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.

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.

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 pituitary-gonadal axis in women with benign or malignant ovarian tumors.

The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione, testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were investigated prior to surgery in 24 postmenopausal women with benign and 28 postmenopausal women with malignant epithelial ovarian tumors. The serum concentrations of hormones were compared with those of 28 healthy, postmenopausal, age-matched controls. Significantly lower serum FSH levels were demonstrated in women with malignant tumors. No significant differences were found between the groups regarding the serum LH levels. The hCG levels were low in all groups. Regarding progesterone and estradiol levels, low postmenopausal steroid levels were found in all groups examined and no significant differences were demonstrated within the groups. No significant correlations between the levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude a central depression of gonadotropin release mediated by the dopaminergic system we examined the thyroid stimulating hormone (TSH) and prolactin. No differences were found between the groups regarding TSH and prolactin levels. A possible relationship between other hormones/factors produced by the tumor and exerting a negative feedback, either centrally or directly, on the gonadotropin release remains to be investigated. A change in biological activity in the gonadotropins might explain the present findings.

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.

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.

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.

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.

Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. II. Secretion of LH, FSH, TSH, prolactin and ACTH.

A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.

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.

[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

The relationship between pregnancy, HCS and B lymphocytes.

The quantitative distribution of the lymphocyte subpopulations (B, T and null) and the serum concentrations of Human Chorionic Somatomammotropin (HCS), immunoglobulins IgG, IgM and IgA, complement component C4 and C1 inactivator, were estimated in venous blood samples from 32 women at various stages of pregnancy and compared with a control series of 7 non-pregnant normal women. A significant decline in the B cell percentage during pregnancy was seen. The fall in the percentage of the B lymphocytes was found to be concomitant with the rise in HCS concentration. No significant changes in the other parameters studied were present.