Masculinizing hormone therapy in latent AIP. First case in Argentina

Masculinizing hormone therapy (MHT) is used in individuals with gender dysphoria to promote the development of secondary sexual characteristics. Testosterone is classified as probably not porphyrinogenic for acute porphyrias (AP) and is used to suppress the menstrual cycle and reduce ovarian estrogen production under medical supervision. Women with AP may experience symptoms related to the menstrual cycle, including acute attacks. MHT is a chronic therapy that presents a particular challenge in AP because synthetic testosterone is metabolized by CYP3A4, potentially affecting the hepatic heme pool. Our aim was to evaluate longitudinal changes in heme pathway parameters in a patient undergoing MHT to monitor clinical and biochemical evidence of acute intermittent porphyria (AIP) activation. A 27-year-old patient with latent AIP, assigned female at birth and carrying the p.Gly111Arg variant, began MHT with daily Androlone gel (1% testosterone) in 2021. The patient developed masculinizing features and became amenorrheic in August 2022. Testosterone levels were adjusted to the desired range (3-7 ng/mL). General biochemical and metabolic parameters remained within normal ranges. The patient reported a marked sense of well-being and no adverse effects. Heme precursors and porphyrin excretion remained close to reference values: 5-aminolevulic acid: 1.3-2.5 mg/24 h (RV:≤4 mg/24 h); porphobilinogen: 1.0-2.9 mg/24 h (RV: ≤2 mg/24 h); total urinary porphyrins: 31-213 μg/24 h (RV:≤250 μg/24 h). This is the first reported case of MHT in a patient with AIP in Argentina. These findings suggest that MHT may be feasible in patients with latent AIP, provided that close biochemical and clinical monitoring is maintained.