Transgender health and the impact of aging and menopause.

Gender affirming hormone therapy (GAHT) is used by many transgender people to reduce gender incongruence and improve psychological functioning. As GAHT shares many similarities with menopausal hormone therapy, clinicians supporting people through menopause are ideally placed to manage GAHT. This narrative review provides an overview of transgender health and discusses long-term effects of GAHT to consider when managing transgender individuals across the lifespan. Menopause is less relevant for transgender individuals who take GAHT (often given lifelong) to achieve sex steroid concentrations generally in the range of the affirmed gender. For people using feminizing hormone therapy, there is an elevated risk of venous thromboembolism, myocardial infarction, stroke and osteoporosis relative to cisgender individuals. For trans people using masculinizing hormone therapy, there is an increased risk of polycythemia, probable higher risk of myocardial infarction and pelvic pain which is poorly understood. Proactive mitigation of cardiovascular risk factors is important for all transgender people and optimization of bone health is important for those using feminizing hormones. With a lack of research to guide GAHT in older age, a shared decision-making approach is recommended for the provision of GAHT to achieve individual goals whilst minimizing potential adverse effects.

Adenosine A1 receptor-mediated inhibition of dopamine release from rat striatal slices is modulated by D1 dopamine receptors.

Dopamine release is regulated by presynaptic dopamine receptors and interactions between adenosine and dopamine receptors have been well documented. In the present study, dopamine release from isolated striatal slices from Wistar rats was measured using fast cyclic voltammetry. Single-pulse stimulation (0.1 ms, 10 V) was applied every 5 min over a 2-h period. Superfusion with the adenosine (A)(1) receptor agonist N(6)-cyclopentyladenosine (CPA), but not the A(2) receptor agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl] phenyl]propanoic acid (CGS 21680), inhibited dopamine release in a concentration-dependent manner (IC(50) 3.80 x 10(-7) m; n = 10). The dose-response curve to CPA was shifted to the right (IC(50) 6.57 x 10(-6) m; n = 6, P < 0.05 vs. control) by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Neither the D(1) agonist 6-chloro-APB nor the D(1) antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol (SCH 23390) altered dopamine release on their own. However, SCH 23390 (3 microm) significantly attenuated the response to CPA (IC(50) 1.44 x 10(-5) m; n = 6, P < 0.01 vs. control). Furthermore, the inhibitory effect of CPA was significantly increased in the presence of 6-chloro-APB (1 microm). In radioligand binding experiments, CPA interacted with high- and low-affinity states of [(3)H]DPCPX-lableled A(1) receptors. The high-affinity agonist binding to A(1) receptors was inhibited by the stable guanosine triphosphate analogue Gpp(NH)p. In contrast, neither the proportion nor the affinity of high-affinity A(1) receptors was altered by dopamine or SCH 23390. These results provide evidence that the inhibition of dopamine release by adenosine A(1) receptors is dependent, at least in part, on the simultaneous activation of D(1) dopamine receptors. While the mechanism underlying this interaction remains to be determined, it does not appear to involve an intramembrane interaction between A(1) and D(1) receptors.