There’s No Such Thing as Feeling Like a Girl or Boy
Jamie Shupe made history when they become the first legally non-binary person in the United States. In this post, Jamie shares their story of creating an extensive web-based archive of media stories on trans issues. The research Jamie conducted for this archive contributed to them desisting from identifying as a transwoman and coming to feel strongly that transitioning children and young people is wrong.
This website is very grateful for Jamie sharing their story. The opinions expressed in the story are theirs. The bloggers at this website agree with Jamie that we ought to be offering children alternative, safe, healthy ways of expressing gender variance. Creating a culturally-sanctioned way to do this without resorting to medical intervention is one way to make room for this, as Jamie has done. Unfortunately, there appears to be a trend toward medicalization of non-binary identities, which we do not support.
As the first person in the United States to have their sex legally declared as non-binary by an Oregon court last year, I’ve had a lot of media coverage for that accomplishment. But what’s been essentially missing from that coverage has been the potential implications that my court ruling can have on the future of transgender children. I had high hopes that I would be able to use the platform that my court victory has brought me to effect real change for these kids. That’s what they need, societal change. They don’t need surgical procedures. They don’t need cross-sex hormones. And they certainly don’t need to be sterilized because of their gender nonconformities. These trans and gender nonconforming kids most need to be able to safely and successfully express their gender and uniqueness. That’s what I needed as a child and what I still need as a 53-year-old adult.
My ultimate hope is that because of what I’ve done to the gender binary and how we see it in the future, this massive shift in thinking that I’ve helped to unleash is going to put the unsavory people that have been cutting on or sterilizing these children out of business. If we properly enact social change, the need for their medicalized services will all but cease to exist. In reality however, these charlatans deserve to be fired at best and jailed at worst. Security literally needs to show up with a box, watch as they empty out their desks, and escort them out of the buildings that are our major medical centers here in America.
But sadly, my hopes for massive change in the way we have been treating these trans kids have been dashed. Despite having had numerous open and frank discussions about transgender children with plenty of journalists to date, my concerns heard about sterilization and misguided medical practices being carried out on these trans kids haven’t been heard. By the time these articles make it into print, the views that I have expressed for a better, different, and less medicalized future for these youth are all conspicuously absent. I want my narrative corrected. I want my views heard.
After all of these repeated incidents of essentially being silenced, I’ve come to the realization that I’ve been no-platformed from speaking on the subject of transgender kids. And this is despite having a vast amount of knowledge to share. Knowledge that’s been previously and formallyrecognized.
I do however understand that my dilemma of being silenced is rather common nowadays. In fact, it has become rather routine, even at formerly great institutions likeBerkeley.
This is undoubtedly because my views about transgenderism and the medical practices being employed on transgender children run contrary to the media’s desired narrative on these subjects. Most media outlets have become entrenched in either affirming gender and medicalizing transgenderism, or labeling it as illness. Infomercials for surgical clinics get passed off as news in this twisted new world of ours.
“And I still don’t get the cutting, and I’m a little bothered by it. It doesn’t seem like the kind of thing a happy person does. But what do I know. Maybe I should try it.”
Common sense would dictate that someone like me would make a good role model for trans kids. I’m a decorated army retiree that survived “Don’t Ask, Don’t Tell” in a dress, as a male. I survived having a mother who used to slap me and call me a sissy for being girly. I’ve never tried to commit suicide. I don’t have any scars on my arms fromcuttingonmyself. I’ve never stood in the bathroom with a pair of nail clippers trying to make my parents think I was going cut my penis off to get what I wanted.
But instead of me, the surgeryqueens get the job of role model. The surgery queens aren’t proper role models for these trans children. They’re what they get to see at the circus. The surgery queens are the advertisements for the Porsche driving surgeons that are cutting penises off.
I reside in the camp that labels all of this nuttiness as craziness and loudly call it that, instead of passing it off as liberal medicine. But that doesn’t make me a conservative any more than hormones made me a woman. I’m otherwise still very much a bleeding-heart liberal, which leaves me in a rather awkward space. I don’t have a platform to stand on.
But for the record: I’m flat-out against sterilizing trans kids for the purposes of stopping discrimination or making them more cosmetically appealing in a sex classification that’s false. It’s legal fiction. It’s medical fiction. And it hasn’t helped them. It didn’t help me. They are just younger versions of me.
So even though I’m not any sort of professional writer (I actually struggle with the task to be honest), because I’ve been no-platformed and silenced on the issue of transgender children, I’m now going to write and share my views, share what I’ve learned, and share some of what I’ve observed myself. I refuse to be silenced. And this issue is far too important for me as a transgender person myself to stand by and witness the harm that’s being done to my very own people. I want my fame used to drain the swamp outside the gender clinics.
When I make the claim of having considerableknowledge on the subject of transgender kids and transgender people in general, I base that statement on several things. I am a transgender person that has suffered my entire life from gender dysphoria. I actually legally transitioned from male to female and lived as a female (whatever that means) for three and a half years. I have been treated with HRT (Hormone Replacement Therapy) for over four years. I’ve been injected, with the same GnHR drugs being used on these trans kids for six months.
In fact, I still take HRT. At this point I’m in it for the experiment to see if it actually ever does make any noticeable changes for me. To date, very little has happened and I’ve suffered a lot of health complications and lifestyle challenges as side-effects of the treatment. I took naked photos before I started back in 2013. I hope I live long enough to take more pictures for my 2023 anniversary. I’m going to take more photos and show off the non-existent changes for everyone. I may even post them on the Internet. All I’ve got to date is two widely spaced little breasts and a dude’s body. That’s where I’m at four years later in this madness. The rest of me is still intact.
Based on my negative experiences with these hormones and anti-androgen medications, I’m of the opinion that we really need to consider the problems with these drugs before we set these transgender kids up for a lifetime of dependence on them. Because of the health effects and the treatment outcomes I’ve experienced, I’ve concluded that these children are better served by working to change society’s rigid gender norms rather than medically changing these kids to fit in. The kids are being medically “normalized.” But who gets to decide what’s normal?
Large numbers of children are now rejecting their birth sex. We need to ask why this is happening. I believe I know the answer to that question, because I have felt the same pressures that these kids have. My age doesn’t make me any different than them. I share their common problems because I am also a gender variant.
This is a difficult thing to admit because of the ridiculousness of it, but I legally transitioned from male-to-female because I lacked permission in this society to be a feminine male. But I also didn’t want to be a male because there’s not much about what it means to be a male that I have any desire to claim as my own. I don’t want to dress like an Amish guy to be accepted. I want to look like George Washington in some stockings and a powdered wig. I think I’m as unique as my DNA and demand to have that uniqueness recognized. You’d use it to recognize me if I committed a crime. I don’t and won’t agree to lumping me in with every other male. I think it’s as ridiculous as calling a Chihuahua and a Great Dane the same thing.
The tragedy is that I had to become a female to be allowed to be feminine. Changing my sex was my license to do that. I’ve struggled to cope in this world as a gender variant adult: how do we expect them to cope as children?
You might find this startling confession about why I transitioned tough to swallow, but the fact is I could have been put out of the military and denied retirement pay for all the years I served simply for the offense of wearing women’s clothing. That’s how far down the rabbit hole this nation is in regards to rigid gender norms and sex stereotypes. Potentially or actuallylosingyourcareer and getting some sort of negative discharge from the military for wearing women’s clothing while being labeled as a male is a pretty stiff penalty in relation to the offense. And it gave me a lot of mental trauma from which I still suffer. The military shrinks described me as having “psychic toughness,” but still no role-model job for me because I won’t cut my penis off.
Admitting my weaknesses, critically analyzing myself and my past behavior as a transgender person is a tough thing to do, but I’m willing to do just that if it can help any of these trans kids or give an insight so that they can hopefully have a better life than I have. Mine hasn’t been very great. I’ve got the mental scars to prove it. They aren’t from wounds I gave myself.
But one thing should be very clear in all of this: I’m not any more or any less authentic than any other trans person. I say that because I fully expect those accusations to come my way as a result of writing this. All of us began life as unremarkable males or females. The problem is what society has done to us along the way, because of who we are. The scientific answers are still in dispute. Which is why it’s way too early in the discovery period to have the scalpels out and to be performing genital lobotomies.
The next thing I have to confess to is that I put the cart before the horse in transitioning. I quickly transitioned from male to female before I even gave myself a chance to understand why I felt the things I did. I was convinced that I actually felt like a girl. I’ve spent most of my life secretly believing that. I really believed that I felt like a girl. And I further believed that this made me a female. As someone who by any measure is quite intelligent, this is a hard thing to admit, but it’s true.
It wasn’t until after I transitioned that I settled down and began to study myself, my situation, and the transgender community itself. The barriers to transition are far too minimal due to activism. People and institutions have essentially been bullied or shamed into accepting us, and letting us have our way with things, regardless of whether those things are healthy for us or not. I readily admit to getting sucked in hook, line, and sinker into all things transgenderism and was convinced that I could actually change my sex.
“Where are you getting your information from, huh?” Kristie asks.
“I’m dead serious!” Joe says. “I looked on YouTube!”
I’m guilty of hangingout in the same places that these transgender kids do, places such as YouTube and Reddit. And I did so because like-minded people there affirmed me and my beliefs about myself. I thought I was a female and everyone else in the support groups I attended agreed. We were telling each other what we wanted to hear and silencing or attacking anyone who disagreed with us.
Former peers, please keep that in mind that if you decide to attack me in the future, because at one point in this all of you agreed that I was the same thing as you are.
I also readily admit to seeing the damage that my actions and the actions of the other male-to-female transsexuals have caused to the women that were actually born as females.
I wish right now that the doctors who are pausing puberty would instead pause for a moment and take a look at the chaos resulting from the mess they’ve created. It’s harming women. The ones that are real women. Trans men have yet to harm men. Testosterone injections have been around for decades and there’s still no trans guy in the NFL. All it’s good for is soldiers in the bathroom war. “See, I have facial hair, that makes me a man! Women you should be scared.” Women aren’t scared of trans men, I’ve asked them. They’re scared of penises or people that used to have penises. That’s why we don’t have a peace agreement for the bathroom war yet with the conservatives.
Transitioning people from male- to- female or from female- to-male hasn’t broken down the patriarchy, increased equality for the LGBTQ community, or done anything at all to break down the rigid gender norms that caused me to transition to begin with. Transitioning hasn’t even helped most of the people who transitioned. Most of them are now worse off. If anything, the process of transitioning people to a sex that’s opposite of their birth sex has just caused more problems and worsened the discrimination problems. A 41% completed or attempted suicide rate isn’t a sign of success. Those numbers haven’t gotten better because people transitioned and trans health care was invented.
Which leads me to question, why we are transitioning people to begin with?
Despite how hard I’ve looked, I’ve yet to uncover any evidence that shows how transitioning females-to-males has hurt men or the patriarchy. But there’s ample evidence that transitioning males-to-females has severely harmed women. I struggle to understand how all parties involved in the transition process can’t see this.
When I say that I settled down and began to study my situation as a transgender person and my community what that means is I put up a website and began to do news aggregation on the topic of transgenderism. I’m retired. I have Complex PTSD from my lifelong journey as a gender variant. And due to my narrow interests and the fact that I have nothing better to do as a retired person, I’ve spent every day of the last four years studying transgenderism through the lens of media articles. I don’t have much use for academia or it’s articles. I like to see what institutions like the Daily Mail have to say about people like me. It’s not uncommon for me to get 100 Google email alerts per day for keywords like transgender or gender dysphoria. That’s how I spend my days.
When I began the news aggregation, I thought I would be providing a useful service for the trans community. But the aggregation eventually led me in an entirely unexpected direction. I learned my way out of thinking that I was a female based on everything that I was finding in those news articles. I also saw firsthand the damage that was being done by the medical community to the transgender community. And I got a pretty shocking view into the damage that the transgender community was doing to women, most notably in sports and in the workplace.
“When you meet someone who has Asperger‘ssyndrome, you might notice two things right off. He’s just as smart as other folks, but he has more trouble with social skills. He also tends to have an obsessive focus on one topic or perform the same behaviors again and again.”
I’m convinced at this point that I’m an undiagnosed, high-functioning autistic person. I most-likely have Asperger’s Syndrome. Which is why, although I was originally indoctrinated by the transgender community tohateandattack Dr. Kenneth Zucker, I now regard him as the smartest guy in the room. I learnedmywayout of being part of the transgender mafia to protect the cause as well. I want science, not pseudoscience.
Knowing what I know now, If I was the parent of a transgender child, I would be more likely to send that kid to a therapist like Zucker than I would a monster like Dr. Norman Spack. I just wish the Dr. Zucker types wouldn’t try to get kids to live as males or females and would instead treat them like mixed-sex kids. That’s what we are. We’re the equivalent of mixed-race kids. And everybody at the gender clinics is doing the equivalent of trying to make us black or white depending on the color of our parents.
“For the last four years, Drs. Gil and Zol Kryger have averaged 100 “top surgeries” a year, each costing $6,000 to $9,000. “Bottom surgery,” constructing genitalia, is comparatively rare and far more expensive, running $75,000 to $100,000.”
Chopping breasts and penises off and building poles or digging holes and implanting puberty blockers are verylucrativecareerfields.
“Johnson is one of the top surgeons for transgender chest reconstruction in the country, performing, she believes, the most such surgeries in New England, and possibly in the Northeast.”
“She adds, “I don’t think one specific surgery defines your gender. Women have their breasts removed for cancer and they’re still female. Males require testicular surgery and are still males.”
And these are career fields where the medical establishment participants are very much aware that theyarenotactuallychanginganyone’ssex.
“So too, gender expression and a broader notion of gender identity has opened my eyes to the fact that there is really no other measure in science or nature where there are only two choices. Gender is clearly fluid and broader than male and female.”
The participants in this medical massacre are also actually very much aware that genderisreallyfluid and not fixed in the patients they are operating on.
“After performing his first gender reassignment surgery, Meltzer vowed never to do another.”
“I have no idea what I’m doing,” he remembers thinking. “I’m going to stick to the things I know.”
And these butchers even admit to notknowingwhattheyweredoing when they began to mutilate trans bodies. (Is there a difference between these folks and thedoctorwhojustgotarrested for genital mutilation?)
“Now, this is relatively rare, so I had relatively little personal experience with this. And my experience was more typical, only because I had an adolescent practice. And I saw someone age 24, genetically female, went through Harvard with three male roommates who knew the whole story, a registrar who always listed his name on course lists as a male name, and came to me after graduating, saying, “Help me. I know you know a lot of endocrinology.” And indeed, I’ve treated a lot of people who were born without gonads. This wasn’t rocket science. But I made a deal with him: “I’ll treat you if you teach me.”
The experts transing the kids further admit tolettingthepatientsthemselvestrainthem about what the patient thinks they need.
“He said in early September that offering services through pediatric care allows patients to start treatment early enough for the best cosmetic outcome, reducing chances of discrimination and allowing for better integration into society – according to the Associated Press.”
And these monsters with medical licenses or medical credentials alsoadmittoknowingly doing what they do to these trans kids under the pretense of stopping discrimination and making trans kids prettier or more handsome at the expense of making them sterile and setting them up for a lifetime of cross- sex hormones.
“This is almost more deadly than anything else I treat,” Adkins said.”
These charlatans can also be observed hypingtheneed for what they do or offer, essentially scaring the parents of transgender kids into hiring them by weaponizing the potential for suicide if treatment is not given.
“Kids do roll through a lot of things as they go through identity formation but our gender is a core part of who we are and we actually all know what our gender is and have pretty solid gender identity by the age of 3 or 4 years old,” Olson said.”
And these modern day equivalents of carnival barkers have been allowed to make allsortsofaudaciousstatements to the media with no one really questioning the validity of what’s been said. It’s all based on opinion, not science.
“She said that the therapist also gave strikingly blunt advice. “She said, ‘Your daughter already knows who she is. Now you have to decide. Do you want a happy little girl or a dead little boy?”
Everywhere the parent of a trans kid turns there’s one of these gender clinic monsters waiting in the wings toscarethem. Suicide is imminent they warn, unless these parents open their checkbooks or turn over their insurance cards to save their children.
The patients themselves also admit a lot about what’s been going on as well.
“What makes it so special for me is a love with someone who gets me on so many levels,” Kara says. “With Jacqui being trans, she gets the dysphoria I still go through sometimes.”
They attest to nothavinghad their gender dysphoria cured despite cutting their penises off and confirming their sex with the creation of a fake vagina. (Has anyone shown the insurance companies this article?)
“Instead of the vagina she had always longed for, Hunter has what she called a “fibrous lump between my legs and a colostomy bag.” Everything she read online and in an information packet, everything her surgeon told her, led her to believe the chances of complications were at best remote”
And then there’s the whispers about people beingmaimedforlife from botched genital surgeries that permeate the dark corners of the interwebz and decorate the pages of secret Facebook groups. The mainstream media largely won’t touch these stories. Doing so would be them admitting complicity in this massacre after all the surgery clinic infomercials they’ve run.
“One day I was making love and something didn’t feel right. There was this little ball of hair like a Brillo pad in my vagina.” In 1995 she went to see a surgeon who pulled the hair out but warned it would grow back. “He said it would always be there because I hadn’t had electrolysis on my scrotum before the sex change made it part of my vagina. When I heard that, I just sat and cried.”
Some of thegorydetails are just flat-out tough to read. I want to cry too.
“I fundamentally regret having had surgery. I could have lived as a woman without mutilating my body, but no one talked to me about the possibility,” she says. “I could have been enabled to live happily as a gay man. Instead I was put in this box – transsexual – simply because I did not conform to what psychiatrists think a real man should be.”
And the signsofregret are everywhere, but still the cutting, injecting, and implanting continues unabated and unchecked.
“Dr. Spack told me “They may be anxious, they may be depressed, but many, many no longer have psychiatric diagnoses after they are treated properly.”
The experts continue to boasttothemedia about the success behind what they’re doing.
“But Dr. Stathis said it was tough and some mental health problems did not go away completely.”
Other experts admit the results are lessthanperfect.
“When I die, do I get to come back as a girl?”
Magicalthinking permeates the air and is rewarded with affirmation. Children are told they are a sex completely opposite of their biology. It’s like “The Emperor’s New Clothes” and everyone is scared to tell the truth.
I’m not. Nobody’s sex has actually been changed.
“She reasoned that it was a good thing that I waited until after she was born to declare my gender identity, so that she could be born,” Oger said.”
And the children of transgender parents express gratitude for having been luckyenoughtohavebeenborn.
All of it, in all of its hideous glory is readily available to witness on the Internet with just a few keystrokes and the right keywords into a search engine. And it’s utterly mind-boggling.
“Things didn’t go quite as planned. Medical tests determined that Moore’s chromosomes were 100 percent male. But Moore’s belief that she was biologically female was so persistent and profound, doctors could not persuade her she was, in their view, inhabiting a male body.”
Getting most trans people to admit to knowing what their actual biological sex is can be difficult or evenimpossible. I fully admit to still knowing what I was the whole time in regard to my own experience, but at the same time I was forced to defend an illusion of what I had. Which is why I am very critical of any form of stealth for trans people.
As someone who had to closely guard my big trans secret in the military at all costs to prevent being discharged or punished, I fully believe that having to protect a secret of that magnitude is very damaging to someone’s mental health. I also think it can cause or contribute to PTSD from living in fear of the secret being exposed. As I’ve stated, I now have Complex PTSD, in part because of the stress of trying to protect my secret.
“In elementary school, Wyatt told classmates that he was a “girl-boy.’’ In the fourth grade, he grew his hair longer and started talking about a name change. That same year, he drew a self-portrait as a girl, and in a class essay, wrote: “Wyatt needs hair accessories, clothes, shoes . . . likes to wear bikinis, high heels, mini-skirts.’’
Initially, on the site I put the trans people I found in the media articles into simple categories such as what state or country they were from. I tracked murders. I tracked the suicides. But as the number of people and their related articles that I amassed climbed higher and higher, I began to notice some very troubling trends in the data.
It was very clear that people didn’t know at young ages that they were trans as was being claimed. This made sense to me because I also didn’t know. Like me, they repeatedly said they lacked language to describe themselves. (Does that mean they could have been led to believe that they are whatever people tell them they are?)
It was also clear that there was no shortage of desisters despite the claims by the activists that nobody ever detransitions. There was evidence of botched surgeries. There were people that had committed suicide or died because of the pressures they faced while trying to be a woman in a male body. And there was lots of evidence that people were all over the map in regards to the various identities that they claimed they were at different periods of their lives. Lesbians had transitioned to being trans men. There were trans women that were previously gay men. There was a famous trans girls whousedtothinkofthemselvesasaboy–girl.
It was shockingly clear that gender wasn’t fixed and permanent like the clinicians at the gender clinics were claiming. Which led me to ask myself the scary question of: if gender isn’t fixed and permanent, then why are the surgeons cutting on these people?
But the most worrisome thing of all that I discovered in the data was all the talk of everyone “feeling different” or “feeling different things.”
I became intrigued with what I later categorized as “self-perception.” It was a complete turning-point for me because I knew by the Janet Mock YouTube video that there was no such thing as “feeling like a girl,” because an actual female had said there wasn’t during the interview. I even asked my spouse to describe how she felt as a female. She couldn’t come up with anything to describe any sort of feeling that would capture her “feeling like a girl.” Yet here all these trans people were talking about feeling like males or females. I began to suspect that Zucker was correct and that this had to be somethingintheautismspectrum.
What they were feeling was feminine or masculine and conflating it with biology.
I can’t speak for all transgender people of course, but I am very sensitive to identity labels. That may be something that’s autism related. And I’m most definitely a fan of thetheorythattransgenderismmayultimatelybetiedtotheautismspectrum. Which is another reason that I believe that surgical interventions and puberty blocking are far too radical at this stage of what’s all still unsettled science.
When I speak of being overly sensitive to identity labels, I often give people the example of asking them how they would feel if I were to pin a sheriff’s badge on them? Would they feel pressured to enforce the law, arrest bad people, and ticket speeders? I would. You made it my job when you pinned that badge on me. I take things seriously. And when I was made into a male, that identity label came with all sorts of stereotypes and pressure that are like that sheriff’s badge. I feel pressured to be what you label me. This is another reason why it’s actually helpful and healthy for me to be non-binary instead of male. It’s a non-surgical, non-hormonal treatment for my gender dysphoria.
I am still haunted by one of the questions on the MMPI-2 test. That true or false question asks something to the effect of: “Ifeelthingsmoredeeplythanothers.”
If I were to buzz through those hundreds of MMPI-2 questions and take them at face value, then I would readily answer true to that question of “I feel things more deeply.” I do feel as if I feel things more deeply than other people. After all, I “felt like a girl,” or convinced myself that I did. But on deeper self-reflection, I perfectly understand that I can’t possibly know what it’s like to understand how others feel, because I’m not that person. I can only know what I feel. And I have no right to claim that I can understand what it’s like to feel like a girl.
I wanted to talk about what I was discovering, but there was nobody to talk about it with. So I just kept collecting the data.
The data I was compiling on the website was quickly becoming a repository of horrors. I knew that trans women were slaughtering women in various sporting events way before World Net Daily even thought about publishing something on the subject. I knew all sorts of things, but nobody wanted me to talk about all the stuff that I was discovering.
By three years into my transition, I knew medical transition was a sham because of the website data. Completely and totally fake. Nobody was actually changing sex. They were just getting sick or killing themselves trying. I was too. The person who had inspired me to transition was now stopping hormones treatments because of kidneyproblems. Other people that had previously inspired me were gettingcalledout for misrepresenting data.
I was beginning to feel just as fake as the claimed-successes of the medical treatments that were supposed to have turned me into a female. Which was a confusing subject. Was I female before or after I transitioned? Since my birth certificate had been changed to female and that my name had also been changed, did all of this now mean that I had been a female since birth? It was troubling to look back and think that it had all been done because “I felt like I was a female.”
By late 2015 it was clear that I was a desister. I’d reached the point where I felt like transgenderism and the idea that you could actually change your sex were as fake as Santa Klaus. But I wasn’t a little boy that had discovered his parents decorating the tree in the middle of the night. At this point I was 52-years-old. I had been featuredinTheNewYorkTimesasatranswoman, cheerleading the trans cause. And now I was quitting.
The big question at that point was: what exactly was I going to desist too? Because even though I now completely agreed that I wasn’t a female, I still also disagreed that I was just an unremarkable male.
At this point, a lot of things were going through my head. My newfound situation reminded of the arguments between the gender clinicians about kids in my situation. Would I now be able to go back to all of the people who had supported me in my transition and tell them that I had concluded that I wasn’t really a female? Or would I commit suicide because the difficulty and shame in reversing course was too great?
Is this internal male or female so gullible that it would be fooled by vaginoplasties and scrotoplasties, by gonadectomies and mastectomies? Is the inner man or woman such a sucker, so brainless, so dimwitted, that it would believe that these cosmetic changes constitute a real reversal of gender and thus feel any happier in its new silicone shell?
Fortunately, I had been both lucky and smart enough to not venture beyond taking hormones. I can’t tell you how thankful I am that I hadn’t gotten any surgeries. I hadn’t done so due to all the complications I’d uncovered. And while the hormone treatment results were an all-around failure on most fronts, I now had some breast growth. Oddly enough, this felt completely natural on me. In fact, I actually liked it. But I still looked like a male with the exception of having those small breasts. I was still just as much male with the breasts as the female who gets them removed is still female. Everything about my previous existence as a trans woman revolved around me constantly trickingmyselfoutofmybiology.
My experience with cross-sex hormones has been mostly a disaster. As a transfeminine person, I like the soft skin that they give me and how they help to reduce body hair growth. Other than those two things, the whole hormone experience bordered on being a train-wreck.
At one point, I’d gotten on injectable Delestrogen to see if it would help me get better changes. It didn’t. And instead I ended up with out of control hormone levels. Three months into the injections my estrogen levels tested at 2,583 on day three of the 14-day injection cycle. On day fourteen, I was still 400. My levels weren’t supposed to have been over 200. It explained why I constantly felt weak and sick. Throughout my first years of HRT, my testosterone levels repeatedly tested at zero. I’m actually supposedtohavesometestosterone.
“I just got my second 6 month shot of Eligard on Monday. I have felt an emotional swing the past two days. Started crying like a 10 year old schoolgirl a little while ago. I also have experienced a feeling of fear and being all alone. Has anyone else had these mood swings? They are new to me and I’ve been on HT for quite some time. The feeling of fear or shall I say no confidence really bothers me. My passion in life is singing. I am scheduled to sing tonight and I am scared to death. Never felt this way before.”
The six months IspenttakinggenericLupron weren’t any better. Actually, they were far worse. I quickly found that I couldn’t stop crying. And I mean literally could not stop crying. The first three months I spent on Goserelin and the second three months were spent on Eligard as the VA switched suppliers. I would have crying spells that would last for hours. I finally did an Internet search and found that what I was experiencing was a common problem with these drugs with on-label use for prostate cancer. I didn’t have prostate cancer and it was being used on me off-label, just like it is on trans kids to pause their puberty. Under the disguise of buying time to figure out what they are. It took me 52 years.
I still remember one particular morning on Lupron quite well, because I thought it was going to lead to my first-ever stay in the psych ward. I had spent the morning crying as usual without being able to stop and then took a shower. When I exited the shower and was drying off, I became overly aware of the two large implants that were in my stomach near my navel. The first one hadn’t yet disappeared like I was told it would, and now I had the second one in as well. I found myself getting psychotic and hallucinating that I was going to surgically remove the two pea-sized pellets myself so that I could stop crying. This was totally out of character for me. Nothing like that had ever happened before. When I finally calmed down, I swore that I would never get another one of these things implanted into me. It took a year for the two lumps to finally go away. I hope I never get prostate cancer and need this stuff to save me. I might just fuck it and die rather than venture back to crying like a 10-year-old schoolgirl.
As a military retiree, I had access to basically everything withintheVA’stransmilitaryHRTarsenal and I was on every bit of it at one point or another. I took Spironolactone, which made me crave salt and made my legs hurt. I used to watch trans women on this drug go to the bathroom to pee four times during a 90-minute dinner outing. I took 5mg doses of Finasteride for two years to see if it would grow my hair back and to block adrenal gland testosterone, I ended up with FinasterideSyndrome after I stopped taking it and it took a year to get my strength back. I did 9 months of Delestrogen injections before quitting and throwing the stuff in the trash. The rest of the time I took oral estrogens and the Prometrium brand of progesterone. At 6 mg doses of estrogen which were the amount recommended for me, I had chronic leg pain and swelling in my lower legs and feet. I recently returned to 2 mg doses after a trip to the emergency room for a potential blood clot. An ultrasound ruled it out and I consider myself lucky. All of this went on despite me being in relatively decent shape and walking each day for exercise. None of it made me look like a female. Whatever changes you’re supposed to get are supposed to happen in the first three years. I took the stuff for four. The extra year didn’t do it either.
The situation I now found myself in as I pondered my desistance was somewhere I had been before, but during my previous visit to this place I had only been a spectator, a reader of the story about others in this position that I now found myself in. The story referred to them as “theinbetweeners.” And now I was the latest real-life character to be joining the cast.
“”I wasn’t real good about dilating the new vagina every day,” she explained. ”I didn’t do what Preecha told me, and it kind of like collapsed on me.”
I had always thought of Walt Heyer as a nuisance to the trans community who was campaigning to save us all from ourselves, so there was certainly irony in me now joining him as a fellow “in-betweener.” But I considered myself lucky. I know Walt’s story and had it on my website. And he had far more medical intervention than I did. I actually admire how tough Walt has been in handling his situation. Desisting after having genital surgery would possibly have pushed me to commit suicide. I’m glad I didn’t test those waters. With my PTSD, I don’t have the mental and physical strength to dilate a fake vagina for the rest of my life. Itwouldprobablycollapseonme.
I’ve never confessed this to anyone before, but the first time I ever encountered the word “non-binary” was in that article about the “in-betweeners.” And that article was my inspiration to make the word non-binary a legal place to exist. Because I now needed that place as my landing zone because of desisting from living as a female.
I’m being completely honest when I tell you that I suspected going into my transition that I would ultimately flame-out and desist. This is one of the reasons I didn’t choose a typically female name when I changed mine. Instead I purposely chose a unisex name. It was another smart move that later paid off when the whole thing that was my transition came flying apart like an unbalanced, high RPM contraption.
While I may have believed I was a female because I “felt like a woman,” I was still very much grounded about what an actual female is. I’ve been married to a female for 30 years. We’ve been together even longer than that. And our two experiences as females were and are alternate realities. I got to wear the clothes and skip all the tough stuff like having a period every 28 days. I didn’t have to worry about soiling the sheets because my pad shifted in my underwear and allowed menstrual blood to leak all over the bed. I’m not the one who carried our child around for nine months, worrying if I could successfully pull off childbirth. I’m not the one who got my belly cut open to get the kid out. Or the one who breastfed that kid all hours of the day and night for the next two years.
Trans women are not these kind of women. And I wasn’t either. I don’t have enough nerve to try and claim ownership of what my spouse has experienced while actually being a woman. I don’t know what it’s like to fear getting pregnant. She’s spent most of her life worrying about it. Dr. Norman Spack and his gender clinic cronies are free to create synthetic trans kids that spout rhetoric about biology being a social construct in an effort to legitimize their identities, but I know otherwise. I know that if you want eggs, you buy a hen, not turn a rooster into one, and claim it’s a hen.
Looking back, most things involving my transition were a catastrophe. I didn’t pass as a woman, nor was I obsessed with it. I refused to wear to makeup because I didn’t think it made me a woman. I routinely clashed with other trans women over trans ideologies; I didn’t agree with medically transitioning children. I refused to get any surgeries because I knew they didn’t change your sex and were just cosmetic procedures. And despite how hard I tried to fit in, I kept finding myself more aligned with radical feminism than transgenderism.
One afternoon at a PFLAG meeting, a trans woman pressed a makeup kit into my hand, with the expectation for me to start wearing makeup. I never went back. Another evening a trans woman threatened to punch me in the face because she couldn’t get me to agree with her views on sex work. No woman has ever threatened to punch me in the face. The whole thing was just a cascading set of disasters. By the time I went to court to become non-binary, I just wanted my life back.
By this time, I had mostly cut myself off from the trans community other than online interactions. I no longer identified as a female, and just wanted to avoid any clashes over that. Beneath the surface of it all, the idea to become legally non-binary was growing like a weed. I had met people that identified as genderqueer in support group meetings, and I really liked them because they were open to discussing and debating gender. They were more grounded in biology like I was. It wasn’t the cult-like experience that the trans women’s support groups were. Genderqueer people weren’t defending ideologies to the death. The genderqueer support group was a total different experience.
Everything about the idea to become non-binary made sense. I began to realize that this is what should have been done with me all along.
Only talking about males and females is an interesting thing because IspentmonthsandmonthsintherapyatPersad in Pittsburgh at their “premiere gender clinic,” which was another disaster altogether. In five months, not a single gender counselor ever mentioned any space between male and female. They didn’t teach me about non-binary space, the desisters did.
And out of all the trans women I met in my first three years of living as a woman, none of them ever mentioned genderqueer people. Everybody pretended like no space between male and female existed.
But also looking back, I realize now that acknowledging such a space would and does invalidate their binary trans identities. Trans women and trans men have a vested interest in the gender binary, even though it’s harming them. Nothing they’re doing is destroying the patriarchy and making the world a better place for trans kids, they’re just reinforcing rigid gender norms, not breaking them down. Especially with the hyper-feminine appearance that trans women are obsessed with.
Thesearemen who now tell actual women and other trans women how to be women. It’s all pretty sickening once you venture down this smoking rabbit hole.
Trans women are like the beast Cerberus, the monstrous multi-headed dog that guards the gates of the Underworld to prevent the dead from leaving. Except they guard the patriarchy and prevent the desisters from leaving the trans community. Theyclaim all sorts of bogus bullshit (andgetcaughtatit) for the cause.
Fuckthem, I was leaving womanhood regardless. I wasn’t a woman and I was leaving town.
A lot of the trans women I had met were absolute monsters. They were just as bad as the gender clinic clinicians that were transing kids and sterilizing them so these kids could be prettier than they are. In fact, a lot of them aregenderclinicians that work in that exact industry.
“Smashing the gender binary is dangerous political provocation in today’s climate. Ignoring stereotypes that are ingrained in the American psyche is inviting failure. Demanding that passing privilege shouldn’t matter, when it clearly always has, and should have no role in marketing the community to its neighbors, is a mistake.”
The quest to become legally non-binary and desist from being a woman was interesting. Around the time I was interviewing private lawyers in early 2016 because the trans legal aid orgs had refused to helped me do it, nut–bagDanaBeyer was ranting and raving and had her panties in a wad about the dangers of smashing the gender binary on The Huffington Post.
“Wayne choked up when thanking the group for its support. He recounted young Wyatt asking him, sadly, “Daddy, why can’t boys wear dresses?’’ Wayne hated to tell his son that society wouldn’t accept that.”
I smashed the gender binary anyway. That’s what had to done to save trans kids. That’s exactly what these trans youth needed. They needunbridledgenderexpression, not meds or sterilization.
Decades of failure during which untold numbers of breasts and penises have been cut off have failed to even get these trans kids a bathroom to use at their local schoolhouse. It’s all been about passing and stealth and anybody who fails to pass because they can’t pull themselves up by their bootstraps can just commit suicide. And the trans community will blame their deaths on society. The transsexual pathway is their killer.
I knew this because of the website data. All the stories I was collecting and putting on the website showed this as clear as day. I knew most of the trans community couldn’t use a public bathroom before the trans survey results even got released. I didn’t need survey results to tell me that, I had thousands of archived news articles telling me this information. Only 21% ofthetranscommunitycanpass as the opposite sex. Transitioning, then, was all a complete and total failure.
Finding a lawyer to help me break the gender binary wasn’t an easy task either. It had it’s interesting moments as well. During an interview with a female attorney, I took my headscarf off, showing her my bald head, and asked her: “what would happen if were to go get a health club membership and go take a shower in the women’s locker room?” She freaked, telling me wouldn’t represent me if I did that. She knew I hadn’t had any surgeries and still had a penis because we’d talked about that. Her reaction just confirmed what I’d already learned about myself: I wasn’t a female. She knew it too. Eventually I found a gay man that was willing to represent me.
On June 10th of 2016, I appeared in a Portland courtroom and became the first person in the United States to legally become a sex other than male or female. I had desisted from being a woman, because I wasn’t one and never should have been made into one. When the news broke, everyone was carrying on like I was some sort of national hero in the LGBT community and the truth was I had desisted. I had just created the promised land for “the inbetweeners.” You no longer had to commit suicide after flunking out of the transsexual academy and desisting, you could just become non-binary instead. And I’d just made it legal.
There was another kind of irony as well in my court decision. Non-binary is a trans identity and I now had that legal trans identity. Trans women used to tell me I wasn’t trans enough and now I was legally trans. IwasnowanAmericanHirja. I was the “other” that trans people didn’t want to be. It’s exactly who I wanted to be. It’s exactly what I am. And exactly who they are as well, but won’t admit it. And it made perfect sense to me, because that is my world history as a trans person. Trans people have never been gender conforming people, it’s the monsters like Dr. Spack at the gender clinics that have trying to turn us into gender conforming people, and failing miserably. It’s killing us!
After my court hearing, I can still remember standing on the sidewalk in front of the Portland courthouse in a daze with tears streaming down my face and thinking “I had my life back.” I literally had my life back. My bald head hadn’t been uncovered outdoors in over three years because every time I went outside I had to pretend to be a woman. I was now totally free to express my gender anyway I chose without feeling like I was a fraud. Three women and a gay man made my court victory possible. I’m sure all of them perfectly understand how shitty the gender binary and patriarchal rule is as well.
I had come to believe from the website data that people really were killing themselves because they couldn’t handle the pressures of trying to maintain the hyper-feminine appearance that being a successful trans woman required. My Wiki site was becoming an Internet graveyard forthesedeadtranspeople. I think a lot of people were also starting to realize that I was intentionally making it one. When the new domain extensions were released, I bought up the extensions like .wiki and .news for the word transgender and I was putting those extensions to work. The site was becoming fairly highly trafficked and I was literally piling the dirt up in the proverbial front yard.
“Growing up in Glastonbury, Rader said, he didn’t know anyone who was transgender and didn’t even understand what it was until he went to a conference during his junior year in high school. But he had always known he felt like a boy and wanted to be a boy. As a child, he spurned skirts, dressed as a boy and played on a boys Little League team.”
“In ninth grade, he concluded that he was gay and began to date a girl. He thought of himself as a lesbian, but he still didn’t feel like a woman. He felt male, not simply masculine, as he put it.”
Ultimately, I had no doubt that some of the transgender community members were beginning to catch onto what I was doing with the Transgender dot Wiki website data categories. I think they not only felt like boys or girls, they also felt like I was discrediting and gutting the very foundation of transgenderism. Actually, I was. I had dead bodies everywhere. I was stacking them like military sandbags during the Korean war. Except these bodies weren’t Korean or Chinese.
Lots of things were showing up in the category data, like how most of the killings of trans women were actually related to sex work. Women don’t hold a day of remembrance for their dead prostitutes, but the trans community does; it’s an activism tool.
I could see that as clear as day by the data. I was displaying the desisters that supposedly didn’t exist. Failedsexchanges. Surgical complications that were describing neo-vaginas with Brillo pad-like furballs growing inside of them. Maimed trans women walking around in heels and wearing colostomy bags because of botched surgeries. Suicides from people who couldn’t cut it being a woman because it was too exhausting trying to remain hyper-feminine 24/7 for years at a time. Tons of people who described “feeling different” or “feelinglikegirlsorboys” and interpreting that to mean they are girls or boys. People who had come out as gay or lesbian before transitioning, which was completely blowing up Johanna Olson-Kennedy’s garbage about most of them knowing at age three what they are.
I had the fact that she’smarriedtoatransguy, who was the therapist for a 14- year-old who’d hadtheirbreastscutoff. I had Jazz’s dead name. I had thirteen families that were all claiming their trans kid was saying “God made a mistake,” when in reality it probably came fromthisbook. I had a mother telling a school Jazz’spenisfairystory and claimingherkidsaidit too so that her trans kid could get into a bathroom they didn’t belong in. I had built an online, trans encyclopedia of gender clinic horrors and I was pissing off a lot of people. And they wanted the website taken down. I had to block JennBurleton on Facebook because of the website.
“Is there anybody out there,” asked Dr. Nick Gorton, a physician and trans-man from California, addressing a room full of older transsexuals, “who would not have taken the shot if it had been offered?” No one raised a hand.”
Once you start deconstructing and untangling the web that is transgenderism you’d be amazed athowmanyoftheparticipants involved in the sterilization of other people’s transgender children are trans themselves and can be traced back to the gender clinics. They’ve made it their professions. Many trans advocates have their own biological children and go out each day to advocate for the sterilization of other people’s kids. Being trans is often their only qualification. Well, that’s my qualification too.
By the time I had surpassed and catalogued 4,000 trans people on the website, plenty of members of the trans community were openly attacking me through email and social media. I woke up Christmas morning in 2016 to find a nasty email in my inbox from a young trans man that was demanding to be removed from the website. He was in the category of “previously a lesbian.” He’s still a lesbian. He’s just a lesbian without breasts now. I blocked his email address. I blocked all of their email addresses. But they just found other avenues to harass me. I didn’t budge and I refused to make any changes to the Wiki site, or to remove anyone. It captures our failed history of trying to be something we are not. My website is our electronic history, our trans legacy, of this horrible period of time where genital lobotomies are being performed by complete quacks to stop discrimination for being a gender variant.
The whole thing got nastier and nastier and I eventually shut down my Facebook account because I was getting all sorts of harassment about the website through the messenger feature. I blocked email address, but senders kept creating new accounts and emailing me from those also, still demanding to be removed from the site. The site was claimed to be a registry for the TERFs. People were having people they thought I was friends with to ask me to get them removed. I unfriended and blocked anyone who did that. I lost a lot of friends. I refused to remove anyone or to hide anything. I wanted people to see the human carnage.
Eventually the harassment reached a point where it was so annoying that I created a page on the Wiki site called “HateMail” and started posting screenshots of the harassment I was getting from Twitter and Facebook. Which turned out to be a huge mistake because trans activist LolaPhoenix filed a DMCA (Digital Millennium Copyright Act) complaint against one of the screenshot images that exposed her harassing me with the on the Twitter message system.
Lola or whatever her real name is was doing some coalition building and trying to recruit people to harass me, but one of my friends sent me a screenshot of a private message that captured her doing it. That complaint to my webhost subsequently gotthesitesuspended for 14 days due to Federal law even though the complaint itself was invalid due to missing information such as a contact address for the person who had filed it, which was Lola Phoenix.
I in turn filed a counter-complaint, claiming ownership of the image, but that didn’t stop the website suspension. The counter-complaint required Phoenix to get a court order stating she actually owned the image within the suspension period. That of course didn’t happen. I doubt that’s even her legal name.
During the website suspension period I just went ahead and nuked the entire site. I knew activists could potentially file more DMCA complaints against it, so I figured the best strategy was to remove all images and everything quoted and to rebuild it with just the links and the categories. And that’s what I’ve been doing since. You can’t file a DMCA complaint against a link to the dirt, can you?
“Parents have told me it’s almost easier to tell others, ‘My kid was born in the wrong body,’ rather than explaining that he might be gay, which is in the back of everyone’s mind.”
So there you have it. All the juicy and gory parts of my story that the mainstream media refused to tell you because they were too scared to piss off the trans activists and the transgender community. It’s all true. I, Jamie Shupe, the first legally non-binary person in America am officially against sterilizing trans children for the sake of making them prettier and to give them better cosmetic outcomes and to stop discrimination. Just stop the fucking discrimination instead, dammit. If you doctors are pillars of the communities you live in, then why can’t you use that clout instead of your scalpels to stop the discrimination against these trans kids? Don’t operate on the kid to stop it. I know it pays well, but just don’t fucking do it. They’re going to write really bad shit about you in a few years. I’m already writing it. The gender binary is what these kids needed destroyed, not their reproductive systems. They need the ability to safely express their gender, not cross-sex hormones. They think the world that’s been created for them sucks and that’s why they’re rejecting their birth sexes. Because they can’t dress as boys or girls unless they’re made into boys and girls. Theycan’tbegay, sothey’rebeingsurgicallymadestraightinstead. They need to kept away from nutty trans women at LGBT community centers that teach them that their penis is a birth defect or teach them to say they were born in the wrong body to explain themselves. Theyneedtostopbeingbullied when they’re gay or lesbian, so they don’t have to become men instead. They need to be taught that cutting on themselves won’t get them puberty blocker and will instead land them in the psych ward. They need parents and gender clinicians to stop telling them that they are boys and girls of the opposite sex and to start telling them they are gender variance is normal.
Leelah Alcorn asked everyone to fix society before walking in front of a semi-truck. Cutting off penises and breasts is not fixing society. It’s not even medicine. It’s a little shop of horrors that’s being ran out the dark wings of America’s medical centers and the insurance companies have been hoodwinked into paying for it by a bunch of mentally ill people who have cut their penises or breasts off. It has to stop. I’ve done my part to stop it. Now the rest of you need to get busy.
So it’s all official now. Rubber stamped. Delivered by fiber optics or cellular data. Stored forever on Internet servers or until Trump destroys the world. This is my coming out as a TERF and a SWERF. I stand with the radical feminists, the conservatives, and the religious folks in their efforts to stop the mutilation of these transgender children.
Salivary gland cancers (SGCs) are a group of uncommon, heterogeneous tumors that account for 0.3% of all malignancies and 6% of head and neck cancers in the United States . The majority of SGCs are found in the parotid gland (59%–81% of cases), but they also arise in the submandibular gland (6%–21%), or in minor salivary glands (7%–22%) that populate the upper aerodigestive tract [2,3,4]. The World Health Organization classifies 24 subtypes of SGC, which show significant variation in histological and clinical features . SGC is generally treated with surgery and, in selected cases, adjuvant radiotherapy (RT) . Systemic therapy has not been adequately tested in many SGC subtypes, and cytotoxic chemotherapy has shown a limited effect in SGCs in general. As a consequence, the prognosis of recurrent or metastatic SGC can be poor [2,6,7]. However, recent studies have investigated the molecular landscape of several types of SGCs, such as adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), polymorphous low grade adenocarcinoma (PLGA), secretory carcinoma and salivary duct carcinoma (SDC), and uncovered molecular targets of interest in selected patients [8,9,10,11,12,13].
The androgen receptor (AR) is a nuclear steroid hormone receptor that is physiologically expressed at low levels in many human tissues . Its main ligands are testosterone and 5α-dihydrotestosterone (DHT). AR regulates the transcription of multiple effector genes through direct DNA binding or interaction with other transcription factors, leading to increased cell growth, differentiation, and survival . Overactive AR signaling is an important oncogenic driver in several tumor types, including prostate cancer and a subset of breast cancers [16,17]. Androgen-deprivation therapy (ADT) has been used in patients with prostate cancer since the 1940s , and has more recently gained interest in a growing number of malignancies [17,19,20,21]. ADT may be achieved by direct inhibition of AR (known as anti-androgen therapy), or by downregulating the gonadotropin-releasing hormone (GnRH) receptor signaling output, which leads to reduced serum testosterone levels (known as chemical castration). These two methods are often combined to achieve what has been termed maximum or complete androgen blockade .
2. AR Expression in SGC
Nuclear AR expression based on immunohistochemistry (IHC) is the most widely used marker of active AR signaling, and correlates with the response to ADT in prostate cancer . The prevalence of AR expression varies substantially between different subtypes of SGC (see Table 1 for a summary of published IHC data). AR overexpression is most frequently associated with salivary duct carcinomas (SDC), the majority of which are positive for AR. Several studies have shown AR immunoreactivity in 64%–77% of cases [8,24,25,26,27,28,29,30], whereas a recent large report detected AR expression in as many as 98% of SDCs . In that study, several tumors initially diagnosed as AR-negative SDCs were reclassified as other tumor entities after a second evaluation by salivary pathologists. Also, for tumors with conventional SDC morphology and a negative first AR IHC, the staining was repeated and showed AR expression the second time in several cases. This may suggest that the prevalence of AR-positive SDC was previously underestimated due to technical issues or diagnostic difficulties.
Our group recently identified AR positivity by IHC in 75% of SDCs, and RNA sequencing confirmed extremely low but detectable levels of AR mRNA in AR IHC–negative cases, all of which had typical SDC morphology at the time of pathologic re-evaluation . Interestingly, three of four AR IHC-negative cases showed AR signaling activity at levels equivalent to AR IHC-positive cases, as measured by expression of AR-regulated genes. Both AR-negative and AR-positive SDCs showed global gene expression patterns highly similar to AR-positive (also termed molecular apocrine) breast cancers. This raises the possibility that some SDCs with low levels of AR may have acquired alternative mechanisms to activate AR signaling pathways. Furthermore, the remarkable biological similarity between the two cancer types may suggest that treatment results in patients with molecular apocrine breast cancer could be of interest for the design of clinical trials in SDC.
The prognostic relevance of AR expression in SDC is difficult to assess, due to the rarity of the disease and the low number of AR-negative cases. Some investigators have identified a trend suggestive of better disease-free survival in AR-positive compared to AR-negative SDC patients [26,29], but this association has not been identified by other groups [8,24,25]. Similarly, one study detected a higher prevalence of AR expression in men than in women with SDC , a finding that has not been replicated in other reports [8,26].
In other subtypes of SGC, nuclear AR expression is found at lower rates. Adenocarcinoma, not otherwise specified (AC NOS) and acinic cell carcinoma (AcCC) are AR-positive in 26% and 15% of the cases, respectively [28,32,33,34,35]. On the other hand, only a small subset of MEC and ACC have detectable expression of AR [27,28,32,33,34,36,37], and some of these cases show weak AR expression (5%–15% stained nuclei) which may not be relevant for the biology of the tumors . Among the rare types of SGC, AR expression has been reported in PLGA and basal cell adenocarcinoma (BCAC) [28,32], whereas all published cases of myoepithelial carcinoma (MECA) have been AR-negative [28,33]. Five cases of AR-positive epithelial-myoepithelial carcinoma (EMC) were reported and suggested to represent a specific variant of the disease, denoted apocrine EMC . However, one study of six unselected EMCs did not detect AR , and the prevalence of AR expression in EMC is unknown. Given the challenging nature of salivary gland pathology, it is possible that some of these AR-positive entities in fact represent SDC.
A subset of SGCs result from the malignant transformation of a pre-existing pleomorphic adenoma (PA). PA is the most prevalent salivary gland tumor, and is typically benign and non-metastatic. Around 6% of PAs develop into different types of carcinoma, denoted carcinoma ex-PA . Whereas PAs are AR-positive in 30% of the cases, 90% of carcinoma ex-PAs express AR. This difference may suggest that AR expression is a risk factor for the malignant transformation of PAs. Alternatively, overexpression of AR may act as an oncogenic event in some carcinomas ex-PA .
3. Expression of AR Splice Variants
The full-length AR (AR-FL) gene consists of eight exons, of which exons 4–8 encode the ligand-binding domain. Expression of alternative AR isoforms lacking the ligand-binding domain (which normally serves as a binding site for anti-androgens, such as enzalutamide) is associated with ADT resistance in prostate cancer [46,47,48,49,50]. AR-V7, a constitutively active AR splice variant that includes only exons 1–3 and a cryptic exon 3, is detected in 37%–50% of SDCs (Figure 1) [8,26]. On average, AR-V7 is expressed at around 5% of AR-FL RNA levels , which is similar to the AR-V7/AR-FL ratio seen in prostate cancer . Another AR isoform, AR-V3, including only exons 1, 2 and a cryptic exon 2, is also found in SDC but at lower rates and only in male patients . AR-45, which lacks the majority of exon 1, including the N-terminal domain that mediates ligand-independent transactivation of AR , is detected in a minority of SDCs . However, the association between the alternative AR isoforms and response to ADT in SDC, and the prevalence of AR-V7, AR-V3, and AR-45 in other types of SGC, remains unknown.
4. Genetic Alterations Affecting AR Signaling
An extra copy of chromosome X, which includes the AR gene, is found in almost 40% of SDCs. This may contribute to overexpression of AR, although some of the tumors with an extra chromosome X are negative for AR in IHC . Unlike in prostate cancer, focal amplification or protein-altering somatic mutations of AR have not been found in SDC or ACC [8,9,26].
Forkhead box protein A1 (FOXA1) is a transcription factor that mediates the transcription of AR target genes by facilitating the AR/chromatin interaction . FOXA1 mutations may potentially be associated with ADT resistance in prostate cancer, although this is being actively investigated . In a recent exome sequencing study reported by our group, we identified alteration (either somatic mutations in the DNA-binding domain or high-level amplification) of FOXA1 in four of 12 AR-positive SDCs. Conversely, no FOXA1 alterations were found in four AR-negative SDCs .
Fatty acid synthase (FASN) is an enzyme that controls fatty acid synthesis and has been shown to promote the growth of prostate cancer as a result of AR signaling. Experimental studies suggest that FASN overexpression can mediate resistance to ADT in prostate cancer, although no clinical data are yet available . In our exome study of SDC, alterations (missense mutations, a frameshift insertion, and high-level amplification) of FASN were found in four of 12 AR-positive but not in AR-negative tumors .
In ACC, which rarely expresses AR, no significant genetic alterations affecting AR signaling have been detected . In other subtypes of SGC, the prevalence of AR-related genetic alterations is unknown.
5. Anti-Androgen Therapy in Patients with SGC
Several ADT drugs have been developed and tested clinically, mainly in patients with prostate cancer. Abiraterone is a CYP17A1 inhibitor which reduces circulating levels of androgen by ultimately blocking the conversion of pregnenolone to DHT. Bicalutamide and flutamide are competitive inhibitors of the AR ligand-binding domain, as is enzalutamide, which was developed more recently and has greater AR affinity compared to the earlier anti-androgens, and may inhibit AR activity via a variety of different mechanisms . Triptorelin and goserelin are GnRH agonists which eventually cause downregulation of luteinizing hormone (LH) and thereby reduced serum testosterone levels .
Inspired by results from other cancers [17,56] and functional studies showing AR-dependency in cultured SGC cells [26,57], a number of patients with AR-positive SGC have been treated with different ADT regimens (see Table 2 for a summary of reported cases). In a retrospective analysis of 17 patients with recurrent or metastatic AR-positive SGC, of which the majority had SDC or AC NOS, the overall response rate was 65%. Treatment was generally well tolerated in these patients, both men and women. However, relapse was commonly seen, leading to a three-year progression-free survival (PFS) of 12%, and a five-year overall survival of 19% . Smaller studies of AR-positive SDC patients have reported somewhat less favorable outcomes, with an overall ADT response rate of 25%–50% [8,59]. Several case reports have shown a good effect of ADT alone in patients with AR-positive SDC or AC NOS, including stable disease for several months as well as cases of complete remission [43,60,61]. A few patients with SDC or AC NOS, who initially responded to a combination of bicalutamide and triptorelin but had a relapse, then showed a response to subsequent abiraterone, suggesting resistance mediated by the reactivation of AR signaling during ADT treatment [62,63]. ADT has also been combined with either definitive RT or palliative chemotherapy with robust responses in several single case reports of SGC [64,65].
Patients with AC NOS have been found to respond well to ADT, with partial or complete response in 10 of 11 reported cases, and a median PFS of 20 months. SDC patients appear to have a lower response rate, with partial or complete response in 11 of 26 (42%) reported cases and a median PFS of eight months (Table 2).
Of note, several dramatic responses to ADT in SGC patients were published only as case reports of extraordinary responders. A recent preliminary study including all SDC patients treated with ADT in the Netherlands showed somewhat more modest results, with partial response in four (13%) cases, stable disease in 10 (32%) cases, and progressive disease in 17 (55%) cases, and a median PFS of 3.8 months . On the other hand, since the majority of SGCs are chemotherapy-resistant, the treatment options for patients with generalized disease are limited and AR is the most promising target for these patients with otherwise incurable disease. Several clinical trials are currently ongoing, investigating the efficacy of ADT in patients with recurrent/metastatic AR-positive SGC, using abiraterone, bicalutamide or enzalutamide in male and female patients (NCT02749903, NCT01969578, NCT02867852). In addition to providing valuable clinical response information, these trials will also collect tumor tissue for correlative research, facilitating further understanding of molecular determinants of response to ADT in AR-positive SGC.
AR is expressed in a majority of SDCs and in a minority of other SGCs such as AC NOS, and ADT has emerged as a promising therapy in patients with AR-positive SGC. Several potential mechanisms of resistance to ADT have been described, including the expression of AR splice variants and mutations in FOXA1 and FASN. Ongoing and future clinical trials will likely shed light on the clinical benefit and limitations of ADT in AR-positive SGC.
Martin G. Dalin was supported by Sahlgrenska University Hospital, The Swedish Medical Society, and Svensson’s Fund for Medical Research. Luc G. T. Morris was supported by NIH K08 DE024774, the Society of MSKCC, the Damon Runyon Cancer Research Foundation, and the Jayme and Peter Flowers Fund.
Manuscript concept: Martin G. Dalin, Luc G. T. Morris. Literature review: Martin G. Dalin, Philip A. Watson, Alan L. Ho, Luc G. T. Morris. Analysis of data: Martin G. Dalin, Luc G. T. Morris. Interpretation of data: Martin G. Dalin, Philip A. Watson, Alan L. Ho, Luc G. T. Morris. Graphic design: Martin G. Dalin. Preparation of manuscript: Martin G. Dalin, Philip A. Watson, Alan L. Ho, Luc G. T. Morris.
Conflicts of Interest
The authors declare no conflict of interest.
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