Faculty Bibliography

Postmenopausal bleeding is "endometrial cancer until proven otherwise". The incidence of cancer is reported as 1-14% although most studies are in the 3-7% range. The majority will actually bleed from inactive atrophic endometrium. In the early 1990's pilot studies began to suggest that a thin distinct endometrial echo <4-5 mm in postmenopausal patients with bleeding was associated with a lack of significant tissue and effectively excluded endometrial carcinoma. Since then several large prospective multinational trials in Europe have corroborated this. Taken together it appears that in patients with postmenopausal bleeding a thin distinct endometrial echo <4mm on transvaginal has a risk of endometrial cancer of 1 in 917. It is crucial that the examiner appreciate that not all uteri lend themselves to a meaningful ultrasound examination. Axial uterus, previous surgery, coexisting myomas, marked obesity, adenomyosis will result in a significant minority of such patients not yielding a reliable endometrial echo visualized with transvaginal sonography. In such cases saline infusion sonohysterography (SIS) may be helpful. SIS should be thought of as a subset of TV/US in cases in which the endometrium is not thin or not well visualized. Blind endometrial biopsy with suction piston biopsy instruments has been a standard approach in spite of a lack of appropriate validation especially in light of the fact that endometrial pathology is not always global. Transvaginal ultrasound can and should be the first approach to the postmenopausal patient with bleeding

Selective estrogen receptor modulators (SERMs) can act as estrogen agonists or estrogen antagonist depending on the target tissue. Tamoxifen was the first clinically available SERM and is highly effective for the prevention and treatment of breast cancer. Tamoxifen however has estrogen agonistic activity in the uterus and has been associated with an increased risk of endometrial hyperplasia and malignancy. Thus endometrial safety has been an important consideration in the development of all SERMs since then. Raloxifene, which is currently approved for prevention and treatment of postmenopausal osteoporosis, and for the prevention of breast cancer, does not result in endometrial hyperplasia or cancer. It does result in a slight increase in endometrial polyps. Lasofoxifene which has been shown to reduce fracture risk and decrease the incidence of breast cancer did not increase endometrial cancers or endometrial hyperplasia but did result in an increased incidence in vaginal bleeding, endometrial polyps ( all of which were inactive and atrophic) and endometrial "thickening" on transvaginal ultrasound. Ospemefene has been shown to have beneficial effects on the vaginal epithelium but does not cause endometrial cancer or hyperplasia. Bazodoxifene is effective in preventing and treating postmenopausal osteoporosis and does not cause endometrial thickening on ultrasound nor any hyperplasia or cancer. Arzoxifene was evaluated in a phase III trials for treating osteoporosis but its clinical development program was suspended. Further investigation of newer SERMs is warranted to more clearly define the endometrial safety of each of these agents

Postmenopausal bleeding is 'cancer until proven otherwise.' A thin distinct endometrial echo on transvaginal ultrasound has a risk of malignancy of 1 in 917 and does not require an endometrial biopsy. If the endometrial echo is poorly visualized, then in such women, saline infusion sonohysterography is an appropriate next step. The prevalence of asymptomatic endometrial thickening (mostly due to inactive polyps) is high, approximately 10% to 17% of postmenopausal women. The risk of malignancy in such polyps is low (approximately 0.1%), and in structures that mimic polyps, it is also low (0.3%). The incidence of serious complications from an operative intervention in such postmenopausal women is not insignificant (1.3%-3.6%). Thus, automatic intervention in such women, without any high-risk status, is not warranted

OBJECTIVE: To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location (PUL), we propose a consensus statement with definitions of population, target disease, and final outcome. DESIGN: A review of literature and a series of collaborative international meetings were used to develop a consensus for definitions and final outcomes of women initially diagnosed with a PUL. RESULT(S): Global differences were noted in populations studied and in the definitions of outcomes. We propose to define initial ultrasound classification of findings into five categories: definite ectopic pregnancy (EP), probable EP, PUL, probable intrauterine pregnancy (IUP), and definite IUP. Patients with a PUL should be followed and final outcomes should be categorized as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. Those with the transient condition of a persisting PUL should ultimately be classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP. These specific categories can be used to characterize the natural history or location (intrauterine vs. extrauterine) of any early gestation where the initial location is unknown. CONCLUSION(S): Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a PUL

OBJECTIVE: The aim of this study was to establish the gynecological effects of 5 years of treatment with lasofoxifene versus placebo in postmenopausal osteoporotic women. METHODS: A total of 8,556 women aged 59 to 80 years with femoral neck or spine bone mineral density T scores of -2.5 or lower were randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or placebo, for 5 years. RESULTS: Endometrial cancer was confirmed for two women in each lasofoxifene group and for three women in the placebo group. Endometrial hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25 mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo), and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo, respectively. Lasofoxifene treatment resulted in a small increase in endometrial thickness versus placebo (least-squares mean change from baseline 1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and -0.72 mm for 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women required surgery for pelvic organ prolapse or urinary incontinence in the placebo and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group: 1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%, 5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene 0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively. CONCLUSION: These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women

The Society of Radiologists in Ultrasound (SRU) convened a panel of specialists from gynecology, radiology, and pathology to arrive at a consensus regarding the management of ovarian and other adnexal cysts imaged sonographically in asymptomatic women. The panel met in Chicago, IL, on October 27-28, 2009, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies, and are thought to represent a reasonable approach to asymptomatic ovarian and other adnexal cysts imaged at ultrasonography

The Society of Radiologists in Ultrasound convened a panel of specialists from gynecology, radiology, and pathology to arrive at a consensus regarding the management of ovarian and other adnexal cysts imaged sonographically in asymptomatic women. The panel met in Chicago, Ill, on October 27-28, 2009, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies, and are thought to represent a reasonable approach to asymptomatic ovarian and other adnexal cysts imaged at ultrasonography.

Abnormal uterine bleeding in women older than age 35 years, and certainly in menopausal patients, mandates evaluation, mainly to exclude cancer and hyperplasia, but also to better diagnose the source of the bleeding to appropriately manage the patient. In the past, dilation and curettage was the mainstay of diagnosis. This gave way to in-office suction pump-generated biopsies. Most recently, disposable biopsy instruments with their own internal piston to generate suction have become the standard of care. Rarely has such a technique received such widespread acceptance with such limited validation. Transvaginal ultrasonography, when technically feasible, is a noninvasive way to image the endometrial cavity. Saline-infusion sonohysterography is a subset of transvaginal ultrasonography reserved for patients in whom an adequate endometrial echo is not seen or when an endometrial echo is seen but not sufficiently thin. Appropriate understanding and use of transvaginal ultrasonography and addition of sonohysterography when necessary can allow a clinical algorithm that can triage patients with abnormal uterine bleeding to 1) no anatomic pathology best treated expectantly; 2) a global endometrial process, in which case random blind endometrial sampling is appropriate; or 3) a focal endometrial abnormality in which case endometrial sampling should be done with the visualization offered by hysteroscopy. Finally, the incidence of thick endometrial echo found incidentally in postmenopausal women with no bleeding is extremely high (10-17%) and should not trigger invasive endometrial sampling automatically

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