Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

The efficacy of oral Lavandula angustifolia Mill. essential oil on menopausal symptoms, serum lipid profile, and cortisol concentration in postmenopausal women: A triple-blind, randomized, controlled trial.

OBJECTIVE: To determine the effect of oral Lavandula angustifolia Mill. essential oil (LEO) on menopausal symptoms, serum cortisol level, and lipid profile in postmenopausal women. METHODS: This was a triple-blind parallel-armed randomized trial. Seventy-two postmenopausal women aged 50-65 years referring to healthcare centers in Tabriz, Iran with a score of 15-42 on the Green scale were included from May 10, 2022 to May 22, 2023. The participants were randomly assigned to two groups with a 1:1 ratio and using four and six blocks. One group received LEO soft gel 80 mg per day, and another group received a similar placebo for 60 days. A demographic questionnaire and a Greene menopause symptom scale were used for data collection. The lipid profile (total cholesterol, triglyceride, LDL, HDL) and the serum levels of cortisol were measured using biochemical methods. Chi-square, Fisher's exact tests, Independent samples t-test, Analysis of Covariance (ANCOVA), Repeated measure ANOVA, and Paired sample t-test were utilized for analyses. A p-value less than 0.05 was considered statistically significant. RESULTS: The demographic and personal characteristics of the participants were similar. After two months of intervention, all symptoms in psychological, physical, vasomotor, anxiety, depression, and sexual dysfunction domains were significantly relieved (decreased) among both groups (p < 0.003), except for sexual dysfunction, the reduction of which was not significant in the placebo group (p = 0.317). The mean (SD) total score of menopausal symptoms reduced from 27.4 (6.3) at baseline to 17.7 (4.9) at the end of the study in the LEO group (p < 0.001). It also decreased from 27.4 (7.1) to 17.6 (5.1) in the placebo group (p < 0.001). However, between-group analyses revealed that this reduction was significantly greater in the LEO group compared to the placebo group only in the sexual dysfunction (Mean (SD): 1.3 (0.6) vs. 1.0 (0.5); adjusted mean difference (95% confidence interval); p: - 0.35 (-0.67 to -0.02); 0.039). No significant within-group changes or between-group differences were observed (p > 0.05) in terms of studied serum markers. CONCLUSION: The oral LEO exhibited a significant enhancement in sexual dysfunction among postmenopausal women. Therefore, it can be used alongside other therapies to improve sexual dysfunction during menopause. LEO did not affect lipid profile and serum cortisol level in this study.

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Oral lasofoxifene's effects on moderate to severe vaginal atrophy in postmenopausal women: two phase 3, randomized, controlled trials.

OBJECTIVE: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause. METHODS: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.5 mg/d, or placebo, for 12 week. Changes from baseline to week 12 in most bothersome symptom, vaginal pH, and percentages of vaginal parabasal and superficial cells were evaluated. These coprimary endpoints were analyzed using analysis of covariance, except superficial cells, which were analyzed by the nonparametric, rank-based Kruskal-Wallis test. RESULTS: The two studies enrolled 444 and 445 women (mean age, ~60 y), respectively. Coprimary endpoints at week 12 improved with lasofoxifene 0.25 and 0.5 mg/d greater than with placebo ( P < 0.0125 for all). Study 1: most bothersome symptom (least square mean difference from placebo: -0.4 and -0.5 for 0.25 and 0.5 mg/d, respectively), vaginal pH (-0.65, -0.58), and vaginal superficial (5.2%, 5.4%), and parabasal (-39.9%, -34.9%) cells; study 2: most bothersome symptom (-0.4, -0.5), vaginal pH (-0.57, -0.67), and vaginal superficial (3.5%, 2.2%) and parabasal (-34.1%, -33.5%) cells. Some improvements occurred as early as week 2. Most treatment-emergent adverse events were mild or moderate and hot flushes were most frequently reported (lasofoxifene vs placebo: 13%-23% vs 9%-11%). Serious adverse events were infrequent and no deaths occurred. CONCLUSIONS: In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause.

Oral daily PTH(1-34) tablets (EB613) in postmenopausal women with low BMD or osteoporosis: a randomized, placebo-controlled, 6-month, phase 2 study.

Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.

Despite the superior benefits of bone-building (anabolic) agents and guidelines supporting their use, these medications are used in a minority of patients for whom they are appropriate, in part because they require daily or monthly injections, which limit patient acceptance. An oral anabolic tablet has potential to address this substantial treatment gap. In this double-blind, placebo controlled, dose-finding randomized study, 161 postmenopausal women with low BMD or osteoporosis were treated with varying doses of the active part of PTH(1-34) or placebo given in daily oral tablets for 6 mo. The highest oral PTH tablet dose (2.5 mg) produced an increase in markers of bone formation while simultaneously decreasing the markers of bone breakdown. Significant gains in BMD of the spine and hip were observed at the end of the 6-mo study and there were no significant safety concerns. The 2.5 mg oral PTH tablet dose was well tolerated when patients were instructed to titrate up to the full dose. We conclude that this PTH tablet might be the first effective orally administered bone building medication and should be studied further in treatment of women with osteoporosis.

A Cost Savings Analysis of Topical Estrogen Therapy in Urinary Tract Infection Prevention Among Postmenopausal Women.

INTRODUCTION: UTIs are some of the most common infections in geriatric patients, with many women experiencing recurrent infections after menopause. In the US, annual UTI-related costs are $2 billion, with recurrent infections creating a significant economic burden. Given the data published on topical estrogen in reducing the number of infections for postmenopausal women with recurrent UTI, we sought to evaluate how this would translate to cost savings. METHODS: We performed a systematic literature review of UTI reduction secondary to topical estrogen utilization in postmenopausal female patients. The cost per UTI was determined based on published Medicare spending on UTI per beneficiary, weighted on reported likelihood of complicated and resistant infections. For a patient with recurrent infections, topical estrogen therapy reported on average can reduce infections from 5 to 0.5 to 2 times per person per year. RESULTS: At a calculated cost per UTI of $1222, the reduction in UTI spending can range between $3670 and $5499 per beneficiary per year. Per-beneficiary spending on topical estrogen therapies was $1013 on average ($578-$1445) in 2020. After including the cost of the therapy, overall cost savings for topical estrogen therapies were $1226 to $4888 annually per patient. CONCLUSIONS: Topical estrogens are a cost-conscious way to improve the burden of UTI on postmenopausal women with the potential for billions of dollars in Medicare savings. System-wide efforts should be made to have these therapies available as prophylaxis for postmenopausal patients and to ensure they are affordable for patients.

Adjuvant zoledronic acid therapy for postmenopausal women with early breast cancer in China: a cost-effectiveness analysis.

Combination therapy of zoledronic acid (ZOL) plus aromatase inhibitor (AI) was found to reduce bone metastasis risk and improve overall survival for treatment-naïve postmenopausal women (PMW) with hormone receptor-positive (HR+) early breast cancer (EBC), when compared with AI alone. The objective of this study was to evaluate the cost-effectiveness of adding ZOL to AI in treating PMW with HR+ EBC in China. A 5-state Markov model was constructed to evaluate the cost-effectiveness of adding ZOL to AI for PMW-EBC (HR+) over a lifetime horizon from the perspective of Chinese healthcare provider. Data used were obtained from previous reports and public data. The primary outcomes of this study were direct medical cost, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed to examine the robustness of the presented model. Over a lifetime horizon, adding ZOL to AI was projected to yield a gain of 1.286 LYs and 1.099 QALYs compared with AI monotherapy, which yielded ICER $11 140.75 per QALY with an incremental cost of $12 247.36. The one-way sensitivity analysis indicated that the cost of ZOL was the most influential factor in our study. The probability that adding ZOL to AI was cost-effective at a threshold of $30 425 per QALY in China was 91.1%. ZOL is likely to be cost-effective in reducing bone metastasis risk and improving overall survival for PMW-EBC (HR+) in China.

Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs.

OBJECTIVES: Sex is well known to influence risk, severity and treatment outcomes of RA, although the underlying causes are uncertain. The aim of this research was to examine whether factors influencing female sex hormones (reproductive status and exogenous sex hormone use) are associated with the efficacy of DMARDs. METHODS: Individual participant data were pooled from five phase 3 clinical trials where RA patients were treated with tocilizumab and/or conventional synthetic DMARDs. The primary outcome was the time to first remission according to the Simplified Disease Activity Index. The relationship between menopausal status or use of exogenous sex hormones and the time of first remission was assessed via Cox proportional analysis. Analysed data included sex, baseline menopausal status (premenopausal, perimenopausal, early postmenopausal and postmenopausal), participant age, body mass index, race, number of previous DMARDs and baseline disease activity. RESULTS: Analysis included 4474 female patients, of whom 2817 (62.9%) were postmenopausal, 202 (4.5%) were early postmenopausal, 1021 (22.8%) were premenopausal and 414 (9.2%) were perimenopausal. Of these, 221 (7.8%), 13 (6.4%), 255 (25%) and 47 (11.4%), respectively, were taking exogenous sex hormones. In the pooled analysis, perimenopausal status was associated with reduced remission compared with premenopausal status [adjusted HR 0.78 (95% CI 0.61, 0.99)]. Sex hormone use was associated with significantly higher remission [adjusted HR 1.20 (95% CI 1.01, 1.43)]. CONCLUSION: Perimenopausal women were less likely to achieve remission compared with premenopausal RA patients. The use of exogenous sex hormones appeared to be associated with more frequent remission in female RA patients, particularly those who were perimenopausal and early postmenopausal, although further research is required to confirm and identify the drivers for this observation and how it interacts with menopausal status.

Long-term effects of a combination of isoflavones, agnus castus and magnolia extracts on climacteric symptoms and cardiometabolic risk profile in postmenopausal women.

OBJECTIVE: To evaluate the long-term effects of a combination of isoflavones, agnus castus and magnolia extracts (combined isoflavone compound [CIC]) on climacteric symptoms and cardiometabolic risk in symptomatic postmenopausal women. METHODS: This interventional, prospective study evaluated climacteric symptoms, mood and sleep disorders using the 21-item Greene Climacteric Scale (GCS) and 7-item Insomnia Severity Index (ISI) questionnaires; and cardiovascular, metabolic and thrombotic risk markers at baseline (T0) and after 12 months of CIC treatment (T1). RESULTS: In healthy postmenopausal women (N = 71), 12-month CIC treatment significantly reduced patient-reported vasomotor symptoms (100% vs. 17%), mood disorders (67% vs. 25%) and sleep disorders (89% vs. 19%%) (all p < .001) compared with baseline; and significantly improved GCS psychological, somatic, and vasomotor domain scores and ISI sleep disturbance scores (all p < .05). CIC significantly reduced systolic (p = .022) and diastolic blood pressure (p < .001), and heart rate (p < .001); glucose concentrations (p = .018), HOMA index (p = .013), and ALT (p = .035), homocysteine (p = .005) and NT-proBNP (p = .003) levels. CONCLUSIONS: Long-term CIC therapy improved vasomotor symptoms, mood disorders, sleep disorders, hemodynamic measurements and cardiometabolic risk markers in healthy postmenopausal women. CLINICALTRIALS.GOV IDENTIFIER: NCT03699150.

Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women.

INTRODUCTION: Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses. METHODS: Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 ± 1 yr) and 17 YW (22 ± 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 ± 1 yr) before and after 1 month of transdermal estradiol (100 µg·d-1). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts. RESULTS: Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 ± 3 vs 8 ± 1 bursts per minute; P < 0.05). During handgrip, the increases in MSNA (PMW Δ16 ± 2 vs YW Δ6 ± 1 bursts per minute; P < 0.05) and MAP (PMW Δ18 ± 2 vs YW Δ12 ± 2 mm Hg; P < 0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (-E2) Δ27 ± 8 bursts per minute versus PMW (+E2) Δ12 ± 5 bursts per minute; P < 0.05) and MAP (Δ31 ± 8 mm Hg vs Δ20 ± 6 mm Hg; P < 0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol. CONCLUSIONS: These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW.

Vaginal health, endometrial thickness and changes in bone markers in postmenopausal women after 6 months of treatment with ospemifene in real clinical practice.

OBJECTIVE: To assess vaginal health, endometrial thickness, and changes in bone markers in postmenopausal women with vulvovaginal atrophy (VVA) treated with 60 mg/day of ospemifene under routine clinical practice. METHODS: The AYSEX study is a Spanish observational and prospective study performed in one center in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated continuously with ospemifene 60 mg/day for 12 months as an appropriate therapeutic option. This article refers to the 3- and 6-months analysis. Vaginal health was assessed by pH and using Vaginal Health Index (VHI) at baseline and 3 months later. Endometrial thickness, measured by vaginal ultrasonography, and bone resorption marker (CTx) were assessed at baseline and 6 months later. RESULTS: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, pH improved from 6.1 to 4.5 (p < .0001), and VHI improved from 10 to 19 points (p < .0001). The percentage of patients with VVA according to VHI decreased from 100% to 5.2% (p < .0001). After 6 months, mean CTx levels decreased from 0.42 pg/ml at baseline to 0.37 pg/ml 6 months later (p = .0018), and mean endometrial thickness changed from 2.24 to 2.15 mm (p = .6066). CONCLUSIONS: Up to date, this is the only prospective and observational study with ospemifene in routine clinical practice conditions and confirms the results previously reported from randomized controlled clinical trials, improving VVA, not increasing endometrial thickness, and decreasing CTx levels by exerting an anti-resorptive function.