On the Science of Changing Sex

Love’s Labour’s Lost

Posted in Transsexual Field Studies by Kay Brown on September 29, 2010

About fifteen years ago, in my mid-30s, my physician switched me from Premarin to the so called, “bio-identical hormones” estradiol and micronized progesterone. She told me that she had seen better results with other clients, and thought I would as well. I can personally attest, she wasn’t kidding! Even after twenty years of taking Premarin (conjugated estrogens from pregnant mare’s urine) and/or Estinyl (17α-ethynylestradiol) with intramuscular injections of medroxyprogesterone, I was still fairly flat-chested. The new ‘meds’ fixed that! While welcome, the real surprise is how much the new protocol improved my libido. As I had begun HRT in my teens, I hadn’t noticed any drop off for the first years, perhaps because I couldn’t afford surgery until I was 23? But even then, the drop off in libido had been slow, only showing a severe drop during and subsequent to a life threatening illness I suffered around my late 20’s. It had taken years to recover my health.

After I shared my observations regarding the new meds and its effect on my romantic life, my doc then told me that she had noticed a bimodal response to the new protocol. While all of her clients showed better breast development and feminizing fat redistribution, her “young transitioners” had nearly universally experienced noticeably increased libido compared to her previous protocol of using Premarin or Prempro for post-ops. However, the effect was not as strong with her “late transitioners”. She hadn’t told me to expect the possible increase in libido because she didn’t want to induce a possible placebo effect. As a primary care physician, she was more concerned with providing the best care for her clients, then for publishing, so I don’t know of any papers where this bimodal response has been noted in the literature.

There is however, a very good paper on the effect of MedroxyProgesterone Acetate in experiments with female macaques. Medroxyprogesterone Acetate (MPA) is the synthetic progestin that is in Prempro, Provera, and Depo-Provera. It’s also in a number of contraceptive pills. Female macaques, like human females, are physically capable of having sex at any time in the estrus cycle, making them ideal candidates for experiments on the effect of hormones on libido. The macaques had had their ovaries removed. This caused them to lose interest in sex. When given estradiol their libido returned. Given a combination of estradiol and MPA their libido was killed. As a side effect, the MPA also makes them more aggressive and irritable. Thus, MPA nullifies the libidinous effect of estradiol in female primates. However, given estradiol and progesterone (the “bio-identical” kind) and although there was a slight decrease in the libidinous effect of estradiol, it had no side effect of increased aggression and irritability. So, we have in the female macaque, confirmation of the improvement in libido while using the estradiol and progesterone combination over estrogen plus MPA.

Another problem with synthetic progestins like MPA is that they lack the neuroprotective effects of progesterone. Progesterone reduces neuron death from cytotoxic chemicals that naturally occur in the brain. It also encourages the healing of damaged myelin that surrounds the axons of nerves. MPA not only fails to be neuroprotective, but actively suppresses the ability of the brain to biosynthesize its own progesterone that would have served as a locally neuroprotective agent. So, taking MPA is worse than using no progestin.

So why is MPA prescribed for women? Largely because of the pharmacokinetics; Progesterone has a half-life in the body of only a few hours, requiring the patient to take it twice daily, while MPA’s half-life is on the order of two to three days, making dosing easier. Why is it prescribed for MTF transsexuals? Perhaps it is a combination of ignorance of the benefits of micronized progesterone on somatic feminization and on the general lack of differentiation by primary care physicians between AGP and HSTS transsexuals? Another possibility is that primary care physicians are focusing on reduction of free testosterone in their pre-op patients and MPA has strong anti-androgen effects.

MPA and cyproterone acetate are used in “chemical castration” protocols for certain types of paraphilic sex offenders, those with courtship disorders and pedophilia. Although ethically and legally controversial, for those paraphilic sex offenders for whom reduction of libido allows rational impulse control, the reduction of recidivism is dramatic.

In pre-op transsexuals MPA alone, or in combination with cyproterone acetate (Androcur), can significantly reduce the levels of free testosterone, reducing the masculinizing effects such as body hair, head hair loss, etc. But along with the reduction of testosterone is the expected reduction of libido. For AGP transsexuals, this reduction has often been noted by clinicians to be a welcome side effect. This is likely because it reduces the intrusiveness of uncomfortable autogynephilic ideation. It is part of the now standard “transsexual myth”, promulgated by the AGP transsexual community that concerns for “gender identity” are their motivation and that sexuality, sexual motivation, plays no part in the decision making of transsexuals to transition. For transkids, this side-effect is most unwelcome, and would only be tolerated as part of the cost of reasonable somatic feminization.

Thus, for pre-op AGP transsexuals, the best course may be to continue to use MPA, as it will help reduce unwanted testosterone and reduce unwanted autogynephilic ideation.

But for pre-op transkids, prescribing estrodiol plus micronized progesterone, possibly in conjunction with cyproterone acetate, appears to be a better choice.

It would appear that for post-op transsexuals of both types, estradiol plus progesterone appears to be the best protocol. It affords maximal somatic feminization for both types, while increasing libido for the transkids and leaving the libido low for AGP transsexual, both welcome effects for each. It would be very helpful, if researchers would report results of hormonal treatments for each of the transsexual types separately to confirm or refute this early clinically observed result.

Addendum 1/12/2019:

A recent paper looking at the risk of venous thromboembolism (blood clots) and various HRT protocols has now shown that the safest is estradiol dermal patches with no increased risk over no HRT… which the worst was Premarin and MPA combination, increasing the risk by 50%.  More reason to avoid this protocol.


Marie Kwan, Judy Van Maasdam and Julian M. Davidson, “Effects of estrogen treatment on sexual behavior in male-to-female transsexuals: Experimental and clinical observations”

Johannes F. L. M. van Kemenade, Peggy T. Cohen-Kettenis, Leo Cohen and Louis J. G. Gooren, “Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals”

Karen Pazol, Mark E. Wilson and Kim Wallen, “Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen Treatment on Social and Sexual Behavior in Female Macaques” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440328/

Michael Schumacher, Rachida Guennoun, Abdel Ghoumari, Charbel Massaad, Françoise Robert, Martine El-Etr, Yvette Akwa, Krzysztof Rajkowski and Etienne-Emile Baulieu, “Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System”

John M. W. Bradford and Anne Pawlak, “Double-blind placebo crossover study of cyproterone acetate in the treatment of the paraphilias”

Barry M. Maletzkya,Gary Field, “The biological treatment of dangerous sexual offenders: A review and preliminary report of the Oregon pilot depo-Provera program”

Vinogradova, et al., “Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases”, https://doi.org/10.1136/bmj.k4810

All The Wrong Moves

Posted in Autobiographical, Transsexual Field Studies by Kay Brown on September 24, 2010

female_scientistBack in mid-90’s, an out of town transactivist, a transwoman who had transitioned in mid-life, asked if she could visit at my home, as she was passing through. I agreed and had her over for lunch. She arrived wearing a respectably skirted suit. She passed fairly well. Nothing about her looks or manner would have told most people that she was a transsexual. However, my nine year old adopted daughter, Liz, insisted on using masculine pronouns. I was deeply embarrassed, mortified. I tried to correct her, but she angrily replied, “But he’s a man!”, with that look on her face that clearly said she thought I must be either blind or crazy. I’ve been told by many AGP transsexuals that it can be very difficult to pass around pre-pubescent children, who always seem to read them instantly.

On another occasion, late at night, I got a call from a very distraught nineteen year old, pre-transition, pre-HRT, transkid that I knew as Stacey. She had had a fight with her folks and they had locked her out of the house. I’m sure you can guess what the fight had been about. For me, it was deja vu, having had the same one with my folks when I was seventeen. I drove out to her place and took her home. She was wearing a polo shirt and pressed slacks, boy’s shoes. I put her to bed in our spare room. The next morning, Stacey had awoken early, gotten dressed in those same boy’s clothes, and went downstairs to scrounge a breakfast. My daughter had gone downstairs before I had gotten dressed. She saw Stacey for a moment and, startled by a stranger in her house, ran back to me. She asked breathlessly, “Who’s the girl in the kitchen?” I calmly replied, “Her name is Stacey…”  My daughter rejoined Stacey and consistently, unreservedly, saw her as a girl, as they happily chatted together.


Kay Brown with her adopted daughter Liz

So, my daughter saw a post-op AGP transwoman as a man, and a pre-transition, pre-hormone therapy transkid as a girl!

What was it about this polished older transwoman that led my daughter to attribute maleness to her in spite of her obviously female attire and appearance? What was it about Stacey that led my daughter to attribute femaleness to her in spite of her obviously male attire? What was it about me during my first weeks of high school that a strange boy should turn to another and ask in genuine confusion, “Is that a boy or a girl?” To which, the second boy simply shrugged.

The answer is likely sex-typed motor behaviors. Children are very aware of opposite sex typed motor behaviors starting at the age of five. That’s also the age which many of the adult sex-typed motor behaviors begin to develop. This process continues into adolescence in a progression from sitting styles, to walking, to standing, to book carry. The female sex-typed book carry style, in which one uses the crook of one’s arm and hip to support the weight is the last to develop.

Both children and adults can imitate some of the opposite sex type motor behaviors, but interestingly, not all. This is of extreme importance to passing, or rather the phenomena of being read or clocked as transsexual. It is widely understood that before transition, MTF “older transitioners” do not perform very many of the female sex typed behaviors naturally. But during the transition process, quickly learn to self-monitor and perform them. However, given that they can’t be continuously monitoring their behavior 24/7, they are likely to relax when they feel in safer environments. But even when fully self-monitoring, as I feel certain my lunch guest was that day, she can’t perform those female sex typed behaviors which most adult males can’t perform. Some of these sex typed motor behaviors are so visible that I personally have been able to accurately clock an AGP from the back, at up to 150 yards away!

On the other hand, transkids perform many of these female typed motor behaviors naturally. As children, before transition, they may try to monitor and suppress these very behaviors that the AGP transsexuals later have to learn to perform. Like the AGP, but in the reversed gendered sense, there are certain behaviors that they can’t control, can’t keep from performing, likely due to their feminized cerebellum. Thus, in high risk situations, such as in front of potentially aggressive boys at school, they may be taken for homosexual or even for girls. This can have negative consequences, even if overt violence is avoided. Gender atypical behavior causes most people to feel uncomfortable. This can lead to ostracism or lack of social cooperation. Thus, transkids suffer from lower grades, fewer social and job opportunities, and lower social status. After transition, these very same behaviors no longer need be monitored, so for transkids, transition is both easier and actually increases their opportunties and status.

But, for the poor AGP transsexual woman, transition often reverses her social status and opportunities, often in subtle ways that she can’t quite pin-point the cause. As one such transsexual put it to me years ago, “… before it was all smiles, now its all frowns (from strangers)”.  The problem is… even smiling is different in men and women.

Epilogue:  A year or so after the events I described above, my lovely daughter was rummaging in my things when she chanced across some photographs of me as a child, “Mommie, why are you dressed like a boy in these pictures?”


{A quick note: Yes, I’m aware that two of these authors are very trans-un-friendly. I just hold my nose when reading them.}

David H. Barlow, Joyce R. Mills, W. Stewart Agras and Debra L. Steinman, “Comparison of sex-typed motor behavior in male-to-female transsexuals and women”

Steven C. Hayes; Rosemary O. Nelson; David L. Steele; Marie E. Meeler; David H. Barlow, “The Development of the Display and Knowledge of Sex Related Motor Behavior in Children”

Steven C. Hayes, Rosemery O. Nelson, David L. Steele, Marie E. Meeler and David H. Barlow, “Instructional control of sex-related motor behavior in extremely masculine or feminine adults”

George A. Rekers, Shasta Mead Morey, “Sex-Typed Body Movements as a Function of Severity of Gender Disturbance in Boys”

Steven C. Hayes and Susan R. Leonard, “Sex-related motor behavior: Effects on social impressions and social cooperation”

Rita Rachkowski and Kevin E. O’Grady, “Client gender and sex-typed nonverbal behavior: Impact on impression formation”

Ugail, H. et al. “Is gender encoded in the smile? A computational framework for the analysis of the smile driven dynamic face for gender recognition”


Comments Off on All The Wrong Moves

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”


Comments Off on False (Scent) Trail