Endocrine Abstracts

The Standards of Care version 8 (SOC 8) for transgender and gender diverse people suggest maintaining estradiol (E2) levels between 100-200 pg/ml in Assigned Male at Birth (AMAB) subjects who desire a complete feminization during gender affirmation hormone therapy (GAHT). However, data about estrogen dose therapy and corresponding serum concentrations are scarce, especially regarding gel formulations. Our aim was to retrospectively compare E2 serum levels in AMAB patients undergoing GAHT according to the different formulations and dose used. All subjects were treated with either oral estradiol valerate (OE) or transdermal estradiol gel 0.1% (TDE), according to SOC 8. Three different groups were identified according to the dose of E2 administered: low dose (LD), medium dose (MD), and high dose (HD) [≤ 2, 3-5, >6 mg/day for OE and ≤ 1, 1.5-2.5, ≥3 mg/day for TDE, respectively]. 135 serum E2 measurements were collected among 79 subjects undergoing GAHT. 34.1% of samplings (46/135) were collected in subjects on OE, while 65.9% (88/135) were collected in subjects on TDE. OE was administered in 23.9% of cases at LD, 60.9% at MD and 15.2% at HD, while TDE was administered in 14.6% of cases at LD, 44.9% at MD and 40.4% at HD. Overall, E2 levels showed a wide spreading: 165.8±264.0 pg/ml (16.7 - 2613.6). Serum levels in patients taking TDE (214.7±311.6 pg/ml) were significantly higher (P<0.001) than those in OE (71.1±61.6 pg/ml). Stratifying by dose, significance was maintained in MD and HD groups (P<0.001), with a trend toward significance for the LD groups (P 0.055). Overall, only 23.7% of the measurements were within the desired range: in subjects taking EO were within, below and above range in 15.2%, 80.4% and 4.3% of cases, while in subjects taking TDE were within, below and above range in 28.1%, 38.2% and 33.7% of cases, respectively (P<0.001). No significant differences were found according to the dosage used for each formulation. In conclusion, despite the dosage of GAHT was consistent with the SOC 8 recommendations, E2 levels were often out of target, with patients taking OE showing lower values than those taking TDE. This result could suggest both a greater efficacy of TDE compared with EO at doses typically used and an underestimation of the measured concentration in EO (as found in recent studies), and it should be considered for the interpretation of estradiol values measured in clinical practice.