Contrary to Abigail Shrier’s “Irreversible Damage”, testosterone use in trans men is not associated with increased reproductive cancers

Zinnia JonesIrreversible Damage by Abigail Shrier has become one of the most celebrated books among anti-trans advocates for its popular and accessible repackaging of their movement’s current master narrative: that trans youth and young adults who come out are largely confused cis youth, mostly assigned female, adopting an inaccurate identity under the malign influence of social contacts, media, and culture. Its central arguments are founded on bad information. The supposedly “epidemic” growth in the population of trans youth constitutes an extremely small share of all youth, and may even represent underrecognition and undertreatment of trans youth. The proposed hypothesis for contagious spread of trans identity in youth, “rapid onset gender dysphoria”, is likely the result of an illusion created by the methodological choice to theorize based only on parents’ external perceptions of another’s onset of gender dysphoria; this shortcoming was later corrected by interviewing trans youth, with substantially different findings on this “rapidity”.

The main thrust of Irreversible Damage is to foment existing discomfort and panic among conservatives about “protecting” “their” “women and children” on the basis of this very thin evidence. Scientific misfires like “rapid onset gender dysphoria” are offered up as justification for political and personal sentiments that would persist anyway: the opposition to recognizing the authenticity and basic equality of trans people, and the belief that trans people are ambassadors of an unnatural and threatening social disease that must be met with hostile suppression. The pseudoscientific narrative dresses these positions in a pretense of respectability, as something a reasonable person could believe.

But there’s also a series of statements in Shrier’s book that have nothing to do with subtleties of statistics, demographics, or methodology. Instead, this appears to be a far more straightforward matter of factual findings. Shrier suggests repeatedly that trans men taking testosterone will experience an increased risk of endometrial, ovarian, or other reproductive cancer due to this transition treatment. However, existing literature on trans men using testosterone indicates that they do not face any higher risk of cancers at all.

Shrier asserts that testosterone is associated with “increased risks of various cancers” such as “endometrial and ovarian cancer”, requiring hysterectomy:

You might have heard that testosterone comes with bad side effects—but you’ll rarely hear them mentioned here. YouTube and Insta gurus are about fun, and increased risks of various cancers and prophylactic hysterectomy are certainly not that. . . . What’s more, even if her daughter did not start puberty blockers and instead waited puberty out and then began cross-sex hormones (testosterone), this carried all sorts of risks of its own. Endometrial and ovarian cancer. Hysterectomy.

She goes on to propose a specific mechanism by which testosterone shots may cause reproductive cancers:

There is one last but inevitable risk, brought on by the fact that no patient on earth takes every dose of her medicine precisely on time: at some point, a young woman on T will give herself a shot a day or two after she was supposed to. . . . In a woman not on testosterone, the fast-growing uterine lining is managed by her pituitary, which either halts its growth for the sake of a placenta or directs the lining to be shed in a period. Testosterone shuts down this signaling, turning a woman’s menstrual cycle off. When a woman forgets to take her testosterone on time, her ovaries will stimulate sudden spurts of fast-growing uterine lining. This could heighten risk of cell mutation—and endometrial cancer. . . . Because of this suspected risk of uterine cancer, after a woman has been on a course of testosterone for five years, many women find themselves contemplating a prophylactic hysterectomy and oophorectomy (removal of uterus and ovaries), often with the encouragement of their physicians.

Similar claims are made by Carey Maria Catt Callahan in the collection Transgender Children and Young People: Born in Your Own Body:

Except my private endeavour was connecting me to women who were quite young, and who had been subject to more medical interventions than I had gotten – longer courses of testosterone, mastectomies. So they position this treatment as the One And Only and, shove us away and onto it and then don’t even research the effects of what they’re giving us. A quick glance over the Society of General Internal Medicine’s 2014 Cancer Risk and Prevention in Transgender Patients makes it clear, repeatedly, how little we know (or at least how little we knew just two years ago): “MTF individuals receiving feminizing hormones experience breast cancer, yet the degree of risk relative to natal females is uncertain.” “There are no long-term studies on endometrial cancer incidence among FTM individuals.” “No long-term studies have investigated ovarian cancer incidence among FTM individuals.” We don’t know. We don’t know. We don’t know. Or maybe, we don’t care. We don’t care. We don’t care.

(The broken link is included as such in the book.) Anti-trans Jungian psychoanalyst Lisa Marchiano, who notably promotes the “rapid onset gender dysphoria” theory, also writes at 4thWaveNow:

Girls who take testosterone will be at increased risk for developing diabetes, cancer of the endometrium, liver damage, breast cancer, heart attack, and stroke. There may be other adverse effects of which we are not aware at this time, since long-term testosterone use in natal females is a relatively new phenomenon that has not been adequately studied.

But the claims made by Shrier and others do not appear to be supported by evidence on the real-world occurrence of reproductive cancers among trans men and transmasculine people taking testosterone. Shrier first cites a 2015 document by the Fenway Health clinic on medical care of trans people throughout transition, which explicitly states there is no need for yearly screening for endometrial or ovarian cancer in trans men on testosterone:

Generally, testosterone treatment results in atrophy of the endometrial lining. A high rate of endometrial hyperplasia was found in one older study, but these findings have not been replicated in subsequent studies. Reports exist of endometrial cancer in FtM patients, but these were patients who started hormone at a later date; quite possibly, cancer already existed prior to treatment. . . . Some protocols have recommended yearly pelvic/uterine ultrasounds to assess the ovaries and endometrial lining, but there is no data to support such screening.

She then cites Grimstad et al. (2018), who state that trans men on testosterone “continue to have typical uterine and endometrial pathology” and have rates of endometrial cancer “on par with baseline population risk”:

These studies have also found that transmasculine persons on testosterone continue to have typical uterine and endometrial pathology such as polyps, leiomyomata, and adenomyosis. Importantly, hyperplasia without atypia was reported in 9 of the 269 subjects and there was 1 reported case of endometrial adenocarcinoma. In addition, we determined that pre-testosterone-use rates of AUB [abnormal uterine bleeding] in our patient population (25.5%) were similar to that of the general cis female population (14-25%). The incidence of endometrial cancer in the United States is 1 in 342 under age 49 years and 1 in 166 between the ages of 50 and 59. It is the fourth leading cause of cancer in the United States among cisgender women. In our review of currently available data, including the original data presented in this article, there was 1 reported case of endometrial cancer in 269 subjects ranging in age from 18 to 53 years. There were 9 patients with simple hyperplasia, which carries a 3% risk of progression to complex hyperplasia. Although we cannot determine the risk of endometrial carcinoma in transmasculine persons on testosterone relative to their cisgender counterparts, it appears to be on par with baseline population risk despite the majority of patients reporting amenorrhea.

Most recently, Andrews et al. (2021), published ahead of print this week, offers a systematic review of reported cases of reproductive cancers and breast cancers in trans men and transmasculine people taking testosterone. Reviewing 80 publications, the authors describe cancer in this population as rare:

The most commonly reported neoplastic finding was adenocarcinoma of the breast, with rare cases of ovarian, endometrial, cervical, vaginal, pituitary, pancreatic, and cardiovascular neoplasia also reported.

Only three known cases of endometrial cancer in trans men on testosterone were reported in the literature. Longer use of testosterone wasn’t associated with greater growth of the endometrial lining or greater likelihood of receiving hysterectomy for abnormal uterine bleeding:

Three cases of endometrial adenocarcinoma were identified as follows: 2 reported as part of a descriptive study and 1 as a case report. . . . Grimstad et al measured the endometrial thickness in 82 cases and found a mean thickness of 2.0+-1.3 mm (95% CI, 1.7–2.3). The range of endometrial thickness was as follows: 35 subjects (42.7%) measuring 1 mm, 27 (32.9%) measuring 2 mm, 10 (12.2%) measuring 3 mm, 8 (9.8%) measuring 4 mm, and 2 (2.4%) measuring 7 mm; endometrial thickness did not correlate with duration of therapy. Grimstad et al also reported endometrial polyps or fibroids in 9 subjects (9.6%), adenomyosis in 7 (7.4%), complex hyperplasia without atypia in 1 (1.1%), and other benign pathology in 4 (4.3%). Another study found endometrial polyps present in 18% (5 of 27) of transgender men, noting that the polyps showed more proliferative features than adjacent endometrium and that polyps were found in persons with a higher body mass index. Divila et al observed endometrial hyperplasia in 4 of 12 uteruses in their series. One study noted no statistically significant difference (P = .09) in frequency of abnormal intrauterine bleeding as the indication for hysterectomy between cisgender women (537 of 850) and transgender men (16 of 33).

A total of five cases of ovarian cancer in trans men on testosterone have been published. Many trans men’s ovaries continue to have normal follicles and these men may continue to ovulate, while longer use of testosterone did not make the occurrence of benign ovarian cysts any more likely:

Three case reports and 1 descriptive study describing 5 cases of ovarian neoplasms in persons taking masculinizing hormones were identified. . . . Variable reports of cortical follicle distribution exist, from near normal with mostly primordial follicles to increased atretic follicles. Divila et al reported surface epithelial hyperplasia in 3 of 12 patients and no increase in follicular atresia. Grimstad et al found no association between the duration of testosterone administration and the presence of cysts in the ovaries. In their studied group, 49.4% (42 of 85) of specimens showed follicular/simple cysts, 5.9% (5 of 85) were polycystic, and 38.8% (33 of 85) had no cysts. Corpora lutei have also been seen, indicating that ovulation has occurred in some ovaries. One study reported recent corpora lutei in 8 of 28 of the examined ovaries.

Six cases have been reported of cervical cancer in trans men taking testosterone. Two of these cases were associated with HPV infection, and another was found incidentally at the time of hysterectomy. When benign changes to the cervix occurred, these were “minimal in most cases”:

Six cases of cervical neoplasia in transgender men taking androgens were identified. Adkins et al reported a case of low-grade squamous intraepithelial lesion and a case of high-grade squamous intraepithelial lesion, each of which was associated with human papillomavirus infection and initially identified by Papanicolaou smear and confirmed on a biopsy specimen. One case of carcinoma in situ was diagnosed by a biopsy specimen and confirmed in the subsequent hysterectomy specimen. A second case of carcinoma in situ was diagnosed at hysterectomy for gender affirmation after recent unremarkable pelvic examination with no visible transformation zone and normal Papanicolaou smear. . . . Six descriptive studies and 4 comparative studies describing benign changes in the cervixes of persons taking masculinizing hormones for the purpose of gender transition were identified. The changes observed in the cervix were minimal in most cases, with 4 of 6 reporting atrophy.

Two cancers of the vulva or vagina were reported, with both being associated with HPV infection:

Two cases of neoplasia in the lower gynecologic tract were identified. One case was a vaginal squamous cell carcinoma in a 60-year-old transgender man who had undergone a hysterectomy and continued on testosterone therapy. The tumor was human papillomavirus DNA positive (genotype 16) by polymerase chain reaction. The second case was in a 41-year-old transgender man, with a history of well-controlled HIV and both cervical and rectal cancers, who presented with a suspicious labial lesion. Microscopic examination revealed a high-grade vulvar intraepithelial neoplasia associated with high-risk human papillomavirus.

Finally, breast cancer does not appear to be any more common with testosterone treatment, and some types of breast cancer could be less common in these trans men:

Two cohort studies performed in the Netherlands found lower incidence of breast adenocarcinoma in transgender men receiving testosterone than in untreated cisgender women. Several studies have shown no observed increase in epithelial hyperplasia or malignancy in transgender men treated with hormones when compared with untreated transgender men or cisgender women. . . . In a recent comparative study, Hernandez et al showed significantly lower rates of neoplastic findings (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, or ductal carcinoma in situ) in transmasculine individuals (n = 211 of which 142 were taking hormone therapy) as compared with hormone naïve cisgender women (n = 273), with rates of 2.8% and 7%, respectively (P = .04).

Benign changes to breast tissue can occur with testosterone treatment, though many types occur just as frequently or even less frequently than in those assigned female who are not taking testosterone:

Fibrocystic changes have also been observed with no difference in frequency identified between treated and untreated individuals in some studies. Baker et al described statistically significant reductions in frequency of cysts (P < .001), fibroadenomas (P = .03), pseudo angiomatous stromal hyperplasia (P < .001), columnar cell change (P < .01), papillomas (P = .02), and mild inflammation (P = .02) in individuals taking gender affirming testosterone. While another study comparing the breast tissue of untreated cisgender women with that of transgender men on testosterone therapy, the only histologic finding that was statistically different between the 2 groups was the presence of microcalcifications in 28% (8 of 29) of transgender men versus 0% of cisgender women (n = 10).

None of these findings reflect what we would expect to see if prolonged use of testosterone was linked to a greater risk of experiencing any of these reproductive or breast cancers or abnormalities. Shrier’s alleged “increased risks of various cancers” are nowhere to be found, because these risks do not actually appear to be elevated above the general population. Claims such as Shrier’s, knowingly or unknowingly, substantially misrepresent the relationship between testosterone usage in trans men and occurrence of these cancers – specifically, there is no relationship. Shrier and others are depicting a landscape of cancer risk for trans men that simply does not exist. They’re making claims about the effects of testosterone that just aren’t correct – and asserting trans youth must be protected from a danger that isn’t there. 

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About Zinnia Jones

My work focuses on insights to be found across transgender sociology, public health, psychiatry, history of medicine, cognitive science, the social processes of science, transgender feminism, and human rights, taking an analytic approach that intersects these many perspectives and is guided by the lived experiences of transgender people. I live in Orlando with my family, and work mainly in technical writing.
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