On the Science of Changing Sex

False (Scent) Trail

Posted in Brain Sex by Kay Brown on September 22, 2010

shrinking brainMuch has been made of a study that seemed to prove that MTF transsexuals have female brains because they respond to human sexual pheromones the same as heterosexual women do, and unlike heterosexual men. The experiment used fMRI to image neural activity in the brain while subjects were exposed to several different odorants. When exposed to androstedienone, the transsexuals brains showed a pattern similar to those of the women, and unlike the non-transsexual, heterosexual men. As controls, the researchers used several odorants that were assumed not to be human pheromones. The experimental results seem all the more powerful proof that MTF transsexuals must all have female brains, because the MTF transsexuals were all pre-HRT and all exclusively gynephilic. As I will point out later, this last point is actually the most intriguing factor of the study, but can only be understood in the full context of the history of pheromone research in mammals.

There are some very troubling aspects of the research, right from the start.

First, not everyone can smell androstedienone to the same degree. Only a small percentage of people can smell it in reasonable concentrations. Most people can’t smell it until it is very concentrated. A similar distribution is found for the ability to smell androstenone, another sometime putative human sexual pheromone. If something is important to a species, something as basic as reproductive behavior, that trait is strongly conserved. A species only loses a trait or has a range of traits, for something that is not important. Thus, the ability to sense this putative pheromone would not be found in only a small subset of a population, if it were a pheromone.

In studies that show that androstedienone has a measurable effect on the levels of cortisol in heterosexual women, it only does so when a man is present. Oops… a live, actual man has to be present? So, which is it, the androstedienone or the visual, aural, and likely tactile stimulation that a man, sitting close, taking saliva samples, is what straight women are responding to?

Most researchers that are trying to track down and prove pheromones are involved in mammalian sexual response usually point to the vomeronasal accessory olfactory system, a second “sniff” system if you will, believed by some to be specialized to detect pheromones. But in humans, the vomeronasal system is vestigial, completely non-functional !

Finally, after many years of study, the very concept of a mammalian “pheromone” is being seriously challenged. Although there can be no doubt that olfaction is an important part of mammalian conspecific (and occasionally of exspecific, e.g. skunks) communication; It is being shown that it is no more important than, and must be learned in the same manner as, visual and aural communications.  Further, the theory of how odorants are detected and identified is in flux, and that in mammals, it may not be possible to uniquely identify a specific molecule from another of similar properties.

But first, we must explore the nature of mammalian olfaction, and our current as well as historic understanding of how it operates and then examine how pheromones might operate to effect human behavior.

When odorant molecules are inhaled, sniffed, into the nasal passages, chemosensory neurons lining the roof respond to their presence. These neurons connect to special processing centers, glomeruli just on the other side of the skull bones, in the olfactory bulbs, before they are sent to the brain. In the popular imagination, because the connection from these centers to the brain is to various so called “primitive” areas, including the amygdala, known to process emotional states, it is thought that olfaction provides a direct path, around our higher cognitive processing, able to effect emotions and sexual arousal directly, perhaps without any conscious knowledge of the odorant.

Historically, there are two primary theories about how olfaction transduction takes place. In one theory, based on the observation that the odor of a chemical highly correlates with the infrared absorption spectra of that chemical, is that there is a mechanism for detecting the molecular vibrations, which cause the absorption of infrared light, of the odorant. This seemed improbable to many biologists in the mid-20th Century, as they couldn’t imagine biologically based micro-infrared-spectroscopes hiding away in the nose. The other theory was that the shape of the odorant molecule fit “lock and key” style into another molecule on the surface of the neurons. Given that this mechanism is known to be correct for the operation of inter-neuron communications using neurotransmitters in the synapses, as well as how hormones are detected by cells of all types, the shape theory of olfaction seemed more likely and was accepted as being “true”, even though it had not been shown to be.

However, recently the vibrational theory has been gaining ground because it not only is better able to predict the odor of a given chemical, but we now have a plausible biological mechanism whereby quantum mechanical effects at the molecular level can give rise to the ability to detect molecular vibrations.

Wikipedia has excellent overviews on these two theories and the current state of flux in this scientific mystery.



Now, take a moment to view this video of Luca Turin, the modern proponent of the vibration theory:


{On a personal note:  I would dearly love to get know Mr. Turin, having read his book on olfaction and his blog regarding purfumes, which I adore.  Oh, and if you’re interested, my personal scent is Mariella Burani.}

Now we come to the historically coincidental development of the shape theory of olfaction and the recognition of chemical signaling in social insects and many other arthropods. Given that hormones are detected by their shape, and that odors were thought to be detected in the same manner, it would seem reasonable to consider external chemical signaling molecules to have developed as an evolutionary extension of the internal chemical signaling molecules. Given that it was thought that olfaction was a process of “lock&key” matching, it was thought that specific receptors for pheromones would have evolved that would selectively respond only to the pheromone, so that other odorants would not be confused for the pheromone.  If mammals were to evolve external chemical signaling molecules, it would seem most likely that they would be odoriferous metabolites of hormones.

Thus, researchers began to examine such odoriferous molecules or sometimes natural odors produced by test subjects, both experimental lab animals and in humans. And lo… many examples of odors being used as chemical signals were found. Clearly, many mammals have scent producing glands that are used to mark territory. But is this an example of a “pheromone”, an “external hormone” that effects members of that same species in a specific and unambiguously instinctive way? Or is this in the same category of signaling as bird song, wolf howls, and dog barks? And what are we to make of a skunk? Clearly the skunk produces an odorant that sends a very strong signal. But are we to suggest that the all of the mammals of the world evolved to understand a skunk pheromone? The very concept of what a pheromone is becomes critically important.

Finally, what about sexual pheromones that signal in an unambiguous way the sex of an individual in such a way as to deeply, instinctively, effect the behavior of another animal? In arthropods, we have many such odorants, the most famous of which is the one used by the Silk Moth female to lay down a scent trail for male Silk Moths to follow. Are there chemicals emitted by one or both sexes in mammals, and most especially, in humans, that has this effect?

Richard Doty in his recent book, The Great Pheromone Myth, explores all of the scientific papers published to date, and systemically demonstrates that each and every time that such a molecule has been held up to be such a pheromone in mammals, careful study to replicate the effect has failed. Each and every time, it has been discovered that either the experiment, or the analysis, was flawed. Many experiments seemed to show an effect, but when studied more closely, it turned out that it was a learned association between the odorant and the target sex. For example, in mice, the smell of male urine effects the behavior of female mice; But only if that female mouse has previously learned that male mice urine has that smell. Female mice raised in isolation, never having encountered a male mouse, are not effected.

This last is the reason that only gynephilic transsexuals were included in the study of the effect of androstedienone. It was in the vain hope that such transsexuals hadn’t associated the smell with sexual encounters with their preferred erotic target, as would be the case for androphilic transsexuals. (On a personal note, I will admit I like the smell of my husband’s skin.)  But wait, that can’t be correct, as humans aren’t lab animals, raised in isolation. Not only have these transsexuals been exposed to men in general, but they have been continuously exposed to that odorant on themselves!

One would be tempted to attribute the results of the transsexual fMRI study as being consequent on the autogynephilic nature of the subjects, perhaps an association with autoerotic AGP arousal, but it’s far more likely that the results are from a flawed experiment, the failure of the double blind, where both the experimenters and the subjects knew that this was about pheromones, and that these straight women and MTF transsexuals knew that something that smelled “musky” was the “male pheromone”, and that they should be reacting sexually to it, while the straight men knew they shouldn’t. Even if it was not deliberate, the expectation that it would happen would ensure that it did.

For more essays on trans-brains see Brain Sex.

Additional Reading on the Web:




H. Berglund, P. Lindström, C. Dhejne-Helmy, I. Savic, “Male-to-Female Transsexuals Show Sex-Atypical Hypothalamus Activation When Smelling Odorous Steroids”

Lundström, Johan N. (Uppsala University, Department of Psychology)
Ph.D. Thesis:Human Pheromones: Psychological and Neurological Modulation of a Putative Human Pheromone

Doty, Richard L., The Great Pheromone Myth, The Johns Hopkins University Press | 2010 | ISBN: 080189347X

Antti Knaapila, Hely Tuorila, Eero Vuoksimaa, Kaisu Keskitalo-Vuokko, ichard J. Rose, Jaakko Kaprio, Karri Silventoinen, “Pleasantness of the Odor of Androstenone as a Function of Sexual Intercourse Experience in Women and Men”


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The Incredable Shrinking Brain…

Posted in Brain Sex by Kay Brown on February 28, 2010

As I’ve noted before, the brain responds to sex hormones.  Androgens tend to cause the brain to grow larger.  It appears that the absence of androgens in males, allows the brain size to shrink to closer to female norms over time.  In fact, such changes can occur quite rapidly.  Significant changes occur in the volume of the hypothalamus.

Lawrence has already critiqued two earlier studies of sexually dimorphic brain structure in (or near, depending on definition) the hypothalamus, in which she questions the author’s assertion that the BSTc is sexually dimophic and is an organizational effect (“locked in” during development) and is sex-reversed in transsexuals.  Lawrence argues strongly that this could not possibly be an organizational effect, since the BSTc is not sexually dimorphic until adulthood.  These studies were conducted in connection to a group of subjects from the Nederlands, with a common author, Dick Swaab.  Here I would like to explore a more recent study involving the very same subjects, joined by a few additional subjects, of another area, the hypothalamic uncinate nucleus, which is known to be sexually dimorphic.  Again, Swaab and his co-author claim this is not only sex reversed, but is again, to some degree, an organizational effect.  I question this conclusion, based on an analysis of their data.

Interestingly, the authors seem to have responded to Lawrence’s criticism regarding including only “Non-Homosexual” transsexuals in their study, in that in this third paper, they include categorization of the subjects into Blanchard’s two groups, “Homosexual” and “Non-Homosexual”.  All of the subjects that were in the earlier two studies are now either clearly identified as “Non-Homosexual” or “Not known”.  Only one new subject is identified as “Homosexual”.  As Lawrence notes, we can infer the likelihood of the not knowns as being “Non-Homosexual” based on the age at which they transitioned, as indicated by when they began HRT.  The youngest “Not known” is 36.  This strongly suggests that they are all “Non-Homosexual”.

The authors also categorized the subjects by “GID type: onset“.  For the life of me, I can’t imagine what meaning this has, as they list a subject who began treatment at age 64 as “early”, and even one who never sought any treatment at all, who died at age 84, as “early”.  I suspect this is a reference to self-reported awareness of their gender dysphoria.

This study uses a group of men who were castrated as part of treating prostate cancer as controls for reduction in circulating androgens, which is a better control group than the previous studies used.

If we accept, uncritically, the analysis of the authors, there appears to be a significant difference between the castrated men and the MTF transsexuals, while at the same time, no difference between the MTF transsexuals and natal females.  However, there is a catch, a BIG CATCH !

When one is studying these anatomic details of the brain, we are not simply slicing and dicing the brain and recording how big a clearly differentiable nodule of the brain is.  Actually, these parts of the brain are largely indistinguishable to the casual observer.  In order to even see these structures, one applies various stains to the thin slices of neural tissue where one hopes to find the structure in question.  These first slices are done literally blind, based on the distances from anatomic landmarks from maps of the “average” human brain.  Sometimes, they miss!  (It’s only about the size of a grain of sand.)  And sometimes, the stains don’t “take”.  And even when the stains do take, the boundaries between the clump of nerves of interest, and the surrounding nerves are often very, very fuzzy!  It takes an experienced bio-technician, working very carefully, to trace the boundary using computer software of photos of the region in question.  To get an idea of how difficult this can be, please examine the photos included in the paper.  Honestly, can you clearly tell where the borders are?  I sure can’t.

So, here’s the catch… Swaab and his co-author have chosen to include those subjects where they couldn’t identify the nucleus in question.  They give the numerical volume of the missing nucleus as “zero”.  This is akin to a school teacher misplacing a pupil’s exam paper and giving that student a score of “zero”!  An assertive student would then argue that they could also be given a score of 100%, given that the teacher can’t prove that they got any of them wrong.  Giving a missing data point a numeric value is very questionable.

Why do I argue that this is questionable?

Note that this makes several of the data groups bimodal, with a cluster at some non-zero value, and a cluster at zero, for each group that had such missing data.  This skews the mean downward.  The authors argue this is an acceptable analysis, noting that the MTF and natal female groups have approximately the same number of subjects in which they couldn’t identify the nucleus.  However, note that one of the control males also had no identifiable nucleus.  Are we to accept that such a bimodal distribution is real?  I don’t.

So, if we throw out these null results, given that we can’t reasonably give them a numerical volumetric value, is there still a significant difference between the groups?  Once again, we note that there is no difference between the MTF and natal female data.  But now, there is also no difference between these two groups and those men who were castrated!

Simply put, the data clearly shows that though the hypothalamic uncinate nucleus of the average MTF transsexual is the same as natal female, after years of HRT, so is that of castrated non-transsexual men.  Thus, the data clearly shows that this is purely an activational effect, and in no way gives us any clues as to the etiology of MTF transsexuals.

Addenda 3/2/2010

If the size of the INAH3 is an activational effect of the absence of androgens in the MTF transsexuals, it would follow that the time spent on HRT might correlate with the size.  It was always possible that it happens too fast to be in the useful time window of this data set, but I plotted the data anyway, just to see what would happen.  Interestingly it looks like the shrinkage of the INAH3 takes on the order of years, as suggested by this graph:

For more essays on trans-brains see Brain Sex.


Hulshoff Pol, H. E., Cohen-Kettenis, P. T., Van Haren, N. E., Peper, J. S., Brans, R. G., Cahn, W., et al. (2006). Changing your sex changes your brain: Influences of testosterone and estrogen on adult human brain structure. European Journal of Endocrinology, 155(Suppl. 1), S107-S114.

Garcia-Falgueras A, Swaab DF. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain. 2008


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This is your brain; This is your brain on hormones…

Posted in Brain Sex by Kay Brown on February 19, 2010

shrinking brainYour brain is like a muscle:  Use it or lose it… and it responds to sex hormones, which are really “growth hormones”, but with specific areas of the body that are targets for sexually dimorphic development.

In exploring the possibility that transsexuals may have a “brain sex” that is similar to their preferred gender identity, we are also stepping into the realm of gender politics in general.  What is the difference between men and women?  Is there a significant difference between them?  Once upon a time, in pre-feminist days, the early 19th Century, scientists supported the then prevailing view that women’s’ minds were inferior to men.  Proof of such was found in the measurable fact that women have, on average, smaller brains than men.  Of course, women also, on average, are both shorter and weigh less, so really, was this difference in brain size a significant one?  Then, came a more unbiased age (relatively speaking) in which it was shown that women and men have similar mental abilities, similar intelligence, and most importantly, similar potential for intellectual achievement.  Thus, came an age where to suggest that men and womens’ brains might differ in significant ways, was academically unpopular.  But nagging differences were still found… in animals.

In animal research, one could side step sexual politics, as well as ethical problems of experimenting on humans.  In animals, in the early to mid-20th Century, it was found that sex hormones, were responsible for brain changes during critical periods in development which led to sexually dimorphic behaviors in adulthood, especially those related to sexual behavior, sexual preference, and rearing of young.  One could castrate a young male rat and that rat would fail to behave in the typical masculine fashion as an adult.  Similarly, one could inject a young female rat with testosterone, and that female rat would later mount other female rats as an adult.  Dissection of these rats showed that certain regions of their brains showed sexually dimorphic structures that were changed to be more like the opposite sex to the presence or lack of testosterone.  Since these behaviors are similar in nature to behaviors found in humans this led to the belief that these changes should be present in human brains as well,  and that humans should have sexually dimorphic brain structures as well.  In the beginning of the research into possible sexually dimorphic brain structures, it was thought that there were be only a few areas involved.  But, as techniques for brain research improved, it was found that more and more areas were involved.  Eventually, it became standard practice to consider each part of the brain sexually dimorphic until proven otherwise!

From the early work, it was recognized that some areas of the brain must be sexually dimorphic from early in embryonic development, while others only become sexually dimorphic later.  It has been found that some effects are ‘locked-in’ by exposure to sex hormones at different times in development.  There are associated behavioral consequences to these locked in changes.  These are referred to as “organizational effects” of the sex hormones.  Other effects were found to occur later, and even be reversible, for example, testosterone will increase both libido and aggressive behaviors, and even improve one’s spatial navigation and mental object rotation skills, while estrogen will increase verbal language skills.  But, stop taking these hormones, and the effects will reverse back to previous levels.  These kinds of effects are called “activation effects”.  Both of these kinds of effects involve changes in both relative size, morphology, and density of neural connections in different areas of the brain.  It turns out, that using cross-sex hormones, even in adulthood, really does make one’s brain look more like the other sex!

Much is made of the research on the sexually dimorphic brain differences between transsexuals and non-transsexuals by transsexuals who find comfort in them and believe that they “prove” that they in fact have the neurological organization of their preferred target sex (gender identity).  But what is this evidence and how significant is it?  Further, are these observed differences from early exposure to anomalous sex hormones (or differences in receptor density or sensitivity, which has the same effect) or are they the result of later, exogenous hormones, from Hormone Replacement Therapy (HRT)?

The most well-known study by Zhou, et. al.  involved a very small number of subjects.  The team specifically searched for areas of the brain that were sexually dimorphic but were not known to also be associated with sexual orientation.  This is potentially most of the brain!  They were specifically looking for an area of the brain which would provide a unitary theory of transsexuality, an area of the brain which would be effected in the same way in both HSTS and AGP transsexuals and thought that they had found it in the BSTc.  The study failed in two ways, first, they failed to include any HSTS subjects, mistakenly using self-reports of sexual orientation, they were all in fact AGP; second, the BSTc turns out to be sexually dimorphic only in adulthood.  That is to say, that this area is very plastic, responding to sex hormones, the sexually dimorphic structure being an “activation effect”, casting serious doubt on the value of the entire study.  Anne Lawrence has a very well thorough discussion of this study, which you may want to read:


For more essays on trans-brains see Brain Sex.


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