When trans boys or transmasculine adolescents (assigned female at birth) are on GnRH agonist puberty blockers such as Lupron or histrelin, this switches off their body’s production of estrogen, and before they begin hormone therapy, there is no testosterone to replace this. In the absence of either sex hormone, greater time spent on puberty blockers translates to greater gains in final adult height. This is because the presence of estrogen would cause the closure of the bones’ epiphyseal growth plates and cause gain of height to stop, and administered testosterone can be aromatized into small amounts of estrogen that produce the same closure of growth plates.
The disadvantage of remaining on GnRH agonists while delaying cross-sex hormone therapy with testosterone for as long as possible is that while these youth may gain height during this time, they are not able to experience the benefits of desired physical masculinization – their bodies experience neither a puberty of feminization or masculinization. Longitudinal studies of trans youth throughout initiation of puberty blockers and initiation of hormone therapy have suggested that while GnRH agonists alone are not associated with a reduction in symptoms of gender dysphoria, the addition of hormone therapy following puberty blockers does produce a decrease in these symptoms. Additionally, youth who reach an age of 15, 16 or 17 without even having started pubertal changes may feel socially and developmentally out of step with their same-age cisgender peers, who would typically have started puberty many years earlier.
This presents the problem of how to enable timely introduction of masculinizing hormone therapy for effective treatment of gender dysphoria while also allowing the continuation of growth for as long as possible to be closer to that of cisgender men. Now, further results from the team behind the original abstract offer support for the use of oxandrolone to accomplish both of these purposes.
Grimstad, Knoll, & Jacobson (2021) studied 154 transmasculine adolescents with data on height collected from 2013 through 2020. Among those who had grown to their adult height while medically transitioning, 34 had taken oxandrolone, 46 had taken testosterone, and 14 had only taken GnRH puberty blockers. 42 others had already reached their final adult height before beginning treatment, and another 14 did not receive any treatment with either puberty blockers or any hormone therapy. The youth taking oxandrolone were divided into early and late oxandrolone subgroups based on their age of starting treatment:
The median age at initiation of oxandrolone was 14.6 years. Those who started treatment before 14.6 years were considered early treatment, and those who started treatment after 14.6 years were considered late treatment.
The 17 youth who began taking oxandrolone at an early age showed a significantly greater final adult height than the 17 who started at a later age, and a significantly greater height than those who received treatment with testosterone, treatment with only GnRH agonists, or no medical transition treatment. The early oxandrolone group started treatment at an average of 13.1 years and achieved an average final adult height of 169.6 cm (66.8 inches) with a standard deviation of 6.4 cm (2.5 inches). In comparison, the late oxandrolone group started at 15.8 years and reached an average height of 162.1 cm (63.8 inches), and the group taking testosterone started at 17.9 years and reached an average of 163.7 cm (64.4 inches). This represents an overall difference in height 5.9 cm (2.3 inches) greater in trans boys who started oxandrolone early compared to those taking testosterone.
The authors also compared trans boys’ final adult heights to those of cis men, finding that youth in the early oxandrolone group reached or nearly reached an adult height typical of cis men far more frequently than any other treatment group:
To compare the final height for TM individuals to that of cisgender males, we examined the number of participants who achieved a height of 168.8 cm or greater, which corresponds to an adult height 1 standard deviation (SD) below the 50th percentile for the Centers for Disease Control and Prevention (CDC) male growth chart (176.8 cm) and approximately the 85th percentile on the CDC female growth chart. For the early oxandrolone group, 9/17 (52.9%) participants achieved an adult height within 1 SD of the CDC male mean height, compared to 1/17 (5.9%) in the late oxandrolone group (p = 0.008), and only 24/120 (20.0%) for all other participants (p = 0.006).
Four patients taking oxandrolone experienced mild or moderate elevations of ALT or mild elevations of AST liver function levels, which either returned to normal on their own or resolved after switching from oxandrolone to testosterone. Oxandrolone treatment was temporary for all patients before later switching to testosterone on a permanent basis, and the authors note that oxandrolone produces more mild or gradual masculinization that could be preferable in those who are “too young for testosterone or not ready for testosterone’s permanent changes” or who “wanted to begin androgenization in a largely reversible manner or with known dose-dependent effects”. This masculinizing steroid is more reversible in its effects than testosterone, serving as a kind of midpoint between puberty blockers alone and testosterone:
Furthermore, the effects of oxandrolone can be considered more reversible than those of testosterone: oxandrolone use in young cisgender girls with Turner syndrome demonstrates that long-term therapy with low doses of oxandrolone [<0.06 mg/(kg•day)] causes mild increased muscle mass and mild clitoromegaly without permanent voice changes. Oxandrolone may help reduce the side effects of GnRHa such as hot flashes in patients who are not ready for testosterone.
Because of the notably greater effect of oxandrolone when started at an earlier age, the authors emphasize that earlier referral to gender clinics for evaluation and possible treatment is crucial, yet trans youth typically present for treatment at age 16 when most growth has already occurred and there is no more potential growth to be boosted by oxandrolone. Although the average final adult height of the early oxandrolone group was still below the average height of adult cis men, oxandrolone nevertheless produced inches greater height than that seen with use of the standard testosterone treatment. This new development represents a meaningful step toward further improvement of medical transition for young trans boys. ■