Thursday, December 17, 2020

What I know about Facial Masculinization Surgery

 When I wrote my essay on puberty blockers, I didn’t mention anything about facial masculinization surgery (FMS). I am unsure whether I should revise the essay to mention FMS. I can confidently recommend facial feminization surgery (FFS). FFS is not something to take lightly, I know several trans women who have gotten FFS. They have good results, without long-term complications. Conversely, I do not know any trans men who have gotten FMS. I believe this is because FMS is more novel and experimental than FFS. The cost might be prohibitive as well. Moreover, FMS is additive while FFS is subtractive. This creates additional challenges for FMS, with respect to longevity and aesthetics. Here is all I know and can advise about facial masculinization procedures. 

There are three types of facial masculinization procedures:

  • Fillers

  • Implants

  • Surgeries


In my honest opinion, I do not think FMS is a good choice for the vast majority of trans men. Fillers are only temporary, and can become addictive. Filler addiction increases the risk of serious complications, such as tissue death and blindness. Implants involve screwing foreign objects to your skull, and carry the risk of infection and/or tissue damage. There is only one surgery that can be recommended. It would only benefit patients with a certain facial structure, and it only alters the chin. It is invasive, and can go wrong.


If you are considering FMS, do read the message from the supposed "first-ever successful case of FTM facial masculinization." He was horrifically botched, and urges others to "Love yourself, give yourself a chance, know that you are worth it." Not to be corny, but I recently watched Robert Hoge's "Own Your Face" TED Talk. I would encourage you to do the same, at least once, if you are considering FMS. It is truly an inspirational talk. Own your face!


Additionally, it may not be necessary to undergo these procedures. It is not uncommon for a biological man to have an unmasculine facial structure (i.e., a smooth brow, a slim jaw, a small nose). The textural cues associated with testosterone can override the structural cues, allowing one to pass for male. Diet and exercise can also make the face appear more chiseled.


....But yeah. At the same time, I believe in the capacity for adults to make decisions for themselves. The most responsible thing for me to do is explain the benefits and risks associated with each procedure. That way, you can truly make an informed choice. I don't think you should get any facial surgery or implants before age 25. Here is more information about fillers, implants, and surgeries:


FILLERS


Example of Dermal Fillers


Fillers are only temporary, lasting a limited number of months or years. They are not very good at achieving a chiseled facial appearance. Fillers can create “fat face”, where the face looks soft and wide, not rugged. They appear most natural when used to achieve subtle changes. If you have obsessive or compulsive tendencies, beware. Fillers can become addictive. Excessive use of fillers can lead to an unnatural, bloated appearance. They also multiply the risk of serious complications (e.g., blood clots, necrosis, scarring, loss of nose/lip, blindness).


Fillers can contain the following materials:

  • Hyaluronic acid (HA)

  • Semi-permanent fillers (e.g., hydroxyapatite or PMMA bone cements) 

  • Fat graft


Hyaluronic acid (HA) is the best option for cheeks, chin, and jaw. HA is naturally produced by the body, while semi-permanent fillers are not. As a result, semi-permanent fillers carry greater risk of foreign body reactions and granuloma formation. Moreover, HA fillers are significantly more reversible than semi-permanent fillers. HA can be easily removed by dissolving it with hyaluronidase. On the other hand, semi-permanent fillers cannot be dissolved. They can require surgery to remove. Sometimes, it is impossible to completely remove semi-permanent fillers without damaging facial structures.


Dermal Filler Danger Zones


Reversibility is important for two reasons. For one, it allows you to undo an unsatisfactory cosmetic result. For two, it can save you from serious complications. Sometimes, fillers are accidentally injected into blood vessels, forming blood clots. These clots can choke off the blood supply to various parts of the face, causing disfiguring scars, necrosis, loss of parts of the face (e.g., nose, lips), or blindness. The risk of blindness increases when fillers are injected into the “dermal filler danger zones”. Two key danger zones are the glabella and the nose. Clotting in these areas can cut off blood supply to the eye(s), causing blindness. Semi-permanent fillers should only be considered for the nose. Because the nose is a danger zone, multiple filler injections increase the risk of clotting. Semi-permanent fillers can last longer than HA, thus requiring fewer injections. The nose should only receive filler injections from a cannela, in the hands of a very experienced practitioner. Filler injections to the forehead or brow are not recommended, because the glabella is a danger zone. A misplaced injection can cause blindness in one or both eyes. 


Example of Facial Fat Graft


An alternative to man-made fillers is a fat graft. A fat sample is harvested via liposuction, then injected into the face. I would advise against this. Fat grafts are more permanent than HA, and the cosmetic outcome is less predictable. If things go wrong, fat is difficult to remove. If things go wrong, they are difficult to remove. Moreover, the long-term cosmetic appearance is unknown. They could shift as the patient ages, causing an unnatural appearance that is difficult to reverse. 


IMPLANTS


Implants are more permanent than fillers. With all implants, you have to worry about foreign body reaction, anaphylaxis, infection, revisions, and aging. Contrary to popular opinion, implants are not necessarily permanent. The skull changes shape as you age. This causes implants to lose their fit and aesthetic with age. In other words, you might have to get them removed or replaced -- especially if you get them at a young age. You also have to consider infection. Cheek and chin implants are often inserted through incisions in the mouth, in order to reduce visible scarring. This increases the risk of bacterial infection, where pathogens travel through the cut in the mouth to colonize the implant. Because implants can get infected at any point in time, they can require surgical removal in one’s lifetime. Additionally, it is common for patients to seek revision after getting implants. Even with customizable implants, it can be hard to get the shape right.


Before getting implants, consider your lifestyle choices. Implants are not a good idea if you participate in combat sports and similar activities. That said, I believe that implants can be a viable option -- at least, for cheek, chin, or jawline augmentation.


Facial implants are generally made from these materials:

  • Silicone

  • Porous polyethylene (e.g., Porex, Medpor)


Silicone’s key advantage over porous polyethylene is reversibility. Silicone can be safely removed and replaced when necessary. It’s key disadvantages are aesthetics, bone resorption, and capsule formation. Similar to fillers, silicone can have a “fat face” effect. Because it is a soft material, it isn’t very good at creating a chiseled appearance. That said, well-placed silicone can create subtle but significant improvements. Bone resorption can occur when the implant is not placed or secured properly. It can also be caused by capsular formation, and inflammation. In addition to bone damage, fibrous capsules can cause an unusual lumpy appearance around the implant.



Capsule formation around silicone implant


Conversely, porous polyethylene integrates into bone more easily. This reduces the risk of bone resorption, but makes it harder to remove the implant. Additionally, the material is harder than silicone, which can create a more chiseled appearance. This trade-off makes it difficult to decide which material is superior.


There are a couple of other things that trans men should consider. The first is age. If you get implants at a younger age, it increases the likelihood that you will have to get them removed. The second is fit. Stock implants come in two styles: masculine and feminine. Masculine styles are designed to fit the faces of biological men, while feminine styles are designed to fit the faces of biological women. Would a stock masculine implant fit correctly on a trans man’s face? An improper fit could create an unusual cosmetic appearance, and increase the likelihood of bone or tissue damage. I would hope this is not an issue. If it is, you might have to opt for custom implants, which are more expensive.


Forehead and brow implants are another story. These regions can be augmented with bone cement or a pre-formed implant. I am not an expert on these techniques, but I am wary of both. For one, I have concerns about the cosmetic result. The forehead and brow play important roles in facial expression. They crease and crinkle, and get wrinkled with age. I would expect facial implants to appear unnaturally smooth -- especially on a man's face. In terms of materials, I have a handful of concerns about the use of bone cement, namely:


  • Bone/tissue damage associated with in situ polymerization

  • Foreign body reaction

  • Infection

  • Residual monomers

  • Bone cement implantation syndrome 

  • Bone damage associated with implant loosening

  • Degradation of cosmetic appearance, with age

  • Difficulty removing the implant


Bone cement contains polymethyl methacrylate (PMMA). Prior to implantation, it comes as a kit containing copolymer powder and a liquid containing methyl methacrylate (MMA) monomer. Shortly before implantation, the powder and liquid are mixed together, forming a PMMA putty. The putty is then applied to the skull, where it hardens and sets. The process of PMMA polymerization gives off heat and free radicals. These can damage the bone and surrounding tissue. As described before, the implantation can also cause foreign body reaction or infection. Furthermore, PMMA implants can break down or fail to polymerize correctly. Unpolymerized MMA is toxic to the body, and can cause severe allergic reactions. In orthopedics, PMMA is associated with bone cement implantation syndrome (BCIS). BCIS is a rare but sometimes deadly condition, characterized by heart attack, hypoxia, hypotension, and cardiac arrhythmia. I am not sure whether there is any risk of BCIS when PMMA is applied to the forehead or brow. Additionally, I am concerned about implant loosening. Polymerization-related bone/tissue damage, residual monomers, poor adherence, and immune responses can cause the implant to loosen. Loose implants can create fine, microscopic scratches on the skull. This can irritate, damage, and/or destroy the underlying bone. Moreover, the face skull volume, and the brow angle recedes with age. This can lead to an unnatural appearance and loosening of the implant. If you regret the implant, bone cement can be more difficult to remove than silicone. I am not sure if the inclusion of hydroxyapatite improves the result. Hydroxyapatite improves the biocompatibility of PMMA bone cement. However, it also increases adhesion to the bone. This could make it more difficult to remove when needed. 


Like other facial implants, pre-formed forehead/brow implants are made of silicone or porous polyethylene. As described previously, silicone forehead implants can cause tissue damage and bone resorption, while porous polyethylene is hard to remove. The forehead and brow constitute a “danger zone” that contains important blood vessels and nerves. For these reasons, I am hesitant to recommend forehead or brow implants. It is entirely possible that my fears are unjustified, I just don’t know. Above all, do not go for cheap forehead/brow augmentation. The risk of nerve damage, vascular damage, and/or disfigurement is too high.




On the subject of implants, a certain Dr. Eppley is renowned for his customizable silicone implants. I don’t know much about Dr. Eppley, but I am leery of him. Many of his clients are young incels with unrealistic expectations. They think silicone implants can achieve “chadification” / “looksmaxxing”. A responsible surgeon would explain why extreme implants do not achieve a natural, masculine appearance. Instead, he performs whatever surgery his client asks for, which can result in freakish, cartoon-like faces. 


Expectation vs. Reality



There’s another thing I found questionable. On one of his websites, Eppley describes how he “snap fit” a custom brow implant without any need for fixation. But the patient’s forehead shape is bound to change as he ages, and the silicone could cause capsule formation or inflammation. Doesn’t this pose a risk of bone resorption and/or removal of the implant? Eppley also has several negative reviews around the internet, accusing him of being a “salesman” instead of a surgeon. For all I know, he could have excellent surgical techniques. Just know that his extreme, customizable implants can have poor cosmetic results. 


SURGERIES


The final option for facial masculinization is surgery. The nose can be surgically augmented with a graft of rib cartilage. I do not know all of the risks associated with these operations. All I can offer is a word of caution about aesthetics. Being the center of the face, the nose is easy to screw up with plastic surgery. A bad nose job leaves your nose looking fake or damaged, and can throw off the entire aesthetic of your face.  A really bad botch job can obstruct breathing. Be very careful with the surgeon you select for rhinoplasty. 


The Adam’s apple can also be augmented with rib cartilage. I am leery of this operation. It was pioneered in 2017 by Dr. Deschamps-Braly. The patient he performed it on almost died, and suffers from several facial deformities. This former patient does not recommend Adam's apple augmentation -- at least, from Deschamps-Braly. 


Example of Genioplasty


Some men seek maxillofacial surgeries, as an alternative to lower face implants. These surgeries include genioplasty, bilateral sagittal split osteotomy (BSSO) and double jaw surgery (bimaxillary osteotomy). These bone-cutting surgeries are more invasive and harder to reverse than silicone implants. Genioplasty can be performed as an alternative to chin implants. Genioplasty does not have the same risk of infection that implants do. The cosmetic result depends on the patient’s facial structure. In some cases, genioplasty can have a better cosmetic result than implants. In other cases, it does not improve cosmetic appearance. On occasion, genioplasty can cause jawline deformities called “step-offs”. Minor step-offs can be corrected, but major step-offs are disfiguring. The surgery also carries risk of damage to the mental nerve, and failure of the bone plate. Nerve damage is associated with lack of sensation and pain.



Bimaxillary osteotomy


Bimaxillary osteotomy is a combination of two procedures: BSSO and Lefort I Osteotomy. BSSO involves cutting both sides of the lower jaw, while Lefort I Osteotomy involves the upper jaw. Either operation can be combined with genioplasty. Bimaxillary osteotomy and BSSO are both more serious than genioplasty. In addition to step-offs and nerve damage, these operations can impact your ability to eat, talk, and smile. They can be very disfiguring, if performed badly. I do not think you should pursue these surgeries if you don’t need them. 


SUMMARY: 


The face can be masculinized with fillers, implants, or surgeries. If you keep your expectations within reason, hyaluronic acid fillers are a safe, temporary option. Implants and surgeries are riskier. Skilled surgeons can place implants at the cheeks, chin, or jaw. Complications can occur, but I’ve seen good, long-lasting results. The only surgeries I would consider are rhinoplasty and genioplasty. I would think twice about bimaxillary osteotomy, BSSO, and brow / forehead augmentation. Be extremely careful about who you pick to perform these procedures. Avoid predatory surgeons who exploit their patients’ dysphoria for a quick buck.

Monday, December 14, 2020

The Problem With Puberty Blockers - Part 7

 CLICK HERE FOR PART 5,6: RISKS/BENEFIT ASSESSMENT

7. CONCLUSION AND FUTURE CONSIDERATIONS


On December 1st, 2020, Keira Bell won her case. The High Court outlawed the use of GnRHas in most gender dysphoric children, on the grounds that they are not competent to consent to the treatment. They deemed puberty blockers “an experimental treatment”, where:


“there is real uncertainty over the short and long-term consequences of [GnRHas] with very limited evidence as to its efficacy, or indeed quite what it is seeking to achieve.”


This was the correct decision. Despite claims to the contrary, we do not know if puberty blockers are safe. In fact, there is some evidence that they are unsafe for use. Furthermore, the claim that they are “fully reversible” is a bald-faced lie. GnRHas undoubtedly have irreversible effects, at least on cosmetic appearance. They could also have several permanent effects on long-term health. That is reason to pull them from the gender clinics. You cannot give a drug to children before establishing its safety. This is done to protect them from iatrogenic harm. The failure to establish safety has resulted in tragedies such as thalidomide, Redux, dexamethasone, and Lupron itself. Children in particular require special safeguarding, for they lack the cognitive development to give informed consent. Moreover, puberty is a critical period of somatic and reproductive development. Tampering with this critical growth period can have long-term, irreversible consequences. There is no strong evidence to support the claims that puberty blockers are “safe” and “fully reversible”. This makes their use unethical.


Keira’s case was a landmark decision. It is a sign of what’s to come. I imagine there will be several other malpractice lawsuits -- including class action lawsuits. These will ban puberty blockers across the Western world. The sooner this happens, the better. 


The following actions should be taken immediately: 

  • All clinics and practitioners should cease prescribing puberty blockers to gender dysphoric children. No new patients should receive GnRHas, until/unless they are proven safe for use.

  • Large retrospective studies should be performed on trans and detransitioned individuals who received puberty blockers. This will help assess the long-term safety of the drugs.


The retrospective studies should account for the following variables:

  • Patient’s natal sex

  • Brand name and active ingredient(s)

  • Combination with add-back therapy

  • Dosage

  • Start age of treatment

  • Duration of treatment

  • Patient’s risk factors (e.g., low baseline bone density, poor baseline body composition, history of smoking, pre-existing endocrine disorder, pre-existing mental disorders...)


This may reveal whether certain treatment conditions are safer than others.


That said, I am sympathetic to the proponents of puberty blockers. I cannot, in good conscience, agree with their position. But I see where they are coming from. There is an unmet need for a safe, effective pharmaceutical that can “pause puberty.” I recognize that a large number of gender dysphoric adolescents resort to self-medication. This is a very risky practice, but kids do it anyways because they have no other option. What can be done about this?


If you truly want to make a “puberty-blocking” drug available to gender dysphoric children, do it the right way. Establish its safety and effectiveness before administering it to human patients. The best way to do this would be official approval from the FDA. Granted, I am unsure whether a medication for gender dysphoria would ever get approved. It would be an unprecedented drug, one that treats a disease of the mind by changing the physical body. How could this treatment get approved by the FDA, when tattoos are not legal until age 18? Even if they could not get officially approved by the FDA, we can still use their protocols as a frame of reference. For the sake of argument, let’s assume that a “puberty-blocking drug” could get approved by the FDA, as a treatment for a mental disorder. There are two possible ways this could be achieved: 


  • 505(b)(1): De novo drug development

  • 505(b)(2): Drug repurposing 



De novo drug development vs. Drug repurposing[1]

This process could take longer for pediatric drugs.


Both of these processes would take at least a decade to complete, and they would be expensive. Of the two, de novo drug development would be costlier and lengthier. Drug repurposing is the more attractive option. Rather than developing an entirely new drug, a new indication is added to the label of a drug that has already been approved. The process of drug repurposing is relatively faster and less expensive than de novo drug development. Both processes culminate in clinical trials, where the drug’s safety and effectiveness is established in human patients. 21 CFR 50 Subpart D describes special requirements for pediatric clinical trials. The code only allows four different pathways for pediatric clinical trials:

§50.51 “Minimal Risk Pathway”

  • Child subjects are only exposed to “minimal risk”.

§50.53 “Low Risk Pathway”

  • Child subjects are only exposed to "a minor increase over minimal risk"

  • The study only involves activities that would be “normal” for the child subjects

  • “The intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition that is of vital importance for the understanding or amelioration of the subjects' disorder or condition”

§50.52 “Higher Risk Pathway”

  • Child subjects may be exposed to greater than “a minor increase over minimal risk”

  • Child subjects are expected to directly benefit from the study

  • “The risk is justified by the anticipated benefit to the subjects”

  • The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches”

§50.54 “Serious Problem”

  • Child subjects are exposed to greater than “a minor increase over minimal risk”

  • The study presents “an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children”

  • The clinical investigation will be conducted in accordance with sound ethical principles”


In this context,“minimal risk” is defined under 21 CFR 56.102 as: 


(i) Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered [by healthy children] in daily life or during the performance of routine physical or psychological examinations or tests.


A “minor increase over minimal risk” is defined as: 


...risk which… poses no significant threat to the child's health or well-being.”


A problem is “serious” if the consequences of exposure are serious and the likelihood of exposure is serious[2]. Consequences of exposure are only considered “serious” if they pose “a crucial obstacle to the growth and development of children”; that is, they are “life threatening, permanently disabling, debilitating, or similarly grave.” Examples include “impending epidemics” (e.g., smallpox, polio), or exposure to chemical warfare (e.g., Sarin gas, “dirty” bombs). 


§50.54 would not apply, because gender dysphoria does not constitute a “serious problem”. It would also be very difficult -- if not impossible -- to meet the “minimal risk” requirement for §50.51. The only pathways left are §50.53 and §50.52. §50.53 can only be met if you can establish that the drug poses “no significant threat to the child’s health or well-being.” §50.52 can only be met if the direct benefits of the drug outweigh the risks. Furthermore, the risk/benefit assessment of the drug in question must be “at least as favorable” as that of alternative treatments. This includes the alternative of “watchful waiting”; that is, no medical interventions before adulthood. 


Additional conditions must be met. First, the treatment must not render children irreversibly infertile. If this cannot be done, don’t proceed further. Second, the treatment must not be administered to children with insufficient cognitive development. The original Dutch protocol set the minimum age to 12 years. Depending on your interpretation, the UK High Court set it to 14 or 16 years. Third, the treatment must be administered under a gatekept system. It must not be administered to patients with Rapid Onset Gender Dysphoria, or those who have been incorrectly diagnosed with gender dysphoria. The treatment should only be administered to confirmed cases of childhood onset gender dysphoria. Finally, the treatment must not artificially inflate the persistence/desistence ratio. Unfortunately, this could only be assessed with a double-blinded study; that is, near the end of the approval process, after establishing safety. 


Before you can get the drug approved, you must conduct clinical trials on human subjects. Before conducting clinical trials, you must use pre-existing research and new studies to establish the drug’s safety. And before establishing safety, you have to investigate several different drug candidates. I do not rule out the possibility that some combination of treatment conditions makes GnRHas safe for use. But I doubt it. Frankly, I have little faith in the safety of GnRHas. I doubt they are the best candidate for a “puberty-blocking” drug.


For one, the company that produces the most marketed GnRHa is known for fraud. This includes fraudulent research. Given this history, I would be skeptical of research which claims that GnRHas are safe for use in GD children. For two, GnRHas probably render children infertile. GnRHas lose their effectiveness at later Tanner stages. But it is unlikely that fertility can be restored in patients who took GnRHas before then. Sterilization of children is, of course, unethical. Moreover, I suspect that puberty blockers are inherently unsafe, due to their underlying mechanism. Puberty blockers shut down the HPG axis. This completely depletes the body of sex hormones. Sex hormones carry out effects on the body by binding to hormone receptors. When a hormone receptor is not bound to anything, it is like a switch in the “off” position. But when a sex hormone binds to the receptor, it is like turning the switch “on”.



Estrogen receptor alpha, modeled as an “on-off” switch


These hormone receptors are found in every system of the human body. By completely shutting down the HPG axis, puberty blockers turn ALL of the switches off -- including the ones in your bones, brain, heart, blood vessels, and mitochondria.



I don’t see how you can completely shut down the HPG axis, without causing serious lasting harm to an adolescent’s body. Rather completely shutting down the HPG axis, it makes makes more sense to selectively adjust the switches that control visible sex characteristics. 



This would be the most logical way to achieve a “pause button” for puberty. Can this be done?


Not currently, but maybe in the future. Maybe a next-generation SARM/SERM could work. “SARM” stands for “Selective Androgen Receptor Modulator”, while “SERM” stands for “Selective Estrogen Receptor Modulator.” This class of drugs binds with greater affinity to receptors in certain tissues, but not other tissues. Unfortunately, no existing SARM or SERM has been developed for the treatment of adolescent gender dysphoria. They would not work for the purpose of “blocking puberty”. Furthermore, it is very unlikely that futuristic SARMs/SERMs will be developed to modulate visible sex characteristics. A drug like this could only be used to treat adolescent gender dysphoria. Transsexuals account for less than 1% of the population. Cut that in half, for the drug would only work for one natal sex. The market is just too small, and the applications are too limited. There are only two types of selective modulators that I could imagine becoming reality. The first would be a SARM that selectively activates the androgen receptors in the muscles. This type of drug could be used to treat patients of both sexes who have muscular degenerative diseases. Maybe it could also be used to safely masculinize the body shape of FTMs. The second would be a drug that adjusts the rate of epiphyseal plate closure. There is a market for parents who want to make their children taller. If this drug comes into reality, it could be used to increase the height of natal females with childhood onset gender dysphoria.


If SARMs/SERMs cannot be used, then what is the next-best option? We must consider the sexes separately. For natal males, I wonder if it is possible to safely lower testosterone levels without flooring them to zero. Natal males display a wide range of testosterone levels. What is the lowest level that a male can have, without causing harm to the bones, cardiovascular system, Leydig cells, Sertoli cells, brain cells, and other tissues? Can pharmaceuticals safely lower testosterone to that level? If it is possible to safely lower testosterone, maybe that should be offered to adolescent males with childhood onset gender dysphoria. This might delay the masculinizing effects of testosterone, effectively giving the patient “breathing room” to explore their identity. If this avenue is explored, I wonder if the treatment should be coupled with “add-back” of low-dose estradiol. The purpose of the estradiol would be to protect the bones and other tissues from damage -- not to induce feminizing effects. 


Natal females are another story. Technically, “puberty blocking” can only de-masculinize or de-feminize sex characteristics. For example, it can prevent masculinization of the vocal cords, or prevent feminization of the pelvis. But “puberty blocking” cannot induce masculinization or feminization. For example, it cannot induce breast growth, and it cannot induce masculinization of the skull. This is unfortunate for FTMs. Ideally, they would want something that can safely induce masculinization of certain sex characteristics, such as the skull, the chest, and shoulders. This can only be achieved with testosterone, which is not safe for use in adolescents. Most likely, the only key benefits for FTMs involve de-feminization; that is, body height, breast growth, and pelvic growth. I have not included cessation of menstrual bleeding, since this can be achieved at a later age with testosterone therapy. Moreover, premature menopause comes with several costs that can outweigh the benefits. I really doubt it is prudent to lower estradiol levels in adolescent females, just to derive these cosmetic benefits. Estradiol has many beneficial effects to the female body. For example, it protects the bones, the neurons, and the mitochondria. Moreover, removing estradiol from the body can have undesired side-effects, which run counter to the goals of female-to-male transition. Estradiol strengthens muscles, just to a lesser extent than testosterone. Removing estradiol from the body would have the undesirable consequence of reducing muscular strength. Estradiol deprivation also increases gynoid fat, which contributes to a less masculine appearance. I would just hold out for drugs that can safely activate skeletal muscle androgen receptors, increase body height, or selectively reduce breast growth.


A final alternative would involve lowering the age for cross-sex hormone therapy. Is it conscionable to do so? For natal females, I cannot see how it is. Testosterone has many damaging effects on a female body, such as: vaginal atrophy, pelvic organ prolapse, cancers (ovarian, breast, uterine), erythrocytosis, cardiovascular disease, increased insulin resistance, mitochondrial dysfunction, severe liver dysfunction, and even blindness. There are only two queries worth investigating:

  • Can a small dose of testosterone be safely applied, if it is combined with vaginal estrogen treatment?

  • Can a localized testosterone treatment safely induce masculinization of the skull, without affecting the rest of the body’s systems?


For natal males, I am less informed. According to the Endocrine Society, estrogen therapy can cause cardiovascular disease, tumors, gallstones, and hypertriglyceridemia [3]. It can also destroy spermatogenesis and the Leydig cells. But there are several different regimens for estrogen therapy. Estrogen therapy can involve oral, transdermal, or parenteral route. It can involve conjugated estrogens, ethinylestradiol, estradiol valerate, or 17-beta estradiol. And it can involve various androgen suppressors, such as spironolactone or cyproterone acetate. How safe is the safest possible regimen? For the sake of argument, let’s assume that the safest CHT regimen renders negligible the risk of CVD, tumor formation, gallstones, and hypertriglyceridemia. This still leaves the testes. You cannot sterilize child patients, or permanently damage their Leydig cells. Could this be avoided by administering a lower dose of estradiol? That is above my pay grade...


Bottom line: I am against lowering the minimum age for CHT, until/unless there is compelling evidence that the dose/duration is safe and effective. Also, a minimum age must be set that accounts for the patient’s cognitive development. There is a difference between 14-year olds and 10-year olds.


No matter which drug candidates are pursued, they must be thoroughly researched before they are studied in humans. Before testing in humans, very strong scientific evidence must demonstrate that the drug(s) does not cause clinically significant:

  • Permanent loss of Peak Bone Density

  • Permanent loss of IQ/memory

  • Permanent loss of Fertility

  • Permanent impairment of Gonadal Steroidogenesis

  • Permanent loss of Sexual Function/Pleasure

  • Increased risk of Seizures/Convulsions

  • Increased risk of Neurodegeneration

  • Increased risk of Cardiovascular Diseases

  • Increased risk of Suicide, and other Psychiatric Events that outweigh the benefits of puberty blockers

  • Increased risk of Cancer

  • Increased risk of Eye/Vision Disorders, Hearing Disorders, Tooth Disease, Immune System Disorders, Endocrine Disorders, Gastrointestinal Disorders, Metabolism/Nutrition Disorders, Blood and Lymph Disorders, Respiratory Disorders, Renal and Urinary Disorders, Hepatobiliary Disorders, and any other Health Risks that outweigh benefits of puberty blockers


Lab and animal studies must establish safety before proceeding to clinical trials. This must be done before marketing the drug to the public. If a “puberty-blocking drug” was proven safe, effective, and reversible, it would then be ethical to administer them to human patients. This would be an expensive, time-consuming endeavor. But it is the only way forward. Anything else is unethical experimentation on human children. 


  1. Dhir, N., Jain, A., Mahendru, D., Prakash, A., & Medhi, B. (2020). Drug Repurposing and Orphan Disease Therapeutics. In Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications. IntechOpen. https://doi.org/10.5772/intechopen.91941

  2. Presidential Commission for the Study of Bioethical Issues. (2013). Safeguarding children: Pediatric medical countermeasure research. Retrieved from: https://bioethicsarchive.georgetown.edu/pcsbi/node/833.html 

  3. Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., ... & T’Sjoen, G. G. (2017). Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 102(11), 3869-3903.


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If you disagree with anything I’ve written here, do leave a comment. I welcome respectful debate and different opinions. Also, it is possible that I made a mistake somewhere. Let me know if you catch one. I do not want to spread misinformation. 

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