atosiban and Dysmenorrhea

In order to study the involvement of oxytocin (OT) and vasopressin (AVP) in mechanisms of uterine activation and to clarify the therapeutic potential of antagonists to these hormones in preterm labour and primary dysmenorrhoea, studies of human uterine contractility in vivo and in vitro as well as measurements of OT and AVP V1a receptors were performed. Good correlations between OT receptor concentrations and effects on contractility were observed in both the pregnant and non-pregnant states, which indicates that OT acts specifically on its own receptor in the uterus. For AVP there was lack of such correlation which may suggest that this hormone influences both the OT and AVP V1a receptor sites. At the onset of labour both preterm and at term no marked increase in the OT receptor concentration was observed, but OT may still be involved in the initiation of labour, being produced locally in the uterus and not detectable in plasma. We observed a reduced OT receptor concentration in advanced labour and after OT infusion, which suggests that OT influences its own receptor. The AVP V1a receptor concentration and the effect of AVP on the uterus were about equal to those for OT, and the concentration of AVP V1a receptors also tended to decrease in advanced labour, observations which support an involvement also of AVP in the mechanisms of labour. In non-pregnant women AVP receptors as well as uterine effects of AVP in vitro and in vivo were about five times higher than those for OT, and the effect of AVP was increased premenstrually. This firmly supports an aetiological role of this peptide in the uterine hyperactivity of primary dysmenorrhoea. We have also shown that the analogue 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-OT, which blocks both the OT and AVP V1a receptor sites, given by intravenous infusion inhibits both preterm labour and dysmenorrhoea, and this is in agreement with our receptor and contractility findings.

Topics: Arginine Vasopressin; Dysmenorrhea; Female; Hormone Antagonists; Humans; In Vitro Techniques; Labor, Obstetric; Obstetric Labor, Premature; Oxytocin; Pregnancy; Receptors, Oxytocin; Receptors, Vasopressin; Tocolytic Agents; Uterine Contraction; Vasotocin

A model to study the effect of vasopressin V1a antagonist in dysmenorrhea.. 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.. 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.. 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.

Topics: Adult; Antidiuretic Hormone Receptor Antagonists; Area Under Curve; Biomarkers; Cross-Over Studies; Double-Blind Method; Dysmenorrhea; Female; Hormone Antagonists; Humans; Ischemia; Pain Measurement; Prospective Studies; Receptors, Vasopressin; Treatment Outcome; Uterine Contraction; Vasopressins; Vasotocin

We compared menstrual pain, uterine contractility and blood circulation, and plasma concentrations of vasopressin and prostaglandin F(2alpha) metabolite in women with versus without primary dysmenorrhea, and determined the effects of a vasopressin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (Atosiban), on these parameters. Our results do not support the contention that vasopressin is involved in the etiology of dysmenorrhea, plasma concentrations of vasopressin being similar in dysmenorrheic women and controls, and the vasopressin antagonist Atosiban having no effect on menstrual pain, intrauterine pressure or uterine artery pulsatility index in dysmenorrheic women.

Topics: Adult; Blood Flow Velocity; Cross-Over Studies; Dinoprost; Double-Blind Method; Dysmenorrhea; Female; Hormone Antagonists; Humans; Uterine Contraction; Uterus; Vasopressins; Vasotocin

In order to study the etiological role of vasopressin in primary dysmenorrhea the therapeutic effect of an antagonist of vasopressin action on the uterus (1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin) was investigated in 14 patients with moderate to severe symptoms. The women participated in the study at two menstruations and each time one intravenous bolus injection of the analogue (10 micrograms/kg body weight) and one of the placebo (saline) were given, randomized and double-blind with at least a 2 hour interval. The effect was monitored by overall ratings and by pain diagrams described by the patients. In the former parameter the vasopressin antagonist was significantly more effective (p less than 0.01). In the pain diagrams, however, a significant reduction of symptoms occurred both after the analogue administrations and after placebo given as second injection. The results support a causative role of vasopressin in primary dysmenorrhea, but further studies with higher doses and/or other routes of administration or delivery systems are required in order to delineate the therapeutic value of vasopressin antagonists in the condition.

Topics: Adolescent; Adult; Clinical Trials as Topic; Double-Blind Method; Dysmenorrhea; Female; Humans; Injections, Intravenous; Pilot Projects; Vasotocin