Does estrogen deprivation affect pelvic floor muscle contractility?

INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle (PFM) function plays a role in pelvic organ support, and estrogen deprivation is commonly seen as a risk factor for pelvic floor dysfunction. This study investigated the association between estrogen deprivation and PFM contractility. METHODS: This was a retrospective study on women attending a tertiary urogynecological unit. The assessment included an interview, POPQ assessment, Modified Oxford Scale (MOS) score, and 4D translabial ultrasound (US) on PFM contraction (PMFC). Hormonal status and details on hormone replacement therapy (HRT) were recorded. Corrected menopausal age was defined as the duration of systemic estrogen deprivation. Offline analysis of stored US volumes was performed to measure the reduction in anteroposterior hiatal diameter and bladder neck elevation on PFMC at a later date. RESULTS: Seven hundred thirty-nine women were seen during the study period. Fifty-three were excluded for missing data, leaving 686. Mean age was 56 (17-89, SD 13.3) years; average BMI was 29 (16-66, SD 6.6) kg/m²; 60.6% (n = 416) were menopausal at a mean duration of 16 (1-56, SD 10.2) years. Forty-nine (7.1%) were currently on systemic HRT, while 104 (15.2%) had used it previously. Mean corrected menopausal age (menopausal age - systemic HRT duration) was 7.4 (0-56, SD 10.0) years. Current local estrogen use ≥ 3 months was reported by 31 (4.5%). Mean PFM contractility measured by MOS was 2 (0-5, SD 1.1,). On multivariate analysis there was no association between menopausal age and PFM contractility. CONCLUSIONS: Estrogen deprivation may not be an independent predictor of pelvic floor muscle contractility.

Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile.

BACKGROUND: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. AIM: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories. METHODS: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. RESULTS: The mean peak diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. CLINICAL IMPLICATIONS: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged. STRENGTHS & LIMITATIONS: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. CONCLUSION: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763-766.

Vitamin D Deficiency and Lower Urinary Tract Symptoms in Women.

OBJECTIVE: The association of vitamin D deficiency and pelvic floor dysfunction has been examined by numerous studies. Lower urinary tract symptoms (LUTS) associated with bladder filling and voiding functions are common in both sexes. A recent study reports a higher incidence of LTUS in men over 50 years old with vitamin D deficiency. The aim of the study is to investigate whether there is a difference in the Lower Urinary Tract Symptoms frequency between women with vitamin D deficiency and the control group or not. STUDY DESIGN: In this case control study, a total of 150 women who had a measured vitamin D level within a month were divided into two groups, one with a serum vitamin D deficiency and the other with a normal vitamin D level. Both groups were evaluated in terms of menopausal status, numbers of pregnancy and delivery, pelvic examination findings, pelvic floor muscle strength, level of pelvic organ prolapse, LUTS scores, and the findings were recorded. Both groups were compared for the presence of lower urinary system symptoms. The BFLUTS validated for Turkish-speaking populations was used to assess lower urinary system symptoms. Statistical analyses were performed via IBM SPSS Statistics 23.0. The results were considered significant at p < 0.05 and a confidence interval of 95%. RESULTS: Vitamin D deficiency was detected in 67.3% of the participants. No significant differences were found between the groups regarding variables that could affect lower urinary system symptoms such as menopausal status, presence of pelvic organ prolapse and neonatal weight (fetal macrosomia) The Pelvic Floor Muscle Strength was significantly lower in the group with vitamin D deficiency than the control group. BFLUTS scores of premenopausal women with vitamin D deficiency were found to be similar to the control group, likewise no significant differences in the BFLUTS scores were detected in postmenopausal women. CONCLUSION: Although vitamin D deficiency causes a significant reduction in pelvic floor muscle strength, no significant correlation was found between lower urinary tract symptoms and vitamin D deficiency. There is a necessity of prospective randomized controlled trials to investigate the relationship between vitamin D deficiency and pelvic floor functions.

Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder.

Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease.

Vitamin D status in women with pelvic floor disorder symptoms.

INTRODUCTION AND HYPOTHESIS: Our aim was to characterize the relationship between 25-hydroxyvitamin D [25(OH)D] status with pelvic floor symptom distress and impact on quality of life. METHODS: A retrospective chart review was performed in women with a 25(OH)D level drawn within 1 year of their gynecology/urogynecology visit. Validated questionnaires including the Colorectal-Anal Distress Inventory (CRADI)-8 and Incontinence Impact Questionnaire (IIQ-7) were used. Multivariate analyses characterized pelvic floor disorder (PFD) symptom differences among women by vitamin D status. RESULTS: We studied 394 women. Mean ± standard deviation (SD) 25(OH)D levels were higher in women without than with PFD symptoms (35.0 ± 14.1 and 29.3 ± 11.5 ng/ml, respectively (p < 0.001)]. The prevalence of vitamin D insufficiency was 51% (136/268). CRADI-8 and IIQ-7 scores were higher among women with vitamin D insufficiency (p = 0.03 and p = 0.001, respectively). Higher IIQ-7 scores were independently associated with vitamin D insufficiency (p < 0.001). CONCLUSIONS: Insufficient vitamin D is associated with increased colorectal symptom distress and greater impact of urinary incontinence on quality of life.