Pheromones, in context

This is a field of research where the opinions of experts range from gung-ho boosterism to outright skepticism, where accusations of data fudging and sexism fly, and where the popular press is always watching from the sidelines, ready to trumpet each new claim and counterclaim to the world as soon as it is made.

On one side of the debate are the pheromone boosters, some of whom have founded companies that sell pheromone-based perfumes and pharmaceuticals. On the other side are skeptics who argue that the phrase "human pheromone" is a contradiction in terms. Between the two extremes lies a middle ground of researchers who are doubtful of the strongest claims but unwilling to ignore the possibility that humans, like many other animals, use chemicals to communicate.

Among them is Martha McClintock, PhD, who can be credited with starting the human pheromone phenomenon. In 1971, the University of Chicago psychologist, then an undergraduate at Wellesley College, published a study showing that the menstrual periods of women who lived together tended to converge on the same time every month, an effect thought to be mediated by pheromones.

Now, more than 30 years later, McClintock and others in the middle ground are finally making progress in understanding the effects of human pheromones. Many aspects of the field remain unclear--including the definition of the term "pheromone" itself (see sidebar on page 48)--but at least one conclusion can be drawn from the research conducted so far: Their effects are far more dependent on social and psychological context than originally suspected.

Stop lights and sweaty underarms

When McClintock first began studying menstrual synchrony in the 1970s, data addressing how one woman could affect the hormonal cycle of another was nonexistent. But it seemed plausible that pheromones were responsible, especially since one of the original definitions of the term described them as "ectohormones," substances that worked between individuals in much the same way that "endohormones," like testosterone and estrogen, worked within them.

There were hints that the pheromones in question were associated with underarm secretions, but it took until 1998 for McClintock and Kathleen Stern, PhD, to show that fluids collected from a donor woman's underarms, when applied to the upper lip of a female recipient, could hasten or delay the recipient's menstrual period. The study fell short of identifying the exact chemicals responsible, but even many skeptics agree that it provides strong evidence for the existence of human pheromones.

The pheromones thought to be responsible for menstrual synchrony are known as "primers"--substances that can influence long-term changes in hormone levels, such as those that take place during the menstrual cycle, the onset of puberty or pregnancy. But researchers were also eager to find evidence for human "releasers"--quick-acting pheromones that in non-human animals can trigger stereotypical behavioral responses, such as sexual intercourse. Although some were skeptical that any stimulus--auditory, visual, tactile or chemical--could elicit stereotyped behaviors in humans, others were more optimistic.

Those researchers focused their attention on so-called sex attractants like androstenone, a substance found in boar saliva, and "copulins," primate vaginal secretions that supposedly triggered male mating behavior. When further research showed that these substances had mixed or minimal effects in humans, however, excitement within the scientific community died down. But interest continued outside the scientific community, and some researchers founded companies to develop and market pheromone-based products intended to boost self-confidence or sexual attractiveness. Two of the substances that received the most attention were the hormone-like chemicals androstadienone and estratetraenol, which are found in human sweat.

"The idea was that men produce androstadienone and that's a sex attractant to women, and women produce estratetraenol and that's a sex attractant to men," explains McClintock, who is critical of the claims made by many commercial pheromone companies. "Then they backed off from the sex attraction and modulated it more, to say, 'Well, it just makes you feel more self-confident and open to social communication.'

"We have found that these compounds do have very interesting effects on psychological state and brain function," she adds, "but it's not the simple picture that was originally portrayed."

In 2000, McClintock and then-graduate student Suma Jacob, PhD, now a medical resident at the University of California, Los Angeles, reported that androstadienone and estratetraenol's effects on behavior were both sex- and context-dependent. In one experiment, the chemicals improved women's mood but had the opposite effect on men; in another experiment, they kept women's mood from deteriorating over the course of the testing session, but didn't improve it. McClintock and Jacob concluded that if the substances were indeed pheromones, they were modulators, not releasers--substances that affect behavior by altering psychological state, not by triggering fixed responses.

Meanwhile, researchers like Winnifred Cutler, PhD, one of those who founded companies to market pheromone-based perfume additives in the 1980s, were trying to show that the substances worked as advertised. In 1998, she reported that her male perfume additive significantly increased men's likelihood of having sex. Last spring, San Francisco State University psychologist Norma McCoy, PhD, reported similar results using Cutler's female perfume additive.

In McCoy's view, their studies show that the pheromones work under real-world conditions, regardless of laboratory results. "I think that we've once and for all demonstrated that this pheromone, however it's constituted, does have powers over the other sex," she says. "There is something that makes women attractive, and it can be very, very powerful."

Charles Wysocki, PhD, of the Monell Chemical Senses Center, disagrees. "There's no good evidence in the biomedical literature that these are human pheromones," he says. According to his analysis of McCoy's data, the additive appeared to work only because women who received the placebo and the "pheromone" started out with different levels of sexual activity, then regressed toward the mean--a statistical flaw disguised by the study's data analysis methods.

McClintock, too, remains skeptical. Social and psychological conditions are important mediators of pheromonal effects, she says, and any claims that a particular product will increase the user's opportunities for sexual intercourse regardless of context are, in her opinion, misleading.

"It's like saying that if you see a red light, you cannot control yourself from stopping no matter the circumstance," says McClintock. "Human behavior just isn't like that in any domain."

A dead-end duct?

The debate over whether pheromones affect human behavior is hardly over, but at least enough evidence has been collected that a consensus has emerged on some effects, such as menstrual synchrony. In contrast, the biological details of how pheromones affect humans remain "a total mystery," according to Cornell University psychologist Robert Johnston, PhD, although a few tantalizing clues are beginning to emerge.

In 1999, Noam Sobel, PhD, and his colleagues at Stanford University used functional magnetic resonance imaging to show that the human brain responded to androstadienone even when subjects were unable to smell it, a result confirmed in a later study by Jacob, McClintock and their colleagues. In 2001, Ivanka Savic, PhD, and her colleagues at the Karolinska Institute in Sweden reported that androstadienone and estratetraenol affected men and women's brains differently: The former boosted hypothalamic activity only in women, while the latter increased hypothalamic activity only in men. The hypothalamus influences the pituitary gland's release of hormones, so it is in a key position to affect reproductive behavior.

Despite these suggestive neuroimaging results, it remains unclear how the presence of pheromones is communicated to the brain. In many animals, a pair of tiny ducts in the nasal septum called the vomeronasal organ (VNO) is responsible for detecting pheromones, but the evidence for a working human VNO is mixed at best. Because the main olfactory epithelium, where ordinary smells are detected, can also detect pheromones in some animals, the absence of a VNO would not rule out the possibility of human pheromones. But its presence would be a major support for the pheromone boosters.

In a series of experiments in the 1990s, researchers at the University of Utah claimed to have shown not only that the human VNO existed, but that adrostadienone and estratetraenol elicited different electrical responses in the VNOs of men and women. The result parallels that of Savic's neuroimaging study and, if true, would provide for a pathway for pheromones to influence the brain. However, because the Utah group is also heavily invested in a pheromone-based pharmaceutical company, many researchers are skeptical of their results, especially since no one has yet discovered a functional nerve linking the VNO to the human brain.

"I don't see any serious scientific flaws in the experiments they've published, but then again, they haven't published everything they've done," says Michael Meredith, PhD, a professor of neuroscience at Florida State University, who recently reviewed the evidence for the human VNO. He concluded that the evidence remains equivocal, and that only further research--by other groups of researchers--will resolve the debate. Bernard Grosser, MD, chair of the psychiatry department at the University of Utah, acknowledges that a pathway from VNO to brain remains to be found, but he says he is confident that one exists. "Anyone who has gone in and duplicated the work we've done has found essentially the same results," he says.

In some ways, the VNO question is a distraction from the main issue, which is how pheromones affect human behavior. Knowing the answer to one question tells you very little about the other, says Sobel, now a professor of psychology at the University of California, Berkeley. Ultimately the question of whether there is such a thing as a human pheromone will depend on tying specific chemicals to specific neural, behavioral or psychological responses--and on coming to some agreement about what a pheromone is in the first place.

Future research

Future studies may settle some of these controversies. McCoy hopes to extend her work on sex pheromones to postmenopausal women. McClintock intends to study the influence of odors given off by breast-feeding women on the fertility of other women. Meredith, Johnston and others plan to continue studying the biological mechanisms by which chemical messages affect social behavior in rodents and other animals.

How important these substances are in everyday life remains an open question. But whether or not one believes that human pheromones are sex attractants, as McCoy and Cutler do, there are still a number of social domains in which chemical messages could have an important effect, says McClintock.

"In animals, [pheromones] are involved very strongly in care of offspring, in recognizing members of your social group, in recognizing family members," she says. "In thinking about what the normal function might be, we know from the animal work that we need to think broadly in social terms and that the same compound might serve differently in different contexts.

"The field of physiological or biopsychology typically looks at how biology causes changes in behavior," she adds. "What we're trying to do is say that that's a very reductionist approach, and what is really important is to realize that psychology and social interaction also regulate the biology."