Copper release from copper intrauterine devices removed after up to 8 years of use.

We studied the copper-releasing ability, weight and microscopic appearance of 2 copper-bearing intrauterine devices (IUDs), Copper-T Cu 200 (CuT) and Nova-T Cu 200 Ag (NovaT), after they had been in utero for up to 8 years. In addition, we studied whether IUDs removed from pregnant women showed different copper release. We found that IUD weight was a linear, negative function of duration of use, and that less than 20% of total copper would be released over a period of 8 years. The average copper-releasing ability was significantly higher for CuT than for NovaT (82.6 +/- 6.4 vs. 42.7 +/- 2.6 micrograms/day). The copper release was constant and thus unrelated to duration of use. Copper-releasing ability was similar in IUDs removed from pregnant and non-pregnant women. Fragmentation or minor defects only occurred in 3% of the IUDs and no correlation was found between deposits or corrosion and copper release rates. We conclude that CuT and NovaT both have constant copper release for at least 5-6 years and that the useful life-span probably can be prolonged to 6-8 years or more.

The post-operative gonadotropin level in post-menopausal women with epithelial ovarian cancer.

Serial estimates of the post-operative hormone levels were made in 15 women subjected to oophorectomy because of ovarian carcinoma. All women were post-menopausal. Pre-operatively, they had significantly lower follicle stimulating hormone (FSH) levels compared with an age-matched control group. Blood samples were collected after a median time of 8 months (139-378 days). After oophorectomy, significantly higher FSH values were found (P = 0.0002), whereas the luteinizing hormone (LH) values were not significantly changed. The inhibin, estradiol and progesterone values were found to be significantly lowered compared with the pre-operative sample. Total and unbound testosterone levels were significantly lower while dehydroepiandrosterone sulphate (DHEAS) and androstenedione levels were unchanged compared with the original sample and compared with controls. Most likely, estradiol and progesterone are produced by the epithelial malignant tumors, as the post-operative values are completely comparable with the primarily included healthy controls. The FSH is suppressed by inhibin and only to a minor degree by the steroid hormones as indicated by the correlation coefficients. Of great interest is the question whether inhibin production is random, or defensive, lowering the gonadotropin levels or influencing tumor growth in some hitherto unknown fashion.

[Contraception]. / Kontraception.

PIP: A technical overview of the status of various contraceptive methods is presented. The World Health Organization coordinates research on an international level to improve communication in the medical field. Manufacturers are developing oral contraceptives with lower hormone levels. Oral contraceptives with natural estrogens have also been developed, which are less effective but have fewer side effects. Pills made of rice paper impregnated with steroid hormones have been introduced in China. Pills with low dosages of gestagen are highly effective, with bleeding disorders as their main side effect. Depot injections and implants are being developed, including hormone-implanted vaginal rings and hormones absorbed through the nasal menbranes that affect the hypothalamus-pituitary gland. Anti-implantation methods are based on the ability of various substances to block hormone receptors. New types of IUDs are being developed, as are vaccinations which inhibit implantation. Substances such as ethinyl estradiol can be used as post-coital contraceptive methods. New methods of induced abortion and sterilization make these procedures more effective and safe. Contraceptive methods to be used by men include combinations of gestagens and androgens and immunologic preparations, e.g. the substance inhibin, which inhibit development of the sperm.^ieng

A description of the intrauterine device, polygon (antigon).

PIP: The polygon (Antigon) is a closed, rodlike figure with the shape of a polygon, 24 mm wide and 30 mm high. It consists of 2 short upper members meeting at an angle, and 2 longer lower members, meeting the upper at an angle, and forming an arc at the base. Pressure on the lower members makes it take the form of a probe so that it can be inserted easily through the cervical canal, and dilation is seldom required. Its elasticity causes it to return to its original form as soon as it enters the uterine cavity, and pressure upon its upper members causes the lower segment to widen, thus reducing the tendency to expulsion. The inserter itself is never introduced into the cervical canal, and the polygon is flexible enough to follow the direction of the canal, thereby reducing the risk of performation to a minimum. The device is designed to remain sterile under storage, and can be introduced without being touched by hand, eliminating the risk of infection. A small powerful magnet in the polygon permits detection without x-rays, probing, or the need of a tail protruding through the cervix. Removal is done by using specially devised "forceps", and can be performed without much discomfort to the patient, and no analgesics or anaesthesia are required.^ieng

Plasma progesterone, serum estriol and plasma HPL determinations during the last trimester to detect changes before spontaneous labor. Comparison of progesterone assay using RIA and CPB.

Conflicting results have been published regarding changes in plasma progesterone during the last trimester of pregnancy. Some have demonstrated a fall in plasma progesterone before labor, and this has been taken as a possible explanation of the onset of labor. It has been suggested that the various results could be due to differences in methods for progesterone determination. In this study the progesterone levels were determined by both RIA and CPB. In 11 women the plasma progesterone, human placenta lactogen, and serum estriol were measured weekly during the last trimester of normal pregnancies and immediately after delivery. All samples were analysed radioimmunologically. In order to compare the radioimmunoassay and competitive protein binding techniques (RIA and CPB), the progesterone levels were determined by both methods. This was also done for 80 successive plasma progesterone routine samples drawn from women who were not pregnant or who were in the early stages of pregnancy. Both methods showed a significant rise in the plasma progesterone level during the last 6 weeks before spontaneous labor. However, the values obtained were lower when assayed by CPB than by RIA, presumably because of a higher specificity and a cross reaction in RIA. Serum estriol exhibited increasing values throughout pregnancy, but without a significant rise during the last few weeks. Plasma HPL settled at a constant level during the last few weeks before labor.

Metabolic changes during the normal menstrual cycle: a longitudinal study.

The effect of sex hormones on lipid metabolism and coagulation during the menstrual cycle was studied in 37 women. Each woman had three samples drawn, corresponding to the follicular phase, midcycle, and the luteal phase. Basal conditions were obtained by taking samples in the morning while subjects were still in bed. No changes were found in lipids and lipoproteins during the menstrual cycle. Antithrombin III and factor VII of the coagulation system did not change throughout the cycle. Fibrinogen increased in the luteal phase, and all samples of fibrinogen correlated positively with progesterone concentration. This increase, therefore, could be a progesterogenic effect. In conclusion, these findings suggest that when studied optimally no changes in lipids and lipoproteins are found and that the day of blood samples is of minor importance, for instance, when used as a control in studies of oral contraceptives. For investigations on some coagulation parameters, the days of the cycle may be of importance.

Is the early growth delay in the diabetic pregnancy accompanied by a delay in placental development?

We have previously shown that some fetuses in early diabetic pregnancy judged by the crown-rump length are smaller than expected from the menstrual history. Nine out of 26 fetuses in the present study were significantly (6 to 17 days) smaller than normal, and at birth they weighed 300 g less than the remainder. To examine whether this early somatic growth delay was accompanied by a delay in placental development, we correlated plasma levels of human placental lactogen (HPL) to menstrual age and growth delay. Multiple regression analysis showed that inclusion of the early growth delay as an explanatory variable significantly improved the correlation. The best correlation was achieved when menstrual ages were corrected by 90% of the early growth delay, suggesting that the somatic growth delay is accompanied by a similar delay in placental development. We recommend that every diabetic woman should undergo an ultrasound examination in early pregnancy, with determination of fetal size, and that management throughout pregnancy should be guided by the ultrasound age rather than that calculated from the first day of the last menstrual period.

Results of serial measurement of estradiol in serum with six different methods during ovarian stimulation.

The aim of the study was to assess the values of serum estradiol (E2) in women undergoing ovarian stimulation with five direct commercial assays (IMX, Amerlite, Spectria, Vidas, CA) and to compare them with the results of an E2 direct method used in our laboratory. The study included 12 infertile women. Thirteen cycles were monitored daily during ovarian stimulation with transvaginal ultrasound and serum E2. Large differences were found between the E2 concentrations measured on the same sample with the different methods. In general the IMX and Amerlite assays gave the highest and CA the lowest results. The results of our own RIA and Spectria assay agreed more closely. The median ratio of the highest E2 value (IMX assay) and the lowest E2 value (CA value) was 1.75 (1.30-3.15). Values of E2 measured in serum depend on the method used. It is not possible to apply criteria from other studies directly to one's own patients. Close collaboration between the laboratories and the clinical staff is essential.

Testicular feminization syndrome and associated gonadal tumors in Denmark.

We studied the incidence of testicular feminization syndrome in Denmark over a 7-year period and found it to be about 1:20,400. Twenty-one patients are described in greater detail. Four patients had gonadal tumors, none of these being malignant. Ten patients (47.6%) had inguinal hernias in early childhood. All patients but one were gonadectomized. Eleven patients (52.4%) disclosed signs of partial androgen function. Only 5 of them had their gonads removed immediately.

Low dose of gestagen as a contraceptive method. A clinical trial.

PIP: The effectiveness of megestrol acatate (350 mcg/day) was studied in 194 women over a total of 2048 woman-months of use. There were 23 pregn ancies, 7 of which could be attributed to patient error, for an adjusted pregnancy rate of 9.4/100 woman-years of use. Abnormal bleeding was the most dominant side effect (22.2%). 11.8% of the women discontinued the regimen because of unwanted pregnancy, and 8.2% did so because of abnormal bleeding. The acceptability rate was 73.3%. Similar results were reported in another trial.^ieng

The effect in post-menopausal women of natural human and artificial oestrogens on the concentration in serum of prolactin.

25 women aged 53--78 years with at least two years menopause were divided in three groups receiving one of the following oral treatments for three weeks: 2 mg oestradiol-17 beta plus 1 mg oestriol, 4 mg oestradiol-17 beta plus 2 mg oestriol or 50 micrograms ethinyloestradiol daily. Blood samples were collected before, during and after the treatment and the effect on the serum concentration of prolactin, oestradiol-17 beta, follicle-stimulating hormone and luteinizing hormonee was evaluated. During treatment with natural human oestrogens serum oestradiol-17 beta levels were significantly higher than before treatment. The serum concentration of prolactin was unchanged in patients receiving 2 mg oestradiol-17 beta plus 1 mg oestriol but increased in patients receiving 4 mg oestradiol-17 beta plus 2 mg oestriol or 50 micrograms ethinyl-oestradiol, thus indicating dose-dependence for natural human oestrogens. However, the increase was moderate, and these higher levels were not significantly different from levels of prolactin in serum found in 16 younger women. Concentrations of follicle-stimulating hormone and luteinizing hormon were depressed during treatment, the former to significantly lower levels when higher doses of oestrogens were used.

Sex hormone levels and intestinal absorption of estradiol and D-norgestrel in women following bypass surgery for morbid obesity.

A report of reduced serum levels of progestins, following oral administration after jejunoileal bypass, promoted the present investigation of the absorption of D-norgestrel and estradiol following different types of intestinal bypass surgery for morbid obesity. A group of non-operated obese patients served as control. Apart from significantly higher gonadotrophin levels, which could be attributed to periovulatory sampling in the non-operated group, there was no significant differences in basal levels of estradiol, estrone, conjugated estrone, androstendione, testosterone, and progesterone. The operation did not influence the pattern of the menstrual cycle. Following a single oral dose of 4 mg micronized estradiol and 125 microgram D-norgestrel, serum levels of estradiol and estrone were equal in the three groups. serum D-norgestrel was equal in the two operated groups, but was significantly higher in the bypass group with 1:3 jejunoileal ratio, compared with the non-operated group. Further, a significant negative correlation between peak levels and weight was found. It is suggested that one year following bypass surgery, obesity - but not intestinal bypass - might be associated with reduced serum levels of exogenous sex steroids following oral administration.

Intra-uterine contraception with a new antigon model, and investigation of the mechanism of action of intra-uterine devices.

PIP: Based on a review of the literature, it was hypothesized that an IUD's effect is local and increases with the size of the area covered by the IUD. This hypothesis was tested by comparing clinical material on the plain Antigon IUD with the newly designed Antigon winged model; the newer design increases the contact area by 50%. Data for 1151 patients over 18,599 woman-months of observation were collected from 2 hospitals in Denmark and 1 in Sweden. Average age ranged from 27.1-29.2 years, with average parity ranging from 2.2-2.9. There were 6.8% pregnancies and expulsions, 10.1% removals, and an 80.3% acceptability rate. Because the pregnancy rate has been halved with the Antigon winged model, it is thought that an IUD effects the local obstruction of blastocyst nidation.^ieng