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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 (C max ) of 31.0 ng/mL was detected at a mean time (T max ) 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., (Copyright © 2019. Published by Elsevier Inc.) more...

Objective: To evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy., Methods: A substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg TX-004HR doses once/d for 2 weeks, followed by twice/wk for 10 weeks. Serum samples obtained at 2, 4, 6, 10, and 24 hours postdose on days 1 and 14, and once on day 84, were analyzed for area under the serum concentration-time curve, tmax, Cmin, Cavg, and Cmax for estradiol, estrone, and estrone conjugates., Results: Seventy-two women (mean 59 y) participated. TX-004HR 4 μg showed no statistical differences from placebo in estradiol pharmacokinetic (PK) parameters. At 10 μg, estradiol Cmax was statistically higher than placebo on day 1, but was not different from placebo on day 14. With 25 μg, estradiol PK parameters were statistically higher than placebo. Estradiol Cavg values for 25 μg were 9.1 pg/mL on day 1 and 7.1 pg/mL on day 14. Estrone and estrone conjugate PK parameters with TX-004HR were lower than or similar to placebo across all doses. No drug accumulation was observed., Conclusions: Vaginal TX-004HR resulted in negligible to very low systemic absorption of estradiol. No statistical differences in estradiol PK parameters were observed on day 14 with 4 and 10 μg, and only minor increases were observed with 25 μg (within the normal postmenopausal range). This PK substudy, in conjunction with the primary efficacy results, demonstrated that TX-004HR provided local benefits of estradiol with limited systemic exposure. more...

Purpose: To assess female sexual functions in women who were affected by vitamin D 3 deficiency., Methods: A total of 50 women with FSD and 58 healthy women controls were included in the study, according to the Female Sexual Function Index (FSFI) questionnaire using a 26.55 cutoff value. Detailed medical histories were obtained from all sexual active women, and all women were evaluated in terms of possible presence of depression with the Beck Depression Inventory (BDI). Serum 25-hydroxyvitamin D 3 , follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total and free testosterone, estradiol, dehydroepiandrosterone-SO 4 (DHEA-SO 4 ), sex hormone-binding globulin (SHBG), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) levels were measured., Results: Mean age of premenopausal women was 34.9 ± 6.3 years. The level of serum 25-hydroxyvitamin D 3 was significantly lower in women with FSD compared with the controls (15.9 ± 8.4 and 26.3 ± 11.7 nmol/L, respectively). Desire (p = 0.0001), arousal (p = 0.0001), lubrication (p = 0.002), orgasm (p = 0.0001), satisfaction (p = 0.018), and pain (p = 0.010) domain scores were also correlated with the levels of serum 25-hydroxyvitamin D 3 . The BDI score showed a significant negative correlation with the total FSFI score (r = -0.492, p = 0.0001). The FSFI score not showed a significant correlation with the hormones (p > 0.05)., Conclusion: There is a relationship with FSD and deficiency of vitamin D 3 . Also, increased depressive symptoms were associated with FSD. more...