[A new transdermal estradiol therapeutic system].
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PURPOSE: Our purpose of this study was to evaluate the effect of a transdermal estradiol delivery system in postmenopausal women with confirmed pollakisuria and urinary incontinence. PATIENTS AND METHODS: We investigated 10 postmenopausal women, age 54-83 years, with pollakisuria and urinary incontinence but did not show distinct urological and/or neurological abnormalities. In this study, estradiol transdermal therapeutic system (Estraderm TTS 2 mg) alone were administrated for total of 8-week and this is observational, not randomized, blinded or controlled. A clinical evaluation were performed two times at before and after administration. RESULTS: In seven eligible cases, the severity of urinary incontinence was graded down in almost of them and the therapeutic effect on urinary incontinence was evaluated as "very effective" in 3 cases, "improved" in 2, "slightly improved" in 1 and "no change" in 1, respectively. In three eligible cases, the severity of pollakisuria was no change in all of them. CONCLUSION: Thus, the estrogen supplement therapy was considered effective for postmenopausal urinary incontinence.
The in vitro release profiles of two sizes of estradiol patches were determined by the paddle method, where the patch was held in position at the bottom of the dissolution vessel by sandwiching it between a watch glass and an aluminum wire mesh or Teflon screen, and also by the manufacturer's paddle-over-disk method. The estradiol content of test aliquots of the dissolution medium was determined by HPLC. The release profiles by both procedures were comparable and showed that approximately 10% of the labeled drug was released in 4 days.
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The natural sex steroids (E2, T, P) may be used in therapeutics. Estradiol and testosterone esters (decanoate and undecanoate) may be administered orally. A local effect always follows the percutaneous application of sex steroids, and this is usually accompanied by a systemic effect. But because of the very important metabolism of progesterone by the skin, it is necessary to administer it by other routes (intravaginal, intrarectal) in order to obtain a systemic effect.
BACKGROUND: About 20% of patients using transdermal estradiol complain of adverse local side effects. CASE: A 47-year-old, postmenopausal woman developed eczematous lesions at the sites of application of a estradiol therapeutic transdermal system and successively at the sites of application of a gel containing estradiol. Due to the topical intolerance, the therapy was switched to oral estrogen, which caused a systemic pruritic rash. Positive patch tests with estradiol led to the diagnosis of type IV allergic dermatitis due to transdermal estradiol and to a gel containing estradiol. Systemic contact dermatitis due to oral estradiol was also diagnosed. CONCLUSION: Even though allergic contact dermatitis from estradiol is extremely rare, local side effects from estradiol systems must be kept in mind and correctly diagnosed. Patch tests allow identification of the causative agent. In the case of primary sensitization to topical estradiol, oral estrogens must be prescribed cautiously to avoid systemic reactions.
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The effects of estradiol benzoate (EB) on the development of anti-CII antibodies and their pathogenic potential were studied during the progress of established CIA in the rat. CIA was induced in mature female Lewis rats by two subcutaneous inoculations containing bovine native CII (BCIIn), emulsified in Freund's incomplete adjuvant. Clinical arthritis fully developed by day 18 and then EB (1 mg/kg body wt per day, diluted in corn oil (CO)) was administered intramuscularly every second day thereafter. Antibodies binding four different CIIs (bovine or rat, either native or heat-denatured) were detected in sera and joint tissue extracts by means of solid-phase ELISA. Pharmacological doses of EB (>0.2 mg/kg body wt per day) caused significant remission of established CIA 5-7 days after treatment, and selectively suppressed the production of antibodies specific for denatured CII. To evaluate the arthritogenic potential of circulating anti-CIId IgG, transfer experiments were performed. IgG anti-CIIn, purified from EB-treated CIA rats, was not arthritogenic, whereas IgG anti-denatured (CIId), purified from CO-treated CIA rats, caused severe passive arthritis. Furthermore, pretreatment with rat CIId protected against subsequent induction of CIA, and this protection was associated with suppressed antibody production against CIId. Collectively, our results indicate that antibodies specific for CIId are involved in the pathogenesis of CIA, and that oestrogen-related remission of clinical arthritis may by caused by a selective suppression of antibodies produced against degraded/denatured CII.
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In man, the major function of calcitonin appears to be prevention of excessive or unwanted bone resorption. There is a striking sex difference in circulating levels, with a relative deficiency in women. Calcitonin secretion in young adults is increased by oestrogens and therefore long periods of oestrogen lack, such as after the menopause, may be associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially since the latter may be due to excessive bone resorption. In a study of the effects of oestrogen treatment on circulating levels of calcitonin, parathyroid hormone, and vitamin-D metabolites in postmenopausal women, the most striking change was a sharp rise in plasma-calcitonin. Oestrogens prevent postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss. Its place in the treatment of postmenopausal osteoporosis warrants further evaluation.
Cellular response to estradiol stimuli ist mediated by different signal transduction cascades. In addition to classical mechanisms like the activation of estrogen response elements, there is increasing interest in the so-called non- nuclear actions of estrogens. It has been shown, that the estradiol-induced activation of cytoplasmic kinases is an important alternative mechanism of the cellular estradiol response. Consequently, the question has been raised, whether estradiol-induced activation of growth factor signaling would be able to interfere with the action of antitumoral substances directed against receptor-tyrosine kinase signal transduction. Recent data demonstrated, that estradiol is able to diminish the effects of antitumoral drugs targeting the HER2 receptor in vitro. Novel insights into the non-nuclear estradiol response and its impact on the efficacy of antitumoral drugs observed in endometrial tumor cells are reviewed.
Estradiol and progesterone levels in maternal plasma after administration of 16, 16-dimethyl-PGE2 p-benzaldehyde semicarbazone ester (16,16-PGE2) 6 hourly for abortion were studied in 27 women in the second trimester of pregnancy and in 49 patients with fetal death in utero. Basal maternal plasma levels of estradiol and progesterone measured before prostaglandin injection were significantly lower in cases of fetal death in utero than in the other subjects. After 16,16-PGE2 injection, plasma levels of estradiol and progesterone fell more rapidly and to a greater extent in cases of fetal death in utero than those with normal pregnancy at corresponding gestations; the decline of plasma estradiol levels was quicker and more marked than that of progesterone. Thus, 16,16-PGE2 appears to exert a differential effect on estradiol and progesterone biosynthesis.
17alpha-estradiol (17alpha-E2) differs from its isomer, the potent feminizing hormone 17beta-estradiol (17beta-E2), only in the stereochemistry at one carbon, but this is sufficient to render it at least 200-fold less active as a transactivating hormone. Despite its meager hormonal activity, 17alpha-E2 is as potent as 17beta-E2 in protecting a wide variety of cell types, including primary neurons, from a diverse array of lethal and etiologically relevant stressors, including amyloid toxicity, serum withdrawal, oxidative stress, excitotoxicity, and mitochondrial inhibition, among others. Moreover, both estradiol isomers have shown efficacy in animal models of stroke, Alzheimer's disease (AD), and Parkinson's disease (PD). Data from many labs have yielded a mechanistic model in which 17alpha-E2 intercalates into cell membranes, where it terminates lipid peroxidation chain reactions, thereby preserving membrane integrity, and where it in turn is redox cycled by glutathione or by NADPH through enzymatic coupling. Maintaining membrane integrity is critical to mitochondrial function, where loss of impermeability of the inner membrane initiates both necrotic and apoptotic pathways. Thus, by serving as a mitoprotectant, 17alpha-E2 forestalls cell death and could correspondingly provide therapeutic benefit in a host of degenerative diseases, including AD, PD, Friedreich's ataxia, and amyotrophic lateral sclerosis, while at the same time circumventing the common adverse effects elicited by more hormonally active analogues. Positive safety and pharmacokinetic data from a successful phase I clinical study with oral 17alpha-E2 (sodium sulfate conjugate) are presented here, and several options for its future clinical assessment are discussed.
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In a prospective trial in 72 postmenopausal women to compare the effects on bone loss of no treatment, treatment with oestrogen, and treatment with calcium the women were followed up for at least two years and examined densitometrically and morphometrically. Women in the untreated control group continued to lose bone during the two years, whereas the oestrogen-treated group lost none. Loss in the calcium-treated group was intermediate. Oestrogen appeared to inhibit endosteal bone resorption and may have stimulated subperiosteal bone apposition.
The introduction of ethambutol and rifampicin has modified the therapy of tuberculosis. Therapy in hospitals or sanatoria can be shortened, and intermittent regimens (once or twice weekly under supervision) are possible. Better knowledge of the side effects of particular drugs, particularly rifampicin, (such as allergic reactions in intermittent administration and reduced effect of oral contraceptives) has been gained. Instead of mere supervision, preventive chemotherapy is given in many cases such as in recently discovered fibrotic lesions and in high risk cases (silicosis, treatment with corticosteroids and immunosuppressive agents)minadequate treatment may lead to functional impairment such as fibrosis and cor pulmonale. These aspects are discussed and the resultant guidelines for the treatment of tuberculosis are presented.