Impotentie brengt een constant ongemak met zich mee, net als fysieke en psychologische problemen in uw leven cialis kopen terwijl generieke medicijnen al bewezen en geperfectioneerd zijn
Microsoft word - catherino-sitrukware_abstract_5-28.doc
Are All SERMs the Same?
William H. Catherino, MD, PhD
Régine L. Sitruk-Ware, MD
• In light of the Women’s Health Initiative, the development of therapies that have the
beneficial effects of estrogens without deleterious estrogen action is in great demand.
• Selective Estrogen Receptor Modulator (SERM) development has resulted in
significant therapeutic advances for breast cancer, osteoporosis, and potentially other
• Future SERMs may have a therapeutic profile that can be tailored to specific patient
Compounds that can be described as SERMs have expanded dramatically over the past
two decades. The ability of SERMs to act as estrogens in certain tissues, while remaining
inert or acting as an anti-estrogen in other tissues, has opened up opportunities for
treating specific estrogen-modulated diseases without accepting the risk of systemic
estrogen activity. After publication of findings from the Women’s Health Initiative,
interest in compound selectivity increased. A key question emerged: Is it possible to
develop a compound that reduces menopausal symptoms while protecting bone, breast,
The first SERM, tamoxifen, provided a glimpse into the potential of SERM therapy.
Tamoxifen functions as an anti-estrogen in the breast, where it inhibits breast cancer
formation and progression. At the same time, however, tamoxifen acts as an estrogen
with regard to bone density and lipid profile. While these dual actions are encouraging,
other SERM-like activity of tamoxifen diminished enthusiasm for this compound as an
ideal peri- and postmenopausal therapy. Tamoxifen has demonstrated estrogen-like
function on the endometrial lining, and prolonged treatment is linked with endometrial
cancer development. Furthermore, it acts as an anti-estrogen centrally, resulting in an
increased frequency of hot flashes. For many women, this therapeutic profile is not
acceptable. Significant effort has been invested to design tamoxifen-like compounds with
A second generation of compounds is represented by raloxifene. Raloxifene (originally
investigated under the name keoxifene) was comparable or slightly inferior to tamoxifen
as a breast cancer therapy in preclinical trials. Importantly, however, data showed notable
benefit to bone maintenance. As a result, raloxifene was reintroduced as a therapy for
osteoporosis and has been an effective addition to clinical therapies for this indication.
Raloxifene also reduces breast cancer risk, and perhaps most importantly, does not have a
tamoxifen-like stimulatory effect on the endometrium. Encouraged by this critical
difference between the two main SERMs, significant investigation demonstrated
evidence of beneficial effect on lipid profiles. However, climacteric symptoms were not
alleviated by raloxifene, and thromboembolic events are increased to a similar extent as
with tamoxifen. Continued investigations into raloxifene congeners have recently
Cuzick J, Powles T, Veronesi U, et al. Overview of the main outcomes in breast-cancer
prevention trials. Lancet.
Dorval M, Vallée MH, Plante M, Chiquette J, Gaudet M, Simard J. Effect of the
Women's Health Initiative study publication on hormone replacement therapy use among
women who have undergone BRCA1/2 testing. Cancer Epidemiol Biomarkers Prev.
Gajdos C, Jordan VC. Selective estrogen receptor modulators as a new therapeutic drug
group: concept to reality in a decade. Clin Breast Cancer.
Jordan VC. The science of selective estrogen receptor modulators: concept to clinical
practice. Clin Cancer Res.
Palacios S. The future of the new selective estrogen receptor modulators. Menopause Int.
Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB. Selective estrogen receptor
modulators: an update on recent clinical findings. Obstet Gynecol Surv.
Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the
risk of developing invasive breast cancer and other disease outcomes: the NSABP Study
of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA.
Gyógyszer beszerzés 2014. évre Közbeszerzési Értesítő száma: Beszerzés tárgya: Eljárást megindító felhívás - 123. §/KÉ/2013.07.01 Hirdetmény típusa: Eljárás fajtája: Közzététel dátuma: Iktatószám: CPV Kód: Közép-dunántúli Országos Büntetés-végrehajtási Ajánlatkérő: 2471 Baracska-Annamajor; 8000 Székesfehérvár Teljesítés he
Minority Groups: Coersion, Discrimination, Exclusion, Deviance and the Quest for Equality Prof. Dan Soen, Dr. Mally Shechory, Prof. Sarah Ben-David (eds.) Society consists of numerous interconnected, interacting, and interdependent groups, which invariably differ in power and status. The consequences of belonging to the more powerful, higher-status majority versus a less powerful, l