Scientists Sniff Out a Clue to Fertility : Human Scents May Play Role

Michael J. Russell was a senior psychology major at San Francisco State University looking for a way to overcome his mediocre grades and get into graduate school when he set out to look for human pheromones, something no one had ever found.

Such chemicals were known to exist in animals, and when released by one animal, pheromones can affect the behavior of other members of the same species in areas such as mating, feeding and congregating.

Scientists for some time had suspected the existence of human pheromones because they knew that the menstrual cycles of women who were roommates or who spent a lot of time together would become synchronized, with menses occurring roughly at the same time. In animals, such synchrony is caused by pheromones.

“It seemed logical that the same thing would happen in humans,” Russell recalled in a recent interview.

His quest not only got him into graduate school but also eventually provided the first experimental evidence that humans also secrete pheromones and that such chemicals elicit biological responses in women in ways that are still not understood.

Mysterious Messages

Scientists now know that women’s bodies respond to female pheromones by altering the timing of their menstrual cycles and to male pheromones by altering the length of menstrual cycles. In fact, these mysterious, unrecognized chemical messages may be essential to women’s fertility.

Scientists have not found any human pheromones that affect men.

Such pheromones are found in perspiration. In normal concentrations, pheromones have no perceptible odor.

In animals, pheromones can produce instantaneous effects. But human pheromones are thought to exert their effects over much longer periods of time, perhaps weeks.

Female pheromones produce their effects over distances of one foot to a few feet, but those of the male pheromone may occur only over distances of inches or less. Hence, close physical contact--such as that involved in sexual intercourse--appears to be necessary for male pheromones to have an effect on a woman.

Studies in recent years have shown that women who have sexual contact with men at least once a week are more likely than other women to have menstrual cycles of normal length and, therefore, more likely to be fertile.

Now, chemist George Preti and psychologist Winnifred Cutler of the Monell Chemical Senses Center in Philadelphia have provided a biochemical explanation for such findings. They showed that the physiological effects of intimacy on cycle length can be simulated in the absence of physical contact by exposing women volunteers to male or female perspiration.

Their work has demonstrated conclusively for the first time that humans do, in fact, have pheromones. Perhaps even more important, it opens the door to new methods for regulating the reproductive cycles of women who have had difficulty conceiving and restoring their fertility.

Scientists have long speculated that insects and animals communicate by means of odors, but the first such pheromone was not isolated until 1959, when a German scientist identified the sex lure of the female silkworm moth. When a male silkworm moth encounters even a few molecules of the pheromone, released by the female, he follows the trail, searching frantically for the female.

Well over 100 animal and insect pheromones have subsequently been identified. Some of these are emitted consciously from specialized organs for purposes such as marking trails, sounding alarms or calling a colony of insects together. Others, such as sex lures in vaginal discharges, are emitted subconsciously.

Dead ants, for example, emit a pheromone that tells other ants to dispose of the body, according to biologist Edward O. Wilson of Harvard University. If the scent is applied to a live ant, other ants will carry it outside the nest and deposit it on their rubbish heap--even though the “dead” ant is literally kicking and screaming all the way. If the ant tries to return to the nest, they will carry it out again and again until all the scent has worn off the ant’s body.

In the early 1970s, British researchers identified a pheromone released by female rhesus monkeys in heat that served as an aphrodisiac to males. Application of the scent to females who were not in heat would cause males--who usually ignored such females--to attempt to mount them. Males who were fitted with nose plugs, however, showed no such interest.

The effect of odors in such close relatives of humans led many scientists to predict that humans also were subject to the influence of pheromones. But that proposition has been difficult to prove.

The strongest evidence for such pheromonal activity was provided during the 1970s by biologist Martha McClintock of the University of Chicago, who studied small groups of women in college dormitories and other women who worked close to one another in offices.

Cycles Synchronize

She found that those who had a great deal of social contact--roommates or close friends--were likely to exhibit synchronization of menstrual cycles. She also found that women who had close social contact with men “had a shorter, more regular pattern of cycles that made them more likely to ovulate,” she said in an interview.

McClintock subsequently studied rats and showed that this phenomenon is caused by a pheromone.

Russell was familiar with McClintock’s work when he contemplated a study of pheromones in the winter months of 1980. But he was also stimulated by practical considerations.

He thought that such a study would be desirable because it could be conducted without any financing or high-tech equipment. All he really needed was little more than a room in which to meet with volunteers and a refrigerator in which to store sweat samples that might contain pheromones.

Russell discussed his ideas with psychology major Genevieve Switz who, coincidentally, “was very conscious of her body and kept accurate records of her menstrual cycle,” he said. Switz noted that her cycles had become synchronized with those of a friend by the end of each of the three summers that they had roomed together in San Francisco, but had become unsynchronized when they lived separately during the school year.

Recruits a Friend

Russell recruited Switz’s friend as a perspiration donor in his experiment.

Around the clock, she wore a 4-inch-by-4-inch cotton pad under her armpit. At the end of each 24-hour period, the pad was replaced and the used pad was cut into small pieces, immersed in a small amount of alcohol to ease recovery of any chemicals in the sweat, and then frozen to keep any chemicals from evaporating.

Subsequently, Russell and Switz thawed the samples and rubbed the pads on the upper lips of five volunteers several times a week over a period of four months. Pads containing only alcohol were rubbed on the lips of six volunteers who served as a control group.

By the end of the study, four of the group receiving the perspiration had synchronized their menstrual cycles to within one day of the donor’s, while the cycles of the control group were unchanged.

Russell, Switz and a third psychology major, Kate Thompson, published their results in 1980 in a psychology journal. (Shortly after the paper was accepted, Russell was admitted to the University of California Medical School in San Francisco. He is expected to get his Ph.D. in psychology next month.)

But few people believed the experiment--largely because it was not conducted on a “blind” basis. That is, the three researchers knew which volunteers received the donor’s perspiration and which did not--a situation that could lead to unwitting bias in the interpretation of results.

“Our paper kind of fell into a void,” Russell said.

But one person who did read it was Preti, who describes himself as “interested in the composition of human body odors.” Preti is on the staff of Monell Chemical Senses Center, a small independent research institute loosely associated with the University of Pennsylvania and located on the fringe of the urban campus.

Every one of the 50 Ph.D. scientists at the center is examining how taste and smell affect human and animal behavior.

Preti and his colleagues, for example, had already found that the onset of ovulation is signaled by the appearance of unusual chemicals in both vaginal secretions and exhaled air--discoveries which may lead to commercial ovulation detectors.

Preti literally bumped into Cutler--who was then studying reproductive physiology at Monell--at a Xerox machine, where they began discussing their mutual interest in pheromones. After several months, they decided that they would like to try to identify a human pheromone.

Key Differences

Ultimately, they decided to do a study similar to Russell’s, but with two key differences: No one would know which subjects were exposed to perspiration and which were not until after the results had been analyzed.

They also decided to incorporate male donors in their studies. This decision was prompted by prior animal studies that had indicated that male secretions could affect the length of the menstrual cycle.

Like McClintock, Cutler had previously shown that women were more likely to have menstrual cycles of normal length if they were sexually active. Among women who participated in heterosexual intercourse at least once per week, Cutler found, 78% had cycles within the normal range of 26 to 33 days. Among women who were celibates, only 59% had cycles in the normal range; among those who engaged in sexual activity sporadically, only 49% were in the normal range.

Through a technician who acted as an intermediary, Preti and Cutler recruited 35 women to participate in the study. “We never met a single subject, so there was no chance for unintentional bias,” said Cutler, who is now at the Athena Institute in Haverford, Pa.

Subjects in Dark

The subjects themselves did not know what the experiment was designed to study, and were told only that they were receiving a “natural fragrance” in alcohol.

To minimize known seasonal effects on reproductive cycles, Preti and Cutler collected samples from donors in the autumn of 1982, stored them in a freezer for a year, and applied them to the volunteers in the autumn of 1983.

At the start of the study, 16 of the 35 female participants had menstrual cycles that were three days longer or shorter than the normal 29.5 days. These women came to the clinic three days a week for 14 weeks to have their lips smeared with either a “male essence” collected from under the armpits of a male donor or with plain alcohol.

By the end of the study, the cycles of these volunteers who received male essence had either lengthened or shortened until most were close to the 29.5-day norm, while those who were swabbed with alcohol showed no change.

Similarly, the remaining women whose menstrual cycles were already normal length came to the clinic three times a week for 10 to 13 weeks to have their upper lips smeared with “female essence” collected from the armpits of female donors or, again, with plain alcohol.

Differences Reduced

At the beginning of the study, the onset of menses in the group who received female essence occurred an average of 8.3 days earlier or later than that of the donors. By the end of the study, that difference had been reduced to 3.9 days.

In those subjects swabbed only with alcohol, in contrast, the difference actually increased from 6.2 days at the beginning of the study to 7.6 at the end.

“I think we’ve finally answered the question,” Preti said. “Pheromone effects are real in human beings . . . and they even occur here in the U.S. where we are all deodorized and perfumed.”

The effects of the male essence are particularly important, Cutler said.

“A very clear pattern has been emerging and it all confirms that a woman’s optimal reproductive health is a part of a finely tuned system and that (contact with) a man, on a regular and sustained basis, is an essential part of it.”

Preti and Cutler’s discovery may eventually be useful in helping infertile women. Cutler had previously demonstrated an association between a woman’s sexual behavior and her monthly fluctuations of body temperature. Fertile women usually have the same pattern of temperature fluctuations during each menstrual cycle, while infertile women have a different pattern.

In previous studies, Cutler found that 90% of women who had weekly sexual relations with men had the fertile type of pattern, whereas only 55% of women who had sex sporadically had the fertile pattern and only 44% of celibate women. The Philadelphia researchers believe that the pheromone they have discovered might be used on a regular basis to normalize cycle lengths and to convert the temperature patterns of infertile women to the fertile pattern.

Preti and Cutler differ somewhat in how they place their discovery in the overall context of human pheromones. Preti is very conservative and refuses to speculate about the role of such pheromones beyond the limits of their study.

Cutler, however, thinks that pheromones may have an even greater importance to women during puberty and menopause.

Sexual Experience

“It matters when a woman begins her sexual life,” Cutler said. Her earlier studies had shown that women who had difficulty getting pregnant did not have their first sexual intercourse until an average of eight years after their first menses.

In contrast, women who conceived readily had their first intercourse an average of six years after puberty, and the two-year difference is statistically significant, she said. Cutler suspects that exposure to a male pheromone during the first sexual intercourse may play an important role in getting the reproductive system functioning properly.

Exposure to males may also be important during menopause, when the reproductive system is shutting down, Cutler speculated. She found that women who engaged in weekly sex had fewer and milder hot flashes during menopause than did women who were sporadic or celibate.

In this case, however, the interpretation is less straightforward, she conceded. It may be that women who have hot flashes and other side effects of menopause simply have less desire for sex.

Regardless, Cutler said, “A man, or his essence, seems essential for an optimally fertile system.”