Effects of E2/P4 oral capsules on bone turnover in women with vasomotor symptoms

Objective: To evaluate bone turnover markers (BTM) in the REPLENISH trial (NCT01942668). Methods: REPLENISH evaluated oral estradiol/progesterone (E2/P4) for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/wk, were <5 years since last menstrual period, and had BTM measurements at baseline, and months 6 and 12. Percent changes for three BTM (bone-specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [P1NP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, and placebo groups. Results: A total of 157 women (40-61 y, 69% White) were analyzed. Mean baseline values ranged from 14.0 to 14.3 U/L for BSAP, 0.34 to 0.39 ng/mL for CTX-1, and 76.9 to 79.3 ng/mL for PINP. Mean differences in percent change from baseline for both E2/P4 doses versus placebo significantly decreased at months 6 and 12 and ranged from −8% to −16% for BSAP (all, P < 0.05), −30% to −41% for CTX-1 (all, P ≤ 0.001), and −14% to −29% for PINP (all, P < 0.01). Conclusions: REPLENISH data provide support for a potential skeletal benefit of E2/P4 when it is used for the treatment of moderate to severe VMS. Further studies are warranted

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Background. We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods. Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. Results. Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion. Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. © 2010 Christiansen et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial

INTRODUCTION: TX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17β-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA). AIM: To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA. METHODS: The REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 μg) with placebo in postmenopausal women (40-75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory. MAIN OUTCOME MEASURES: Changes from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo. RESULTS: All three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 μg (P < .05) and 25 μg (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 μg significantly improving baselines scores for pain and lubrication at 12 weeks (P ≤ .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 μg vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm. CONCLUSION: TX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Estradiol; Estrogen Therapy; Female Sexual Dysfunction; Female Sexual Function Index; Menopause; Vaginal Atroph