Human Pheromones Influence Fertility and Mood

By Tom Hollon
With an unusual collection of toolsa frozen archive of hundreds of used underarm pads, an ancient Macintosh SE computer, and a perfume ingredientthe existence of human pheromones has been demonstrated. The tools belong to Martha McClintock and her group at the University of Chicago. In 1998, she and her colleagues used the underarm pads to show how pheromones could alter women's menstrual cycles. In a paper in press in Hormones and Behavior, they now report that a steroid found in blood, saliva, and semenand also in a perfume called Realmis a pheromone with mood altering effects.
Pheromones and Social Behavior
The Ovarian Cycle Connection
Pheromones in a Bottle
Pheromones and Social Behavior (Back to Top)
In the popular view, pheromones equate to airborne sex signals. The typical mind's image of pheromone action conjures a male insect rendered instantly randy by the faintest whiff of pheromone, and helpless to do anything but follow its trail to a waiting and irresistible female. Actually, that's accurate only as an example of what is called a releaser pheromone, which is said to release a behavior such as mating.
More generally, pheromones are odorless airborne signals that help members of the same species behave appropriately in a social environment. Among insects and animals, pheromones mark territory, mediate dominance, aid navigation, and affect the timing of reproductive senescence, just to name several of their uses.
Demonstrating the existence of human pheromones marks a career milestone for McClintock, who began her research some 30 years ago with an observation that women living together tend to synchronize their menstrual cycles. That work suggested that compounds that women could not smellpheromoneswere behind synchronization.
The Ovarian Cycle Connection (Back to Top)
Most of McClintock's subsequent pheromone research was done with lab animals and mathematical modeling, however, until a discovery she made a few years ago with female rats led her back to experiments with humans. She found that female rats living together will time their ovarian cycles so that they give birth within a few weeks of each other. They receive a double benefit from this. Nursing is less work, because it can be done in turns when pups from different mothers are pooled into common crèches. The females also receive more stimulation for lactation, and as a result, pups are heavier at weaning and more likely to survive.
McClintock found that two pheromones controlled ovarian cycle synchrony in rats. One worked during the ovulatory phase, lengthening the cycle. The other was a preovulatory pheromone that made the cycle shorter. Computer simulations imply that the two pheromones are together sufficient to control synchrony.
Do similar pheromones exist in women? On the assumption that human pheromones might be released from the skin, her team tested whether underarm pads could capture pheromones capable of altering the length of the menstrual cycle.
The team assembled an archive of hundreds of used pads, taken from volunteers who changed pads daily through a couple of menstrual cycles. Each used pad would be frozen to preserve any skin-released compounds it may have captured. By noting dates of menses and measuring lutenizing hormone in urine samples (a big surge of lutenizing hormone triggers ovulation), the team could tell which pads were worn in preovulatory and ovulatory phases of the cycle.
To test the pads for pheromones, volunteers wiped thawed pads under their noses every day for several months. Each woman had a control cycle during which she wiped herself with inert pads. That was followed by two months of exposure to ovulatory phase pads, and then by two months of preovulatory pads. The length of each subject's control cycle was then compared to her cycle lengths when exposed to the used pads.
The results were similar to the results of the rat experiment. McClintock and her colleagues found evidence of a human ovulatory pheromone producing lengthened cycles and a preovulatory pheromone making cycles shorter. They also found that the pheromones changed neither the length of menses nor the phase from ovulation until menstruation. The pheromones altered only the length of the follicular phase between the end of menses and the beginning of ovulation. The chemical identities of the pheromones are at present unknown.
Why would women have ovarian cycle pheromones? McClintock speculates that thousands of years ago, when humans lived in hunter-gatherer societies, synchronized cycles might have given women benefits similar to the ones rats still enjoycommunal nursing and heavier babies more able to survive after weaning.
Pheromones in a Bottle (Back to Top)
Her next pheromone experiments began with a biotechnology company's claim that the steroid androstadienone is a human pheromone. According to McClintock, Pherin Pharmaceuticals, a California company exploring the possibility of making medicines based on human pheromones, claimed the compound made women feel more relaxed, friendly, and self-assured. When McClintock was unable to find published evidence to support that claim, she and her team decided to investigate. They've come up with evidence that androstadienone is indeed a mood-influencing pheromone, but their picture of its effects is more complex than Pherin's.
McClintock wanted to know if androstadienone could emotionally affect women at concentrations too low for them to smell. To find out, her group exposed women to tiny amounts of androstadienone for two-hour periods during which they occupied themselves with a simple nonsocial and nonsexual taskclicking a mouse whenever circles dimmed on the screen of an old Macintosh.
The scientists found that androstadienone was responsible for an "overall positive mood" in their subjects. McClintock describes women as "less irritated, less anxious, less dysphoric, and less depressed" when exposed to androstadienone.
But she doesn't describe the effects in the same way as the biotech company. Pherin, she said, claimed that androstadienone made women feel better. McClintock's data suggested it prevented them from feeling worse, which isn't the same thing. Her data showed that women not exposed to androstadienone tended to become irritable, probably as the novelty of participating in an experiment wore off and boredom set in. With androstadienone, however, they tended to maintain their initial mood throughout the two-hour experiment.
McClintock calls these compounds modulator pheromones because she believes they modulate rather than release behaviors. As she puts it, modulators influence neural systems underlying a complex behavior that is happening at a particular time. She also thinks it may turn out that human pheromones work in some behavioral contexts, but not others. As for human releaser pheromones, she adds that there is no evidence that they exist.
"We are gathering evidence," McClintock says, "that there are pheromone modulators that act without conscious awareness. There is no doubt that humans have social chemosensory pathways involving pheromones that regulate fertility and emotional states." She adds that if scientists can understand how they work, it might one day be possible to manipulate the fertility cycle and moods with fewer side effects than with the drugs in use today.
Which brings up the question of whether androstadienone might have potential as an antidepressant. It's certainly worth investigating, McClintock says, but the answer may be quite complicated. It will depend on in how many contexts it works. And it is certain already that it won't work on everyone: Her team found strong individual differences in response to androstadienone. Although it made most women feel better, on some it had distinctly the opposite effect.
Does that mean it would exacerbate depression in some people? Could the different responses to androstadienone be due to genetic differences? Those questions and many more about human pheromones are left to the future.
For more information: Martha K. McClintock, Department of Psychology, The University of Chicago, 5730 Woodlawn Avenue, Chicago, Il 60637, phone: 773-702-2579 Fax: 773-702-0320
Tom Hollon is a science writer and editor based in Rockville MD. He was the founding editor of the journal Modern Drug Discovery. Prior to that, Tom conducted research at the National Institutes of Health, the Pasteur Institute, and the University of Washington. Tom can be reached at thollon@starpower.net.