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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. [ABSTRACT FROM AUTHOR]

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Copyright of Climacteric is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The US Preventive Services Task Force (USPSTF) Draft Recommendation statement on Menopausal Hormone Therapy: Primary Prevention for Chronic Diseases, released in May 2017, perpetuates a major disconnect between the primary population affected, women within roughly 10 years of menopause, and the data cited. Furthermore, major elements of the evidence relied upon have been misinterpreted or misstated, particularly in regard to coronary heart disease and breast cancer, for which there is no statistically significant evidence of harm. As currently drafted, the recommendations reiterate the USPSTF statements of 2012, 2005 and 2002, and will perpetuate egregious harm to the public health. In an attempt to avoid that outcome and to facilitate a return to rational discourse regarding menopausal hormone therapy, an ad hoc group of experts in menopausal health submitted this comprehensive response to the USPSTF. [ABSTRACT FROM AUTHOR]

Objective: The aim was to analyze the opinion of the male partner of women treated for vulvovaginal atrophy (VVA) with intravaginal 0.50% DHEA (prasterone), thus providing information on both members of the couple.Methods: On a voluntary basis, in a prospective, randomized, double-blind and placebo-controlled phase-III clinical trial, the male partner filled a questionnaire at baseline and at 12 weeks stating his observations related to his penis and intercourse before and after VVA treatment.Results: Sixty-six men having a partner treated with intravaginal DHEA and 34 others having a partner treated with placebo answered the questionnaires. Concerning the feeling of vaginal dryness of their female partner, the severity score following DHEA treatment improved by 81% (0.76 units) over placebo (p = 0.0347). Thirty-six percent of men having a partner treated with DHEA did not feel the vaginal dryness of the partner at the end of treatment compared to 7.8% in the placebo group. When analyzing the situation at 12 weeks compared to baseline, an improved score of 1.09 units was the difference found for the DHEA group compared to 0.76 for the placebo group (p = 0.05 vs. placebo). In the DHEA group, 38% of men scored very improved compared to 18% in the placebo group. No adverse event has been reported.Conclusion: The male partner had a very positive evaluation of the treatment received by his female partner. [ABSTRACT FROM AUTHOR]

Objective While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. Method Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. Results Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 μg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant ( p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo ( p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. Conclusion The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing. [ABSTRACT FROM AUTHOR]

The article focuses on the 2013 International Menopause Society (IMS) recommendations on menopausal hormone therapy (MHT) and the strategies to maintain the health of middle-age women. Topics discussed include the lifestyle recommendations for peri- and postmenopausal women, the importance of MHT, and the prevention of postmenopausal osteoporosis.

Objective To assess effects of desvenlafaxine (administered as desvenlafaxine succinate) on secondary outcomes of mood, climacteric symptoms, and treatment satisfaction in postmenopausal women with moderate to severe menopausal vasomotor symptoms (VMS). Methods A 12-week, multicenter, double-blind, placebo-controlled trial was conducted in postmenopausal women with ≥ 50 moderate to severe hot flushes per week. Participants were randomly assigned to desvenlafaxine 100 mg/day, desvenlafaxine 150 mg/day, or placebo. Secondary outcome efficacy variables included Profile of Mood States (POMS), Greene Climacteric Scale (GCS), and Menopausal Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) scores. Change from baseline in POMS total mood disturbance (TMD) score and subdomain scores were evaluated using analysis of covariance, adjusting for treatment and study site as factors and baseline score. GCS total and subdomain scores were analyzed similarly. Treatment satisfaction was analyzed using the row mean score test. Results A total of 458 women were enrolled. At week 12, desvenlafaxine 100 mg/day significantly improved POMS TMD scores (p< 0.001) and four of six POMS subdomains compared with placebo (all p ≤ 0.005). Women taking desvenlafaxine 100 mg/day experienced significantly greater improvement in GCS total scores (p< 0.001) and five of six subdomains (all p≤ 0.029) compared with placebo. Treatment with desvenlafaxine 100 mg/day resulted in significantly greater treatment satisfaction overall and in six of seven additional MS-TSQ items (all p ≤ 0.042). Desvenlafaxine 150-mg/day results were similar. Conclusions Desvenlafaxine treatment improved mood and climacteric symptoms in postmenopausal women with moderate to severe VMS compared with placebo, and more women were satisfied with desvenlafaxine treatment than with placebo. [ABSTRACT FROM AUTHOR]

Prior to 1996, the use of postmenopausal estrogen was not believed to increase the risk of venous thrombosis. Subsequent studies, particularly the prospective, randomized, double-blind, clinical trial of the Women's Health Initiative, have clearly shown an increase in the incidence and risk of venous thrombosis in postmenopausal women using conjugated equine estrogens with or without medroxyprogesterone acetate. The risk of venous thrombosis in postmenopausal women is also increased by obesity and age. Oral hormone therapy has been used principally for management of menopausal symptoms. Transdermal estrogens have not been used as extensively in the United States but have a significant use in Europe. Recent observational studies have indicated no increased risk of venous thrombosis with use of transdermal estrogens. Norpregnane derivatives have been associated with an increased risk of venous thrombosis, suggesting that progestins may contribute to the increased risk in postmenopausal women using estrogen plus progestin therapy. [ABSTRACT FROM AUTHOR]

Objective An overview of the current knowledge on the etiology and treatment of vasomotor symptoms in postmenopausal women. Materials and methods Acknowledged experts in the fi eld contributed a brief assessment of their areas of interest which were combined and edited into the fi nal manuscript. Results Women around the world experience vasomotor symptoms as they enter and complete the menopause transition. Vasomotor symptoms, specifi cally hot fl ushes, are caused by a narrowing of the thermoneutral zone in the brain. This effect, although related to estrogen withdrawal, is most likely related to changes in central nervous system neurotransmitters. Peripheral vascular reactivity is also altered in symptomatic women. Estrogen replacement therapy is the most effective treatment for hot fl ushes. Of the other interventions investigated, selective serotonin and selective norepinephrine reuptake inhibitors and gabapentin show effi cacy greater than placebo. Objective monitoring of hot fl ushes indicates a robust improvement with hormone replacement therapy but little to no change with placebo. These data suggest that the subjective assessment of responses to therapy for vasomotor symptom results in inaccurate data. Hot fl ushes have recently been associated with increased cardiovascular risks and a lower incidence of breast cancer, but these data require confi rmation. Conclusions Vasomotor symptoms are experienced by women of all ethnic groups. They are caused by changes in the central nervous system associated with estrogen withdrawal and are best treated with estrogen replacement therapy. Objective monitoring of hot fl ushes indicates that placebo has little to no effect on their improvement. Subjective assessments of hot fl ushes in clinical trials may be inaccurate based on objective measurement of the frequency of hot fl ushes. Based on preliminary reports, women experiencing hot fl ushes have an increased risk of cardiovascular disease and a reduced incidence of breast cancer. [ABSTRACT FROM AUTHOR]

Objective To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. Methods This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤≤ 5%% and pH > 5.0 at both screening and day 1. Results At the standard duration of 12 weeks of treatment, increasing doses of 0.25%%, 0.5%% and 1.0%% DHEA decreased the percentage of parabasal cells by 48.6 ±± 6.78%%, 42.4 ±± 7.36%% and 54.9 ±± 6.60%% ( p < 0.0001 vs. placebo for all) with no change with placebo ( p == 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%%, 0.5%% and 1.0%% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001. Conclusions Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens. [ABSTRACT FROM AUTHOR]

Agricultural production responds to social, political, economic, environmental, and technological drivers that influence producers' decisions and shape the individual systems through modification of management practices, crop and livestock mix, and marketing strategy. We use an interview and discussion approach with producer panels to examine production systems in the eastern United States and explore key drivers impacting their unique characteristics and development. The internal social driver that values the farming lifestyle is a principle factor that leads people to choose farming. Irrespective of location, farming is first and foremost a lifestyle choice. The choice of type of production system is partly a lifestyle preference and partly influenced by other external factors, including economic and environmental elements. A second principle driver is economic, arising from a need to make a living, and tempers the internal social driver. Economic return is partially a function of the marketability of products. Marketing channels are dependent on social drivers, including education of producers and consumers, community support and community values. Farmers in the Northeast are able to take a more active role in determining contract terms than those in the Southeast, and are also more aggressive in developing new markets. Development of local markets and community support strengthens the link between farmers and consumers, and reinforces the economic sustainability of Northeastern production systems. With decreased reliance on external risk reduction approaches, Northeastern producers bear greater risk, but also have greater flexibility in altering the crop and livestock mix and are better able to respond to consumer demand. [ABSTRACT FROM AUTHOR]

Premature menopause and bilateral oophorectomy in young women are associated with an increased incidence of cardiovascular disease, myocardial infarction and overall mortality. Observational studies suggest an interval of 5-10 years between loss of ovarian function and the increased risk of cardiovascular disease. This finding is consonant with a published autopsy study of women who had undergone bilateral oophorectomy. The progression of atherosclerosis is retarded with the use of estrogen replacement therapy in non-human primates and women. Hormone therapy reduced the incidence of cardiovascular disease in women following bilateral oophorectomy. These findings support the use of hormone therapy in young women who have lost ovarian function. [ABSTRACT FROM AUTHOR]

The article offers information on the updated recommendations for hormone replacement therapy (HRT) in the peri- and postmenopause. It states that updated recommendations are derived from the original consensus group guidelines of experts and modified by a new expert working group in October 2007. It offers information on whether or not to use HRT, and mentions that new guidelines prescribe low and ultra-low doses to maintain the benefits and to minimize side-effects and risks.

Objective To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding. Methods A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval and informed consent were obtained prior to initiation and enrolment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound at baseline and on completion. An endometrial biopsy was obtained when indicated clinically. Results In months 1-6, the amenorrhea rates with E2/NETA 0.1 were 89%, 89%, 86%, 85%, 89% and 89%, respectively and the no-bleeding rates were correspondingly high: 95%, 94%, 93%, 90%, 95% and 95%. The amenorrhea and spotting-only rates were similar with both ultra-low-dose combinations. The withdrawal rates due to bleeding were very low and the same in all three treatment arms (n = 1; 1%). There was a slight increase in the mean endometrial thickness in all three groups, which remained less than 5 mm. Conclusions The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment or placebo. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy of two ultra-low-dose 17β-estradiol plus norethisterone acetate (NETA) treatment regimens for relieving menopausal symptoms. Design A total of 577 postmenopausal women were enrolled, in three treatment groups in a double-blind, randomized, placebo-controlled study of 0.5 mg 17β-estradiol + 0.1 mg NETA or 0.5 mg 17β-estradiol + 0.25 mg NETA or placebo. Participants returned at weeks 4, 8, 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record. Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated. Results Treatment with ultra-low-dose 0.5 mg 17β-estradiol + 0.1 mg NETA (0.1 Group) or 0.5 mg 17β-estradiol + 0.25 mg NETA (0.25 Group) effectively reduced the severity and number of hot flushes within the initial weeks of therapy. Compared to placebo, a rapid, statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3, followed by further improvement which continued throughout the study. There were no statistically significant differences between the active treatment arms. Conclusions The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo, with good safety profiles. [ABSTRACT FROM AUTHOR]

The efficacy of estrogen with or without a progestogen as hormone replacement therapy (HRT) for menopausal symptoms is well-established. Recent large-scale randomized studies with combined estrogen/progestogen therapy (EPT) have raised a number of safety issues, specifically the potential risk for coronary heart disease. Subsequent analyses and other studies have indicated that HRT may be cardioprotective in younger postmenopausal women. A new continuous EPT combines natural 17β-estradiol (E2) 1 mg with the novel progestin, drospirenone (DRSP) either 0.5 or 2 mg. DRSP has a physiological profile closer to that of natural progesterone than any other synthetic progestin. This paper reviews recent clinical trial data demonstrating the efficacy and safety of combined DRSP/E2 therapy as EPT in postmenopausal women. DRSP/E2 provides symptomatic relief of vasomotor symptoms and improvement in genitourinary atrophy. DRSP/E2 protects against endometrial hyperplasia and reduces the risk of osteoporosis. Combined DRSP/E2 therapy has a favorable impact on cholesterol and triglyceride levels, and decreases blood pressure in women with elevated blood pressure. The favorable efficacy and safety profile of DRSP/E2, and potential for long-term health benefits, represents a new option for the effective management of menopause and its clinical sequelae. [ABSTRACT FROM AUTHOR]

Chronic use of chloroquine has been shown to induce numerous pathophysiological defects in the retina. This drug has the ability to alter pH of intracellular compartments and lyso-somal function of the retinal pigment epithelium (RPE) and retina! neurons may constitute the basis of chloroquine retinopathy. The aim of the current study was to investigate pathogenic alterations in retinal cells continuously exposed to chloroquine using appropriate in vivo and in vitro models. Male hooded Lister rats were implanted with osmotic mini pumps which released chloroquine continuously over a period of seven days. The eyes were processed for electron microscopy and ultrastructural abnormalities determined in the neural retina and quantified using stereology in the retinal pigment epithelium (RPE). RPE were also exposed to chloroquine in vitro and lysosomal pH changes were investigated using a pH sensitive probe. Degradative capacity was also analysed using FITC labeled rod outer segments (ROS). Chloroquine-treated animals displayed several ultra-structural abnormalities including numerous membranous cytoplasmic bodies (MCBs) in retinal neurons. Cone photoreceptors displayed numerous MCBs although rods did not. The RPE of the treated groups all showed significantly higher numbers of lysosomal associated organelles (LAO) than the control group (p < 0.001). The in vitro experiments demonstrated chloroquine-mediated rises in lysosomal pH and an increase in lysosome/phagosome accumulation of ROS in the chloroquine treated group (p < 0.01). The current study demonstrates that chloroquine disrupts lysosomal function in retinal neurons and RPE. The evidence presented provides a clear pathogenic basis for the functional defects experienced by patients with chloroquine retinopathy. [ABSTRACT FROM AUTHOR]

This is a review of 21 patients with meningiomas involving the region of the cavernous sinus. All underwent surgery, and the fronto-zygomatic (F-Z) approach, first described by Fujitsu and Kubawara, was employed in every case. The mean age at presentation was 47 years; seven patients were male and 14 female. The mean duration of symptoms before surgery was 4 years. In 10 patients, resection was considered to be complete. Peri-operatively there were two deaths, but the majority of deficits in the survivors were temporary and quickly resolved. The mean follow-up period was 48 months. In that time, five patients experienced recurrence or progression of tumour, of whom three required repeat operation (followed by radiotherapy); and two patients were referred for radiotherapy alone. These five patients appear to be disease-free 2-5 years after their additional treatment. Of the 19 patients who left hospital, 17 were able to live independent lives. It would appear from this review that: (1) F-Z craniotomy usually gives excellent exposure to the region of the cavernous sinus; (2) selected patients should undergo angiography with balloon occlusion to evaluate the collateral vascular supply; (3) regular review should include annual MRI. Evaluation over a much longer time of both surgery and radiotherapy, individually and in combination, is needed before it will be possible to furnish a treatment protocol for individual cases at initial presentation or recurrence. [ABSTRACT FROM AUTHOR]