[CURRENT VIEWS ON THERAPY OF METASTATIC CANCER OF THE BREAST].
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OBJECTIVE: To study the direct effects of progesterone (P) and its antagonist RU486 (mifepristone) on sperm hyperactivation (HA) and acrosome reaction. DESIGN: Prospective evaluation of semen samples incubated in capacitation media with P and/or RU486. SETTING: University-affiliated tertiary care center. PATIENTS: Normal healthy volunteers. INTERVENTIONS: Semen samples were incubated in media with P or RU486 alone or in combination, and aliquots were taken at 10 minutes, 1, 5, and 24 hours for HA analyses by computer-aided sperm analysis system, and at 0, 5, and 24 hours for assessment of acrosome reaction by fluorescein-labeled Pisum sativum (pea) agglutinin. MAIN OUTCOME MEASURES: HA and acrosome reaction. RESULTS: Sperm HA was significantly increased at 10 minutes by P both at 10(-7) M (9.27 +/- 1.59%; mean +/- SEM) and 10(-6) M (9.39 +/- 1.94%) when compared with untreated spermatozoa (5.62 +/- 1.59%). The stimulatory effect of P on sperm HA was transient because this was not observed after 1, 5, and 24 hours of incubation. The antiprogesterone RU486 (10(-6) M) alone had no effect and did not abolish the stimulatory effect of P on HA. The %HA was further enhanced by the addition of RU486 at 10(-6) M to P at 10(-7) M (12.43 +/- 3.31%) or P at 10(-6) M (13.52 +/- 4.10%); however, this effect was not significantly different from P alone. Coincubation of P or RU486 with spermatozoa during capacitation did not stimulate the acrosome reaction in the concentrations tested. CONCLUSION: Progesterone directly stimulates human sperm HA transiently. Progesterone has no significant effect on acrosome reaction in capacitating spermatozoa. The effects of P are rapid and not counteracted by RU486, suggesting that the mechanism of action of P may not be mediated by specific P nuclear receptors.
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Endometrium was studies histologically, histochemically, and ultrastructurally in a series of biopsies taken from 3 normal, ovulating patients on Days 1-9 of the cycle. The occurrence of ovulation and the adequacy of progesterone were determined by radioimmunoassay. The most striking feature of menstruating endometrium was its vigorous attempt to survive. This was manifested by lysosomal activity, lipid accumulation, expulsion of glycoproteins, and the uptake of stromal debris by epithelial cells for passage to the uterine cavity. Regression, rather than cell death, was the chief event of menstruation. While some cells of the spongiosa underwent necrosis, the vast majority remained viable and underwent remodeling to participate in the new cycle. These studies may lead to further understanding of the process of menstruation and the pathophysiology of anovulatory bleeding and irregular shedding of the endometrium.
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Prediction of ovulation was established by correlation of clinical parameters, follicular development by ultrasound, and estradiol, progesterone, and luteinizing hormone (LH) determination in 71 menstrual cycles. Laparoscopic follicular aspiration was accomplished in 41 of those cycles. A 28-hour interval from the ascending limb of the LH seems to be the "ideal time" for retrieval of a preovulatory oocyte. The variability in the amount of LH to which the follicle is exposed during the LH surge seems to indicate that there is a relatively low specific value necessary for ovulation. Ovulation occurs approximately 10 +/- 5 hours from the LH peak. Progesterone occurs in relation to the LH surge and is helpful for the retrospective analysis of the menstrual cycle.
Fifteen patients presenting one or more risk factors for cancer of the breast, who also received medication with prolactin-stimulating effects, were selected. The medication was by hormone derivatives or by non-hormone drugs used for processes other than oncologic . In all cases the medication was for long periods, three or more years, with the exception of one case, where the correlation with the unfavourable evolution of the cancer process was more evident. In patients presenting the classic risk factors for cancer of the breast, it is recommended to avoid the prescription of drugs having a prolactin-stimulating effect. The association of both circumstances (risk factors and prolactin-stimulating medication) is considered as an increased risk for cancer of the breast.
The effects of a 6-month contraceptive system of biodegradable norethisterone (NET) implants on the menstrual cycle, estradiol and progesterone levels, the presence of side effects, its contraceptive effectiveness, and the NET levels achieved were studied in a group of nine women. There was practically no disruption of the menstrual cycle and no important side effects. Ovulation was inhibited in four subjects, and another four subjects remained ovulatory. In all the subjects a cyclic secretion of estradiol was maintained. No pregnancies occurred. The circulatory levels of NET were very stable throughout the 6-month period of implant use.
Intracellular localization and the heat-dependent redistribution of estrogen and progesterone in human endometrial cells have been investigated by a fluorescent steroid-antibody technique. The dispersed endometrial cells were incubated with 5 X 10(-8) M estradiol-17 beta and progesterone in TC medium 199 containing 10% calf serum for 1--3 hr at 4 degrees C or 37 degrees C. An indirect immunofluorescent technique using FITC-labeled anti-rabbit IgG and steroid antibodies raised from rabbits immunizing with estradiol-6-oxime-BSA and progesterone-3-oxime-BSA was applied to the smear specimens. In normal endometrial cells in both proliferative and secretory stages, specific fluorescences to estradiol and progesterone were generally observed in the cytoplasm after incubation with the steroids at 4 degrees C for 1 hr. When these cells were incubated with the steroids at 37 degrees C for 1 hr, cytoplasmic and predominant nuclear fluorescences were detected, whereas the 3 hr-incubation at 37 degrees C resulted in disappearance of cytoplasmic fluorescence, remaining nuclear fluorescence alone. These fluorescences were remarkedly eliminated when endometrial cells were incubated with diethylstilbestrol and R-5020 prior to the incubation with estradiol and progesterone, respectively. These results indicate that the fluorescent steroid-antibody technique used in this study enables us to visualize subcellular localization of estradiol and progesterone possibly bound to receptors in each endometrial cell.
A 23-year-old woman with a uterus didelphys and a totally occluded left tube had a hysterectomy one year after having a child. Endometrial estrogen and progesterone receptors, both cytoplasmic and nuclear, were determined in five longitudinal sections of each horn. The amount and distribution of these receptors were normal, but the receptor content of the right horn was higher than that of the left.
In early pregnancy up the 7th week of pregnancy PGF2alpha was infused and 15(S)-methyl-PGF2alpha was applied i. m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGF2alpha is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGF2alpha produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnancy.
OBJECTIVE: To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function. DESIGN: Three different regimens of RU486 were tested. PARTICIPANTS: Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization. INTERVENTIONS: Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10-day intervals for 80 days. MAIN OUTCOME MEASURES: Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects. RESULTS: The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation. CONCLUSION: Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration.