornography industry.

But the reasons for that difference may be as much cultural as they are physiological. Dr. Julia Heiman, a psychologist and director of the Reproductive and Sexual Medicine Clinic at the University of Washington Medical School, is one of a growing number of researchers who think it's misguided to see men as simple and linear and women as complex and circular. "I don't think we've taken the time to talk to men about what desire is," she says. "If they are emotional about their sexuality, they don't feel in step with other men."

Women who don't fit stereotypes don't fare much better, says Jim Pfaus, a psychologist at Concordia University in Montreal who studies behavioral neurobiology. "What is a woman who expresses arousal in response to blatantly visual sexual cues? I hope we've moved beyond calling her a slut while calling a man who does the same a stud." But the cultural prejudice behind those labels persists, he says.

Research by Meredith Chivers at the Center for Addiction and Mental Health, affiliated with the University of Toronto, shows that women do respond to sexy visual stimuli. In fact, in a study recently presented at a Kinsey Institute conference on female sexuality, Chivers found that women show physical signs of arousal in response to a wider variety of images (including films of bonobo chimps mating) than men do. But unlike in men, this physical arousal is not closely paired with a subjective feeling of being turned on. In short, physical arousal for women can come before or even in the absence of conscious desire--doubtless a source of much confusion between the sexes. Arousal and desire can also happen at once.

But while arousal and desire are intimately intertwined and probably involve all sorts of feedback between brain and genitalia that have yet to be untangled, at least some of the underlying biochemistry is becoming clear. Here is a catalog of some of the key chemicals of love:

--LETTING IT FLOW

Desire is complicated. Arousal, by contrast, is pretty straightforward: fill the penile arteries with blood or divert blood to the vagina and clitoris, and you're there. "Once the brain gets turned on--however it gets turned on--it's a relatively simple concept to increase blood flow," says Dr. Alan Altman, a specialist in menopause and sexuality at Harvard Medical School. In men, a chemical that facilitates the flow is vasoactive intestinal polypeptide, a hormone that also directs the expansion and contraction of smooth muscles in the gastrointestinal tract.

But the primary chemical in charge of that function is nitric oxide. It's a vascular traffic cop, activating the muscles that control the expansion and contraction of blood vessels. If the mind is in the mood--or when you pop a nitric-oxide-boosting drug such as Viagra or Levitra--the body responds. Men tend to be more focused on genital stimulation than women, so they are more likely to perceive an increased blood flow to the genitals as arousal, while women may be unaware of it. That may be one reason why trials of Viagra on women have been disappointing.

--FUELS FOR LUST

If there's one substance that ultimately makes it possible to get turned on in the first place, testosterone is probably it. "When testosterone is gone," says UCLA's Berman, "for whatever reason--aging, medication--men experience erection and libido problems." Restore the testosterone, and you usually fix those problems.

Women too seem to have problems getting interested in sex when their testosterone levels are too low, which is why Procter & Gamble is experimenting with testosterone patches. Says Altman: "When women are having normal menstrual cycles in their prime reproductive ages, their ovaries make two times more testosterone than estrogen." A few days before ovulation, triggered by surging levels of testosterone--along with other hormones including progesterone and estrogen--sexual desire peaks, according to new research by Martha McClintock of the University of Chicago that dispels a long-held theory that fertility precedes desire.

But for women, at least, estrogen may also be crucial. "Give estrogen to women with decreased desire," says Pfaus, "and you don't restore desire. Give them testosterone alone, and you get a little increase in desire. Give them estrogen and testosterone together, and you get a whopping increase." Why? Some research suggests that testosterone's role in women is diversionary: it attaches to so-called steroid-binding globulins in the blood that would otherwise latch onto estrogen molecules and render them inert. The testosterone is taken away to the liver, while the estrogen is free to make a lust-inducing dash for the brain.

Pfaus argues further that estrogen may be the ultimate love hormone for men as well. "A lot of studies on rats and birds," he says, "show that brains are like giant ovaries, in the sense that testosterone and other androgens are converted into estrogens in the hypothalamus. And this conversion appears to be critical to the expression of male sexual behavior."

--THE FEEL-GOOD CHEMICAL

Both testosterone and estrogen trigger desire by stimulating the release of neurotransmitters in the brain. These chemicals are ultimately responsible for our moods, emotions and attitudes. And the most important of these for the feeling we call desire seems to be dopamine. Dopamine is at least partly responsible for making external stimuli arousing (among other things, it's thought to be the pleasure-triggering substance underlying drug addiction). "Being low on dopamine," says the University of Washington Medical School's Heiman, "correlates with being low on desire." And in men dopamine-enhancing drugs (including some antidepressants and anti-Parkinson's medications) can increase desire and erections. So can apomorphine, a Parkinson's drug that latches directly onto the dopamine receptors in brain cells and turns them on.

Another neurotransmitter almost certainly involved in the biochemistry of desire is serotonin, which, like dopamine, plays a role in feelings of satisfaction. Antidepressants like Prozac, which enhance mood by keeping serotonin in circulation longer than usual, can paradoxically depress the ability to achieve orgasm. But "dopamine and serotonin," says Heiman, "appear to interact with each other in a complicated way to impact desire."

So, researchers suspect, do the neurotransmitters epinephrine and norepinephrine, whose usual job is to pump up our energy when we're in danger. Blood-plasma levels of both chemicals increase during masturbation, peak at orgasm and then decline, and by-products of norepinephrine metabolism remain elevated for up to 23 hours after sex. It's not yet clear, though, whether this is a cause or an effect of arousal.

--THE CUDDLE HORMONE

Endocrinologists have known for years that oxytocin, released by the pituitary gland, ovaries and testes, helps trigger childbirth contractions, milk production during nursing and the pelvic shudders women experience during orgasm (and possibly the contractions during male orgasm as well). The hormone is believed to play a vital role in mother-child bonding and may do the same for new fathers: oxytocin surges when a new dad holds his bundle of joy. Some researchers also think of oxytocin as a cuddle chemical. Preliminary studies by psychiatrist Kathleen Light at the University of North Carolina have found that oxytocin levels rise after couples hold hands, hug or watch romantic movies. It also may be what makes you want to stay with your partner until the morning after sex. Those who can relate to Billy Crystal's "How long do I have to lie here?" scene from When Harry Met Sally might question whether oxytocin affects both genders equally.

But there's increasing evidence that oxytocin is also involved in deeper bonding. It certainly plays that role in a much studied little rodent called the prairie vole, which is famous for its fidelity to its mate. The critter's brain releases a rush of oxytocin as it bonds with its beloved. Block the chemical, and voles fail to make a connection. Inject more of the hormone, and they fall for each other even faster.

A similar kind of imprinting might take place in humans. "Oxytocin release may help us bond to certain features in our partners," says Pfaus. "It's probably part of the mechanism that generates the template of what we find attractive." The next time you see your partner or someone like your partner, he theorizes, "the oxytocin is activated. It doesn't mean you have to be aroused. You just think, God, what a beautiful woman"--which might explain why we're attracted to the same type over and over.

--ATTRACTIVE AROMAS?

Probably the most controversial issue in the chemistry of sexuality is the role of pheromones. In 1971 the University of Chicago's McClintock, then a Wellesley undergraduate, proved scientifically what women in dorms had known for decades: menstrual periods become synchronized when women live together. It's probably because of pheromones, she said--olfactory chemicals that we can detect even though we're not aware of them. In 1998, she did experiments that proved this hypothesis, but, unlike animal pheromones, no human versions have been isolated.

Because menstrual cycles and sexuality are part of an overall system, it's possible that pheromones could trigger desire. Perfumemakers that market pheromone-based scents have latched onto this notion. It's plausible, says Altman, "but I don't think the science is very good on it." Pfaus agrees: "I hope it's true. Totally on faith, I believe it. The problem is that the scientist in me says, 'O.K., but what are these pheromones, and who has shown it?'"

--A DOUBLE SHOT OF LOVE

A newly identified substance that has captured Pfaus's interest is alpha melanocyte polypeptide, also known as melanocyte-stimulating hormone (MSH). In clinical trials, this pituitary hormone had the dual effect of giving men erections and heightening their interest in sex. Pfaus is studying a synthetic version for Palatin Technologies of Cranbury, N.J., which is developing it as a nasal spray. "It's astonishing that you have a little peptide that has such a big, specific effect," he says. It interacts with dopamine, but how, precisely? "We don't know," he says.

Like all substances that promise to increase desire and performance, whether they are prescription drugs or folk aphrodisiacs sold next to the cash register at the quick-stop store, MSH is tough to investigate because of the placebo effect. As Procter & Gamble discovered with its testosterone-patch study, arousal and desire are so entangled with one's state of mind that it's tough to figure out cause and effect. Says Altman: "If you're in a tribal society and taught that something is an aphrodisiac, it probably will be. But someone in Los Angeles taking the same thing probably won't get the same effect."

Maybe that's just as well. For those who suffer from a lack of interest in sex, like Roslyn Washington, it's great to have a treatment that works. But like the women in the testosterone study who responded to a placebo showed, the real point is to create a sex life that works. Feeling is believing, and vice versa. We experience attraction and sexual desire as a sort of magic, a phenomenon filled with delightful mystery. And if scientists continue to be overwhelmed by the complex interplay of dozens of substances percolating from mind to body and back, that keeps the mystery nicely intact. --Reported by Sonja Steptoe/Los Angeles

With reporting by Sonja Steptoe/Los Angeles