[Parenteral estrogen--a safe therapeutic alternative in prostatic cancer seen from the cardiovascular point of view?].
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Biomedical subjects
Publications and source records attributed to L Collste.
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The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.
Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.
Oral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver-derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.
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Thirty-eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections--160 mg, 240 mg, and 320 mg--in this nonrandomized study. In contrast to studies with oral estrogens, there have been no cardiovascular complications at a mean follow-up of 12.9 +/- 0.7 months (SEM). Twenty-nine of the 38 patients (76%) have responded to therapy.
Serum concentrations of testosterone (T) and estradiol-17 beta (E2) were analyzed in prostatic cancer patients treated with 160, 240, or 320 mg polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period. Estrogen effects on the liver were studied by analyzing serum levels of sex hormone binding globulin (SHBG) in the 320 mg group and compared with values obtained in patients treated with 80 mg PEP i.m. every fourth week + oral ethinylestradiol (EE2) 150 micrograms daily, or by orchidectomy. Orchidectomy levels of T were reached within 3 weeks in the 320 and 3 months in the 240 mg group. In the 160 mg group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1,300-2,500 pmol/L at 6 months. At 6 months, SHBG levels had increased to 617% of pretreatment values in the oral EE2 group, to 166% in the 320 mg group, and were unaffected by orchidectomy. No cardiovascular side effects occurred during single-drug PEP treatment.
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Twenty-four women with stress urinary incontinence of slight to moderate grade were treated with phenylpropanolamine (PPA), po 50 mg twice daily, and placebo for periods of two weeks according to randomized double-blind cross-over schedule. A significant increase in maximum urethral closure pressure (MUCP) was found after treatment with PPA compared to placebo, but functional urethral length was unchanged. Number of leakage episodes were significantly reduced during PPA treatment, but micturition frequency was unchanged. Fourteen women preferred PPA, 4 preferred placebo, and 6 considered PPA and placebo to be ineffective. The scored improvements obtained by PPA were highly significant when tested against the scored placebo effect. There was a significant correlation between subjective assessment and improvement in number of leakage episodes and increase of MUCP. Plasma-PPA levels showed no significant correlation with any of the effect variables. Adverse reactions were few and negligible.
Inflammatory cells are commonly present in cytologic specimens obtained for flow cytometry, and may interfere with the analysis of epithelial cells. We have found that detergent (Triton X-100) pretreatment in the two-step acridine orange staining procedure disrupts granulocyte cell membranes to yield bare nuclei; bladder epithelial and squamous cells on the other hand are quite resistant to the detergent treatment. Being deprived of their cytoplasmic RNA, the granulocytes lose red fluorescence. Moreover, the shearing forces in the cytometer extend the multisegmented granulocyte nuclei and align them in the direction of flow. Thus, they present as elongated objects in the measuring system, giving a large DNA fluorescence pulsewidth (nuclear size). These two phenomena make it possible to identify granulocytes in the recorded data, where they are discernible from the mononucleated leukocytes and from epithelial cells. By data selection the granulocytes can be excluded, rendering epithelial cell populations more amenable to analysis. This method may make it unnecessary to remove physically leukocytes from the specimen before flow cytometry; it may also provide a way to analyze the morphology of granulocyte nuclei and to assess methods to manipulate their membrane stability. Full protection from membrane disruption is accomplished by alcohol fixation, and partial protection by 20-30% serum.
Two cases of priapism treated with fibrinolysin (streptokinase) are presented. Comparisons are made between medical and surgical treatment in the literature. It is concluded that fibrinolysin may be useful in some cases of early priapism, but should be chosen only after serious consideration of the circumstance that its use precludes early surgery.
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In patients receiving cadaveric kidneys and treated with antilymphocyte globulin (ALG) the one-year graft survival 59%. The corresponding figures with living related donors were 87% and 83%, respectively. Side effects of ALG, of which allergic reactions were the most common, prompted its withdrawal in 33% of the cases. All patients studied developed antibodies against horse gammaglobulin when tested with a passive haemagglutination inhibition technique. ALG seems to act upon the T-cells since the number of cells forming rosettes with sheep red blood cells was reduced.