Monurelle Biogel® vaginal gel in the treatment of vaginal dryness in postmenopausal women.

OBJECTIVES: To evaluate efficacy, tolerability and safety of Monurelle Biogel® vaginal gel for treatment of vaginal dryness. METHODS: Multicenter, national, randomized, controlled vs. no-treatment, open-label study. Ninety-five postmenopausal women were randomized (48 to Monurelle Biogel® and 47 to no treatment). Primary endpoint was the change of Verbal Rating Scale (VRS) total score of vaginal atrophy (VA) symptoms after 8-week treatment. The main secondary endpoints were VRS single-item score, Vaginal Health Index (VHI) score, Maturation Index (MI), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R). RESULTS: The VRS total score was statistically significant in favor of the treatment group on day 28 (p = 0.001) but not on day 56 (p = 0.064). By excluding women who were not sexually active, the total VRS scores reached the criteria for clinical success in 27/43 subjects (62.8%) in the control arm and in 38/46 subjects (82.6%) in the treatment arm (p = 0.035) on day 56. The VHI score significantly changed in the active arm (4.71 ± 4.85 vs. 0.28 ± 1.71) (p < 0.001) on day 56. Even the MI significantly improved, with an increase in the percentage of superficial cells (p = 0.01). The improvements in both VHI and MI were still present at the follow-up visit after the discontinuation of the treatment (day 84). Sexual function and distress showed a statistical significant difference on day 56. CONCLUSIONS: Monurelle Biogel® vaginal gel applied twice daily for 8 weeks is effective in relieving vaginal dryness and other VA symptoms. Such a clinical meaningful effect persists at least 4 weeks and is supported by an improvement in the vaginal environment. Trial Registration clinicaltrials.gov Identifier: NCT02994342.

Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women.

Recognition of a major genetic component in bone mass determination represented the basis for studies aiming to the identification of underlying major and minor genes. Bone mineral density (BMD) represents the continuous trait to be quantified in order to evaluate segregation of candidate genes with risk of osteoporosis. Polymorphisms at the vitamin D receptor (VDR), estrogen receptor, (ER), collagen type I, and interleukin 6 (IL6) gene loci have been correlated to BMD. However, in a polygenic disorder, such as osteoporosis, the number of genes expected to influence BMD is very large. In the present study we examined the presence of restriction fragment length polymorphisms (RFLPs) for the calcitonin receptor (CTR) gene in postmenopausal women. We identified a polymorphic (Tt) site at the CTR gene locus using the Taq I restriction fragment enzyme. Three genotypes were observed, whose Tt was the most frequent in our population (49.7%). In addition, Ancova analysis and Tukey's test showed that women with tt genotype had significantly lower lumbar BMD in comparison with Tt genotype (Tukey's test: p = 0.005). In conclusion, evidence of RFLPs at the CTR gene locus in Caucasian postmenopausal women of Italian origin made it possible to identify the involvement of another gene, the CTR gene, in the determination of bone mass.

Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: evidence of multiple gene contribution to bone mineral density.

Bone mass and bone turnover are under genetic control. Restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus have been recently correlated to bone mineral density (BMD) and rate of bone loss. However, agreement on this relationship is not universal. The existence of ethnical and environmental differences between populations, a health-based selection bias in several previous studies, and the involvement of other genes could explain these discordant findings. In this study, we examined the relationship of VDR and estrogen receptor (ER) gene RFLPs with lumbar spine and upper femur BMD in 426 Italian postmenopausal women, 57.7 +/- 0.4 yr old (144 normal, 106 osteopenic, and 176 osteoporotic). VDR gene RFLPs for ApaI, Bsm I, and TaqI restriction endonucleases and ER RFLPs for PvuII and XbaI restriction endonucleases were assessed by Southern blotting analysis and were indicated, respectively, as A-a, B-b, T-t, P-p, and X-x (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). After correcting for potential confounding factors (age, height, weight, age since menopause, osteophytosis, and facet joint osteoarthritis), a statistically significant VDR genotype effect on lumbar BMD (P = 0.01, analysis of covariance), but not on femoral BMD, was detected, with subjects in AABBtt genotype showing a 13% lower BMD than those with aabbTT genotype (P < 0.05, Tukey's test). Moreover, a statistically significant prevalence of AABBtt genotype in osteoporotics, and of AabbTT and aabbTT genotypes in nonosteoporotics, were detected. Conversely, there was no significant relationship of ER genotype to either lumbar or femoral BMD, even though a trend for higher BMD values in women with the ER PP genotype (with respect to those with ER pp genotype) was detected. When mean lumbar BMD was calculated for women grouped by ER and VDR genotype, we observed a significant difference between those within the 2 opposite associations AABBtt-PPXX and aabbTT-ppxx (0.71 +/- 0.05 vs. 0.97 +/- 0.03 g/cm2, P < 0.05 Tukey's test). These results are consistent with a segregation of the VDR AABBtt genotype with a higher risk of developing osteoporosis, in the Italian female population. The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.