Quantifying testosterone’s suppression of estrogen levels in trans men

Disclaimer: I am not a medical professional and this is not medical advice.

While trans women on HRT typically require testosterone blockers in addition to estrogen to reduce testosterone to the desired levels and produce effective feminization, trans men generally require only testosterone to achieve physical masculinization. However, one potential concern is the effect of aromatase, an enzyme which can convert testosterone into estrogen. Testosterone treatment in cis men has been associated with high estrogen levels in 20% of men in one study (Tan, Cook, & Reilly, 2015), and can produce physical effects such as gynecomastia (Rhoden & Morgentaler, 2004).

Testosterone treatment for trans men aims to induce testosterone levels within the typical male range (Hembree et al., 2017), while levels of estrogen are not usually as much of a concern, although clinicians have raised the possibilities that testosterone treatment could cause either unwanted high estrogen levels through aromatization or unhealthily low estrogen levels through suppression of estrogen production. A recent study of 746 trans men and transmasculine people taking testosterone seeks to answer these questions, measuring the effects of testosterone on their estrogen levels.

Defreyne et al. (2020) recorded trans men’s estradiol blood levels at baseline before starting testosterone, as well as after 3, 6, 9, 12, 18, 24, and 36 months of testosterone. The authors found that estradiol levels decreased by an average of 17.1 pg/mL over the first three months of treatment, and there was also a statistically significant decrease of an average of 19.6 pg/mL between months 12 and 18. Additionally, over a 1-year followup, use of longer-acting injectable testosterone undecaonate was associated with lower estradiol levels than use of other shorter-acting injectable testosterone esters or testosterone gel, with the authors noting that testosterone undecaonate “is less susceptible to fluctuations in serum testosterone levels and may provide a more sustained gonadotropin and menstrual cycle suppression and may result in less aromatization to estradiol”

Interestingly, by 36 months, trans men who had undergone hystero-oophorectomy (which includes removal of the ovaries) had estradiol levels similar to those who still had ovaries. However, overall, the trans men in the study still had estradiol levels higher than those typical of cis men even after testosterone treatment. The authors conclude that testosterone does not appear to produce higher estradiol levels or physical effects in trans men: “it is unlikely that testosterone therapy in AFAB people could be a risk factor for undesired estrogenic effects, including persistent menstrual cycle, pelvic pain, and gynecomastia.” Testosterone produced “suppression of endogenous estradiol production”, and moreover, “the observed decrease in serum estradiol levels does not lead to adverse outcomes, unlike in hypogonadal females.” They further state that aromatase inhibitors, which block testosterone from being converted into estrogen, should not be used due to the potential harm of unhealthily low estrogen levels:

Lower estrogen levels at menopause lead to accelerated bone loss. Therefore, aromatase inhibitors should not be used in the masculinizing hormone regimen due to potential bone loss.

These findings confirm the results of another study of 34 trans men treated with testosterone over the course of six years (Chan et al., 2018). In this study, testosterone was given as short-acting testosterone enanthate or testosterone cypionate, typically injected weekly. Estradiol levels were observed to decrease from an average of 81 pg/mL at baseline to a steady average of 54 pg/mL during treatment. The authors note that “it is extremely unlikely that there was an unappreciated rise in serum estradiol levels secondary to aromatization from exogenous testosterone”, and that “the decrease in serum estradiol levels provides some support for more recent proposals that there is no extra risk to female reproductive tissues, such as endometrium, cervix, and breast tissue, from androgen exposure at normal male levels.” They likewise conclude that there does not appear to be a need for the use of aromatase inhibitors to decrease estradiol levels.

Altogether, it appears that trans men using testosterone do not need to be concerned about the possibility of increased estradiol levels or reproductive cancers resulting from estrogenic effects, and do not require any additional medication to suppress estradiol. ■