In our last scientific episode, we had cake and pork chops.
Oh, and we also talked about the effects of transitioning on a person’s scent.
But really, that post gave only half of the story. To explain what I mean, I refer the reader to the comments that were posted by Liberty Wolf, who wrote:
“I know that my own anecdotal evidence is that women who are attracted to me tend to love my scent and definitely claim that it smells very masculine! … My one femme girlfriend also claimed that one of the big differences that she experienced with me physically from women was that I smelled different. I’ve also been told, and this is not as flattering, that my room smells like a male locker room! This, when it is messy, I try not to let it go that far, needless to say. And, this comment, again, from a woman, but only a friend. And, I am not the only trans man to receive these comments, I’ve heard other guys say similar things about smelling more ‘male’ or manly or whatever you wish to call it. As you know, our urine changes smell also. I mostly know this from the observations of women, since the smell is invisible to me.”
His comments contain not only anecdotal information about the changes in his scent after he transitioned, but he also touches on the other side of the coin: sensitivity to scent. What we read in Liberty Wolf’s comments are references to his own sense of smell and also to that of women he knows. And as you might have guessed by now, there are sex-based differences in the human sense of smell. Read on for more insight…
Since the end of the 19th century, scientists have been studying human sensitivity to odors, partly by determining the minimum threshold of detection of certain odorants by males and females (reviewed in Doty & Cameron, 2009). Some of the early agents used in these studies included camphor, acetone, various butanols, hydrogen sulfide, safrol, eucalyptus, xylenes, octanols and the artificial musk Exatolide. I hope the subjects who participated in those studies were paid well because some of those agents are pretty darned stinky.
Nevertheless, over a century of study has shown that, on average, females have a greater sensitivity than males in detecting some (but not all) odiferous agents. This difference in odor detection between the sexes is not large and is not seen for all females, (but enough to be significant), which leads scientists to ask, why would Mother Nature bother to make a difference at all if it’s only going to be a small one? (It’s these unanswered questions that keep us scientists busy.)
Another way that females outperform males in the sense of smell department is their ability to identify the origin of certain odors, such as those coming from varnish, machine oil and even human body odor. Females were found to be better than males in reporting whether axillary (underarm) and breath odor came from a male or a female, or even whether a test body odor came from themselves, which goes back to what Liberty Wolf was talking about.
Additional sexual dimorphisms with regard to odor detection by humans have been found when studying how people rate the attributes of odors (intensity, pleasantness, coolness and warmth, irritation, familiarity). The differences between the sexes for these ratings, as for other odor assessments, depended on the odorants examined, which also included bodily scents.
The sensitivity to odors by human females appears to fluctuate with the stage of the menstrual cycle, with some correlation with body temperature noted. When taking all these data into account, scientists have assumed that sex steroids have effects on the human sense of smell, with estrogens improving and testosterone dampening odor detection.
But if females have a heightened sense of smell due to the actions of estrogen, then hormonal changes that occur during pregnancy or menopause should affect odor sensitivity as well, but the data do not support this hypothesis.
For example, pregnancy has been studied as a factor that affects the sense of smell. Although one survey showed that 2/3 of pregnant females reported an enhanced sensitivity to odors, the data were anecdotal.
Studies have not shown consistent results with regard to heightened odor sensitivity or identification during pregnancy. Similarly, hormone replacement therapy to post-menopausal females has not consistently shown effects on the sense of smell. The problem is that well-controlled, amply powered studies are lacking in both of these areas.
There are indications that there may be time-dependent events at play with regard to the actions of sex steroids on the sense of smell. Some sex-based differences may not be the result of post-pubertal hormones, evidenced by the better performance of prepubescent girls compared to prepubescent boys in several different aspects of odor perception. Before puberty, if our hypothesis holds regarding the actions of sex steroids on the sense of smell, there shouldn’t be a difference between girls and boys with regard to sensitivity to odors, but there is. What gives?
Well, it’s possible that sex steroids render some effects on the olfactory (sense of smell) system during an earlier stage, perhaps during development, some effects occur later in life (from puberty onward), and some may require the actions of sex steroids both early and later.
Steroidal hormones might be working to affect odor sensitivity in a number of different ways. Sex steroids could alter airflow through the nasal passages, change the ability of odorants to reach the olfactory receptors in the nasal passages by affecting mucus permeability or perhaps blood flow of the olfactory epithelium, or alter, either directly or indirectly, the neural activity in the brain that reads, transmits and/or receives the olfactory signals. There is some circumstantial evidence for the latter in particular neurotransmitter signaling systems.
Case in point: there are a gajillion neurons that project from the olfactory bulb of the brain into the olfactory epithelium of the sinuses. Odorant molecules bind to receptors on those neurons, which instigates transmission of odor signals to the olfactory bulb and then to other areas of the brain.
Propagation of the signals for those olfactory neurons is dependent on the neurotransmitter glutamate, and glutamatergic neural signaling is increased by the action of estradiol. Therefore, estrogen action in females might enhance the sense of smell by intensifying neural signal transmissions from the nose to the brain.
Circumstantial evidence also exists for the effects of sex steroids on another neural signaling system. The neurotransmitter γ-aminobutyric acid (GABA) reduces neuronal excitability in different regions of the brain. The levels of some GABA receptors in the olfactory bulb fluctuate with the estrous cycle in rodents, and so could have an effect on olfactory neural excitability in correlation with sex steroid fluctuations. At this point, however, the data are complicated and circumstantial, so this is highly speculative.
(All of the above was reviewed in Doty & Cameron, 2009 and the references therein.)
We can’t really have a discussion about the sense of smell and the sexes without talking about pheromones. (Well, we could, but what fun would that be?)
In the early 1900’s, a French scientist named Jean-Henri Casimir Fabre was the first to deduce the existence of pheromones by studying the mating behavior of moths. It was 51 years ago when the first chemical structure of a pheromone was determined by Adolf Friedrich Johann Butenandt (Butenandt et al., 1959), a winner of the Nobel Prize for Chemistry in 1939. (Read the history of this pheromone here.)
What Butenandt had characterized was bombykol, a chemical that the female silk moth, Bombyx mori, secretes in order to attract a male for mating. Since then, quite a number of pheromones and the responses they elicit have been investigated, and some have even ended up in things like insect traps that you can buy at the hardware store.
Originally, pheromones were typified as either releasers or primers. Now, there are four flavors of pheromones: releasers, primers, signalers and modulators (Wysoki & Preti, 2004, and references therein).
An example of a releaser pheromone is the one we’ve just learned about: bombykol. When attracting a mate, the female silk moth remains in one location and releases her pheromone. The males find her by flying in the direction of the pheromone, traveling up the concentration gradient of the chemical in the air. As a releaser pheromone, bombykol stimulates an immediate behavioral response in the target recipient, the male moth.
In mammals, one releaser pheromone that we’ve already learned about is androstenone, one of the steroids produced by male pigs (see previous blog post on this subject). When sows that are in heat detect this pheromone, they show a lordosis response, meaning that they stand to be mounted and mated by the boar. With pigs, deposition of all of the phases of the ejaculate — which can reach a liter in quantity! — can take some time, as you might imagine, so the lordosis response of the estrus sow ensures that she will stand still and be receptive to the boar. It’s an immediate, automatic reflex in the female brought on by the releaser pheromone produced by the male.
The responses to primer pheromones, on the other hand, take more time. One example would be in mice, where introducing urine from an adult male into a cage of females around the time of puberty can stimulate the endocrine systems of the females so that their estrous cycles begin. The primer pheromone in the male mouse urine affects the reproductive endocrinology of the females, which takes some time to manifest.
Then there are signaler pheromones which allow animals to recognize each other. For example, ewes (female sheep) identify their lambs by scent and reject lambs that do not smell like their own. If a newborn lamb is handled too much by humans, the scent of the lamb might be changed so that the ewe will reject it and not let it suckle. If a young lamb is orphaned or its mother does not provide enough milk, the lamb can be “grafted” onto another ewe that already has lamb by using scent transfer.
For one of several ways to do this, a large sock or stocking made of knitted cloth (like wool) with holes cut for the head and legs is placed onto the lamb belonging to the ewe that will be the foster mother. After a little while, the sock is removed from the foster mother’s lamb and placed on the “alien” lamb that will be grafted to the foster mother.
In about 85% of the cases, the foster mother ewe will accept the grafted lamb because she detects on it the odor of her own lamb. There is some debate, however, as to whether a signaler “pheromone” is responsible or simply an odor print comprised of multiple ordorants.
Whether humans have these different types of pheromones is an ongoing debate.
Modulator pheromones were described only relatively recently, and in humans (Jacob & McClintock, 2000). They are believed to affect mood or emotions, as in one study, where, after human male axillary sweat was applied to the upper lip of females, they reported to be “more relaxed” and “less tense” (Petri et al., 2003).
Signaler pheromones, similar to their actions in other mammals, are claimed to be at play when human mothers are able to recognize the scent of their newborn babies (Kaitz et al., 1987). Again, is this due to a pheromone per se or the odor signature of the babies? The debate on that question will likely continue.
With regard to releaser pheromones, there is one that has been documented in humans — babies will crawl in the direction of breast odors from their mothers (Varendi & Porter, 2001). In the animal kingdom, however, releaser pheromones are usually associated with attraction and mating, as with the moths and pigs mentioned above, but their existence in humans has yet to be proven in that type of situation, regardless of the boasts by ads in the back of certain magazines.
The best studied and documented type of pheromone in humans is the primer pheromone. Although there are conflicting reports in the literature, fairly good evidence exists that human pheromones can affect the menstrual cycles of females. Multiple studies report menstrual synchrony of females living together in group housing, such as in college dorms (Weller & Weller, 1993). Some scientists speculate that there are pheromones from a “driver female” that synchronize the cycles of the females around her (Petri et al., 1986; Stern & McClintock, 1998), but this hypothesis has had its detractors (Wilson, 1992; Whitten, 1999).
Data also exist that show the potential for pheromones to induce asynchrony in human females. Jacob and coworkers (2004) published a report stating that the odors from the breasts of lactating women induced a significant variability in the menstrual cycles of females around them who had never had children.
In addition to these female-to-female pheromonal influences , the scent of males can also have effects on female menstrual cycles (Cutler et al, 1986). In an in-depth study, Preti and coworkers (2003) found that extracts of male axillary (underarm) sweat directly influenced and altered in females the secretion patterns of luteinizing hormone, a reproductive hormone from the pituitary gland. Altering this hormone would have a direct effect on the menstrual cycle.
The actual pheromone responsible for inducing menstrual synchrony is thought to be one we’ve seen before: androstenol. Indeed, females living in a college dormitory who showed menstrual synchrony also had a more sensitive detection threshold for 3α-androstenol (Morofushi et al., 2000), and exposure of human females to this alleged pheromone has been shown to affect luteinizing hormone pulsatility (Shinohara et al., 2000).
Detection of Scents
In many animals, there are actually two anatomical systems for the detection of scent. There is the main olfactory epithelium in the nasal passages, and then there is a structure called the vomeronasal organ (VNO). It is present in many (but not all) amphibians, reptiles and mammals.
The best definition I can find on-line for the VNO is:
“A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans.”
Although the VNO is important for detecting pheromones, the main olfactory epithelium is also known to be involved. Some mammals display a characteristic behavior called the Flehmen response when detecting scents with the VNO. In ungulates, this behavior entails curling of the upper lip to draw in air over the organ, whereas felids (cats) partially open their mouths in what looks like a grimace.
The story is a little different for humans. Although we know that there are pheromones that elicit responses in humans, the data largely point to a lack of function of the human VNO (Mast & Samuelsen, 2009), which might be a good thing. Can you imagine people walking around curling their upper lip or grimacing with their tongue partially hanging out when they want to catch a whiff of pheromones from an attractive person who’s walking by?
(I should note that some scientists firmly believe that the VNO in humans is functional. Click here for one example.)
So now, when we consider how scents and odors are detected at the level of the cells in the olfactory epithelium, that’s when things get even more interesting. Young and coworkers (2008), in their paper on the olfactory receptor gene family, do such a nice job describing odor receptors, that I’m going to quote them here:
“A first step in the perception of smells is recognition of odorants by olfactory receptors, or odorant receptors (ORs). ORs are seven-transmembrane G protein-coupled receptors that are expressed in the nasal olfactory epithelium.1 ORs comprise one of the largest gene families in mammalian genomes, with ~400 apparently functional members in the human genome2,3 and ~1200 apparently functional members in mice.4,5 An exquisite yet mysterious transcriptional regulatory regime ensures that each neuron in the olfactory epithelium expresses only a single allele of a single member of the OR gene family.6–8 The axons of neurons that have chosen to express the same OR gene converge in the olfactory bulb of the brain,9 thus allowing integration of signals elicited in functionally identical neurons and highly sensitive odorant detection. It has been difficult to comprehensively determine the odorant ligands that activate each OR, but from initial studies, it is clear that a combinatorial code operates, whereby one receptor type can respond to several different odorant molecules (perhaps with varying affinities) and a single odorous compound can be recognized by a number of different receptor types.8 This combinatorial coding regime allows the detection and discrimination of far more odorant molecules than the number of distinct receptors in the genome, explaining how humans can detect thousands of odorants despite possessing only ~400 distinct functional OR genes. In this study, we investigate human genotypic variation in functional OR repertoire size. This variation could explain some of the observed phenotypic variation in our sense of smell.”
Okay, so what does all that mean in plain English?
There are specialized receptors in the cells of the olfactory epithelium in the sinuses that are docking stations for different types of odor molecules. When you catch a whiff of an onion or a rose, it’s because the odor molecules released from those odiferous items are wafting in the air and are drawn into your sinuses where they come in contact with the receptors expressed by the gajillion of neurons that are extending from the brain’s olfactory bulb into the sinuses.
Now each of those neurons expresses only one of about 400 odorant receptor (OR) genes that are in the human genome. So there will be groups of neurons that have in common the single OR gene that they express, and their axons all run back up into the olfactory bulb where they are integrated.
We know that even though there are only about 400 functional OR genes in humans, there are way more than 400 odor molecules that can be detected. If we refer back to my previous post on this subject, we know that human sweat alone contains over 30 volatile compounds. Imagine the number of odor molecules that reside in your spice cabinet, refrigerator or back yard in the springtime. There must be thousands of odor molecules all around us! How can we detect so many with only 400 odor receptors in our snouts?
Well, a single odor receptor can recognize more than one kind of odor molecule, and it’s likely that the various odor molecules that bind to a single odor receptor do so with varying affinities (i.e. strengths). Therefore, the strength of the odor-detection signal that is sent from a single neuron to the brain is dependent upon the affinity of the receptor expressed by that neuron to the different odor molecules that bind to it. In other words, an odor molecule that binds with high affinity will send a stronger signal to the brain than an odor molecule that binds with low affinity. When all those different signals at varying intensities run up the axons of the olfactory neurons to the olfactory bulb of the brain, they are integrated into discrete signals to other parts of the brain that help us to discriminate different odors.
There is added complexity in that the genetics of each person is different, so different people express different combinations of the odor receptor genes, and there are some people who can’t smell particular odors. Someone who cannot detect a particular odor is said to be “specifically anosmic” to that odor. People who cannot detect any odors have “anosmia.”
So if we go back to our discussion about the human pheromone androstenol, we know that some people can and some cannot detect the odor of this or a similar steroid, androstenone (Morofushi et al., 2000). It’s only been relatively recently that scientists identified the odor receptor that responds, at least in cells in a culture dish, to androstenone (and androstadienone; Keller et al., 2007).
This odor receptor is called OD7D4.
Keller and coworkers not only identified the human OD7D4 gene, but they also discovered that the gene comes in several genetic variants that function at different levels when bound by androstenone (Keller et al., 2007; Zhuang et al., 2009). It’s likely that the other odor receptor genes also exist in different genetic variants in humans, which would then add another layer of complexity to odor detection and signals to the brain.
What we don’t know at the moment is whether expression of odor receptor genes by olfactory neurons is regulated by sex steroids. If so, that would add another contribution to the sexual dimorphism of the sense of smell in humans and the changes in odor detection that might occur during transition of trans people.
(And in a side note – the significant difference in the quantity of functional odor receptor genes, which is lower in humans compared to other animals, explains, in part, why our sense of smell is not as sensitive as theirs.)
So going back to Liberty Wolf’s comments about the masculinization of his scent after his transition, the detection of his scent by his female friends, and his inability to detect his own scent, we now understand some of the mechanisms behind his anecdotal observations.
From the previous post on scent, we know that sex steroids affect a person’s skin biology and chemistry, and so a medical transition has the potential to change a person’s scent. From the current post, we learned that sex steroids can also affect the detection of scent, with females being, on average, more sensitive and discerning about odor detection and identification than males.
We also learned that a potential pheromone in humans, androstenol, can affect human female reproductive hormones and menstrual cycles and similar steroids are recognized by a specific odor receptor expressed in humans, and we learned from the previous post on scent that the content of 16-androstene steroids (like androstenol) in sweat has the potential to increase under the influence of transitional testosterone treatment in transmasculine folks.
What this might mean to a transitioning trans man is that his female partner could detect a change in his scent after he goes on testosterone therapy, and that change in his scent could alter the timing of her menstrual cycles.
I have heard anecdotal information to this effect from people in our community and I am looking forward to the time when scientists will confirm our anecdotal observations with solid data.
Note: As the First Event transgender conference approaches and demands more of my time, I will likely make only one more scientific post in 2010, and I am hoping to write it about polycystic ovary syndrome in trans men. In the meantime, I will continue to make narrative and commentary posts, as they don’t require the time-consuming literature research and reading.
Cutler, Preti, Krieger, Huggins, Garcia, Lawley, 1986. Human axillary secretions influence women’s menstrual cycles: the role of donor extract from men. Horm Behav 20:463-473
Doty & Cameron, 2009. Sex differences and reproductive hormone influences on human odor perception. Physiol Behav 97:213-228. (Free article)
Jacob & McClintock, 2000. Psychological state and mood effects of steroidal chemosignals inwomen and men. Horm Behav 37:57-78
Jacob, Spencer, Bullivant, Sellergren, Mennella, McClintock, 2004. Effects of breastfeeding chemosignals on the human menstrual cycle. Hum Reprod 19:422-429
Kaitz, Good, Rokem, Eidelman, 1987. Mothers’ recognition of their newborns by olfactory cues. Dev Psychobiol 20:587-591
Keller, Zhuang, Chi, Vosshall, Matsunami, 2007. Genetic variation in a human odorant receptor alters odour perception. Nature 449:468-472
Mast & Samuelsen, 2009. Human Pheromone Detection by the Vomeronasal Organ: Unnecessary for Mate Selection? Chem Senses 34: 529–531
Morofushi, Shinohara, Funabashi, Kimura, 2000. Positive relationship between menstrual synchrony and ability to smell 5α-androst-16-en-3α-ol. Chem Senses 25:407-411
Petri, Cutler, Huggins, Garcia, Lawley, 1986. Human axillary secretions influence women’s menstrucal cycles: the role of donor extracts from women. Horm Behav 20:474-482
Petri, Wysocki, Barnhart, Sondheimer, Leyden, 2003. Male axillary extracts contain pheromones that affect pulsatile secretion of luteinizing hormone and mood in women recipients. Biol Reprod 68:2107-2113
Shinohara, Morofushi, Funabashi, Mitsushima, Kimura, 2000. Effects of 5alpha-androst-16-en-3alpha-ol on the pulsatile secretion of luteinizing hormone in human females. Chem Senses 25:465-7
Stern & McClintock, 1998. Regulation of ovulation by human pheromones. Nature 392:177-179
Varendi & Porter, 2001. Breast odour as the only n=maternal stimulus elicits crawling towards the odour source. Acta Paediatr 90:372-375
Weller & Weller, 1993. Human menstrual synchrony: a critical assessment. Neurosci Biobehav Rev 17:427-439
Whitten, 1999. Pheromones and regulation of ovulation. Nature 401:232-233
Wilson, 1992. A critical review of menstrual synchrony research. Psychoneuroendocrinol 17:565-591
Wysocki & Petri, 2004. Facts, fallacies, fears, and frustrations with human pheromones. Anat Rec Part A 281A:1201-1211
Young, Endicott, Parghi, Walker, Kidd, Trask, 2008. Extensive copy-number variation of the human olfactory receptor gene family. Am J Hum Genet 83:228-242
Zhuang, Chien, Matsunami, 2009. Dynamic functional evolution of an odorant receptor for sex-steroid-derived odors in primates. PNAS 106:21247-21251
References from quote of Young et al: