Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

A medical device containing purified bovine colostrum (Monurelle Biogel) in the treatment of vulvovaginal atrophy in postmenopausal women: Retrospective analysis of urinary symptoms, sexual function, and quality of life.

OBJECTIVE: This study assessed the effectiveness and safety of a medical device containing purified bovine colostrum (Monurelle Biogel; Zambon, Bresso, Italy) in improving vulvovaginal atrophy (VVA), sexual function, urinary symptoms, and quality of life (QoL) in postmenopausal women. METHODS: In all, 172 postmenopausal women with VVA were included in the study. All women were treated with vaginal Monurelle Biogel daily for 12 weeks. Patients underwent clinical examinations, completed a 3-day voiding diary, and had VVA graded using the Vaginal Health Index (VHI) at baseline and 12 weeks. Patients also completed the Female Sexual Function Index (FSFI), overactive bladder questionnaire (OAB-Q), and the Urogenital Distress Inventory (UDI-6), among others. RESULTS: After 12 weeks, there were significant increases in mean (± SD) VHI (12.53 ± 3.67 vs. 19.31 ± 3.49; P < .0001), the number of patients engaging in regular sexual activity 102 (59.3%) vs. 144 (83.7%), and in the total FSFI score (21.64 ± 2.99 vs. 28.16 ± 1.93; P < .0001) compared with baseline. In addition, there were significant reductions in the mean number of 24-hour voids (9.57 ± 2.12 vs. 7.13 ± 1.22; P < .0001), urgent micturition episodes per 24 hours (1.75 ± 0.76 vs. 1.14 ± 0.87; P = .001), nocturia episodes (1.58 ± 0.85 vs. 0.97 ± 1.18; P = .0002), and urinary incontinence episodes per 24 hours (0.74 ± 0.59 vs. 0.28 ± 0.52; P = .003). Finally, after 12 weeks treatment, there were significant differences in UDI-6 (7.85 ± 0.81 vs. 5.56 ± 1.40), OAB-Q symptom (53.60 ± 12.57 vs. 22.08 ± 9.63), and OAB-Q health-related QoL (21.75 ± 8.51 vs. 69.34 ± 14.59) scores compared with baseline (P < .0001 for all). The Patient Impression of Global Improvement scale revealed global improvement in 143 women (83.14%). CONCLUSIONS: Monurelle Biogel is an effective treatment for VVA in postmenopausal women, improving sexual life, urinary symptoms, and QoL.

Combining topical tretinoin with mometasone furoate in the treatment of vulvar lichen sclerosus: Results of dermoscopic assessment.

The main purpose of the present study was to compare the dermoscopic changes on vulvar lichen sclerosus (VLS) induced by two different 12-week treatment protocols, namely mometasone furoate 0.1% ointment plus tretinoin 0.05% cream in short-contact therapy (group A) versus the same corticosteroid plus emollient (group B). All dermoscopic images captured before and after treatment were assessed. Each dermoscopic variable selected for the study purpose was arbitrarily graded according to a 4-point scale by dermatologists blinded to both the time at which the images were captured and treatment allocation. Seventeen patients in group A and 15 in group B were included. The vessel mean dermoscopic scores increased significantly after treatment, whereas the scores of (a) patchy, structure-less, whitish areas, (b) whitish background, (c) comedo-like openings, and (d) purpuric blotches decreased. At the control visit, the two protocols did not differ significantly for any of the dermoscopic parameters, both in terms of mean score change and in the number of patients showing changes. Although the complementary action of the two molecules may suggest a therapeutic benefit, the association of tretinoin in short contact therapy with a potent corticosteroid did not induce significant changes in the dermoscopic features of VLS compared with the same corticosteroid alone.

Influence of treatment of vulvovaginal atrophy with intravaginal prasterone on the male partner.

OBJECTIVE: The aim was to analyze the opinion of the male partner of women treated for vulvovaginal atrophy (VVA) with intravaginal 0.50% DHEA (prasterone), thus providing information on both members of the couple. METHODS: On a voluntary basis, in a prospective, randomized, double-blind and placebo-controlled phase-III clinical trial, the male partner filled a questionnaire at baseline and at 12 weeks stating his observations related to his penis and intercourse before and after VVA treatment. RESULTS: Sixty-six men having a partner treated with intravaginal DHEA and 34 others having a partner treated with placebo answered the questionnaires. Concerning the feeling of vaginal dryness of their female partner, the severity score following DHEA treatment improved by 81% (0.76 units) over placebo (p = 0.0347). Thirty-six percent of men having a partner treated with DHEA did not feel the vaginal dryness of the partner at the end of treatment compared to 7.8% in the placebo group. When analyzing the situation at 12 weeks compared to baseline, an improved score of 1.09 units was the difference found for the DHEA group compared to 0.76 for the placebo group (p = 0.05 vs. placebo). In the DHEA group, 38% of men scored very improved compared to 18% in the placebo group. No adverse event has been reported. CONCLUSION: The male partner had a very positive evaluation of the treatment received by his female partner.

Vaginal effects of ospemifene in the ovariectomized rat preclinical model of menopause.

Ospemifene is a unique tissue-selective estrogen agonist/antagonist (also known as a selective estrogen receptor modulator [SERM]) with demonstrated efficacy in Phase 3 studies of postmenopausal women with vulvar and vaginal atrophy (VVA). This report describes preclinical studies on the effects of ospemifene in the ovariectomized (OVX) rat model of menopause. Ospemifene (10mg/kg/day) and the SERM comparator, raloxifene (10mg/kg/day) were administered for 2 weeks and both increased vaginal weight; ospemifene was more effective than raloxifene. In addition, ospemifene had a greater effect on increasing vaginal epithelial height compared with raloxifene. The effect on uterine weight was less pronounced for both ospemifene and raloxifene. The ED50 of ospemifene on vaginal epithelial height was 0.39mg/kg/day and the magnitude was nearly the same as was seen with the positive control, 17α-ethinyl estradiol (EE2). In a histological analysis of ospemifene-treated rat vaginas, basal cells were overlaid by 2 to 3 cell layers of thickened goblet-like mucified cells apically; however, the cornification observed with EE2 was absent. Estrogenic activity of ospemifene was confirmed by upregulation of progesterone receptors in vaginal epithelium and stroma. Ospemifene showed similar affinity for estrogen receptor (ER)-α and ER-ß, but an overall lower affinity than estradiol. Ospemifene antagonized estrogen response element (ERE)-mediated transactivation on MCF-7 cells, confirming its anti-estrogenic activity in breast cancer cells. The dose response for ospemifene in the rat is consistent with that observed in clinical studies of ospemifene 30 and 60mg, showing that the OVX rat is a highly predictive model of SERM activity in postmenopausal VVA.

Effect of different photoperiods and melatonin treatment on rabbit reproductive performance.

BACKGROUND: Rabbit production in Egypt exhibits a seasonal pattern with much higher yields from September to May. This variation might be explained by reproductive performance as controlled by annual photoperiodicity. HYPOTHESIS/OBJECTIVES: The aim of this study was to investigate whether the reproductive performance of rabbits can be improved by either increasing the photoperiod or by administering melatonin supplement. ANIMALS AND METHODS: In total 78 White New Zealand rabbits (60 does and 18 bucks) were used during September and October reared in a private Rabbitary in Menuofia Governorate, Egypt. The animals were randomly assigned to six treatment groups of 10 does and three bucks each (8, 10, 12, 14, and 16 h light and melatonin (1 mg/kg BW/day orally for two weeks). Ejaculate traits, sexual activity of bucks, sexual receptivity and reproductive performance of does were recorded. RESULTS: The results revealed that exposure of rabbits to long photoperiods (14 and 16 h light) or treatment with melatonin improved the quantity and quality of ejaculate traits and buck sexual activity as well as doe's sexual receptivity, feed intake, litter size, weight at birth and time-to-weaning. On the other hand, gestation period and pre-weaning mortality percentage decreased. CONCLUSIONS: Application of long photoperiods is beneficial to rabbit producers and 14 h light combined with 10 h dark is optimal for satisfying the physiological requirements of the rabbits. Finally, from an economic point of view, the light schedules are cheap and easy to apply and can be used as biostimulation instead of melatonin.

Randomized, placebo-controlled, double blind, crossover design trial of the efficacy and safety of Zestra for Women in women with and without female sexual arousal disorder.

Zestra for Women is a botanical feminine massage oil formulated to enhance female sexual pleasure and arousal when applied to the vulva. We conducted this randomized, double-blinded, crossover study to evaluate the efficacy and safety of Zestra for Women compared to placebo oil in 10 women with and 10 women without female sexual arousal disorder (FSAD) in conditions of home use in conjunction with sexual activities. Subjects were screened by physical examination, sex therapist interviews, and questionnaires. We randomized qualified subjects to treatment paths and gave them 5 doses of test article and diaries to use at home. At Visit 2, we assessed them by questionnaires and gave them 5 doses of crossover test article and diaries to use at home. At the final visit, we assessed them with questionnaires. We assessed safety by adverse event reports and primary efficacy by responses to a diary question regarding satisfaction with arousal. Secondary efficacy instruments included remaining diary questions, recall-based questionnaires, global assessment questions, and a consumer-testing questionnaire. All 20 subjects completed the study. Three subjects reported single incidences of mild genital burning sensations lasting 5-30 min after use of Zestra for Women. Both normal and FSAD women showed statistically significant improvements, relative to placebo, in level of arousal, level of desire, satisfaction with arousal, genital sensation, ability to have orgasms, and sexual pleasure. Although FSAD women showed greater magnitude of response, the presence of FSAD had no effect on response rates. Zestra for Women was just as effective in women using selective serotonin reuptake inhibitor antidepressants as in women not using antidepressants. Zestra for Women improved sexual function in normal and FSAD women under conditions of home use.

Effect of vulvovaginal estrogen on sensorimotor response of the lower genital tract: a randomized controlled trial.

OBJECTIVE: To assess the effect of vulvovaginal estrogen on mucocutaneous sensory threshold and circumvaginal motor strength. METHODS: Thirty-nine postmenopausal, hypoestrogenic women with mixed lower-genitourinary-tract complaints were placed in four masked treatment arms by permuted-block randomization for 6 weeks. One group received topical estradiol (E2) cream and pelvic muscle biofeedback training, the second received topical E2 cream and sham biofeedback, the third received placebo cream and pelvic muscle biofeedback training, and the fourth received placebo cream and sham biofeedback. Circumvaginal muscle strength was measured by averaging maximum intravaginal pressure (mmHg) generated over a set of four pelvic muscle contractions. Absolute changes in von Frey threshold (mN) and maximum intravaginal pressure (mmHg) over 4 and 6 weeks were reported as summary measures. Of 39 subjects, 30 completed the study. RESULTS: Topical estradiol cream significantly improved mechanical sensitivity of the vulvar vestibule to von Frey hairs, a -1.2-mN threshold decrease at 4 weeks (F = 10.29; P = .004), and a -1.6-mN threshold decrease at 6 weeks (F = 8.24; P = .009) compared with placebo cream. Stratification by age showed significantly greater improvement in mechanical sensitivity in the older (70-79 years) age group randomized to estrogen cream and a -5.49-mN threshold reduction (F = 17.65; P = .002). Maximum intravaginal pressures during circumvaginal muscle contraction did not differ between estrogen and placebo cream users (F = 0.00; P = .99). CONCLUSION: Improved sensation to mechanical stimuli can result from a rapidly acting, direct effect of topical E2 cream on the vulvar vestibule.