Lars Franch Andersen

Inhibition of uterine contractions of premature labour with an oxytocin analogue. Results from a pilot study

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.

Effects of hormone replacement therapy on hemostatic cardiovascular risk factors

OBJECTIVES From observational studies, there is evidence that hormone replacement therapy in postmenopausal women causes a decrease in cardiovascular events. It remains unknown, however, precisely by which mechanisms this reduction is achieved. The primary aim of this work was to study the effects of hormone replacement therapy on established hemostatic risk factors during 1-year treatment of healthy postmenopausal women. The secondary aim was to investigate whether there was any significant difference in these risk factors between hormone replacement therapy administered as a cyclic estrogen/sequential progestogen or continuous estrogen/sequential progestogen regimen. STUDY DESIGN Sixty postmenopausal women were randomized to treatment with estradiol valerate 2 mg/day either continuously or cyclic (days 1 to 21; placebo on days 21 to 28). Both groups received cyproterone acetate 1 mg/day on days 12 to 21. Blood samples were collected before treatment and on cycle days 17 to 22 in cycles 3, 6, and 12. Thirty women with basic characteristics identical to the women included in the treatment group were included as a reference group. Blood samples were collected after 0, 6, and 12 months of observation. RESULTS Hormone replacement therapy during 1 year caused a marginal but significant increase in plasma concentration of factor VIIc after 12 months of treatment (P <.05), a significant decrease in fibrinogen, and a significant decrease in the protein concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and lipoprotein(a) after 3, 6, and 12 months of treatment (P <.05). Possible differences in the integrated response between the reference group and the hormone replacement therapy group were evaluated by comparison of the area under the curve as estimated in each individual on the basis of each analyte in the sampling periods. The area under the curve of fibrinogen was significantly lower in the hormone replacement therapy group than in the reference group (P <.03), whereas other variables did not deviate significantly between the groups. The areas under the curve did not deviate significantly between the group that received cyclic estrogen/sequential progestogen and the group that received continuous estrogen/sequential progestogen. CONCLUSIONS One-year treatment with hormone replacement therapy influenced favorably a number of prognostic cardiovascular risk factors in healthy women. The most important effect was the lowering of fibrinogen. Furthermore, in this study the effect of hormone replacement therapy on hemostasis did not deviate between a cyclic estrogen/sequential progestogen regimen and a continuous estrogen/sequential progestogen regimen.

Ampicillin‐metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial

Objective To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity.

Sequelae of induced first-trimester abortion: A prospective study assessing the role of postabortal pelvic inflammatory disease and prophylactic antibiotics

A follow-up study was undertaken in 493 women who had participated in a clinical, controlled trial with the object of assessing the role of postabortal pelvic inflammatory disease and prophylactic antibiotics in the development of sequelae. Information about dysmenorrhea, dyspareunia, chronic pelvic pain, episodes of pelvic inflammatory disease, infertility, births, induced and spontaneous abortions, and ectopic pregnancies were obtained from 382 of the women and from 38 of 40 women who had contracted postabortal pelvic inflammatory disease during the previous study. Significantly elevated rates in women with postabortal pelvic inflammatory disease compared with women without this disease were found for spontaneous abortion (22% versus 5%, p less than 0.0005), secondary infertility (10% versus 2%, p less than 0.05), dyspareunia (20% versus 5%, p less than 0.005), and chronic pelvic pain (14% versus 2%, p less than 0.001). Nonsignificant differences were observed for ectopic pregnancy and dysmenorrhea. A new episode of pelvic inflammatory disease within the first year after abortion was observed more often in women with postabortal pelvic inflammatory disease than in women without infection (41% versus 5%, p less than 0.0001). Prophylactic antibiotics decreased the rates of spontaneous abortion and dyspareunia (p less than 0.05 in both instances).

Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: A randomized trial

Objective. To determine which treatment should be offered to women with a non‐ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. Design. Prospective, randomized, open multicenter study. Setting. Seven Danish departments of obstetrics and gynecology. Sample. A total of 106 women diagnosed with ectopic pregnancy (EP). Methods. Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were randomized to either medical (MTX; 53) or surgical (laparoscopic salpingotomy; 53) treatment. Follow‐up by questionnaire and through national patient databases for a maximum of 10 years. Main outcome measures. Uneventful decline of plasma‐human chorionic gonadotropin to less than 5 IU/L, rates of spontaneous, subsequent intrauterine, and recurrent ectopic pregnancies. Results. The success rates were 74% following MTX treatment and 87% after surgery (n.s.); the subsequent spontaneous intrauterine pregnancy rate was 73% after MTX and 62% after surgery; and the EP rate was 9.6% after MTX and 17.3% following surgery (n.s.). Conclusions. In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment modalities seemed to be similar in outcome, it is crucial that the diagnosis is based on a high‐quality ultrasonographic evaluation, as two patients had intrauterine pregnancies despite fulfilling the diagnostic algorithm for EP.

Thermal balloon endometrial ablation : Safety aspects evaluated by serosal temperature, light microscopy and electron microscopy

OBJECTIVES Thermal balloon endometrial ablation is a new method for treating menorrhagia. The technique appears to be less difficult compared to standard hysteroscopic ablation techniques and to be significantly safer. The influence into the uterine wall of the thermal balloon ablation procedure was investigated with special reference to the ability of total destruction of the endometrium and the thermal action on the myometrium and the serosa. STUDY DESIGN Temperatures were measured at the uterine serosal surface during thermal balloon endometrial ablation for 8-16 min in eight patients. After subsequent hysterectomy the extent of thermal damage into the myometrium was assessed by light and electron microscopy. RESULTS The highest temperature measured on the uterine serosa was 39.1 degrees C. Coagulation of the myometrium adjacent to the endometrium could be demonstrated by light microscopy in all patients, with a maximum depth of 11.5 mm. By electron microscopy no influence of heat could be demonstrated beyond 15 mm from the endometrial surface. CONCLUSION Up to 16 min of thermal balloon endometrial ablation therapy can destroy the endometrium and the submucosal layers. The myometrium is only coagulated to a depth where full thickness necrosis or injury is unlikely.

The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes.

The occurrence of prior cervical conization and the cervical microbial colonization was investigated in 38 women with idiopathic preterm labor, 35 women with preterm premature rupture of the membranes (PPROM) and 75 normal pregnant women at 26-34 weeks of gestation. Data were analyzed by Fishers exact test (two-tailed). The frequency of prior cervical conization was significantly higher in PPROM patients compared to normal pregnant women (P < 0.001) and to patients in preterm labor (P < 0.01). Lactobacilli occurred with a lower frequency in patients with PPROM compared to patients in preterm labor (P < 0.05) and control patients (P = 0.0543)-and with a lower frequency in patients with prior cervical conization (P < 0.05). All other microorganisms occurred with the same frequencies in all groups. The absence of lactobacilli may indicate changes in the cervical flora, which could increase the risk of PPROM. Prior cervical conization may impair the antimicrobial defense-mechanisms in the cervix, which could facilitate ascending microbial colonization. This may lead to a release of prostaglandins and proteolytic enzymes and subsequently preterm labor and rupture of the membranes.

Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We conclude that the treatments were followed by a compensated decrease in insulin sensitivity that was unrelated to changes in triglycerides, t-PA, or PAI-1 antigen.

Termination of second trimester pregnancy with gemeprost vaginal pessaries and intra-amniotic PGF2α. A comparative study

152 women admitted for legal abortion in the second trimester of pregnancy were included in an open, randomized, controlled six-centre study. 75 patients received gemeprost 1 mg vaginal pessaries at 3 hours intervals up to a maximum of 5 mg and 66 patients were treated with a single 40 mg intra-amniotic dose of PGF2 alpha. The 24-hour success rate was 81% (n = 61/75) in the gemeprost and 64% (n = 42/66) in the PGF2 alpha group (p less than 0.02). The mean abortion times were 14.3 and 14.8 hours in the gemeprost and the PGF2 alpha groups, respectively. The mean time to onset of pain was shorter and more patients experienced blood loss over 100 ml during the induction in the PGF2 alpha group than in the gemeprost group (p less than 0.02). Apart from that, the nature and severity of side effects were comparable between the two groups. Besides significantly better efficacy, the non-invasive gemeprost treatment was found to be easier and safer as compared to the PGF2 alpha treatment.

Micturition pattern in hyperthyroidism and hypothyroidism

Micturition pattern was investigated in 61 consecutive patients with thyroid disease. The patients were divided into three groups: hyperthyroid, hypothyroid, and euthyroid. Micturition pattern was examined after the first visit to the hospital and again six months later, when thyroid function had been restored to normal. Hyperthyroid patients had significantly increased micturition frequency as well as nocturia compared with their own control group when euthyroid (p less than 0.01). Hypothyroid patients had reduced micturition frequency compared with their own control group (p = 0.05). No significant changes were found in the euthyroid group. Which mechanisms might be responsible for the relationship between thyroid function and micturition pattern is debatable, and calls for further urodynamic and electrophysiologic studies. One conclusion is that thyroid disease should be borne in mind when patients present with unexplained urinary frequency or retention.