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Notizen: Objective To compare two oral contraceptive pills, both containing 150 μg desogestrel, but with either 20 μg (Mercilon®) or 30 μg (Marvelon®/Desolett®) ethinyl oestradiol (EE), regarding reliability, cycle control and side effect profile.Design A double blind, randomised, multicentre study over one year with follow up after three, six and 12 months. The women noted tablet intake and all bleedings on specifically designed diary cards.Setting University clinics, central hospitals and private gynaecological practices in Norway, Sweden and Denmark.Subjects One thousand women aged 18 to 40 years requesting oral contraceptive pills.Main outcome measures Reliability, cycle control, side effects, blood pressure, body weight and haemoglobin.Results In a total of 4543 cycles with the 20 μg EE dose pill and 4688 cycles with the 30 μg EE dose pill, the number of pregnancies ascribed to method failure were 0 and 2, respectively. Irregular bleeding (breakthrough bleeding or spotting) was signficantly more frequent with the 150/20 combination in about two-thirds of the cycles randomly distributed over the one year of the study. Mean blood pressure decreased slightly, particularly in the group on the 150/20 combination (about 1 mmHg), whereas mean body weight increased approximately 0.5 kg in the group with the 150/30 combination after 12 months. Haemoglobin did not change. Side effects other than bleeding problems were rare, but dizziness and mood changes were more frequent in the group on the 150/20 combination. Due to side effects, more women on the 150/20 combination discontinued the study during the one to three and four to six month periods, and women on this pill were also less positive about continuing the study drug at the end of the trial.Conclusions Both pills have high contraceptive reliability and are well tolerated, but with the 150/20 combination the cycle control is less effective. However, in view of the potentially increased safety profile of the 150/20 combination, many women can be expected to accept some additional discomfort due to irregular bleeding.

Notizen: Objective To study in nonpregnant women myometrial actions of vasopressin and oxytocin and the involvement in these effects of specific uterine receptors.Subjects Twenty-eight women undergoing hysterectomy for benign gynaecological disorders.Interventions Intrauterine pressure recordings. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin and oxytocin. Repeated blood sampling for measurement of vasopressin and oxytocin concentrations in plasma. Recording of effects of vasopressin and oxytocin on isolated myometrium. Estimation of myometrial concentrations of vasopressin V1a and oxytocin receptors. Measurement of plasma oestradiol and progesterone.Main outcome measures Vasopressin- and oxytocin-induced increases of the area under the in vivo recording curve over 10 minutes and EC50 concentrations of dose-responses in vitro. Concentrations of vasopressin V1a and oxytocin receptors.Results Vasopressin was on average four times more potent than oxytocin in vivo. The effect of vasopressin premenstrually was more pronounced than in women under oestrogen influence only (proliferative phase-hyperproliferation; P= 0.02), and tended to be more marked than in those in the luteal phase (P = 0.07). No significant variation in oxytocin response with the hormonal state was observed. EC50 concentrations of vasopressin were more than 20 times lower than those of oxytocin. The median concentration of the vasopressin V1a receptor was 208 (range 139–343) fmol/mg protein and that of the oxytocin receptor 49 (38–87) fmol/mg protein. Vasopressin receptor concentrations and in vivo effects of this peptide did not correlate, whereas for those of oxytocin a significant correlation was observed (P= 0.02).Conclusion The high potency of vasopressin in nonpregnant women, particularly premenstrually, firmly supports an aetiological importance of this peptide in the uterine hyperactivity of primary dysmenorrhoea. Oxytocin seems to be less important in this condition in view of its much smaller potency and the absence of increase in effect premenstrually. Vasopressin appears to influence both the oxytocin and the vasopressin Vla receptor sites in the uterus, whereas oxytocin acts specifically on its own receptor.

Notizen: Objective To study the influence of the position of the threads of an intrauterine contraceptive device (IUCD) on the development of genital tract infection.Design A multicentre randomized controlled trial. Subjects Women requesting an IUCD.Interventions The women were randomized to be fitted with an IUCD either with the threads contained in the uterine cavity (threads-up group) (n= 208) or passing through the cervix to the vagina in the usual way (threads-down group) (n= 237). Multiple centre study with follow-up at three months, 1 and 2 years. At the final visit ‘missing’ threads were retrieved using a disposable instrument (RetrievetteR).Main outcome measures The occurrence of infection in the lower or upper genital tract.Results 63 women in the threads-up group and 78 in the threads-down groups dropped out. Previous gynaecological infection was reported by 21 and 48 women in the threads-up and threads-down group, respectively (odds ratio 0.44, 95% CI 0.24 to 0.79), 21 and 53 subjects had signs of infection at gynaecological examination (odds ratio 0.39,95% CI 0.21 to 0.69) and a wet-smear was pathological in 33 and 79 (odds ratio 0.38, 95% CI 0.23 to 0.61). In the threads-up group the vaginal pH was also lower at the final check up after 2 years. Spontaneous descent of the threads occurred in 11% of the threads-up group and in six women in the threads-down group the threads were in the cervix. In 93 women the threads were easily retrieved by means of the RetrievetteR, four women insisted on the threads remaining in the uterus and in 18 thread removal was performed under local or general anaesthesia.Conclusions Infectious complications in women using an IUCD are more frequent if the threads lead from the uterine cavity to the vagina. This problem can be reduced by inserting the threads so that they remain entirely within the uterine cavity, a feasible procedure now that an effective instrument for IUCD thread retrieval is available.

Notizen: Objective To study aspects of the aetiology of primary dysmenorrhoea and mechanisms underlying the therapeutic effect in this condition of an oral contraceptive.Intervention Intrauterine pressure was recorded before and during infusion of hypertonic saline (5% NaCl, 0.06 ml/kg/min) over 75 min on the first day of bleeding in women with dysmenorrhoea and after 3 weeks of oral contraceptive treatment. Plasma sampling every 15 min of ongoing infusion for the estimation of osmolality, arginine vasopressin, oxytocin and the prostaglandin (PG) F-metabolito, 15-keto-13, 14-dihydro-PGF2α.Subjects Ten healthy nulliparous women with moderate to severe primary dysmenorrhoea.Main outcome measures Plasma levels of posterior pituitary hormones and the PGF-metabolite. Total pressure area (TPA) of the recording curve.Results In dysmenorrhoea before infusion the plasma concentration of vasopressin was in mean 2.18, oxytocin 5.05 and the PGF-metabolite 321.5 pmol/1, and the TPA 3.8 kPa ≥ 10 min. After oral contraceptive treatment the vasopressin level and the TPA were significantly reduced. At both sessions apart from intensifying the pain, the saline infusion increased vasopressin and oxytocin levels as well as the TPA, whereas the concentration of the PGF-metabolite at both sessions decreased.Conclusion Confirmation is provided of the elevated secretion of arginine vasopressin and PGF2α, as well as increased uterine activity in primary dysmenorrhoea. The observations are in agreement with the concept that a lowered level of vasopressin and a decreased uterine activity contributes to the beneficial effect of OCs in the condition. Stimulation of the secretion of vasopressin increases the uterine activity and symptoms of primary dysmenorrhoea, but results suggest that this effect does not involve a mechanism of increased PGF-synthesis. The role of oxytocin in dysmenorrhoea can not yet be defined.

Notizen: Summary. Three analogues of posterior pituitary hormones, 1 - deamino - 2 - D - Tyr(OEt) - 4 - Val - 8 - Om - vasotocin(dE - VVT), l-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 μg/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40–50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 1/h. The bioavailability of 100 ng/kg given intra-nasally was about 5·5%. Further studies are recommended.

Notizen: Summary. In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation.

Notizen: Summary. A competitive inhibitor of the action of oxytocin on the uterus, l-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, was studied for the first time in 13 patients with established, uncomplicated premature labour. Intravenous infusion of 10–100 μg/min of the analogue was given for 1–10 h and the effect was monitored by external cardiotoco-graphy. In all women an inhibition of uterine activity was observed, and in the majority of patients infused with 25 μg/min and a total dose of about 5 mg or more of the drug total inhibition of uterine contractions was achieved. There were no effects on the maternal and fetal pulse rates, nor were there any other side-effects. The results of this preliminary study support the concept of an increased concentration of uterine oxytocin receptors being aetiologically important in uncomplicated premature labour. They also suggest that the present oxytocin antagonist could be an interesting therapeutic alternative in the condition, primarily because of the marked selectivity of its effect.

Notizen: Summary. Local endometrial blood flow was measured by a thermistor technique and myometrial activity by intrauterine pressure recording in 10 women before and during menstruation. The effect of lysine vasopressin infusion (1 pmol/kg body-weight per min) and of bolus injection of a synthetic oxytocin analogue, l-deamino-2-d-Tyr(OEt)-4-Thr-8-Orn-oxytocin (10 nmol/kg body-weight), were studied. Spontaneous variations in blood flow were seen synchronous with clearly demarcated uterine contractions, the myometrial activity being significantly increased in early (day – 1 to day +2) compared with late (day +3 to day +5) menstrual phase. The vasopressin infusion decreased blood flow, stimulated uterine activity and caused slight to moderate dysmenorrhoea-like pain. These effects were completely inhibited by the injection of the oxytocin analogue. In-vitro studies on uterine arteries confirmed that the analogue also inhibited the vasopressin-induced constriction of the uterine arteries. This antagonist was more effective than two other analogues, l-deamino-2-d-Tyr(OEt)-4-Val-8-Orn-oxytocin and l-deamino-2-Tyr(OEt)-oxytocin. The counteracting effect of l-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on the vasopressin-induced decrease of blood flow and increase of contractions supports the therapeutic value of the drug in primary dysmenorrhoea and preterm labour.

Notizen: Objective  To study oxytocin mRNA in the human endometrium at different phases of the menstrual cycle.Design  An exploratory study in non-pregnant women.Setting  The Department of Obstetrics and Gynecology, Lund University Hospital, Sweden.Participants  Thirty-three women of fertile age undergoing hysterectomy or endometrial curettage on routine benign gynaecologic indications.Methods  Endometrial tissue was obtained throughout the menstrual cycle. The presence of oxytocin mRNA was investigated by in situ hybridisation and by real time PCR.Main outcome measures  Oxytocin mRNA signalling intensity found by in situ hybridisation of tissue obtained at different times of the menstrual cycle. Relative amounts of oxytocin mRNA measured by real time PCR.Results  The signal for oxytocin mRNA obtained by in situ hybridisation was more pronounced in glandular epithelial cells than in stromal cells. Furthermore, it was most marked around mid-cycle. The expression of oxytocin mRNA was confirmed by real time PCR.Conclusions  The results indicate that oxytocin may be synthesised in the endometrium of non-pregnant women, particularly in the glandular epithelial cells. Hormone released from these sources may have a paracrine action on the uterus. Oxytocin mRNA expression seems to be ovarian hormone dependent with the highest concentration around mid-cycle.