ORF46-06 - Use of Progesterone and GnRH Agonists as Adjunctive Therapies for Transgender Patients on Estrogen at a Single Institution

Background: Transgender people pursuing feminization via hormone therapy often seek the use of adjuvants, such as progesterone and GnRH agonists, in addition to estrogens. The extent to which these medications impact gender transition and health are not well understood. We assessed safety of these drugs and their impact on endogenous testosterone (T) in a retrospective study.

Methods: An initial cohort of 428 charts within the Phoenix Veteran’s Affairs Medical Center from October 1999 through October 2023 was identified using ICD codes consistent with or similar to a diagnosis of gender dysphoria. From this initial cohort, we conducted a chart review of 104 patients who received estrogen-based hormone therapy through the Endocrinology division. Data collected included a range of demographic information, treatment type and duration, hormone concentrations and adverse events.

Results: Patients studied were 53±2 years old, 85% white, and were prescribed estrogen (E) for 4.6 ± 0.5 years. Three groups were created based on medication regimens: E only (EO, n = 53), E + progesterone (EP, n =38), and E + GnRH agonist (EG, n = 20). Patients in the EO group (mean age 57 ± 2 years) were significantly older than those in the EP group (45 ± 2 years; Welch’s t = 3.80, p < 0.001), while EO and EG (53 ± 3 years) did not differ significantly (p = 0.33). Optimal therapy was defined as ≥180 days of any E-based therapy. Thirty-nine patients reached optimum therapy in the EO group, 19 in EP and 8 in EG. There was no significant difference in rates of adverse effects between groups.

On optimal therapy, EO patients had a significantly higher likelihood of an endogenous testosterone measurement ≥50 ng/dL compared with EP (OR 2.6, p = 0.032) and EG (OR 5.9, p = 0.003) groups respectively. Among patients treated with E for ≥180 days, the proportion of testosterone readings < 50 ng/dL increased after addition of an adjuvant from 72% to 80% in the EP (p=0.19), and from 50% to 88% in the EG group (p < 0.001). Paired analysis of six EP patients showed no significant testosterone reduction after the addition of progesterone (p=0.175).

Only 6 of the 86 patients who received ≥180 days of estrogen therapy had a majority of estradiol readings within the target range (100 to 200 pg/mL). Overall, estradiol readings skewed below this range (62% across all readings), and the within‑range proportion was lower in EO than EP (13% vs 26%; p = 0.002) and EG (13% vs 23%; p = 0.024).

Conclusions: Progesterone and GnRH agonists were safe adjunctive therapies in conjunction with estrogens. Testosterone values in patients prescribed either adjuvant appeared more likely to be within the target range. However, in our small sample, addition of GnRH, but not progesterone, after ≥180 days of estrogen significantly reduced testosterone levels. Thus, our evidence suggests that GnRH but not progesterone is effective as adjunctive therapy in estrogen-based GAHT.