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OBJECTIVES/OBJECTIVE:Women who experience postmenopausal bleeding (PMB) are considered to have endometrial cancer (EC) until proven otherwise. Initially, dilatation and curettage (D&C) was the gold standard of diagnosis. This was largely replaced by blind endometrial (EM) biopsy. However, recently, the relatively high false negative rate of such blind sampling in women with EC has become understood. Concomitantly, numerous studies indicate that an EM echo of ≤ 4 mm on transvaginal ultrasound (TV U/S) is a reliable enough test to exclude EC such that biopsy is not needed in initial cases of PMB. However, not all PM women will have anatomy that lends itself to a meaningful determination of EM thickness. This study was undertaken to evaluate the frequency of, and reasons for, an inability to adequately visualize an EM echo. METHODS:472 consecutive asymptomatic PM women had TV U/S as part of routine gynecologic care. Their charts and TV U/S were reviewed, and, if adequate, EM thickness was recorded. If EM thickness was not adequately visualized the reason, as judged by the examiner, for inadequacy was recorded. Other demographics included years since menopause, body mass index (BMI), and current use of hormone therapy. RESULTS:Of the 472 women, 292 (61.9%) had an EM echo that was well visualized and reliably measured (mean 3.0 mm, range 1.0 -28.0). Thus, in 180 PM women (38.1%), a distinct measurable EM echo was unable to be adequately visualized. The reasons were: fibroids (n=95, or 20.1% of overall cohort), adenomyosis (n=35, or 7.4% of overall cohort), axial uterus (n=50, or 10.6% of cohort). Mean years since menopause was 14.0 in those visualized (range 1-50), and 14.1 in non-visualized (range 1-40) (N.S.). Mean BMI was 23.9 in those visualized (range 16-41) and 25.4 (range 18-40) in those non-visualized (p=.015). CONCLUSIONS:TV U/S has become an accepted first step in the evaluation of PMB. However, in this cohort 39.8% of women had anatomic reasons for non-visualization of a reliable EM measurement including fibroids, adenomyosis, and axial uterus. There was no significant difference between groups based on years since menopause or current use of hormone therapy, but the mean BMI of the non-visualized group was significantly higher than those visualized. Clinicians should be cognizant of these potential limitations of TV U/S in the initial evaluation of women with PMB. This article is protected by copyright. All rights reserved.

Video Summary:http://links.lww.com/MENO/A765.

Video Summary:http://links.lww.com/MENO/A763.

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17β-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18-54%), ethinyl estradiol/NETA (31-61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9-27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin^®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin^® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin^®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin^® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

OBJECTIVE:The aim of the study was to evaluate the effect of a single-capsule 17β-estradiol/progesterone (E2/P4), TX-001HR, on endometrial safety, to report on amenorrhea and bleeding patterns of users, and to identify predictors of amenorrhea. METHODS:The REPLENISH trial (NCT01942668) evaluated use of TX-001HR in menopausal women (40-65 y) with vasomotor symptoms (VMS) and a uterus. Women were randomized to daily E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, or 0.25/50), or placebo for 12 months. Incidence rate of endometrial hyperplasia was calculated from endometrial biopsies conducted at screening and study completion. Women reported bleeding and spotting in daily diaries. The number of bleeding and/or spotting days and the proportion of women with no bleeding or amenorrhea were compared between treatment and placebo using the Fisher exact test. Predictors of cumulative amenorrhea were assessed by univariate analyses. RESULTS:Women (n = 1,835) who took at least one study dose comprised the safety population; 1,255 had baseline and 12-month biopsies and comprised the endometrial safety population. Incidence of endometrial hyperplasia was ≤0.36% with any dose of TX-001HR after 1 year of use (one-sided upper 95% confidence interval ≤4%). Cumulative amenorrhea (no bleeding/spotting) rates increased over time and were relatively high from cycle 1 to 13 with TX-001HR (56%-73%; placebo 79%; P < 0.05 except with 0.25/50 dose). Few vaginal bleeding adverse events (1.0%-4.6% TX-001HR vs 0.7% placebo) were reported and discontinuations due to bleeding were low (0.4%-1.4% vs 0%). Cumulative amenorrhea was significantly more frequent in older women, those further from their last menstrual period, and those with lower baseline E2 concentrations (all; P < 0.01). CONCLUSIONS:All doses of TX-001HR provided endometrial protection and were associated with an improved bleeding profile over time; older age, further last menstrual period, or lower baseline E2 may predict amenorrhea with TX-001HR.