[Hemorrhages in abnormal production of gonadotropins].
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The authors describe the epidemiology and the physiopathological aspects of ischemic strokes in patients with a history of oestroprogestogen use. They then study their main radiological correlates: arterial infarcts at CT scan and angiographic non-specific lesions which can be included in the extremely wide framework of arteritis and, much more rarely, venous thrombophlebitis.
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A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described. The prototype system consists of microcapsules made of the biodegradable polymer d, l-polylactic acid, in which micronized crystals of NET are homogeneously dispersed. NET is slowly released from the microcapsules following intramuscular injection at a rate of 0.90 microgram NET/day/mg of microcapsule by diffusion of the steroid from the polymer matrix. Three different doses of a standard preparation of microcapsules were tested in normally cycling female babbons (4 to 5 baboons/group). Following injection of either 300, 200, or 100 mg of microcapsules containing 75, 50, or 25 mg of NET, blood samples were collected at selected intervals and analyzed for NET, estrogen, and progesterone by radioimmunoassay. All three doses provided continuous NET release for 6 months following injection. The NET serum profiles for the different doses are parallel, and ovulation was inhibited in all baboons for 6 months following treatment.
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Plasma levels of norethisterone (NET), ethinyl estradiol (EE), Ampicillin or Metronidazole were estimated in 16 women, who were taking low-dose oral combination contraceptive pills (containing norethisterone acetate 1 mg and ethinyl estradiol 30 microgram) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither Ampicillin nor Metronidazole therapy altered the 'peak' or 24-hour plasma levels and area under the curve, for NET and EE. Furthermore, oral contraceptive treatment did not alter the 'peak' levels of Ampicillin or Metronidazole. Progesterone (P) levels were in the anovulatory range in all Ampicillin treated cycles. However, in Metronidazole treated group, two out of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole, where only one women showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by P rise of more than 4 ng/ml in three out of 25 Metronidazole treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that one out of three women showing a P rise (greater than 4 ng/ml( during concurrent Metronidazole therapy, also showed ovulatory P values in oral contraceptive-only treated cycles. Furthermore, in the control group also, one out of 10 women had ovulatory P levels (greater than 4 ng/ml) in oral contraceptive-only treated cycles.
The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage.
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Progesterone, the natural hormone produced by the corpus luteum and other steroid-secreting glands, is endowed with antiestrogenic action and has a fundamental role in the initiation and maintenance of pregnancy and in the regulation of gonadotropin secretion. Although it was discovered half a century ago, it has found little clinical use as a therapeutic agent due to its low potency and extensive degradation following oral administration in comparison with a variety of highly potent synthetic analogs that became available in the last three decades. When delivered systemically, a large proportion of the dose bypasses degradation in the gut and liver, and progesterone can achieve effective levels in target tissues for clinical use. Sustained administration via compressed pellets implanted subdermally or silicone rubber rings placed in the vagina produced circulating levels of progesterone within the lower third of those found in the luteal phase of the human menstrual cycle. Those levels were shown to delay the recovery of fertility in nursing women without adverse effects to the mother or the infant. Progesterone transferred to the babies via the breast milk did not change their rate of pregnandiol-3-alpha glucuronide excretion. It is concluded that sustained administration of the natural hormone progesterone may be an effective and safe contraceptive method for nursing women.
The secretion of 17 beta-estradiol (E2) and the effect of exogenous E2 on progesterone (P) production by granulosa-luteal cells from 18 women attending an in vitro fertilization (IVF) program were studied. The cells were separated from follicular fluid and precultured in medium containing fetal calf serum. On the third day of culture E2 (0.25-2.0 micrograms/ml) was added onto the cells and its effect on both hCG-stimulated and basal P production was measured. E2 inhibited both basal and hCG-stimulated P production. 1 microgram/ml of E2 caused mean decrements of 55 and 56% in basal and hCG-stimulated P production, respectively. The maximal inhibition by E2 occurred at 6 hours of incubation, but when the cells were allowed to react with E2 for longer periods of time the effect became less significant and more variable. At 48 h no inhibition was observed. At 6 h E2 (1.0 microgram/ml) increased both basal and hCG-stimulated pregnenolone production by approx. 10-fold, suggesting that the suppression of P production was due to inhibition of 3 beta-hydroxysteroid dehydrogenase. Exogenous androgen, 5-Androsten-3 beta-ol-17-one sulfate, dehydroepiandrosterone sulfate (DHEAS), in a dose-dependent manner increased granulosa-luteal cell E2 production. The maximal response was about 1000-fold above the E2 production of unstimulated cells and was not affected by hCG. However, the maximal amount of E2 produced was minor in comparison to exogenous doses required for the suppression of P production and did not have the inhibitory effect. It is concluded that the production of E2 by granulosa-luteal cells is mainly regulated by the availability of androgen substrate, and that E2 functions as a modulator of luteal P production.
This trial compared the termination of early pregnancy (amenorrhoea less than 43 days) by 600 mg orally of the antiprogesteron Mifepristone to the traditional method of vacuum aspiration. Fifty women were randomly assigned to either of the treatments. All the patients treated with vacuum aspiration had a complete abortion. Three of these patients developed pelvic inflammatory diseasae (PID) after the aspiration. Another patient had the uterus perforated during the procedure, and an emergency laparotomy had to be performed. The patients in the evacuation group spent more days in bed and needed longer sick leave after the treatment than the patients in the Mifepristone group. In the Mifepristone group, six patients had incomplete abortions and all were treated by evacuation. Three of the patients developed PID after the evacuation. A decrease of 40% or more in beta hCG from the initial value to the value 1 week later were invariably associated with complete abortion. In both groups the changes in hemoglobin were insignificant and no patients needed blood transfusion or emergency evacuation. The Mifepristone treatment is a simple and safe alternative to vacuum aspiration for termination of early pregnancies.
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In a controlled cross-over design study performed with 14 female subjects, serum hormone levels, the EEG and a number of performance tests were recorded during spontaneous and oral contraceptive-controlled menstrual cycles. The mean alpha-frequency showed cyclic changes, i.e. slower alpha-waves during the follicular phase and faster alpha-waves during the luteal phase. Smaller cycle stage-dependent differences in the power of the theta- and beta-bands also were noted. An increase in several performance task scores was noted during the periovulatory period, whereas lowest performance scores were recorded during the late luteal and early menstrual phases. No such effects were observed in the same subjects while they were taking oral contraceptives. These results demonstrate that the gross electrical activity of the brain changes in a parallel with changed hormone levels. The changes in performance tests coincide with increasing or decreasing alpha activities in the EEG. The common underlying mechanism may be an activation of central nervous system monoaminergic pathways which are known to be involved in steroid feedback.
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