Menopause hormone therapy and urinary symptoms: a systematic review.

IMPORTANCE: Urogenital changes associated with menopause are now classified as genitourinary syndrome of menopause (GSM), which includes symptoms of urgency, frequency, dysuria, and recurrent urinary tract infections for which the recommended treatment is estrogen. However, the association between menopause and urinary symptoms and the efficacy of hormone therapy for these symptoms is uncertain. OBJECTIVE: Our objective was to define the relationship between menopause and urinary symptoms including dysuria, urgency, frequency, recurrent urinary tract infections (UTIs), and urge and stress incontinence by conducting a systematic review of the effects of hormone therapy (HT) for urinary symptoms in perimenopausal and postmenopausal women. EVIDENCE REVIEW: Eligible studies included randomized control trials with perimenopausal and postmenopausal women with a primary or secondary outcome of the following urinary symptoms: dysuria, frequent UTI, urgency, frequency, and incontinence, included at least one treatment arm of estrogen therapy, and were in English. Animal trials, cancer studies and pharmacokinetic studies, secondary analyses, and conference abstracts were excluded. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched until April 2022. Two authors reviewed each article with discrepancies resolved through whole group consensus. Data extracted included the following: publication date, country, setting, subject number, follow-up, duration, age, race/ethnicity, study design, inclusion criteria, and main findings. FINDINGS: There is insufficient evidence to confirm that menopause is associated with urinary symptoms. The effect of HT on urinary symptoms depends on type. Systemic HT may cause urinary incontinence or worsen existing urinary symptoms. Vaginal estrogen improves dysuria, frequency, urge and stress incontinence, and recurrent UTI in menopausal women. CONCLUSIONS AND RELEVANCE: Vaginal estrogen improves urinary symptoms and decreases the risk of recurrent UTI in postmenopausal women.

Patient Perceptions Impact Progression to Third-Line Therapy for Treatment of Overactive Bladder.

PURPOSE: We aimed to understand the reasons patients choose to pursue third-line overactive bladder (OAB) therapy. MATERIALS AND METHODS: We conducted a mixed methods study that included patient interviews and survey data. Eligible patients were diagnosed by symptoms, had tried behavioral modifications, and OAB medications enrolled from October 2018 to August 2019. In addition to interviews, patients completed 4 surveys: the Pelvic Floor Distress Inventory, Overactive Bladder Questionnaire Short Form, Life Orientation Test-Revised, and a patient confidence in the health care system survey. Qualitative interview data were analyzed thematically. Logistic regression and chi-square analysis was used to analyze survey data. RESULTS: A total of 69 patients were consented, 4 withdrew, and 51 completed both interview and survey data. Overall 55% of patients were Caucasian, 45% were African American, and their average age was 71 (SD=10.4); 75% intended to pursue third-line OAB therapy and 31 (61%) expressed interest in a specific third-line therapy. Major interview themes included a desire for a better quality of life, embarrassment with accidents, and problems with medication. Themes leading patients away from third-line OAB treatment included concern about invasiveness and side effects of treatments, and restrictions to accessing care. CONCLUSIONS: Most patients desired to progress to third-line OAB therapy, were motivated by embarrassment, but were concerned about treatment side effects. We found that economic burden of OAB treatment is associated with patient interest in and decision to receive third-line therapies to include onabotulinumtoxinA and percutaneous tibial nerve stimulation. Improved quality of life, medication frustration, and concerns about side effects of further therapy are themes patients identified when patients considered third-line overactive bladder therapy.

Postoperative pain and perceptions of recuperation after suture- and mesh-based apical sacrospinous ligament suspension.

OBJECTIVE: To compare the incidence of postoperative pain after suture- or mesh-based sacrospinous ligament suspension (SSLS). METHODS: In a retrospective study, data were reviewed from patients who underwent suture- or mesh-based SSLS at a center in Skokie, IL, USA, between 2006 and 2011. The primary outcome was self-reported postoperative pain scores (range 0-10) on the day of surgery (day 0) and 1 day later (day 1). RESULTS: Overall, 90 women were included in the study: 66 underwent mesh-based SSLS and 24 underwent suture-based SSLS. Day-0 mean pain score was 4.65 ± 1.57 in the mesh group and 5.24 ± 1.44 in the suture group (adjusted P=0.159). Day-1 mean pain score was 4.06 ± 1.78 in the mesh group and 4.31 ± 1.21 in the suture group (adjusted P=0.596). CONCLUSION: Postoperative pain did not differ between patients undergoing suture-based and those undergoing mesh-based SSLS. These observations should be considered in preoperative counseling of patients.

Minimal mesh repair for apical and anterior prolapse: initial anatomical and subjective outcomes.

INTRODUCTION AND HYPOTHESIS: Here we describe anatomic and quality of life (QOL) outcomes of an anterior and apical compartment prolapse repair involving a reduced mesh implant size and apex-only fixation. METHODS: One hundred and fifteen patients undergoing the repair at a single urogynecology center were assessed using the Pelvic Organ Prolapse Quantification (POP-Q) and inpatient chart reviews. A horizontal incision eliminated overlap with the mesh, and each sacrospinous ligament was approached anteriorly by blunt dissection. Recurrence was defined as apical (C), or anterior (Aa or Ba) ≥0, and secondary analyses were performed using POP-Q ≥ -1 as the anatomic threshold. Pelvic Floor Distress Inventory (PFDI), Surgical Satisfaction Questionnaires (SSQ) and a dyspareunia symptom scale were analyzed pre- and postoperatively. RESULTS: Fifty-three women with uterus in situ demonstrated a combined anterior-apical recurrence rate of 1.89 %, including no anterior (Ba ≥ -1) and one apical (C ≥ -1) recurrence. Forty-seven women undergoing repair for vault prolapse had recurrence rates ranging from 0 % in those with prior hysterectomy to 4.2 % in those undergoing concurrent hysterectomy. The rate of mesh exposure was 3/115 (2.6 %), including two in women with concurrent hysterectomy. Self-reported dyspareunia was more common preoperatively (13.4 %) than postoperatively (9.3 %). PFDI scores improved in all domains, and 93 % completing the SSQ reported they were satisfied and would choose the surgery again. CONCLUSIONS: This technique resulted in successful outcomes within both anterior and apical compartments with a low rate of mesh complication, and no cases required mesh removal or hospital readmission. High rates of satisfaction and improved condition-specific QOL were observed.

Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells.

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.

Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme q(10), vitamin e, and total antioxidant activity.

The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research.

Expression and proteasomal degradation of the major vault protein (MVP) in mammalian oocytes and zygotes.

Major vault protein (MVP), also called lung resistance-related protein is a ribonucleoprotein comprising a major part (>70%) of the vault particle. The function of vault particle is not known, although it appears to be involved in multi-drug resistance and cellular signaling. Here we show that MVP is expressed in mammalian, porcine, and human ova and in the porcine preimplantation embryo. MVP was identified by matrix-assisted laser-desorption ionization-time-of-flight (MALDI-TOF) peptide sequencing and Western blotting as a protein accumulating in porcine zygotes cultured in the presence of specific proteasomal inhibitor MG132. MVP also accumulated in poor-quality human oocytes donated by infertile couples and porcine embryos that failed to develop normally after in vitro fertilization or somatic cell nuclear transfer. Normal porcine oocytes and embryos at various stages of preimplantation development showed mostly cytoplasmic labeling, with increased accumulation of vault particles around large cytoplasmic lipid inclusions and membrane vesicles. Occasionally, MVP was associated with the nuclear envelope and nucleolus precursor bodies. Nucleotide sequences with a high degree of homology to human MVP gene sequence were identified in porcine oocyte and endometrial cell cDNA libraries. We interpret these data as the evidence for the expression and ubiquitin-proteasome-dependent turnover of MVP in the mammalian ovum. Similar to carcinoma cells, MVP could fulfill a cell-protecting function during early embryonic development.