Faculty Bibliography

Menopausal symptoms (eg, hot flushes and vaginal symptoms) are common, often bothersome, and can adversely impact women's sexual functioning, relationships, and quality of life. Estrogen-progestin therapy was previously considered the standard care for hormone therapy (HT) for managing these symptoms in nonhysterectomized women, but has a number of safety and tolerability concerns (eg, breast cancer, stroke, pulmonary embolism, breast pain/tenderness, and vaginal bleeding) and its use has declined dramatically in the past decade since the release of the Women's Health Initiative trial results. Conjugated estrogens paired with bazedoxifene (CE/BZA) represent a newer progestin-free alternative to traditional HT for nonhysterectomized women. CE/BZA has demonstrated efficacy in reducing the frequency and severity of vasomotor symptoms and preventing loss of bone mineral density in postmenopausal women. CE/BZA provides an acceptable level of protection against endometrial hyperplasia and does not increase mammographic breast density. Compared with traditional estrogen-progestin therapy, it is associated with lower rates of breast pain/tenderness and vaginal bleeding. Patient-reported outcomes indicate that CE/BZA improves menopause-specific quality of life, sleep, some measures of sexual function (especially ease of lubrication), and treatment satisfaction. This review looks at the rationale for selection and combination of CE with BZA at the dose ratio in the approved product and provides a detailed look at the efficacy, safety, tolerability, and patient-reported outcomes from the five Phase III trials. Patient considerations in the choice between CE/BZA and traditional HT (eg, tolerability, individual symptoms, and preferences for route of administration) are also considered.

Objective: This in vitro study was designed to determine whether Relizen's mechanism of action is serotonergic. Relizen1 (also known as Serelys1/Femal1/ Femalen1) has been shown to reduce symptoms associated with menopause. A double-blind, placebo-controlled study (Winther et al, 2005) showed that Relizen reduced hot flashes associated with menopause, and alleviated mood swings and tiredness. While other herbal products have been shown to reduce menopause symptoms, their activity appears to be due to an estrogenic effect from phytoestrogens. In the above study, measurements of follicle-stimulating hormone (FSH), estrogen, testosterone and sex hormone binding globulin (SHBG) did not suggest any hormonal effects from Relizen. Further testing of Relizen has confirmed its mechanism of action is not hormonal. Samples of Relizen's active ingredient, a Swedish flower pollen extract, were analyzed by high-performance liquid chromatography (HPLC) and found to contain subpharmacologic levels of phytoestrogens. Additionally, the flower pollen extract was tested for estrogenic activity in an immature rat uterotropic bioassay. Treatment of immature female rats with high doses of Relizen did not promote uterine growth, suggesting a non-hormonal mechanism of action. Additionally, in an in vitro study, Relizen produced no proliferation of MCF-7 breast cancer cells, an effect that depends on interaction with cellular estrogen receptors, in contrast to an active control, 17-beta estradiol, which produced proliferation. Since Relizen does not work through any estrogenic mechanism, we sought to determine whether its activity might be mediated by a serotonergic pathway. Design: Relizen, as a powder mixture of 75% pollen/pistil extract P182 and 25% pollen extract GC Fem, was tested for serotonergic effects. Synaptosomes were isolated from the cortex of Wistar rats and incubated with tritium-labeled serotonin and 9 concentrations of Relizen ranging from 0.1mug/ml to 1000mug/ml. Results: Relizen inhibited the uptake of [3H]-serotonin in a dose-dependentmanner with an EC50 value of 60mug/ml, a level considered to be physiologically achievable. Conclusion: This study suggests that Relizen's positive effects on menopausal symptoms may be mediated by some inhibition of serotonin reuptake at synaptosomal junctions. Further study in preclinical and clinical models to confirm these results is warranted

OBJECTIVE: Tamoxifen, used for treatment and chemoprevention of breast cancer, is converted to 4-hydroxy-tamoxifen and other metabolites by cytochrome P450 (CYP) enzymes. It can often initiate or exacerbate vasomotor symptoms (VMS). Selective serotonin reuptake inhibitors (SSRIs) have been prescribed for VMS in such participants in which estrogens are contraindicated. However, SSRIs are strong CYP2D6 inhibitors and can reduce the efficacy of tamoxifen. A nonhormonal purified Swedish pollen extract (Relizen is also prescribed in other countries under different registered trade names: Serelys, Femal, Femalen), has shown efficacy versus placebo in treating VMS in a randomized, double-blind controlled trial. The objective of this study was to evaluate the in vitro effects of purified Swedish pollen extract on the CYP2D6 enzyme. METHODS: PE-F/S, the powder form of purified Swedish pollen extract, contains 75% pollen/pistil extract P182 and 25% pollen extract GCFem. It was tested for its potential to inhibit the human CYP isoenzyme, CYP2D6, in pooled human liver microsomes. Quinidine, a known inhibitor of CYP2D6, was used as a reference. Concentrations of purified Swedish pollen extract ranged from 1.65 to 400 mug/mL, approximately five times the recommended daily dose for VMS. RESULTS: Inhibition of CYP2D6 with purified Swedish pollen extract was negligible at all concentrations and ranged from -6.53% to 10.67%. Inhibition of CYP2D6 enzyme with Quinidine increased in a linear dose-related fashion from -7.07% at 2.06 nM to 84.05% at 500 nM. CONCLUSIONS: Purified Swedish pollen extract is a nonhormonal treatment of VMS that does not show inhibition of the CYP2D6 enzyme. This may have important clinical utility for women using tamoxifen for breast cancer treatment or chemoprevention who experience VMS.

The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented

PURPOSE: Cystadenofibromas are benign ovarian neoplasms. Their most typical features on sonography (US) are unilocular cysts with small, shadowing hyperechoic, solid papillae without internal vascularity. In the past, they were virtually always surgically removed to exclude malignancy. This study was undertaken to review the sonographic appearances of benign cystadenomas. METHODS: We retrospectively reviewed the transvaginal US studies of 32 cases of pathologically proven ovarian cystadenofibromas. RESULTS: Twenty-two of the tumors presented as unilocular cystic structures with one or more solid, hyperechoic, shadowing, mural nodules with no discernible blood flow projecting from the inner cyst wall. Ten lesions were multiloculated with multiple small solid areas, with scant or no blood vessels. CONCLUSIONS: Cystadenofibromas do not always have a classic appearance on transvaginal US and color Doppler imaging. In our series, however, the majority (69%) presented as unilocular cysts with one or more small solid, avascular projections from the inner cyst wall. These features had 100% reliability for a diagnosis of benign cystadenofibroma in this small series. Further study is necessary to confirm the reliability of this finding for benign cystadenofibroma, thus possibly avoiding or minimizing any surgical exploration. (c) 2014 Wiley Periodicals, Inc. J Clin Ultrasound, 2014.

Ultrasound technology has evolved dramatically in recent years and now includes applications such as 3-dimensional volume imaging, real-time evaluation of pelvic organs (simultaneous with the physical examination), and Doppler blood flow mapping without the need for contrast, which makes ultrasound imaging unique for imaging the female pelvis. Among the many cross-sectional imaging techniques, we should use the most informative, less invasive, and less expensive modality to avoid radiation when possible. Hence, ultrasound imaging should be the first imaging modality used in women with pelvic symptoms.