Testosterone & young females: What is known about lifelong effects?

by Kerry Smith, MD

Kerry Smith [a pseudonym], MD, is a board-certified internist in the US who has been practicing since 2004. She is the mother of several children, including a 12-year-old daughter who suddenly developed the notion that she is transgender after being exposed to the idea in her 6th grade classroom. It was this development that led Dr. Smith to research the protocol for medical transition of children. She believes that most physicians are blissfully unaware, as she recently was, of the current standards which aggressively promote unstudied and off-label irreversible medical interventions in children too young to drink, smoke, vote, drive, consent to sex, or even watch an R-rated movie.

Dr. Smith is available to interact in the comments section of her article.


What are the risks of giving testosterone to a female for a lifetime?

As the mother of a girl trying on a trans identity, and as a practicing physician, I need an answer to this question.

I’m not the only one. Every day more of us join this club, as the rate of girls questioning their “gender identity” continues to skyrocket, outstripping boys at a previously unimaginable pace. Surely, those who advocate for the medical interventions known as “transitioning” must have a risk-benefit analysis available for parents and patients, before committing young people to a lifetime of pharmaceutical (and potentially surgical) treatment for a poorly defined psychiatric condition?

As a physician who has sworn to do no harm, that’s what I would have assumed.

As it turns out, the WPATH-inspired standard of care, adopted by the US Endocrine Society, has pushed boldly ahead where no medical society has gone before, promoting radical, irreversible body modifications for adolescents using powerful, off-label hormone regimens in the absence of any longterm data about safety.

They are perfectly open about this choice, stating in the standards:

These recommendations place a high value on avoiding the increasing likelihood of an unsatisfactory physical change when secondary sexual characteristics have become manifest and irreversible, as well as a high value on offering the adolescent the experience of the desired gender. These recommendations place a lower value on avoiding potential harm from early hormone therapy.

I suppose it is considered “transphobic” of parents to persist in the nit-picky demand for actual data about what that “potential harm” might consist of, but so be it. Teenagers have always resisted parental concerns about their risky activities. Last time I checked, that didn’t keep us from trying to stop them from using dangerous drugs. Why should testosterone (a schedule III drug in the same category as Suboxone and ketamine) get a free pass?

Sex hormones have a long and checkered history in the US, having been widely celebrated as the fountain of youth before falling from grace after studies belatedly showed multiple adverse health outcomes. This was most striking when the evidence from huge studies WHI, HERS and HERS II demonstrated that, contrary to what earlier observational studies seemed to show, hormone replacement therapy for postmenopausal women actually increased rather than decreased the risk of heart attack, stroke and cancer.

Testosterone had its day in the sun as well, being prescribed not just for the medical condition of hypogonadism, but gleefully promoted as a panacea for the vitality and wellbeing of aging men, for the supposed diagnosis of “low T.” Recently the serious risks of this approach have been described, including increased heart attack and stroke; the FDA eventually placed a warning on testosterone products, and lawsuits are underway; however the shameless promotion to men continues unabated.

As a physician, my first stop for drug information is usually the evidence-based clinical resource UpToDate, which contains full prescribing information for medications available in the US and Canada including dosing, indications, risks, interactions, and other details. I reviewed the entry on testosterone and found that, to my surprise, there is no mention of any suggested dosing regimens for female to male transsexuals.

In the US, once a drug is FDA approved for one use, it is often used “off-label” for other conditions, which is a generally accepted practice. These common, accepted off-label uses will be listed in resources such as UpToDate along with relevant dosing information and warnings. For example, the entry for modafinil, a stimulant, has dosing information listed for the FDA approved indications of narcolepsy, obstructive sleep apnea, and shift-work sleep disorder, as well as for the off-label indications of ADHD, cancer related fatigue, major depressive disorder, and multiple sclerosis related fatigue.

In contrast, the UpToDate entry for testosterone makes no mention of any approved or off-label use for the treatment of transgenderism or gender dysphoria. The only indication for testosterone in females listed is for the adjuvant treatment of postmenopausal women with metastatic breast cancer.

I then checked the FDA prescribing information for Depo-Testosterone (injection) and Androgel (topical), and found a total lack of any reference to use in females for any purpose whatsoever.

testosterone

Testosterone:  Schedule-III controlled substance. The US FDA doesn’t acknowledge or mention its use, on- or off-label, for FTMs

This absence speaks volumes. While the WPATH Standards of Care would have us believe that “[f]eminizing/masculinizing hormone therapy – the administration of exogenous endocrine agents to induce feminizing or masculinizing changes – is a medically necessary intervention for many transsexual, transgender, and gender nonconforming individuals with gender dysphoria,” the reality is that this treatment is so far out of the mainstream of modern medical standards that it is not yet anywhere reflected in basic prescribing reference materials, even as an off-label use.

Because “transgender medicine” is a new field, there is as yet no meaningful body of data that can definitively answer the question of what risks my daughter might face if she embarks on decades of testosterone injections. Studies promoting this treatment as “safe and effective” are generally limited to a few dozen patients and a year or two of follow up. A review article in the Lancet published in April 2016 touted as providing “an evidence-based overview of the benefits, risks, and effects of testosterone therapy in transgender men” observed that “testosterone decreases HDL cholesterol, increases triglycerides, might increase systolic blood pressure, and might increase the incidence of [type 2] diabetes and metabolic syndrome” but was forced to ultimately conclude that the long term effects are largely unknown due to “a paucity of high-quality data” in this area, a disclaimer found in most articles regarding cross-sex hormone treatment.

The desired effects of testosterone for transgender-identified females are the development of male secondary sex characteristics: hair growth on the face and body, changes in bone structure, increased muscle mass, redistribution/decrease of body fat, deepening of the voice, cessation of menstruation, decreased fertility and clitoral growth are all expected. Of note, even these desired effects may not live up to the hype; clitoral growth can cause pain or numbness and, in some cases, appears to lead to difficulty attaining orgasm; voice changes may not reach the desired pitch, leading some patients to seek out voice deepening surgery; some reports suggest increased muscle mass on a female frame can lead to thoracic outlet syndrome.

Of these effects, the changes to body composition, menstruation and fertility may be reversible (if testosterone is started post-puberty; if administered immediately after puberty blockers, irreversible sterility is the norm). Though testosterone is a known teratogen, there is no shortage of glamorous stories celebrating transmen who manage to conceive and give birth after stopping testosterone. However, changes to voice, bone structure, hair distribution and genitals are usually permanent, even if the hormone is stopped.

Then there are the undesired effects. The most commonly reported one is acne, which is often severe enough to require treatment. Male pattern baldness is also unmasked in those who are genetically predisposed.

More important than cosmetic effects are the changes in markers for cardiovascular disease. Studies tend to show that exogenous testosterone increases LDL (bad cholesterol), lowers HDL (good cholesterol), increases erythrocytes (red blood cells) potentially leading to venous thromboembolism (blood clots) from polycythemia, and increases blood pressure. It has also been shown to increase fluid retention which can contribute to heart failure.

Studies suggest as well that in women (but not men), higher endogenous testosterone levels correlate with insulin resistance and the development of diabetes, and studies suggest that adding testosterone in the form of a drug may increase risk for diabetes.

Even in male patients, studies clearly indicate that testosterone therapy increases the risk of cardiovascular disease including heart attack. One review article notes dryly:

“The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.” [emphasis added.]

In other words, all studies showed an increase in cardiovascular disease, but this effect was “less prominent” in Big Pharma funded studies. What a surprising coincidence!

Testosterone may cause mood changes. Small studies suggest testosterone treatment in transmen can increase anger, which makes sense, given that abuse of testosterone by bodybuilders is known to sometimes result in “roid rage,” a condition of unchecked anger and aggression. One article reports a case of late onset psychosis associated with testosterone use in a trans-identified female, in whom no other cause could be found.

Testosterone has also been associated with liver damage or tumors, though more often in oral formulations rather than the injectables favored by transgender medicine practitioners. It has been known to impair kidney function. It has been shown to impair mitochondrial function leading to oxidative stress. The list of recommended laboratory tests for monitoring is long.

The effects of testosterone on the ovaries and uterus are not well defined. Early research suggested testosterone administration causes enlarged and cystic ovaries similar to what is seen in polycystic ovary syndrome. While studies in postmenopausal women suggest that testosterone does not stimulate abnormal growth of the endometrium (uterine lining), small studies of young FTM patients suggest that in younger females, testosterone administration does induce proliferative changes in the endometrium, which could theoretically progress to cancer. Cases of ovarian cancer have been noted in females treated with testosterone. These changes to the ovaries and endometrium explain why removal of the uterus and ovaries are often suggested for FTM patients on long term testosterone treatment, though there is no medical consensus on this as there is minimal data.

There is some experience giving testosterone off-label to postmenopausal women for hypoactive sexual desire disorder (HSDD); indeed this treatment is still promoted online and prescribed by some physicians. However, despite promising results for women’s libidos, studies suggest that even low dose testosterone may increase risks for endometrial and breast cancer, and as of yet there is no FDA approval for any form of testosterone for this indication.

So, the state of the art of transgender medicine for a young girl who believes she is a boy is to affirm this belief using hormones and possibly surgery. Current standards promoted by WPATH include puberty suppression using Lupron as young as age 10, followed by cross-sex hormone treatment with testosterone by age 16. It should be noted that in the United States, top gender doctors who see the greatest number of patients often begin cross-sex hormone treatment much earlier (as young as 12 in this recently published study).

We don’t know all the side effects this regimen may produce, but when started before puberty, one effect is certain: permanent sterility.

Aside from that pesky side effect, the expected effects of testosterone treatment include changes in body fat and muscle composition, changes in bone structure, facial/body hair growth and male pattern hair loss, clitoral growth, changes in sexual function, voice deepening, cessation of menstruation, and increased acne.

Likely side effects include adverse changes in cholesterol and blood pressure, leading to increased risk for heart attack and stroke; increased red blood cell mass which increases risks for blood clots; and changes in the ovaries and uterus potentially leading to increased risk of cancer, for which many experts recommend hysterectomy and bilateral salpingo-oophorectomy.

Possible side effects include increased risk of diabetes (another risk factor for heart disease and stroke), possible liver damage, possible kidney damage, risk of mitochondrial damage, and perhaps an increased risk for psychiatric disease.

How significant are these risks? Will they be worth it to a generation of “gender nonconforming” kids as they start their adult lives already committed to a lifetime as chronic medical patients? Will they face premature disability and death?

No one knows. Maybe it will all work out fine. Maybe testosterone really is the fountain of youth, providing strength, energy, vitality and virility to brave young gender outlaws, as they sacrifice their fertility to give birth to their authentic selves with the eager assistance of the medical and pharmaceutical industries.

Maybe.

But medical history is littered with miracle cures gone wrong. Future historians will judge whether the massive increase in girls and young women prescribed testosterone will go down as a triumph of medicine–or an ill-begotten disaster.

 

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An RN & mum of a trans-identified young adult on perils of off-label cross-hormones as first-line treatment for gender dysphoria

Mumtears is a registered nurse, a wife, and mum of two daughters, currently aged 23 and 20 years old. She lives with her husband of 27 years, the father of her two daughters. She says: “Because of my currently unpopular thoughts, and because of not wanting to cause harm to my family, I feel I need to remain anonymous. I also started a blog a while ago, but- frankly- I haven’t kept it up. I am not very technologically sophisticated. If you want to read what there is in my blog, you can find it at myheartandhope.wordpress.com.” She can be found on Twitter @Mumtears1 and is available to interact in the comments section of this post.


by Mumtears

I have been a registered nurse for 30 years. From childhood, I always wanted to be a nurse. I really feel like being in the nursing profession was a “calling” for me.

While going through my post-secondary studies, studying for my Bachelor of Nursing degree, I recall being taught that, in all conditions, medical and nursing treatments should always begin with the least invasive way to treat that condition. I was taught that this was best practice care for the human body.

I have had many years’ experience working in Acute Care Pediatrics at our local children’s hospital. It was there that I learned that children are not simply “little adults”. Pediatric patients require specific attention and care, due to their rapidly developing minds and bodies. Their bodies and minds function very differently from adults. Medications and treatments are all prescribed based on the child’s body weight. They also cross different developmental stages at different rates on their way to becoming adults.

For the past 7 years, I have been working at a very busy family practice, caring for all types of patients with all types of concerns, from birth to the very elderly. I work with a family physician who also specializes in transgender care and sexual health. I have seen, assessed and cared for countless adult transgender patients. They comprise a combination of male-to-transgender and female-to-transgender patients.

Almost 5 years ago, my youngest (then 16) daughter expressed to her dad and me that she “thought she should be a boy”. That was the day our family life changed in ways we never anticipated. Throughout childhood, our daughter never presented as stereotypically “masculine”. She never outwardly expressed to us any kind of discomfort. She appeared to be mostly happy. A bright spark. She loved to play outside: doodle with chalk on sidewalks, sandbox play, climb trees, ride bikes. She smiled often. She loved building with Lego, playing Polly Pockets and with tiny toy horses. She enjoyed making tiny crafts, including models of people and animals made of Sculpey clay.

She was also very academically smart, reading beginner short novels before entering Grade 1. She taught herself how to tie her shoes and how to ride a bike. With the help of her father, when she was about 8 years old, she built one amazing bicycle from two used bikes purchased at a garage sale. In Grade 4 she challenged a Math unit about fractions and passed the final exam with flying colours, even before the unit began. She was musically advanced, playing beautiful piano tunes at age six, wonderful tenor saxophone solos in junior high. We had her tested for giftedness by a school psychologist. He told us that she was “just below” the gifted category.

We parents did begin to notice some general, social discomfort in late junior high, but we assumed that this was normal teen awkwardness, which can happen during puberty, so we were not concerned about it. We were absolutely blindsided by her proclamation that she thought she would be a boy.

My older daughter never had a temper tantrum when she was a toddler. I thought it was down to good parenting. How wrong I was. When our younger daughter was born, she behaved quite differently from her sister. Different personalities, which was not surprising to us because my husband and I are also very different from each other. Our youngest daughter started having temper tantrums at 18 months of age, which lasted 4 long years. Then, it was like a light switch turned on. Suddenly she realized she could settle her emotions down by reading quietly, alone on her bed. After just over 4 years of a frequently chaotic time, our house and family seemed to be at peace again. It was lovely.

Thinking back to this time in early childhood, I thought my daughter’s gender discomfort might be a similar phase for her. I still think it might be. I pray that, with time and life experience, she will develop an acceptance and comfort about her female body, and a knowledge that being the female sex does not have to place limits on her happiness and what she can accomplish in life.

drawing-testosterone-injectionBefore daughter told us she thought she should be a boy, I had already seen and assessed countless adult transgender patients. They comprised a combination of male-to-transgender and female-to-transgender patients who ranged in age from late 20s to early 50s. I admit that I when I first started working in family practice, I was very naïve about what “transgender” means. I noticed that all of the adult transgender patients I met also had comorbid mental health issues, which had not been fully resolved and, in some cases were severe/debilitating. My professional duty was (and still is) to provide excellent, compassionate nursing care to these patients. My personality is compassionate, empathetic and caring. I learned some of the transgender lingo; for example, “top” and “bottom” surgery. I’ve administered countless testosterone injections. I’ve changed the dressing on the donor arm of a young 20-something female-to-transgender patient who had recently undergone phalloplasty surgery. And now, after I administer these injections, I’ve found myself in the staff washroom, trying to compose myself for my next patient. Watching female erasure (in particular) causes me much sadness, partly due to what is going on with my own daughter. But mostly due to the fact that I am an adult female-born woman.

As I already said—but it’s worth saying again–I was taught that, in all conditions, medical and nursing treatments should always begin with the least invasive way to treat that condition. I was also clearly taught that pediatric patients have smaller, ever changing and rapidly developing bodies and minds, and need to be treated differently from adult patients. I was taught that physical, mental, and emotional development in children is ongoing, well into the early to mid 20s. Because of my knowledge about child development, both body and mind, I don’t understand why the medication Lupron is being given to healthy-bodied children. This medication is approved for use to treat adults with advanced prostate cancer and endometriosis. In children it’s used to slow down precocious (early-onset) puberty. It’s only in the past few years that it’s being prescribed for children who have gender dysphoria. This is an off-label use for this drug and it’s being given to healthy-bodied children even though there has been no research done to determine its safety or efficacy regarding gender dysphoria.

And we know that puberty blockers lead in most cases to cross-sex hormones. Why is the current first-line treatment for gender dysphoria in young, healthy bodies off-label, unstudied cross-hormone prescriptions? Young adult females can go into a family doctor’s office, state “I’m transgender”, and be handed a Rx for Androgel. This is what happened with my daughter, over a year ago. She never filled that particular prescription. However, last week she notified her father and me that she plans to start taking testosterone. She’s in a lengthy queue to be seen by our city’s gender specialist/psychiatrist and is impatient. She gave us no concrete reasons for wanting to start taking testosterone. She demonstrates little outward discomfort when she is in our home or when interacting with extended family.

She had one visit with the same family doctor who gave her the previous Androgel Rx. She told us that he told her what side effects could occur (while reading from a computer screen). She told us that he did not discuss reproductive planning with her, and that he gave her no written information about any of the side effects. She told us that he gave her the prescription and some bloodwork requisitions. This family doctor did not take a multidisciplinary team approach; he acted on his own. He did not refer her to an endocrinologist to check her hormone levels. He did not send her to any mental health professional, who could have assessed her for the source of her discomfort and possibly provided her with other less-invasive treatment options, such as cognitive behavioural therapy. How is the way in which this family doctor gave my daughter this off-label cross-hormone prescription medically ethical? In my province, family physicians can be the primary prescriber of cross-hormones. While using a multidisciplinary approach might be a good practice, it is not mandated. I’m currently trying to find answers via our provincial and national medical associations. The answers I’m looking for aren’t forthcoming.

I know that in no other medical or other health-related case would something like this happen, with regard to the prescription of off-label medications. I’d like to give you another home-based, common-sense example: Young adult child says to parent: “I have a really bad headache.” Think about this. Would it make any sense for the parent’s first response to be, “Your dad has some leftover oxycodone from his recent surgery, which he no longer needs to take- here, have some!”? Of course not. What would make medical/practical sense would be to first check that the young adult isn’t dehydrated. It is known that dehydration can cause headaches. “Try drinking some water and see if you feel better”. That would be the least invasive thing to try at first. If drinking water didn’t help the headache and if the young adult child had no know allergies or health conditions, it would be appropriate to next offer them acetaminophen, dosed per the package instructions. It is known that acetaminophen is a very effective analgesic, with a low incidence of side effects. If the headache persisted, perhaps it would be appropriate to then try a non-steroidal anti-inflammatory, such as Advil. There might be some inflammation in the neck or jaw muscles, causing the headache, which, if reduced, could relieve the headache. It is known that Advil is a mostly safe anti-inflammatory medication, with low potential side effects.

Recently I attended a Medical Education Session, which was held at a recent clinic retreat. The session was about low testosterone levels in adult males and testosterone replacement therapy. What I learned is, that for male bodied patients, the recommendation is that if the testosterone bloodwork result is low, it is important to clearly understand the patients’ symptoms concerns and general health. If the patient’s symptoms are low and the patient is not concerned, then giving the patient a prescription for testosterone is not advised. This is because there are also many side effects that can happen from taking testosterone, which can cause negative symptoms/concerns for the patient–especially if these male-bodied patients also have other health concerns. I learned that this is appropriate safe medical care for male-bodied patients.

I’ve done my own learning about testosterone. The pharmacy companies’ printed drug information about testosterone products states that this medication should not be given to women. It has never been studied in female bodies. Also, there are no long-term studies which indicate safety or a positive result for females who take this medication. Physicians are prescribing it “off label”.

I have been trying to learn as much as I can about gender dysphoria and its treatment. I have read many studies, documents, medical association websites, etc., and continue to do so.

When I learned about the newly recognized “rapid onset gender dysphoria”, I realized that much of its description matched what we were/are witnessing in our youngest daughter. Currently there is little known regarding care or treatments for young people presenting with rapid onset gender dysphoria. And few physicians are even aware of this phenomenon. There has been a dramatic increase, over a short period of time, in the number of teens and young adults who are seeking care for being transgender. And the demographic for which sex is declaring transgender has also changed. There are now more natal females than males with this concern.

With all that I have learned about rapid onset gender dysphoria and current treatments for it, I have more questions: Why are these off-label testosterone prescriptions being given to young healthy-bodied female patients as a first-line treatment for gender dysphoria? Especially since it is known that testosterone causes permanent body changes in female bodies, making it an invasive and irreversible treatment. Why are physicians prescribing these off-label cross-hormones without doing further assessments to ensure that this is the best treatment for their patients? I believe these are reasonable questions to ask. I believe these are prudent questions to consider. It is not transphobic to ask these questions. Many parents are asking questions like these. If you’re a parent wanting to learn more and connect with other parents, you can check out: https://gendercriticalresources.com/Support/index.php


Afterword:

I have recently learned that my daughter has likely started her testosterone prescription already. I found the receipt for it in her room at home, for low dose Androgel, from a pharmacy our family never uses, so I know that she has purchased it. She is currently living away for university, in a city which is a 2-hour drive from our home, studying in an arts program there. She has never told any of our close extended family anything about her gender dysphoria. We all live in the same city and see each other fairly frequently. Our older daughter (a graduate with a degree in Cultural Anthropology) knows and supports her sister’s claims, but that is all.

androgelOur younger daughter had the opportunity over Christmas (two Christmas dinners actually), to tell anyone in her extended family about her plan to start testosterone. She hasn’t said anything to any of them. Nothing about her gender dysphoria. I’m sure that it will be upsetting to many of them. My daughter and I text back and forth. We text about her activities (theatre, parkour). About her classes (she studies hard and gets excellent grades). About her saxophone practice (she recently was accepted into the university’s wind orchestra). I am proud of the person she is. I see so much potential for her to become an amazing woman and I am sad that she wishes to erase her female body. Frankly, I believe that “gender” is a crap concept, which is why I don’t discuss this with her. Ever since she first told us her thoughts, we have been clear in telling her our concerns. It’s up to her to think about what we have told her. We hope that she will undergo some work to understand the source of her discomfort, but we know that the decision will be hers to make. She tells us that she loves us. We have clearly told her that we love her and always will. We financially help support her post-secondary education. We want her to have many good job opportunities. We want her to have a good life and be happy and healthy. I dread her voice changing. I dread seeing her beautiful face change. And I find myself wondering if she actually needs to go through all of this, in order for her to “find herself” and come out the other side. The birth name we gave our youngest daughter means “strong”. I thought this would serve her well. We continue to use her birth name because we have not given up hope. As parents, we were never prepared for any of this. And as a registered nurse, I am very disturbed by all of it.