PubMed · 12851525
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Evan R Simpson. Tibolone.. https://doi.org/10.1097/00042192-200310040-00021
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Despite the historical use of estrogens in the treatment of prostate cancer (PCa) little is known about their direct biological effects on the prostate, their role in carcinogenesis, and what mechanisms mediate their therapeutic effects on PCa. It is now known that estrogens alone, or in synergism with an androgen, are potent inducers of aberrant growth and neoplastic transformation in the prostate. The mechanisms of estrogen carcinogenicity could be mediated via induction of unscheduled cell proliferation or through metabolic activation of estrogens to genotoxic metabolites. Age-related changes and race-/ethnic-based differences in circulating or locally formed estrogens may explain differential PCa risk among different populations. Loss of expression of estrogen receptor (ER)-beta expression during prostate carcinogenesis and prevention of estrogen-mediated oxidative damage could be exploited in future PCa prevention strategies. Re-expression of ER-beta in metastatic PCa cells raises the possibility of using ER-beta-specific ligands in triggering cell death in these malignant cells. A variety of new estrogenic/anti-estrogenic/selective estrogen receptor modulator (SERM)-like compounds, including 2-methoxyestradiol, genistein, resveratrol, licochalcone, Raloxifene, ICI 182,780, and estramustine are being evaluated for their potential in the next generation of PCa therapies. Increasing numbers of patients self-medicate with herbal formulations such as PC-SPES. Some of these compounds are selective ER-beta ligands, while most of them have minimal interaction with ER-alpha. Although many may inhibit testosterone production by blockade of the hypothalamal-pituitary-testis axis, the most effective agents also exhibit direct cytostatic, cytotoxic, or apoptotic action on PCa cells. Some of them are potent in interfering with tubulin polymerization, blocking angiogenesis and cell motility, suppressing DNA synthesis, and inhibiting specific kinase activities. Further discovery of other compounds with potent apoptotic activities but minimal estrogen action should promote development of a new generation of effective PCa preventive or treatment regimens with few or no side-effects due to estrogenicity. Further advancement of our knowledge of the role of estrogens in prostate carcinogenesis through metabolic activation of estrogens and/or ER-mediated pathways will certainly result in better preventive or therapeutic modalities for PCa.
We report the successful treatment with tibolone of a postmenopausal woman affected by primary Sjögren's syndrome. One year after the beginning of treatment, the woman does not need artificial tears and vaginal lubricants. This is the first report of an effective pharmacologic treatment for primary Sjögren's syndrome in humans.
There is an intense discussion in the scientific and even more so in the public community as well as regulatory agencies about the potential benefits or detrimental effects of plant-derived compounds that may affect the endocrine system, especially estrogen signaling pathways. These so-called phytoestrogens are found in the normal western diet and predominantly in an eastern or soy-based diet and the potency of the isolated compounds to interact with the known receptors for estrogen varies tremendously. The estrogen receptors, ER alpha and ER beta, mediate the effects of endogenous estrogens, i.e. regulation of reproductive function, tissue development, cell proliferation and differentiation. In this review, in vitro test systems available to date for the screening of estrogenic and antiestrogenic activity including mechanism-based assays are described. The potency of phytoestrogens determined using these in vitro assays are compared with the potency of endogenous estrogens and results obtained in vitro are compared with effects in vivo. Finally, the impact of in vitro assays to determine estrogenicity on human hazard assessment is discussed as well as other non ER-mediated mechanisms that may contribute to potential beneficial or adverse effects of phytoestrogens in man.