Background: Suppression of the hypothalamic-pituitary-gonadal axis with gonadotropin-releasing hormone (GnRH) analogs is commonly used as androgen deprivation therapy (e.g., prostate cancer) to reduce circulating sex steroid levels. Sex hormones play a critical role in regulating cerebral blood flow (CBF), and men receiving androgen deprivation therapy show a higher risk of ischemic stroke and cognitive impairment. Estrogen promotes vasodilation, while testosterone has context-dependent effects on vascular tone. Both hormones regulate cyclooxygenase (COX), which produces prostaglandins that maintain baseline and region-specific CBF. Short-term suppression of sex hormones may reduce baseline CBF and affect cerebrovascular control differently across brain regions, where COX expression and sex hormone receptors vary. This study tested the hypotheses that sex hormone suppression will: (1) reduce global CBF; (2) reduce CBF differentially across brain lobes; and (3) decrease the contribution of COX to resting CBF. Methods: Eight healthy males (24 ± 5 yr; 23 ± 1.3 kg/m 2 ) completed four 3 T MRI sessions using pseudo-continuous arterial spin labeling to quantify regional CBF. Participants underwent two baseline visits with a placebo and COX inhibition with indomethacin (INDO; ~1.5 mg/kg oral) in a randomized, double-blind, placebo-controlled design. This was followed by the same pair of visits after ~4–6 days of hormone suppression (HS). HS was achieved with a GnRH antagonist (elagolix, 200 mg twice daily) plus an aromatase inhibitor (Anastrozole, 1 mg/day) to prevent the conversion of testosterone to estrogen. Data were analyzed using ANOVA and paired t-tests, with results reported as mean ± SD. Results: HS significantly reduced testosterone (4.02 ± 0.62 vs 1.51 ± 1.45 ng/mL; p = 0.004) and estrogen below the assay detection limit (0.0063 ng/mL; p = 0.033). HS decreased resting CBF by ~13–27% in whole brain, grey matter, white matter, frontal, parietal, and occipital lobes (all p 0.07). COX inhibition with INDO reduced CBF at baseline by ~16–29 mL/100 g/min and during hormone suppression by ~11–26 mL/100 g/min across most regions (all p 0.05), indicating that COX-mediated cerebrovascular responses were preserved despite lower CBF during hormone suppression. Conclusion: Short-term suppression of the hypothalamic-pituitary-gonadal axis reduces resting CBF in healthy young males, supporting a role for sex hormones in maintaining global and regional cerebral perfusion. The preserved CBF response to COX inhibition suggests hormonal suppression decreases basal CBF through COX-independent pathways. These findings may have implications for understanding cerebrovascular regulation during clinical or therapeutic states involving hormonal suppression. Funding: NIH (R01 HL150361) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Ortíz et al. (Fri,) studied this question.