Mental Healthcare Utilization of Transgender Youth Before and After Affirming Treatment.

OBJECTIVE: Transgender and gender-diverse (TGD) adolescents experience increased mental health risk compared to cisgender peers. Limited research suggests improved outcomes following gender-affirmation. This study examined mental healthcare and psychotropic medication utilization among TGD youth compared to their siblings without gender-related diagnoses and explored utilization patterns following gender-affirming care. METHOD: This retrospective cohort study used military healthcare data from 2010-2018 to identify mental healthcare diagnoses and visits, and psychotropic medication prescriptions among TGD youth who received care for gender dysphoria before age 18, and their siblings. Logistic and Poisson regression analyses compared mental health diagnosis, visits, and psychotropic prescriptions of TGD youth to their siblings, and compared healthcare utilization pre- and post-initiation of gender-affirming pharmaceuticals among TGD adolescents. RESULTS: 3,754 TGD adolescents and 6,603 cisgender siblings were included. TGD adolescents were more likely to have a mental health diagnosis (OR 5.45, 95% CI [4.77-6.24]), use more mental healthcare services (IRR 2.22; 95% CI [2.00-2.46]), and be prescribed more psychotropic medications (IRR = 2.57; 95% CI [2.36-2.80]) compared to siblings. The most pronounced increases in mental healthcare were for adjustment, anxiety, mood, personality, psychotic disorders, and suicidal ideation/attempted suicide. The most pronounced increased in psychotropic medication were in SNRIs, sleep medications, anti-psychotics and lithium. Among 963 TGD youth (Mage: 18.2) using gender-affirming pharmaceuticals, mental healthcare did not significantly change (IRR = 1.09, 95% CI [0.95-1.25]) and psychotropic medications increased (IRR = 1.67, 95% CI [1.46-1.91]) following gender-affirming pharmaceutical initiation; older age was associated with decreased care and prescriptions. CONCLUSION: Results support clinical mental health screening recommendations for TGD youth. Further research is needed to elucidate the longer-term impact of medical affirmation on mental health, including family and social factors associated with the persistence and discontinuation of mental healthcare needs among TGD youth. Hisle-Gorman E, Schvey NA, Adirim TA, et al. Mental Healthcare Utilization of Transgender Youth Before and After Affirming Treatment. J Sex Med 2021;18:1444-1454.

The orphan nuclear receptor NR4A1 specifies a distinct subpopulation of quiescent myeloid-biased long-term HSCs.

Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1(GFP) BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin(-) Sca-1(+) c-Kit(+) CD48(-) CD150(+) long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1(GFP+) and NR4A1(GFP-) HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1(GFP+) HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs.