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Endometrial safety: a key hurdle for selective estrogen receptor modulators in development [Review]
Pinkerton, JV; Goldstein, SR
Selective estrogen receptor modulators (SERMs) have the ability to provide mixed functional estrogen receptor (ER) agonist or antagonist activity, depending on the target tissue. Tamoxifen, the first SERM available for clinical use, is regarded as a highly effective agent for the prevention and treatment of breast cancer. However, tamoxifen exhibits ER agonist activity in the uterus and is associated with an increased risk of endometrial hyperplasia and malignancy. Endometrial safety has been an important consideration in the clinical development of SERMs, with improved benefit-risk profiles. Raloxifene, which is currently approved for the prevention and treatment of postmenopausal osteoporosis and for the prevention of breast cancer, seems to have neutral effects on the uterus. Promising results have been observed with the targeted development of newer and more tissue-specific SERMs, many of which are under investigation for postmenopausal osteoporosis. Of the newer SERMs in development, lasofoxifene has been shown to reduce fracture risk and decrease the incidence of breast cancer but has been associated with an increased incidence of vaginal bleeding, endometrial thickening, and endometrial polyps. Lasofoxifene and ospemifene have shown beneficial effects on the vaginal epithelium. Phase 3 clinical data have shown that bazedoxifene is effective in preventing and treating postmenopausal osteoporosis, without adverse effects on the endometrium or breast. Arzoxifene has been evaluated in phase 3 trials for postmenopausal osteoporosis and has been studied for the treatment of uterine malignancies but is no longer in clinical development. Further investigation of newer SERMs is warranted to more clearly define the endometrial safety of these agents
ISI:000277501600026
ISSN: 1072-3714
CID: 109708
Reply [Letter]
Goldstein, Steven R
ORIGINAL:0007303
ISSN: 0002-9378
CID: 107923
Selective estrogen receptor modulator: the saga continues [Editorial]
Goldstein, SR
ISI:000275485200004
ISSN: 1072-3714
CID: 108778
Terms, definitions and measurements to describe the sonographic features of the endometrium and intrauterine lesions: a consensus opinion from the International Endometrial Tumor Analysis (IETA) group
Leone, F P G; Timmerman, D; Bourne, T; Valentin, L; Epstein, E; Goldstein, S R; Marret, H; Parsons, A K; Gull, B; Istre, O; Sepulveda, W; Ferrazzi, E; Van den Bosch, T
The IETA (International Endometrial Tumor Analysis group) statement is a consensus statement on terms, definitions and measurements that may be used to describe the sonographic features of the endometrium and uterine cavity on gray-scale sonography, color flow imaging and sonohysterography. The relationship between the ultrasound features described and the presence or absence of pathology is not known. However, the IETA terms and definitions may form the basis for prospective studies to predict the risk of different endometrial pathologies based on their ultrasound appearance
PMID: 20014360
ISSN: 1469-0705
CID: 134424
The role of transvaginal ultrasound or endometrial biopsy in the evaluation of the menopausal endometrium
Goldstein, Steven R
All postmenopausal women with vaginal bleeding need endometrial assessment. Disposable suction piston biopsy devices have virtually replaced dilatation and curettage despite little scientific validation. In patients with known carcinoma, false-negative rates with such devices range from 2.5-32.4%. Large prospective studies have shown that an endometrial thickness <or= 4 mm on transvaginal ultrasound in postmenopausal women with bleeding has a risk of malignancy of 1 in 917. Thus, in postmenopausal patients with bleeding, biopsy is not indicted when endometrial thickness is <or= 4 mm. The significance of a thick endometrial echo in nonbleeding postmenopausal women has not been validated and need not require automatic tissue sampling
PMID: 19576369
ISSN: 1097-6868
CID: 100628
Raloxifene use in clinical practice: efficacy and safety
Goldstein, Steven R; Duvernoy, Claire S; Calaf, Joaquim; Adachi, Jonathan D; Mershon, John L; Dowsett, Sherie A; Agnusdei, Donato; Stuenkel, Cynthia A
OBJECTIVE AND METHODS: In this article, we provide an interdisciplinary concise review of the effects of raloxifene on breast, bone, and reproductive organs, as well as the adverse events that may be associated with its use. RESULTS: Raloxifene has been shown to prevent osteoporosis in postmenopausal women (PMW) with low bone mass and prevent vertebral fractures in those with osteoporosis/low bone mass; it has not been shown to reduce the risk of nonvertebral fractures. Raloxifene reduces the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. The risk of venous thromboembolism has been consistently shown to be increased with raloxifene, so it should not be used in women at high risk of venous thromboembolism. Although raloxifene does not increase, nor decrease, the risk of coronary or stroke events overall, in the raloxifene trial of PMW at increased risk of coronary events, the incidence of fatal stroke was higher in women assigned raloxifene versus placebo. CONCLUSIONS: Based on its approved indications, it is appropriate to prescribe raloxifene to prevent or treat osteoporosis, as well as to reduce the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. Women at increased risk of both fracture and invasive breast cancer are those most likely to receive a dual benefit with raloxifene. Decision making must involve the incorporation of the woman's personal feelings about the risks and benefits of raloxifene therapy, balanced with her interest in reducing risk of fractures and breast cancer through pharmacological intervention
PMID: 19092711
ISSN: 1530-0374
CID: 99317
Vaginal Effects of Lasofoxifene: 3-Year Results from the PEARL Trial [Meeting Abstract]
Goldstein, SR; Cummings, SR; Eastell, R; Ensrud, K; Reid, DM; Vukicevic, S; LaCroix, A; Thompson, D; Thompson, J; Proulx, J; Johnson, M; Sriram, U
ISI:000260858500156
ISSN: 1072-3714
CID: 90947
Ultrasound scanning in reproductive medicine and infertility. Preface [Editorial]
Goldstein, Steven R
PMID: 18504695
ISSN: 1526-8004
CID: 80290
Early pregnancy: normal and abnormal
Goldstein, Steven R
The understanding of early pregnancy both normal and abnormal as seen by transvaginal ultrasound is an essential skill of any clinician involved in reproductive medicine and infertility. The 'sonomicroscopy' of the vaginal probe results from the high level of magnification and close proximity to the structure being studied. In addition, the ability to detect minute levels of human chorionic gonadotropin, often by over-the-counter home pregnancy tests, has caused patients to present to clinicians earlier then ever before. It is essential that the sonologist or sonographer understand what early pregnancy looks like on transvaginal ultrasound and why it looks like that, so that one can distinguish early pregnancies that are normal from those that are absolutely destined to fail. In addition, understanding the use of ultrasound and human chorionic gonadotropin in the modern diagnosis of ectopic pregnancy as well as a newly emerging category of pregnancies of unknown location is essential to clinical practice. This article will review the fundamental principals outlined above
PMID: 18504702
ISSN: 1526-8004
CID: 80291
To the editor. Use of transvaginal ultrasonography and sonohysterography [Letter]
Goldstein, Steven R
PMID: 18426000
ISSN: 1072-3714
CID: 135330