Endometriosis 1991: a discussion document.
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Endometriosis↗
Biomedical subjects
K Bühler
Publications and source records attributed to K Bühler.
Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study.
During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
Adult↗
Influence on hormone levels, lipid metabolism and reversibility of endocrinological changes after leuprorelin acetate depot therapy.
The effect of leuprorelin acetate depot on the endocrine system and on lipid metabolism was evaluated in a multicentre, noncomparative study. During the first month of treatment, suppression of serum oestradiol levels to below 20 pg/ml was achieved and luteinising hormone and follicle-stimulating hormone levels were reduced to less than 50% of pretreatment values. A negative influence on lipid metabolism was not recorded. The high-density lipoprotein/low-density lipoprotein ratio did not change during therapy. Resumption of menstruation occurred within a mean period of 3 months after the last leuprorelin acetate depot injection.
Bone Density↗
Plasmatic haemostasis in gonadotrophin-releasing hormone analogue therapy: effects of leuprorelin acetate depot on coagulatory and fibrinolytic activities.
The plasmatic parameters of coagulatory and fibrinolytic activity were studied in 15 patients with biopsy-proven endometriosis treated with leuprorelin acetate for 6 months. Bleeding time remained constant, indicating the absence of increased bleeding tendencies. The activity of the main inhibitor of the fibrinolytic response, plasminogen activator inhibitor, was reduced by 25%, suggesting an improvement in fibrinolytic reactivity. Plasma levels of fibrin degradation fragments were reduced by 35%, suggesting a marked reduction in the rate of fibrin generation and degradation. A simultaneous reduction in thrombin-antithrombin III complexes and prothrombin fragment 1 + 2 (-10%) indicated that this effect was induced by reduced procoagulant activity, ie, thrombin generation. These data indicate that in gonadotrophin-releasing hormone (Gn-RH) analogue therapy the basal rate of coagulatory processes is reduced. The frequency and extent of fibrin-generating and degrading processes are reduced, suggesting a beneficial effect of Gn-RH analogues on the risk of thromboembolic disease.
Antithrombin III↗
Experience with leuprorelin acetate depot in the treatment of fibroids: a German multicentre study.
Between October 1988 and October 1990 in a noncomparative multicentre study, 114 patients were treated for uterine fibroids with the gonadotrophin-releasing hormone (Gn-RH) agonist, leuprorelin acetate depot. The mean age of the women was 33 years and 55.3% of them had a history of infertility. After confirmation of the diagnosis by ultrasound and/or operation, treatment began between day 1 and 3 of the cycle with leuprorelin acetate depot 3.75 mg subcutaneously. Therapy was carried out for a total of 6 months with one injection every 4 weeks. Treatment was paralleled by measurements of endocrine and metabolic parameters, estimation of myoma and uterine size by ultrasound and self-reporting of the patients of drug-related complaints. Four of the 114 women did not complete the whole treatment, two of them because of general side effects, one because of carcinophobia and unsatisfactory regression of the myoma and the last one for unspecified reasons. During treatment, a mean reduction of the uterine volume of about 67% was observed, in conjunction with shrinkage of the myoma in 92.1% of cases (mean decrease of 56% of the fibroids) with a large interindividual difference. Maximal diminution of uterine and fibroid size had been nearly completely reached within the first 12 weeks of therapy. After 4 weeks of the Gn-RH agonist depot most of the patients had achieved postmenopausal status, which continued throughout the remaining 20 weeks of treatment. In accordance with this finding, the majority of general side effects was due to the hypo-oestrogenic endocrine status. Liver and lipid metabolism was almost unaffected, although increasing calcium and alkaline phosphatase serum levels as well as an increased urinary calcium/creatinine ratio demonstrated an increased metabolic turnover of the bone. Haemoglobin concentrations, however, increased in those cases with fibroid-related anaemia. Thus the slow-release form of leuprorelin acetate is an adjunct to myomectomy especially in those women in whom family planning is not yet completed.
Adult↗
[Temperature-controlled bipolar electrocoagulation].
The safety of electrocoagulation for laparoscopic surgery has been greatly improved by the introduction of the bipolar coagulation technique. But complications caused by coagulation, especially by the overheated forceps, are still reported. In order to reduce those complications, a temperature controlled bicoagulation system was developed. This system allows coagulation with lower temperatures which can be kept constant during the coagulation process. In experiments with human fallopian tubes obtained by adnexectomy and rabbit uterine horns it is shown that those lower temperatures are sufficient for homogeneous coagulation. On line monitoring of the temperature during coagulation provides the surgeon with the possibility of directly controlling the actual temperature at the tip of the forceps. The temperature curves can easily be stored in order to be able to demonstrate the particular coagulation process even after years.
Animals↗
[Nuclear magnetic resonance imaging in gynecology. An evaluation of its current applications].
The authors present a research carried out by the Universities of Essen, Tubingen (RFA) and Grenoble, France, on the use of magnetic resonance imaging (M.R.I.) in gynaecology. After clarifying our knowledge of the normal anatomy of the pelvis and of the tissular characteristics of MRI the principal indications are discussed and set out. The investigation is shown to be particularly valuable in working out the aetiology, the volume and the spread of a pelvic mass whether it is benign or malignant when it is important to be exact in finding the origin of the tumour. This research has been illustrated by analysing 35 case histories including 28 malignant tumours. A second study was carried out on 30 cases of cancer of the cervix. In this field MRI is the only test that can be carried out before therapy to give a tridimensional assessment of the size of the tumour and whether it has spread into the parametrium. The visual impressions obtained by MRI illustrate each chapter: of the gynaecological anatomy, of the pathology, in cancers of the cervix, in pelvic masses and particularly in ovarian tumours.
Female↗
[Fetal monitoring sub partu in West Germany. III. Associations].
If the number of births per year at a clinic is divided by the number of available cardiotocographs, a variable is obtained, designated Q, which reflects the electronic fetal monitoring situation: the larger Q is, the more births per cardiotocograph, and the less satisfactory is the fetal monitoring situation. The smaller Q becomes, the greater the probability that every fetus can be monitored sub partu. Q has an empirical distribution pattern. The median of Q is between 139 and 215 births per year and per monitor, depending on the size of the clinic. There is a significant relationship between the monitoring value Q and the percentage frequency of cesarean and forceps deliveries: the higher the potential monitoring capacity, i.e., the smaller Q is, the higher the number of cesarean and forceps deliveries of a clinic. Intensive monitoring therefore increases the number of surgical deliveries, though no drop in the unadjusted perinatal mortality rate was observed. No association could be established between Q and the risk of fetal acidosis - possibly due to a lack of data. The conclusion drawn from these data is that the theoretical and practical training of obstetricians and midwives in cardiotocography should be further intensified.
Cesarean Section↗
[Fetal monitoring sub partu in West Germany. II. Effect of clinic size and clinic type on monitoring practice].
Data from 690 clinics concerning obstetric management and intensive monitoring of the fetus sub partu were classified according to the type of hospital (e. g., municipal clinic, district hospital...) and the size of the hospital based on the number of births per year. On the basis of the annual number of births four groups (I-IV) were formed, each with 172 clinics. While the average number of surgical deliveries (cesarean, forceps, vacuum) is not related to the hospital (Table 3), it is related to the type of hospital (Table 6): the average number of cesarean deliveries is highest in university clinics (n = 24; 14.9%), and on average more forceps (6.5%) than vacuum extractions (5.7%) are performed. In all other hospitals vacuum extraction is clearly preferred (7-8%). The quotient Q of the annual number of births per CTG unit is not constant, but increases with the size of the clinic: In large hospitals (Group IV) significantly more births are monitored with a CTG unit (maximum 607, average 215), so that there is a numerical "monitoring deficit" as compared to smaller departments. The monitoring capability is numerically highest in the university clinics (Q = 147) and lowest in the academic teaching hospitals (Q = 192). The larger the clinic, the more frequently fetal blood is analyzed: the figure in large clinics is 40%. Small clinics are less familiar with this method (approx. 16%). The larger the clinic, the more often intrauterine catheters are used to measure labor; the figure rises from 7% to 29%.(ABSTRACT TRUNCATED AT 250 WORDS)
Birth Rate↗
Identification and quantitation of angiotensins.
The introduction of pharmacological inhibitors of renin and angiotensin (ANG) converting enzyme in cardiovascular therapy drew new attention to the role of the renin-angiotensin system in regulating circulatory homeostasis. Accurate measurement of very low concentration of the biologically active peptides ANG II and ANG III sometimes in the presence of large amounts of inactive precursors and metabolites is needed. Active and inactive angiotensins have been measured specifically in attomolar quantities by radioimmunoassay after rapid extraction on bonded-phase silica and subsequent high-performance liquid chromatography. ANG II was found to be generated in cold plasma containing conventional inhibitors; it was concluded that renin, converting enzyme, and angiotensinases must be inhibited if physiological ANG concentrations are to be estimated. Modification of the antigen enhanced the specificity of the ANG II antisera. Monoclonal antibodies to ANG II were produced.
Angiotensin II↗
[Fetal monitoring sub partu in West Germany. I. Basic data].
An inquiry was circulated among all Departments of Gynaecology and Obstetrics in West Germany and West-Berlin with regard to their procedure to effect foetal intensive-care management and monitoring, obstetrical management, and the results obtained. 58% of these Departments responded. With an average number of 55 beds, the annual birth rate is 628. A mean of 191 births are covered by one CTG unit, the scatter being 110-290 births per year and per unit (10th and 90th percentile). The mean incidence of Caesarean section is 11%, the mean incidence of forceps delivery 3.6%, and the mean incidence of extraction by suction 8.0%. An estimated 95% of all births are monitored via cardiotocography. 25% of all Departments use other monitoring methods as well, microanalysis of blood gas after Saling being by far the most prominent one (94%). Transcutaneous foetal pO2 measurement has been adopted by 8 centres only. 74% of the Departments are using CTG units recording beat-to-beat with a chart speed of 1 cm per minute (82.2%). Few (18%) Departments employ intrauterine pressure measurement for recording labour pains. Telemetry is used by 27.7% of the Departments. In most cases (72.9%) the cardiotocograms are jointly assessed by the physician and the midwife. From the obstetrician's point of view it would be desirable to achieve greater technical perfection of external monitoring methods, as well as further miniaturisation and computerisation of the CTG equipment.
Acid-Base Equilibrium↗
[Gestational age and birth weight. Part 2. The placenta and maternal cofactors].
A comparison of median values of intrauterine fetal growth curves (UFK Tübingen) with those contained in all-German and international literature reveals that these data are in close agreement with the results achieved at UFK Heidelberg and by Kyank et al. and Voigt et al. The analysis of 16,740 placental weights indicates that intra-uterine weight development is primarily dependent upon the weight of this organ: Rank correlations were calculated between placental weights and birth weights for various gestational times and parities, the length of gestation remaining constant. As would be expected, the associations encountered were highly significant. After studying the distribution structure of the placental weights in the different weeks of gestation, a table of placenta percentiles (from weeks 24 to 42 of gestation) was drawn up. The dynamics of intra-uterine placental development was compared to the dynamics of fetal weight development. It has been demonstrated that this parameter is dependent on the maternal weight prior to conception as well as on the mother's height and age (only primiparae) (alpha less than 0.001). However, the "extragenital" weight gain of the mother, which increases with rising parity, seems to have no effect on intra-uterine growth. The authors conclude that constitutional, i.e. genetically governed maternal factors exert a greater influence on intra-uterine growth than would have been anticipated. No data were available about the fathers.
Birth Weight↗
[Gestational age and birth weight. 3. Ponderal Index, fetal acid-base metabolism and hypotrophy].
3rd communication: Ponderal-Index, fetal acid-base balance, acidotic risk and minimal placental weight (MPW). The Ponderal-Index of Rohrer (RI), the weight-centile of the newborn and the fetal weight-length-coefficient (FWLC) were evaluated and compared as to the correlation with the variables of the fetal acid-base balance. Using the example of continuous nicotine abuse in pregnancy, a new variable, the minimal placental weight (MPW), was defined. Its clinical applicability was preliminarily tested on the basis of selected cases. RI, FWLC and fetal weight-centiles show highly significant correlations with variables of the fetal acid-base balance. The closest statistical correlation was found for the fetal weight-centile. RI and FWLC did not proof to offer any advantages over this variable. The curve of the acidotic risk of the newborn showed a u-shaped distribution with maximum values in SGA-infants as well as macrosomic babies. Complex umbilical cord-entanglement were more frequently encountered in SGA-fetuses. Macrosomic infants did not show an increased risk in this respect. The preliminary data of this evaluation suggest a predictive value of the MPW for the acidotic risk of the newborn.
Acid-Base Equilibrium↗
[Gestational age and birth weight. 1. Intrauterine growth curves].
Intrauterine growth curves for male and female newborns from the completed 23. to the 42. week of gestation were calculated and drawn using an obstetrical data bank containing data of 17893 neonates. The influence of parity on intrauterine growth was studied and documented. Clinically important weight-centiles were computed and tabulated for both sexes independently and for all neonates on the basis of mean-values and standard deviations of the birth weights, that were predominantly Gaussian-distributed. The statistical consequences of this observation are discussed. The implications of "smoothing-procedures" of weight centiles are outlined.
Birth Weight↗