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Poster Abstracts POSTER PRESENTATIONS P-3. Cognitive Dysfunction Among Women with a History of Breast Cancer P-1. Experiencing Frequent Night Sweats and Longer Sleep Duration John S. Bark2,3, Jessica S. Fogel2,3, Ece Kilic3, Shannon Dowty3, Rachel Horwitz2, Targeting Enhancer of Zeste Homolog 2 (EZH2) with Methyl Jasmonate, David R. Walega1, Suzanne Banuvar1, Pauline M. Maki, PhD2,3. 1Department of a Promising Natural Compound against Human Uterine Fibroids Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL; 1,2 1 Mohamed Ali, Masters of clinical pharmacy , Ayman Al-Hendy, MD, PhD , Qiwei Yang, 2Department of Psychology, University of Illinois at Chicago, Chicago, IL; 3Department 1 1 PhD . Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL; of Psychiatry, University of Illinois at Chicago, Chicago, IL 2 Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt Objective: Vasomotor symptoms (VMS) (i.e., daytime hot flashes and night sweats Objective: Uterine Fibroids (UFs) are the most common benign tumors in women of [NS]) represent a hallmark of menopause and contribute to sleep deficits. VMS can be reproductive age with a prevalence increases with age, peaks during the fifth decade of measured objectively with ambulatory skin conductance monitors. Previous research from life and tends to decline after menopause. UFs have subsequent significant quality of life our group has demonstrated that objective VMS are associated with decreased memory, and economic impact. They are characterized by excessive deposition of extracellular raising the possibility that NS may be a modifiable risk factor for cognitive decline during matrix (ECM) as well as an increase in cell proliferation, which explains accompanied menopause. Here we extend this working hypothesis to women with a history of breast bleeding and bulk symptoms. Current treatment options for UFs are primarily surgical cancer to examine how objective NS and objectively measured sleep relate to cognition and no FDA approved medical treatment is available so far. Natural compounds may among this population. Design: We conducted secondary analyses of baseline data from be beneficial for UFs patients as a safe long-term cost effective therapeutic option. a feasibility study of Stellate Ganglion Blockade (SGB) for the treatment of VMS among EZH2 is linked with many diseases including reproductive diseases such as UFs. Methyl women with a history of breast cancer (n=33) who reported ≥4 daily VMS. Participants Jasmonate (MJ) is a natural compound isolated from jasmine with a potent anti-EZH2 completed neuropsychological testing, ambulatory skin conductance assessments of activity. In this study, we determine the effect of MJ on UFs. Design: Human uterine VMS, and actigraphy-based sleep monitoring (i.e., total sleep time). Three women were leiomyoma (HuLM) and normal uterine smooth muscle cell (UTSM) cells were treated excluded from the final analysis for invalid data and/or having <4 daily VMS. Using with concentration ranges (100 µM-3 mM) of MJ and the growth inhibitory effect was linear models, we examined the main effects of NS and daytime hot flashes on TST, the assessed by MTT assay after 24 and 72 hr. treatment. Total cell lysates from MJ treated main effects of TST and NS on cognition, as well as interactions between NS and TST or untreated HuLM cells for 24 hr. were examined by western blot (WB) and RT-qPCR on cognition. Results: More frequent NS were associated with greater sleep duration for measurement of protein and gene expression of the following; fibrosis related markers (β=9.16;p<.05), while daytime hot flashes were unrelated to TST (β=-3.20;p=.17). {collagen type 1 (COLL1A) and Fibronectin (FN)}, proliferation markers {Cyclin D1 Controlling for NS, TST was not significantly associated with performance in any (CCND1) and proliferating cell nuclear antigen (PCNA)}, tumor related marker (P21, cognitive domain. However, there were significant interactions between NS and TST EZH2 and β-catenin). Since activated Wnt/β-catenin pathway has been identified to be on semantic fluency (β=-0.02,p=.01), digit span forward (β=-.01,p=.003), and digit span involved in UF pathogenesis, we determined the alteration of gene expression in WNT backward (β=-.004,p=.01). Specifically, the association between TST and cognition signaling pathway using Prime-PCR array containing 84 related genes. Unpaired student depended on the number of NS such that the association between TST and cognitive t-test was used to measure statistical significance. (P< 0.05) is considered significant. performance was positive among women with fewer NS. Furthermore, the association Results: Using MTT assay, MJ showed a potent, statistical significant, concentration and between TST and cognitive performance was negative or neutral among those with more time dependent anti-proliferative effect on HuLM cells (P< 0.05) reaches 80% growth frequent NS (Figure 1). TST alone or in combination with NS was unrelated to memory inhibition at doses over 1mM at 72 hr. Interestingly, dose ranges between 100-500 µM performance. Conclusion: Results suggest that sleep duration was associated with showed selective growth inhibitory effect on HuLM cells, but not on normal UTSM improved attention and fluency in women without NS, but that paradoxically women who cells. At molecular level, MJ treatment at 500 µM for 24 hr. significantly decreased both experience NS may be vulnerable to prefrontal cortex deficits (i.e., decreased attention protein and gene expression of EZH2, along with decreased expression of COLL1A, and executive function) as their sleep duration increases. This work presents novel FN, CCND1, PCNA, and β-catenin while increased p21 in HuLM cells as compared insights into the influence of menopausal symptoms on cognitive performance among to untreated control using WB and qPCR respectively (P< 0.05). PCR array data women with a history of breast cancer and raises the possibility that VMS treatments showed that MJ treated cells exhibited downregulation of 35 genes including CTNNB1, could benefit cognition in these women through effects on sleep. CCND1, Wnt3, Wnt5A, Wnt5B and upregulation of 36 genes including Wnt antagonist Sources of Funding: The Donald Kirk Foundation. genes WIF1, PRICKlE1 and DKK1 while 13 genes remain unchanged as compared to untreated control. Conclusion: Our studies demonstrate for the first time that MJ, via EZH2 downregulation, promotes the anti-UFs effect by decreasing cell proliferation through suppression of activated Wnt/ β-catenin pathway. In addition, MJ exhibited an anti-fibrotic effect through downregulation of the expression levels of ECM related markers. MJ might offer promising therapeutic option as safe non-hormonal and cost- effective treatment against UFs with favorable long term clinical utility especially for women seeking future fertility in addition to women at perimenopause who suffer from the anti-hormonal side effects of current available short-term treatment options. Sources of Funding: NIH grants: RO1 ES028615, U54 MD007602. P-2. Vulvar fusion as a late complication of Genitourinary Syndrome of Menopause Dr. Dominguez Bali, MD1, Guarina Molina, MD1,2, Sindhuri Gollamudi, MD1,3. 1Miami Center for Obstetrics Gynecology and Human Sexuality, Miami, FL; 2Universidad Iberoamericana, Santo Domingo, Dominican Republic; 3American University of Antigua, Miami, FL Objective: Genitourinary syndrome of menopause (GSM) comprises of the vulvovaginal, bladder, and urethral changes associated with decreased estrogen levels. These changes include genital dryness, recurrent urinary tract infections, and atrophic changes to the labia, introitus, vagina and urethra. Although these changes are common in menopausal P-4. women, they may occur at any age if the patient presents a decrease in estrogen levels. An Efficacy of Paroxetine (7.5 mg) in the treatment of menopause-associated uncommon manifestation of genitourinary syndrome of menopause is vulvar fusion (also vasomotor symptoms known as labial fusion, labial agglutination, labial adhesion and vulvar synechiae) which Maria A. Belardo. Climacteric Section, Italian Hospital, Buenos Aires, Argentina has been defined as the total or partial adherence of the labia minora and/or majora. Two Objective: Primary: describe the results obtained with the use of paroxetine for the of the main etiologic factors for vulvar fusion include low estrogen levels and cessation of treatment of menopause-associated vasomotor symptoms. Secondary: evaluate the sexual activity. This pathology can be congenital or acquired, and although common in the impact on body weight and on sexual function as well as on the overall quality of life pediatric population, few cases have been reported in post-menopausal women. Design: Design: Prospective clinical trial that evaluates the impact of the use of paroxetine 7.5 Discussion of 3 cases of labial agglutination in women of marked advanced age Results: mg in the treatment of vasomotor symptoms. 52 peri and postmenopausal women were This study presents 3 cases of labial agglutination in women of marked advanced age, included at the Climacteric Section of the Italian Hospital of Buenos Aires between who presented with complaints of urinary incontinence and dribbling, urinary retention, January 2018 and March 2019, 18 of 52 women (34.64%) had contraindications to difficulty voiding, dysuria, and urodynia due to urethral outlet obstruction by the labia Menopausal Hormone Therapy
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