Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.

IMPORTANCE: Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). OBJECTIVE: The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe. EVIDENCE REVIEW: Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses. FINDINGS: A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment. CONCLUSIONS AND RELEVANCE: Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.

Is temporal summation of pain and spinal nociception altered during normal aging?

This study examines the effect of normal aging on temporal summation (TS) of pain and the nociceptive flexion reflex (RIII). Two groups of healthy volunteers, young and elderly, received transcutaneous electrical stimulation applied to the right sural nerve to assess pain and the nociceptive flexion reflex (RIII-reflex). Stimulus intensity was adjusted individually to 120% of RIII-reflex threshold, and shocks were delivered as a single stimulus or as a series of 5 stimuli to assess TS at 5 different frequencies (0.17, 0.33, 0.66, 1, and 2 Hz). This study shows that robust TS of pain and RIII-reflex is observable in individuals aged between 18 and 75 years and indicates that these effects are comparable between young and older individuals. These results contrast with some previous findings and imply that at least some pain regulatory processes, including TS, may not be affected by normal aging, although this may vary depending on the method.

Reduced pain inhibition is associated with reduced cognitive inhibition in healthy aging.

The analgesic effect of heterotopic noxious counter-stimulation (HNCS; "pain inhibits pain") has been shown to decrease in older persons, while some neuropsychological studies have suggested a reduction in cognitive inhibition with normal aging. Taken together, these findings may reflect a generalized reduction in inhibitory processes. The present study assessed whether the decline in the efficacy of pain inhibition processes is associated with decreased cognitive inhibition in older persons. Healthy young (18-46 years old; n=21) and older (56-75 years old; n=23) adult volunteers participated in one experimental session to assess the effect of HNCS (cold pain applied on the left forearm) on shock pain and RIII reflex induced by transcutaneous electrical stimulation of the right sural nerve. In the same session, participants also performed a modified Stroop task, including a target condition requiring the frequent switching between inhibition and no inhibition of the meaning of color words. The analgesic effect induced by HCNS was significantly smaller in older participants for both shock-pain ratings (P<0.001) and RIII-reflex amplitude (P<0.05). The Stroop effect was significantly larger in elderly participants in the inhibition trials of the switching condition. Increased cognitive interference (ie, larger Stroop effect) correlated with smaller inhibition of the RIII reflex by HNCS across groups (r=-.34, P=0.025). This association was independent from the age-related slowing observed in control reading and naming tasks. These results suggest a generalized age-related reduction in inhibitory processes affecting both executive functions and cerebrospinal processes involved in the regulation of pain-related responses induced by competing nociceptive threats.

Facial nerve outcome after microsurgical resection of vestibular schwannoma.

The risk of facial nerve palsy after microsurgical removal of vestibular schwannoma cannot be totally eradicated. Beyond the functional problem, patients have to overcome the consequences of cosmetic disturbances, particularly the psychosocial difficulties and the decrease in quality of life due to this palsy. Taken together, the data from our personal experience and analysis of the literature indicate that the major predictor of postoperative facial deficit is tumor size. This information must be given to the patient when counseling for treatment option. When confronted with large tumors, we personally changed our surgical goals and considered that facial nerve conservation and tumor control are interconnected priorities instead of radical removal.