Sexy Scents

Searching for chemicals that trigger human sexual behavior.

Posted Jun 28, 2018

Original Cartoon by Alex Martin
Source: Original Cartoon by Alex Martin

Magic charms that trigger attraction between men and women are part of folklore. Supposedly aphrodisiac scents are widely advertised, so is this age-old notion now reality? Take, for example, Erox perfumes “proven to increase arousal in men and women,” marketed by Human Pheromone Sciences Inc. A particularly persuasive advocate is Dr. Winnifred Cutler, co-author of a pioneering 1986 paper reporting experimental evidence for a male chemical signal affecting women. Extracts from men’s armpit-secretions were regularly rubbed on women’s upper lips for about three months, and their menstrual cycles were monitored. Women exposed to armpit secretions had less variable cycles than controls. Cutler later founded Athena Institute for Women's Wellness Inc. for research and selling substances identified as biological signals: Athena Pheromone 10X to enhance men’s aftershave, and Athena Pheromone 10:13 to boost cosmetic fragrances for women.

What is a pheromone?

Briefly stated, a pheromone is a chemical signal that evolved for communication between individuals within a species. Peter Karlson and Martin Lüscher coined the name—from the Greek roots pherein (to transport) and hormõn (to excite)—less than 60 years ago. Pheromones resemble hormones in some ways, but also show key differences. Whereas hormones are chemical messengers secreted by endocrine glands into an individual’s bloodstream for internal regulation, pheromones are agents discharged outside the body for communication between individuals. But pheromones do share with hormones crucial features in that that minute quantities are effective and operate in a lock-and-key fashion.

Reliable scientific evidence for pheromones was first reported for insects, which remain at the forefront. Sexual attractants of female butterflies and moths are particularly well known. A few molecules on a male antenna trigger a specific response: readiness to copulate. In silk moths, for instance, the female sex pheromone bombykol—the first pheromone to be isolated and synthesized—evokes wing fluttering in males.

Images from Wikimedia Commons. Adults with cocoon by Yercaud Elango (own work); file licensed under the Creative Commons Attribution-Share Alike 4.0 International license. Close-up of antennae by CSIRO; file licensed under the Creative Commons Attribution 3.0 Unported license. Bombykol molecule by Jü (own work); file made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.
Silkworm moths. Left: Two adults with cocoon. Right: Close-up of adult male showing large, feathery antennae. Inset: Molecule of the pheromone bombykol.
Source: Images from Wikimedia Commons. Adults with cocoon by Yercaud Elango (own work); file licensed under the Creative Commons Attribution-Share Alike 4.0 International license. Close-up of antennae by CSIRO; file licensed under the Creative Commons Attribution 3.0 Unported license. Bombykol molecule by Jü (own work); file made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.

Pheromone detectors in mammals

Pheromones, being chemical signals, are typically detected by the sense of smell (olfaction). But mammals actually have two separate olfactory systems. Sensors for the main system reside in the nose cavity, where airborne odor molecules trigger receptors in sensory tissue lining bony scrolls. Beneath the main nasal cavity, however, most mammals have a pair of accessory structures—the vomeronasal organs (VNOs)—that detect fluid-borne molecules. VNOs are cigar-shaped hollow tubes with a sensory tissue lining, lying in cartilage gutters on either side of the partition between right and left halves of the nasal cavity.

 Henry Gray (1918) Anatomy of the Human Body; after Kollmann. Work in the public domain in the USA because it was published (or registered with the U.S. Copyright Office) before January 1, 1923.
Vomeronasal organs (VNOs) in mammals. Top: Diagram of longitudinal section alongside the midline nasal septum (yellow = nasal cavity; green = VNO cavity). Bottom Left: Cross-section of the nasal region (yellow = nasal cavity; green = VNO cavity). Bottom Right: Frontal section of nasal cavities of a human embryo 28 mm. long.
Source: Top and Bottom Left images adapted from Martin (1990). Bottom Right figure from Wikimedia commons; author: Henry Vandyke Carter (1831-1897). Source: Henry Gray (1918) Anatomy of the Human Body; after Kollmann. Work in the public domain in the USA because it was published (or registered with the U.S. Copyright Office) before January 1, 1923.

The two olfactory systems in mammals also have distinct pathways to the brain. Signals from the nose cavity enter a pair of main olfactory bulbs at the front end of the brain, whereas inputs from the VNOs pass to accessory olfactory bulbs above.

Not all mammals have VNOs

Most mammals, including egg-laying monotremes, marsupials, and most placentals, have functioning VNOs. But in some placentals, they are extensively reduced or even absent. Most bats lack VNOs. Certain aquatic mammals—dolphins and whales, manatees and sea-cows—completely lack not only VNOs but olfactory bulbs as well. With primates, things are complicated. All lower primates (lemurs, lorises, tarsiers) possess well-developed VNOs and accessory olfactory bulbs. Among the higher primates, the New World monkeys also have VNOs and accessory olfactory bulbs, although they are rather small. By contrast, Old World monkeys, apes and humans completely lack VNOs and accessory olfactory bulbs. Human olfactory bulbs are actually smaller, relative to body size, than in any other primate. This reflects a particularly extensive reduction of the human olfactory apparatus.

Evidence for mammal pheromones

By the 1970s, it became widely accepted that VNOs serve a special function in mammals for detecting species-specific pheromones. Pheromones are commonly present in mammalian urine, most notably as indicators of female reproductive condition.

Particularly good evidence for pheromones exists for certain rodents, especially mice. After substances acting as chemical messengers, notably between males and females, were identified, it proved possible to synthesize them for experimental tests. This, in turn, clearly revealed the special function of the VNOs and facilitated identification of neural pathways and focal brain regions. Both males and females responded to urine from either sex, even when greatly diluted. Perhaps the most striking finding with sexual behavior of mice is the part played by pheromones in triggering lordosis, a special female posture with the rump arched downwards. This signals readiness for mating.

 Yohan Castel. File licensed under the Creative Commons Attribution-Share Alike 4.0 International license.
Diagram showing the main phases of mating in mice and the participation of pheromones, olfactory circuits, neural organization and the lordosis reflex.
Source: Wikimedia Commons; Author: Yohan Castel. File licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

Preliminary evidence for pheromones has also emerged with lower primates, notably through Martine Perret’s research on mouse lemurs. Both males and females mark their home ranges with urine bearing chemical cues. Dominant males have ranges overlapping those of several females and also perform urine-marking more frequently than subordinate males, whose ranges are peripheral. If a female is introduced to a group of males in captivity, both inter-male aggression and the frequency of scent-marking increase. Perret and colleagues eventually showed that female urine activates the VNO in male mouse lemurs—but the identity of the potential pheromone remains unknown, as is true for all other lower primates.

Comparable evidence for pheromones has been reported for New World monkeys.* In particular, David Abbott and colleagues reported a striking effect in common marmosets: The dominant, breeding female in a group partially or completely inhibits sexual cycles in her mature daughters or other subordinate females. If a female subordinate is removed from the group, her cycles are no longer inhibited—but exposing her to scent marks from the dominant female delays the release. It has been shown that the VNO mediates the apparent pheromonal effect.

Do human pheromones exist?

Various investigators have claimed that pheromones also exist in humans. Indeed, four steroids have been specifically identified as human pheromones: androstenone, androstenol, androstadienone, and estratetraenol. However, the evidence remains controversial and it is unlikely that pheromones contribute significantly to the sexual behavior of any Old World higher primates (monkeys, apes, and humans). They all lack VNOs and accessory olfactory bulbs, and evolutionary loss following divergence from New World monkeys surely reflect a major decrease in the importance of pheromones.

In recent commentaries, Tristram Wyatt presents a very skeptical assessment of evidence for human pheromones. He emphasizes the need to apply the rigorous guidelines that successfully yielded results in research on other species: a clear demonstration of an odor-mediated response, identification and synthesis of the bioactive agent, and confirmation of pheromonal activity of the synthetic version with bioassays. Moreover, Wyatt has noted several common problems in research on potential human pheromones, including small sample sizes, overestimated effect sizes, lack of replication and positive publication bias.

Encouraging evidence does, however, indicate the activity of a human pheromone in a non-sexual context. In a study published in 2009, Sébastien Doucet and colleagues exposed 3-day-old babies to secretion from areolar glands surrounding the nipples of unrelated, unfamiliar lactating women. The secretion stimulates suckling by any baby, not just a mother’s own infant, and the babies’ responses seemingly developed independently of any experience with breasts or milk. If it eventually proves possible to isolate, identify and synthesize the active factor, this will be the first demonstration of a pheromone in a mammal without a VNO.

*Possible pheromones have been reported for Old World monkeys as well. Research by Richard Michael, Barry Keverne, and others indicating that a vaginal cue can influence behavior in male Rhesus macaques aroused particular interest. In a 1968 paper, Michael and Keverne reported experiments in which the sense of smell was suppressed in male macaques by inserting plugs into their nasal cavities. By repeatedly pressing a bar, males could gain access to ovary-less females treated with estrogen to restore their sexual activity. Bar-pressing frequencies increased markedly after removal of the nasal plugs, indicating some kind of olfactory cue. Subsequent experiments with vaginal lavages indicated that the active factor was a mixture of non-aromatic hydrocarbons. Michael and colleagues gave the name copulin to this inferred vaginal pheromone. However, subsequent research by David Goldfoot and colleagues failed to replicate their findings.

References

Barrett, J., Abbott, D.H. & George, L.M. (1990) Extension of reproductive suppression by pheromonal cues in subordinate female marmoset monkeys, Callithrix jacchus. Journal of Reproduction & Fertility 90:411-418.

Cutler, W.B., Preti, G., Krieger, A., Huggins, G.R., Celso, R.G. & Lawley, H.J. (1986) Human axillary secretions influence women's menstrual cycles: The role of donor extract from men. Hormones & Behavior 20:463-473.

Doucet, S., Soussignan.R., Sagot, P. & Schaal, B. (2009) The secretion of areolar (Montgomery’s) glands from lactating women elicits selective, unconditional responses in neonates. PLoS One 4,e7579:1-10.

Estes, R.D. (1972) The role of the vomeronasal organ in mammalian reproduction. Mammalia 36:315-341.

Goldfoot, D.A. (1981) Olfaction, sexual behavior, and the pheromone hypothesis in rhesus monkeys: a critique. American Zoologist 21:153-164.

Herz, R.S. (2009) The truth about pheromones, part 1: How we communicate chemically. https://www.psychologytoday.com/intl/blog/smell-life/200905/the-truth-about-pheromones-part-1

Herz, R.S. (2009) The truth about pheromones, part 2: Will a real human sex pheromone be found and bottled? https://www.psychologytoday.com/intl/blog/smell-life/200906/the-truth-about-pheromones-part-2

Karlson, P., & Lüscher, M. (1959) Pheromones: a new term for a class of biologically active substances. Nature 183:55-56.

Martin, R.D. (1990) Primate Origins and Evolution: A Phylogenetic Reconstruction. New Jersey: Princeton University Press.

Michael, R.P. & Keverne, E.B. (1968) Pheromones and the communication of sexual status in primates. Nature 218:746-749.

Michael, R.P., Keverne, E.B. & Bonsall, R.W. (1971) Pheromones: Isolation of male sex attractants from a female primate. Science 172:964-966.

Perret, M. (1992) Environmental and social determinants of sexual function in the male mouse lemur (Microcebus murinus). Folia Primatologica 59:1-25.

Wyatt, T.D. (2015) The search for human pheromones: the lost decades and the necessity of returning to first principles. Proceedings of the Royal Society of London B 282:1-9.

Wyatt, T.D. (2017) Pheromones. Current Biology 27:R739-R743.