Systematic review of PSA reference intervals in the gender diverse population with prostates

ObjectivesTo determine mean/median serum total prostate‐specific antigen (PSA) levels in transgender women and non‐binary people with prostates (TWNBPP) who have received gender‐affirming hormone therapy (GAHT) or an orchidectomy. The secondary objective was to identify other quantitative information that influences PSA levels in this population.MethodsSystematic review of existing publications from primary studies published in English, excluding case reports and guidelines. Included studies: TWNBPP who have received GAHT/post‐orchidectomy, without a diagnosis of prostate pathology, with recorded serum PSA levels. MEDLINE and Embase databases were searched, up to July 2024.ResultsFour papers met the inclusion criteria, with 290 participants. Two papers measured the mean PSA level after 4 and 12 months of GAHT (mean [range] age 30 [18–45] years). A third paper measured the mean PSA level after a median of 9 years of GAHT (mean [range] age 40.1 [19–67] years). The fourth study measured 852 PSA levels in 210 participants receiving oestradiol therapy, over a 23‐year period (mean [range] age 60 [40–79] years). The mean and median PSA levels ranged from 0.020 to 0.525 ng/mL. Meta‐analysis of these data was unfeasible, due to low quantity, comparability, and quality of the studies.ConclusionsExisting data for serum PSA reference intervals for TWNBPP without prostate pathology were from four studies and cannot be used to make clinical recommendations. The evidence indicates that GAHT in TWNBPP lowers PSA levels from baseline, below expected levels for age‐matched cisgender controls. Not all TWNBPP over the age of 40 years should be offered PSA testing; however, those with a genetic predisposition, family history, or symptoms of prostate cancer, may request or be offered a PSA test. There are currently no clinical PSA thresholds to guide interpretation of PSA levels in TWNBPP when being evaluated for suspected prostate cancer or for those seeking PSA testing.