Physical function and age at natural menopause: two take-home messages No abstract available

Persistent concerns over the use of compounded hormone therapies No abstract available

NAMS 2018 Utian Translational Science Symposium, October 2018, San Diego, California New therapies for leiomyomas: when surgery may not be the best option The North American Menopause Society (NAMS) held the 2018 Utian Translational Science Symposium on October 2, 2018, in San Diego, California, to discuss new therapeutic approaches to uterine leiomyomas when surgery is not the optimal choice. Uterine leiomyomas arise from a single clonal cell and are the most common gynecologic disorder affecting reproductive and perimenopausal women worldwide. The prevalence of this disorder is approximately 40% to 70% in white women and 60% to 80% in black women. Recent research suggests that both estrogen and progesterone modulate the growth of leiomyomas, with progesterone being a major stimulator of leiomyoma growth. Women with symptomatic uterine leiomyomas experience heavy uterine bleeding, bulk symptoms, miscarriages, and pregnancy complications. Surgical therapies such as myomectomy or hysterectomy are highly effective; however, medical therapy with progestin-predominant contraceptives or gonadotropin-releasing hormone (GnRH) agonists are in many ways inadequate to address the unmet need for better, noninvasive, and cost-effective treatments. Recent advances in medical treatment, such as selective progesterone receptor modulators, new oral GnRH analogs, and clinical trials that provide new therapeutic approaches, were presented by speakers at the symposium. Research on why there is a prevalence of leiomyomas in black women, the racial and genetic effects on leiomyoma growth, and potential molecular mechanisms also were discussed.

Age at natural menopause and physical functioning in postmenopausal women: the Canadian Longitudinal Study on Aging Objective: The aim of this study was to evaluate the association between categories of age at natural menopause (ANM) and gait speed (slowness) and grip strength (weakness), common measures of physical functioning in older women. Methods: We analyzed data from the Canadian Longitudinal Study on Aging, which included participants from seven cities across Canada collected in 2012. The sample was restricted to women who reported to have entered menopause (N = 9,920). Women who had a hysterectomy before menopause were excluded since the age at which this surgical procedure was performed was not available. ANM was categorized into five groups: less than 40 (premature), 40 to 44 (early), 45 to 49, 50 to 54, and more than 54. We conducted linear regressions to assess the association between ANM and gait speed (m/s) and grip strength (kg) adjusting for participant age, education, body mass index, smoking, use of hormone therapy, height, and province of residence. Results: Mean ANM was 49.8 (95% confidence interval [CI]: 49.7-50.0), with 3.8% of women having a premature menopause; the average gait speed was 0.98 m/s (standard deviation: 0.22), the average grip strength was 26.6 kg (standard deviation: 6.39). Compared to women with ANM of 50 to 54, women with premature menopause had 0.054 m/s (95% CI −0.083, −0.026) lower gait speed when adjusting for age and study site. In the fully adjusted model, the association was attenuated, 0.032 m/s (95% CI −0.060, −0.004). ANM was not associated with grip strength. Conclusion: Our study suggests that premature menopause (<40 years) may be associated with lower gait speed (slowness) among Canadian women. No association was observed between ANM and grip strength. Future studies should include a life course approach to evaluate whether social and biological pathways modify the association between age at menopause and physical function in populations from different contexts.

Determination of estradiol and progesterone content in capsules and creams from compounding pharmacies Objectives: To analytically characterize the doses of estradiol and progesterone found in compounded combined forms of oral capsule and transdermal cream formulations, and determine the consistency of the hormone formulations within a batch. Methods: Prescriptions for combined estradiol/progesterone capsules (0.5 and 100 mg, respectively) and creams (0.5 and 100 mg/g, respectively) were sent to 15 custom-compounding pharmacies. Estradiol and progesterone levels were measured by radioimmunoassays. Hormone levels were measured in 2 capsules and 2 creams from each pharmacy; 10 capsules from 3 pharmacies; and top/middle/bottom layer of cream containers to assess consistency. The magnitude and sources of variation for the measurements were examined by analysis of variance models. Results: Thirteen pharmacies filled the prescriptions. Measured estradiol levels were 0.365 to 0.551 mg for capsules and 0.433 to 0.55 mg/g for creams, and progesterone levels were 90.8 to 135 mg for capsules and 93 to 118 mg/g for creams. Greater variations in estradiol levels were observed between pharmacies for estradiol in capsules than in creams; however, measured estradiol levels within pharmacies were more consistent in the capsules than the creams. Similar results were obtained for progesterone levels. Conclusion: The variations in estradiol and progesterone levels observed in compounded hormone therapy formulations justify concerns regarding risks as a result of variability, which have been outlined by The North American Menopause Society, the American College of Obstetricians and Gynecologists, and the US Food and Drug Administration (FDA) in their statements regarding compounded hormone use. These data support the need for an US FDA-approved bioidentical hormone therapy. Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A425.

Cognitive behavior therapy for menopausal symptoms (CBT-Meno): a randomized controlled trial Objective: To evaluate the effectiveness of cognitive behavioral therapy for menopausal symptoms (CBT-Meno) compared with a waitlist condition (no active intervention). A randomized controlled trial was conducted with 71 perimenopausal or postmenopausal women who were seeking treatment for menopausal symptoms. Methods: Blind assessments were conducted at baseline, 12 weeks postbaseline, and 3 months post-treatment. An intention-to-treat analysis was conducted. CBT-Meno sessions included psychoeducation, and cognitive and behavioral strategies for vasomotor and depressive symptoms, anxiety, sleep difficulties, and sexual concerns. Primary outcomes were scores on the Hot Flash Related Daily Interference Scale (HFRDIS) and Beck Depression Inventory (BDI-II). Secondary outcomes were scores assessing vasomotor and sexual concerns on the Greene Climacteric Scale (GCS-vm, GCS-sex), the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the Female Sexual Function Index (FSFI). Results: There were significantly greater improvements in CBT-Meno compared with waitlist in vasomotor symptom interference (HFRDIS; P < 0.001, η2P = 0.21) and “bothersomeness” (GCS-vm; P = 0.04, η2P = 0.06), depressive symptoms (BDI-II; P = 0.001, η2P = 0.15), sleep difficulties (PSQI; P = 0.001, η2P = 0.17), and sexual concerns (GCS-sex; P = 0.03, η2P = 0.07). These results were found even when controlling for menopausal staging and medication use. Gains were maintained at 3 months post-treatment. Conclusions: CBT-Meno was particularly effective in improving self-reported vasomotor symptoms, depressive symptoms, sleep difficulties, and sexual concerns. Although future studies will be needed to confirm the impact of CBT-Meno on anxiety symptoms, these results suggest that this protocol is effective in targeting commonly reported menopausal symptoms. Video Summary: Supplemental Digiatl Content 1, http://links.lww.com/MENO/A416

Focus group reactions to an arts-based educational exhibit on menopausal hot flashes Objective: To assess public reactions to an arts-based educational exhibit designed to immerse and engage people in scientific facts to increase their conceptual understanding of hot flashes. Our ultimate goals were to stimulate learning and conversations about menopausal hot flashes to change interactions between menopausal women and providers, and menopausal women and other people (family, friends, etc). Focus groups reacted to the concept art (graphics, miniaturized model); and a questionnaire for quickly assessing reactions. Methods: Using a qualitative descriptive methodology, six focus groups of diverse people (n = 50) aged 13 to 64 years described their reactions to the art and questionnaire. Recruitment methods were word of mouth, advertisements on university websites, and a university-based participant registry. Data were analyzed using qualitative content analysis and inductively derived codes. Results: Reactions to the concept art were generally favorable. Participants remarked on appealing and less appealing aspects and age appropriateness. Appealing aspects were resonance with women's experiences, clear information, use of symbolism, and overall design. Less appealing aspects lacked resonance, contained confusing information, or unappealing design elements. Participants felt the exhibit should be open to all ages. The final questionnaire reflected participants’ descriptions of the art's ability to stimulate learning, dispel myths, spur dialog, and increase empathy. Conclusions: The concept art is an appropriate tool for improving knowledge and communication about hot flashes. Displaying the concept art and/or future full-scale exhibit in healthcare settings or public venues may facilitate learning and communication among three groups—menopausal women, healthcare providers, and others.

Public survey reactions to an arts-based educational menopausal hot flash exhibit Objective: The aim of this study was to obtain public survey reactions to concept art for an exhibit about menopausal hot flashes designed to stimulate learning, dispel myths, spur dialogue, and increase empathy. Methods: Immediately before viewing the art, participants provided demographic information and answered one open-ended question. Immediately after viewing the art, participants answered the same open-ended question, one additional open-ended question, and completed quantitative survey questions. Results: Overall, public reactions to the concept art were positive. Qualitative and quantitative data indicated that the public thought the exhibit was appealing, stimulated learning, dispelled myths, spurred desire to have conversations about hot flashes, and increased empathy for women with menopausal hot flashes. Conclusions: The exhibit concept art was appealing and was reported to have a positive impact on the public. Study findings provide support for building the exhibit full-scale as a traveling educational resource that might change public discourse around menopausal hot flashes.

Effects of ospemifene on genitourinary health assessed by prospective vulvar-vestibular photography and vaginal/vulvar health indices Objective: To prospectively evaluate the effects of ospemifene on the vulva and vagina in postmenopausal women using vulvar-vestibular photography and direct visual assessments. Methods: Postmenopausal women (aged 40-80 years) with moderate to severe vaginal dryness as their most bothersome symptom (MBS) were randomized to daily ospemifene 60 mg or placebo in this 12-week, multicenter, double-blind, phase 3 study. Vulvar-vestibular photographic images were captured at baseline and week 12 and were independently assessed with the Vulvar Imaging Assessment Scale (VIAS). Changes from baseline in Vaginal and Vulvar Health Indices (VHI and VuHI) with ospemifene versus placebo were analyzed at weeks 4, 8, and 12. Correlations between VIAS, VHI, and VuHI, with vaginal dryness severity and the Female Sexual Function Index (FSFI) scores were also assessed. Results: In all, 631 eligible participants were randomized (ospemifene 316, placebo 315) and included in the intention-to-treat population. Compared with placebo, ospemifene significantly improved total scores for VIAS (P = 0.0154), VHI (P < 0.0001), and VuHI (P < 0.0001) from baseline to week 12; significant VHI (P < 0.0001) and VuHI (P = 0.002) improvements were observed at week 4. Most VHI and VuHI individual items were significantly better with ospemifene versus placebo at week 12 (P < 0.05). Most correlations between the vulvovaginal assessment total scores versus vaginal dryness severity and FSFI scores were significant (P < 0.05). Conclusion: Improvements observed in vulvovaginal health with ospemifene assessed by prospective vulvar-vestibular photography and other direct visual assessments support its efficacy in addition to the treatment of moderate to severe vaginal dryness due to menopause and the use of photographic and direct visual evaluations in future clinical trials. Video Summary Supplemental Digital Content 1, http://links.lww.com/MENO/A415

Menopausal hot flashing and endothelial function in two vascular beds: findings from a cross-sectional study of postmenopausal women Objective: We sought to examine the association of menopausal hot flashing with vascular reactivity in two different vascular beds in the same cohort of postmenopausal women and explore the relationship between hot flashing and cardiovascular disease (CVD) risk profile. Methods: A cross-sectional study of 79 healthy postmenopausal women, 23 of whom have never had menopausal hot flashes and 56 of whom have reported hot flashes. Endothelial function at a microvascular level was measured with Laser Doppler Imaging with Iontophoresis which assesses the response to both acetylcholine (Ach, endothelium dependent) and sodium-nitroprusside (SNP, endothelium independent). Reactive Hyperemia Index (RHI) was measured with peripheral arterial tonometry as a marker of endothelial function mainly at a macrovascular level. Metabolic biomarkers including insulin sensitivity were assessed. Results: Women with hot flashes had enhanced microvascular response to Ach by ∼30% (P = 0.04) and to SNP by ∼31% (P = 0.02), but lower RHI by ∼13% (P = 0.05) compared with women without flashes. Hot flashing was associated with enhanced response to SNP and lower RHI after adjustment for confounders and conventional CVD risk factors. Women with hot flashes were more insulin resistant than nonflashers (HOMAIR: 1.9 (1.2-2.6) vs 1.4 (0.8-1.9), P = 0.03). Conclusions: Our data support the association of hot flashing with greater insulin resistance and lower macrovascular response. The paradoxical enhanced microvascular response in hot flashers could be the result of the net effect of thermoregulatory and nonnitric oxide-related pathways rather than of endothelial integrity.