[Is the therapeutic estrogenic effect of mud baths definite?].
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Contraceptive Agents, Female↗
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Results for “ESTRADIOL, THERAPEUTIC”
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[ON THE THERAPEUTIC USE OF HORMONAL OVULATION BLOCK].
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Contraception↗
[Therapeutic results in recurrent breast cancer with the use of Bestrabucil (KM2210)].
We administered Bestrabucil, a benzoate ester of a complex of beta-estradiol and chlorambucil, continuously to six patients with breast cancer recurrent to local and regional lymph nodes, at a dose level of 200 mg/day. Of these six cases, one achieved CR, two PR, one MR, and two were NC. The drug was thus effective in 50% of the cases, with mild side effects. At the same time, since the concentration transfer to lymph nodes was satisfactory, Bestrabucil was thought to be an effective drug for the treatment of locally recurrent breast cancer.
Adult↗
[Therapeutic results with a new estrogen preparation in climacteric symptoms].
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Adult↗
[A case of adult T cell leukemia treated with a new chemotherapeutic agent, KM2210].
A 58-year-old man, born in Nagasaki prefecture, was admitted to our hospital because of anorexia and general fatigue on November 22, 1984. Hepatosplenomegaly was found without skin eruption. The blood examination on admission revealed leukocytosis (50,800/microliter) and atypical lymphocytes with hyperlobulated nuclei. He had hypercalcemia, and hepatic and renal damage. A diagnosis of adult T cell leukemia (ATL) in the acute stage was made. Treatment with KM2210, a conjugate of chlorambucil and estradiol, was started, and his peripheral leukocytes decreased gradually reaching, 19,700/microliter by the end of this medication. His leukocyte count continued to decrease after discontinuation of KM2210 and reached a nadir of 4,700/microliter. Hepatosplenomegaly and hypercalcemia also improved. About one month later, recurrence of the disease occurred and he was again treated with KM2210. Although the second course of the KM2210 therapy was also successful in relieving hepatosplenomegaly and leukocytosis, it proved impossible to ameliorate his poor condition and he died of DIC. Our case suggests that KM2210 has a remarkable cytotoxic effect against ATL cells even in the acute stage but the optimal schedule of treatment with this new drug should be established in order to obtain more satisfactory therapeutic results.
Antigens, Viral↗
[Steroid hormone receptors and their relevance for the therapy of mammary cancers (author's transl)].
Estradiol receptors which are detectable in the cytoplasma of cells of human breast cancers can be used successfully for evaluating the hormone sensitivity of these tumours. Receptor negative cancers generally do not respond to endocrine therapeutical procedures whereas receptor positive cancers respond in 60% of cases. It is conceivable that this non sufficient correlation is caused by an impairment in the hormone receptor interaction, The simultaneous determination of estradiol and progesterone receptors in the tumour tissues increases the correlation between receptor status and hormone sensitivity to 80 percent. There exists a high degree of conformity between the receptor status of primary tumours and metastatic lymph nodes as well as recurrences.
Adrenal Cortex↗
Estrogen content and DNA unwinding in tumor and normal endometrial tissue of aging endometrial cancer patients.
Over the past years, data on the role of DNA damage in hormonal carcinogenesis have been accumulated. In 21 endometrial cancer (EC) patients (mean age 61.8 +/- 1.6 years), no difference between malignant and normal endometrium in estradiol content (radioimmunological assay) and in alkali-induced DNA unwinding as a measure of DNA strand breakage (fluorometrical assay) was discovered. At the same time (contrary to normal endometrium), there were no correlations between the estradiol content in malignant endometrium with DNA unwinding or blood estrogen level. The estradiol concentration in malignant endometrium increases with age in menopausal EC patients, though no correlation between estrogen content in endometrial tissue and body weight was discovered. DNA unwinding rate in malignant endometrium correlates only with the concentration of steroid receptors in normal endometrial tissue. It may be possible that before the appearing of any neoplastic changes in the endometrium, a higher level of estradiol in the target tissue leads to DNA damage which may be considered as a factor predisposing to tumor development. Practically speaking this would mean that the estradiol content and DNA unwinding level in endometrial tumors may be used in future as indicators for therapeutic intervention (first of all, during the hormone therapy of EC) and also as markers for the evaluation of the effectiveness of the latter.
Aged↗
Ovarian origin of plasma and peritoneal fluid prorenin in early pregnancy and in patients with ovarian hyperstimulation syndrome.
Prorenin is the major product of renin gene expression in the ovary. Plasma levels of prorenin are elevated in ovarian-stimulated patients and during early pregnancy. To further elucidate the source of the elevated plasma levels of prorenin, we measured prorenin, renin activity, angiotensinogen, and steroid hormone levels in the plasma, luteal fluids (luteal cysts), ascitic fluid, and in ovarian venous samples collected from a patient with severe ovarian hyperstimulation syndrome (OHSS) and ectopic pregnancy. Prorenin/renin was also measured in plasma and in peritoneal fluid obtained during, therapeutic paracentesis from four patients with OHSS. Several corpora luteal fluids were obtained that were rich in estradiol (E2) and progesterone (P). Ovarian venous E2 and P were 20-fold higher than in arterial blood and as high or higher than the levels detected in the luteal fluids. The ratios of the hormonal levels in ascitic fluid and plasma were 1.9 for P and 1.4 for E2. A wide range of prorenin concentrations [1279 +/- 918 SD ng/mL/hr, n = 6] were found in corpora luteal fluids, but in each the prorenin concentration was higher than in plasma (494 ng/mL/hr). Prorenin but not renin was higher (+23%) in ovarian venous than arterial blood. Prorenin in the 7 liters of ascitic fluid aspirated (2686 ng/mL/hr) was 5-fold higher than in plasma and similar to the levels measured in the corpora lutea with the highest prorenin concentrations. Renin in luteal cysts and ascitic fluid constituted 3% and 6% of the total renin (renin+prorenin), respectively. Total renin was also higher in peritoneal fluid (1538 +/- 925 ng/mL/hr) than in plasma (375 +/- 237 ng/mL/hr) of the 4 additional patients with severe OHSS. These findings indicate that the ovary secretes prorenin during early pregnancy and that its secretion is directed preferentially from the luteal cysts into the peritoneal cavity. In light of recent evidence of an effect of prorenin on the vascular system, the presence of a huge reservoir of prorenin in the peritoneal cavity of patients with OHSS suggests a potential role for prorenin in the pathogenesis of this syndrome.
Adult↗
Estrogen therapy for gonadal dysgenesis: a rational approach.
The administration of estrogens for gonadal dysgenesis is sometimes associated with the development of endometrial neoplasms. An approach which minimizes the inadvertent side effects while still providing the desired therapeutic effects may be to imitate the hormonal milieu of the normal menstruating woman. Oral administration of estradiol will not necessarily accomplish this, because of the intestinal conversion of estradiol to estrone. That problem can be overcome by the vaginal administration of estrogens.
Adolescent↗
The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women.
OBJECTIVE: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). METHOD: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. RESULTS: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.
Cholesterol↗
ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis.
BACKGROUND: ICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus). METHODS: Three independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus) or sea bream received intra-peritoneal implants containing estradiol-17 beta (E2), ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream. RESULTS: E2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2. CONCLUSION: These results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but its actions are tissue-specific. The mechanisms for the ICI agonistic activity are still unknown; although the ICI induced up-regulation of ER alpha mRNA could be one of the factors contributing to the cellular response.
Animals↗
Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis.
Estrogen has been shown to stimulate osteoblasts in cell culture and increase bone formation in animal models. Such an anabolic effect of estrogen replacement therapy (ERT) would be beneficial to postmenopausal women with osteoporosis. Hence, we assessed the total collagen content and collagen crosslink maturity in iliac crest bone biopsy from 18 such women before and after 6 years of higher-dose ERT. These results were compared with the serum estradiol level and bone mineral density (BMD). Total collagen content of both cortical and cancellous bone increased, showing a median (95% CI) percent change of 6.7 (0.3-14.2) and 25.6 (13.5-33.8), respectively. Increase in collagen synthesis was supported by a rise in intermediate crosslinks in both cortical and cancellous bone, and mature crosslinks in cortical bone only. At the same time, BMD showed a substantial rise both at the lumbar spine and proximal femur with a median (95% CI) percent change of 28.6 (19.8-37.3) and 14.5 (8.4-20.7), respectively. Serum estradiol and BMD results correlated with cortical bone collagen levels. Our results suggest that long-term higher-dose ERT has a therapeutic role due to its anabolic effect on bone in postmenopausal women with osteoporosis.
Absorptiometry, Photon↗
Choosing the best oral contraceptive.
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Contraceptives, Oral↗
[Pituitary-gonadal hormonal evaluation in male patients with alcoholic liver cirrhosis].
Pituitary-gonadal plasmatic hormonal values were measured in 26 alcoholic cirrhotic males and 20 healthy subjects. Total testosterone and luteinizing hormone mean levels were lower in the cirrhotic group (p < 0.05). Estradiol and prolactin were significant higher (p < 0.05 and p < 0.001, respectively). Follicle stimulation hormone mean values were normal. Pituitary-gonadal axis luteinizing hormone-testosterone and follicle stimulating hormone-estradiol were abnormal since the retrofeedback mechanism failed to work in each system. These results show a wide disturbance of the sexual hormonal function in our patients which certainly contributes to puzzle the complexity of the clinical and therapeutic aspects in these kind of patients.
Adult↗
Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice.
BACKGROUND: The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) are secreted by the different cell populations of the vascular wall and have been suggested to promote atherosclerosis. METHODS AND RESULTS: Their respective roles in fatty-streak formation in apolipoprotein E-deficient mice were investigated by use of IL-1 receptor antagonist and TNF binding protein. Estradiol-17beta was used as a positive control. Blocking TNF seemed to be active in female animals but not in males. IL-1 receptor antagonist was as effective as or more effective than estradiol in both sexes. CONCLUSIONS: IL-1 plays a crucial role in the initial step of the atherosclerotic process in this animal model, and blocking the activity of this cytokine should be considered as a therapeutic possibility.
Animals↗
Gender differences in human sepsis.
BACKGROUND: In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE: In a prospective study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS: In a prospective study, tumor necrosis factor alpha and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS: In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.
APACHE↗
Role, control and expression of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase activities in human breast cancer.
Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol (E2) and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, Tibolone (Org OD14) and its metabolites (Org-OM38, Org 4098 and Org 30126), as well as Danazol, can block the conversion of estrone sulfate to E2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of E2 is the conversion of estrone (E1) to estrogen by the action of 17 beta-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E2) in hormone-dependent cells, but oxidative (E2-->E1) in hormone-independent cells. Using intact hormone-dependent cells, it was observed that Nomegestrol acetate. Promegestone as well as Danazol, can block the conversion of E1 to E2. Clinical trials of these "anti-enzyme" substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
17-Hydroxysteroid Dehydrogenases↗
Treatment of mastalgia with tamoxifen in male patients with liver cirrhosis: a randomized crossover study.
OBJECTIVE: Mastalgia is occasionally found in patients with liver cirrhosis, especially in those receiving spironolactone for treatment of ascites. The pathogenesis is still unclear. Estrogen excess in cirrhotic patients and estrogenic effects of the spironolactone are possible leading causes. Treatment directed against the preponderance of estrogenic stimulation in these patients has never been investigated. This study was designed to investigate the efficacy and safety of tamoxifen, an estrogen antagonist, on mastalgia in patients with liver cirrhosis. METHODS: A total of 16 male cirrhotic patients with mastalgia were randomly assigned to two groups. One group was treated with tamoxifen (20 mg p.o., b.i.d.) for 1 month, followed by placebo for the next month. The other group was treated in the reverse order. All patients received spironolactone for ascites and/or peripheral edema, and the drug was continued during the study period. The size of the breasts and the degree of breast pain and tenderness were recorded in all subjects before and after the treatment periods. Serum levels of estradiol and testosterone were measured using the radioimmunoassay method. RESULTS: Of the 16 patients, 14 experienced a decrease or disappearance of the breast pain and/or tenderness during the tamoxifen treatment period, whereas only two of the 16 patients felt an improvement during the placebo period (p < 0.05). There were significant improvements in the breast pain and tenderness scores and decreases in the breast sizes during the tamoxifen treatment period (before vs after: 1.4+/-0.3 vs 0.4+/-0.2, p = 0.002; 1.9+/-0.2 vs 0.5+/-0.2, p < 0.001; and 6.8+/-0.6 vs 5.5+/-0.6 cm, p = 0.02, respectively), whereas no obvious change was seen during the placebo period. Serum levels of estradiol and testosterone did not change significantly after the tamoxifen or placebo treatments (p > 0.05). No major side effects were noted during the therapeutic periods. CONCLUSIONS: Tamoxifen is effective and safe in the management of mastalgia in male cirrhotic patients taking spironolactone.
Aged↗