EFFECT OF DIFFERENT TESTOSTERONE FORMULATIONS FOR GENDER AFFIRMING HORMONAL THERAPY ON MENSTRUAL PATTERN IN PEOPLE ASSIGNED FEMALE AT BIRTH

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Abstract Objectives Menstrual dysphoria is defined as a condition of distress or anxiety due to the persistence of menstrual cycles during Gender Affirming Hormonal Therapy(GAHT)in transgender people Assigned Female at Birth(AFAB), associated with increased rates of depression, and of self-harm and suicidal ideation. The aim of the current cohort study was to evaluate modifications of menstrual pattern in AFAB people according to the duration of GAHT and to the different testosterone formulations used in the treatment. Methods Sixty-four AFAB people with gender incongruence, treated with testosterone as 250 mg intramuscular(IM)testosterone enanthate/propionate every 28 days(N = 26)or 10-69 mg transdermal(gel)testosterone daily N = 38), for at least 3 consecutive months and with an up to 36-month follow up, were retrospectively investigated, in order to determine the association between different testosterone formulations and amenorrhea at different time-points(3,6,12,24,36 months). Results A progressive increase in the occurrence of amenorrhea was observed in 12.5%after 3 months, in 24.48% after 6 months, in 29.03% after 12 months, in 29.41% after 24 months, and in 40% after 36 months of GAHT with testosterone. Comparing IM vs gel testosterone formulation, the former was associated with a significantly higher prevalence of amenorrhea at 3 and 24 months from the beginning of GAHT. In particular, at 3 months of GAHT, in the IM vs gel formulation group, amenorrhea was achieved in 26.92% vs 2.63%; p = 0.006,whereas menses persisted in 73.08% vs 97.37%; p = 0.006. At 24 months of GAHT, in the IM vs gel formulation group, amenorrhea was achieved in 81.25% vs 35.71%; p = 0.024,whereas menses persisted in 18.75% (3/16) vs 64.29% (9/14); p = 0.024. No significant association between either testosterone formulation and the prevalence of amenorrhea was detected at 6,12 and 36 months of GAHT. Conclusions In the current single-center experience, the occurrence of amenorrhea progressively increased over time during GAHT with testosterone, up to 36 consecutive months of treatment. Moreover, IM testosterone formulation more efficiently induced the achievement of amenorrhea after 3 and 24 months of consecutive treatment, compared to gel formulation. Further studies are required to confirm the superiority of efficacy of testosterone IM formulation over gel formulation; the choice of IM formulation to the purpose of achieving amenorrhea should be weighed in relation to the evidence that gel formulation is safer and guarantees more stable serum testosterone levels. Conflicts of Interest None.

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