Intrauterine pressure, ischemia markers, and experienced pain during administration of a vasopressin V1a receptor antagonist in spontaneous and vasopressin-induced dysmenorrhea.
BACKGROUND
A model to study the effect of vasopressin V1a antagonist in dysmenorrhea.


METHODS
A double-blind, randomized, placebo-controlled, cross-over trial was performed. Eight patients with primary dysmenorrhea and eight tuballigated, healthy subjects participated on days 1-2 of two consecutive menstruations. At each menstruation a bolus injection of 10 pmol/kg of vasopressin was administered before and during infusion of either 300 microg/min of atosiban or placebo. Intrauterine pressure was measured as area under the curve throughout the experiments. Ischemia markers in plasma and pain recorded by a visual analog scale were measured before and after each vasopressin injection as well as before and after the start of either atosiban or placebo infusion.


RESULTS
Vasopressin injections elevated area under the curve in both healthy volunteers and dysmenorrhea subjects. The vasopressin-induced rise in area under the curve was lower during atosiban administration than during infusion of placebo in both groups. None of the ischemia markers differed between or within groups at vasopressin injections or atosiban/placebo infusions. In subjects with dysmenorrhea the increase in pain following the administration of vasopressin was significantly lower during atosiban than during placebo infusion. Healthy volunteers experienced only slight discomfort after the vasopressin injections.


CONCLUSIONS
Atosiban reduces vasopressin-induced intrauterine pressure in both healthy volunteers and dysmenorrheics, and reported pain in subjects with dysmenorrhea. The ischemia markers are not a useful biomarker index in women with dysmenorrhea. The dysmenorrhea pain evoked by vasopressin correlated poorly with area under the curve, which may suggest that the effect is mediated by more than one V1a-like receptor. We conclude that this model with recordings in healthy women is useful in the evaluation of drug candidates for primary dysmenorrhea.
Liedman
Ragner
R
Department of Obstetrics and Gynecology, University Hospital of Lund, Sweden.
Grant
Lee
L
Igidbashian
Sarah
S
James
Ian
I
McLeod
Alison
A
Skillern
Laurence
L
Akerlund
Mats
M
D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004412:Dysmenorrhea / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000097:blood; D010147:Pain Measurement; D011446:Prospective Studies; D017483:Receptors, Vasopressin / Q000378:metabolism* / Q000502:physiology; D016896:Treatment Outcome; D014590:Uterine Contraction / Q000187:drug effects*; D014667:Vasopressins / Q000502:physiology; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D065092:Antidiuretic Hormone Receptor Antagonists; D015415:Biomarkers; D006727:Hormone Antagonists; D017483:Receptors, Vasopressin; C047046:atosiban; D014667:Vasopressins; D014668:Vasotocin