Effect of naproxen on the hypothalamic-pituitary-adrenal axis in healthy volunteers.
OBJECTIVE
To study the effect of the nonsteroidal anti-inflammatory drug naproxen on the activity of the hypothalamic-pituitary-adrenal (HPA) axis in healthy volunteers.


METHODS
A double-blind, randomized study in two groups of 20 healthy volunteers was performed. The activity of the HPA axis was measured before and after the use of naproxen or placebo during a period of 2 weeks. Basal plasma adrenocorticotropic hormone (ACTH) and cortisol, 24-h urinary cortisol, and circadian cortisol rhythm in saliva were determined. Plasma ACTH and cortisol were also measured during submaximal physical exercise.


RESULTS
There were no significant differences between the placebo and naproxen groups in basal plasma ACTH [09.00 h 3.1 pmol l(-1), 95% confidence interval (CI) 2.0, 4.2, and 2.8 pmol l(-1), 95% CI 1.9, 3.7, respectively], cortisol levels (09.00 h 0.45 micromol l(-1), 95% CI 0.39, 0.51, and 0.40 micromol l(-1), 95% CI 0.35, 0.44, respectively), 24 h urinary cortisol excretion (67.5 nmol 24 h(-1), 95% CI 54.3, 80.7, and 86.8 nmol 24 h(-1), 95% CI 54.4, 119.2, respectively), circadian cortisol rhythm measured in salivary samples, or ACTH and cortisol concentrations after physical exercise. After the use of placebo or naproxen for 2 weeks, no significant change in any of the parameters occurred (ACTH 09.00 h 3.0 pmol l(-1), 95% CI 2.0, 3.9, and 3.0 pmol l(-1), 95% CI 2.2, 3.8, respectively; cortisol 09.00 h 0.45 micromol l(-1), 95% CI 0.37, 0.52, and 0.39 micromol l(-1), 95% CI 0.34, 0.44, respectively; cortisol urine 79.5 nmol 24 h(-1), 95% CI 59.5, 99.4, and 81.7 nmol 24 h(-1), 95% CI 64.0, 99.4, respectively), and no significant differences were found in these parameters between the placebo and naproxen groups.


CONCLUSIONS
The use of naproxen does not influence the activity of the HPA axis in healthy volunteers under basal circumstances or in response to physical stress.
Eijsbouts
Agnes M M
AM
Department of Rheumatology, Sint Maartenskliniek, Radbound University Nijmegen Medical Centre, Nijmegen, The Netherlands. a.eijsbouts@maartenskliniek.nl
Kempers
Marlies J E
MJ
Kramer
Renske S A
RS
Hopman
Maria T E
MT
van den Hoogen
Frank H J
FH
Laan
Ronald F J M
RF
Hermus
Ad R M M
AR
Sweep
Fred C G J
FC
van de Putte
Leo B A
LB
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002940:Circadian Rhythm; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012463:Saliva / Q000737:chemistry; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone