toremifene and Osteoporosis--Postmenopausal

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues, most likely due to the receptor conformation changes associated with that SERM's binding and the subsequent effect on transcription. Clinical trials aim to differentiate amongst SERMs on selected target tissues for use in postmenopausal women including effects on breast, bone, cardiovascular venous thrombosis risk, endometrium, vagina, vasomotor symptoms, and brain. This paper describes differences in clinical effects on selected target tissues of SERMs that are approved, discontinued or in development. FDA approved SERMs include tamoxifen and toremifene used for prevention and treatment of breast cancer, raloxifene approved for prevention and treatment of osteoporosis and prevention of invasive breast cancer, and ospemifene approved for treatment of dyspareunia from menopausal vaginal atrophy. The FDA approved first tissue selective estrogen complex (TSEC) a pairing of conjugated equine estrogens with the SERM, bazedoxifene. This pairing reduces the risk of endometrial hyperplasia that can occur with the estrogenic component of the TSEC without the need for a progestogen in women with a uterus. It also allows for the estrogenic benefits on relief of hot flashes and prevention of bone loss without stimulating the breast or the endometrium. In clinical practice, the tissue-selective actions of SERMs, alone or paired with estrogens, allow for individualization in meeting the treatment needs of postmenopausal women by providing targeted tissue effects. This article is part of a Special Issue entitled 'Menopause'.

Topics: Breast Neoplasms; Clinical Trials as Topic; Dyspareunia; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Indoles; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Pyrrolidines; Raloxifene Hydrochloride; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen; Tetrahydronaphthalenes; Toremifene

Selective estrogen receptor modulators (SERMs) represent a growing class of compounds that act as either estrogen receptor gonists or ntagonists in tissue-selective manner. SERMs with the appropriate selectivity profile offer the opportunity to dissociate the favorable bone and cardio-vascular effects of estrogen from its unfavorable stimulatory effects on the breast and uterus. The triphenylethylene drug tamoxifen proved to be invaluable to treat and protect against breast cancer and bone loss, probably reduces cardiovascular risk, but had side effects on uterus similar to natural estrogens. The tamoxifen derivate toremifene is also used to treat breast cancer, but has less effect on bone. The non-steroidal benzothiophene derivate, raloxifene, is the best SERM available thus far. It has the potential to prevent breast cancer (like tamoxifen), but has better profile in its actions on bone and cardiovascular system (produces a rapid reduction of serum cholesterol, decreases fibrinogen and lipoprotein, improves the vascular epithelial function, attenuates vascular intimal thickening, etc.). It does not increase the incidence of endometrial cancer. Compounds of this class are the first step in developing the perfect hormone replacement and other multitargeted therapy. This review summarizes the recent important knowledge about SERMs.

Topics: Breast Neoplasms; Coronary Disease; Estrogen Antagonists; Estrogens; Female; Humans; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen; Toremifene

Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Endometrial Neoplasms; Estrogen Antagonists; Female; Genes, BRCA1; Humans; Italy; Neoplasms, Hormone-Dependent; Osteoporosis, Postmenopausal; Piperidines; Raloxifene Hydrochloride; Tamoxifen; Toremifene; United Kingdom; United States

Based on the data and clinical experience derived from tamoxifen usage, the properties of an ideal antiestrogen is described that could have applications as a breast cancer preventative agent, long-term adjuvant therdpy, or as a treatment for osteoporosis. Each of the new antiestrogens currently being tested is discussed in terms of laboratory development, toxicology, pharmacology, endocrinology, and clinical evaluation. And each new compound is assessed according to the properties of an ideal antiestrogen.. A review of all published reports was facilitated by the use of Medline computer searches.. Numerous compounds are being evaluated in clinical trials and can be categorized as triphenylethylenes or tamoxifen analogs, pure antiestrogens, and targeted antiestrogens. Several of these compounds may have fewer uterotropic properties and greater effects on maintaining bone density compared with tamoxifen; however, the clinical experience (ie, patient-years of treatment) with any of these compounds is minimal.. Although many of these compounds appear promising, further evaluation will be necessary to determine the role these compounds may serve as preventive agents, adjuvant therapies, treatments for advanced disease, or other medical indications such as osteoporosis.

Topics: Antineoplastic Agents, Hormonal; Bone Density; Drugs, Investigational; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Humans; Osteoporosis, Postmenopausal; Piperidines; Raloxifene Hydrochloride; Tamoxifen; Toremifene