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 effect of vitamin D2 on lipid profile, anthropometric indices, blood pressure, and inflammatory and glycemic biomarkers in humans: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Even though the role of D2 (ergocalciferol) on cardiovascular disease risk components has been studied, conflicting results have been reported. Moreover, no single study has studied all these parameters and the role of vitamin D2 individually has not been assessed; hence, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of vitamin D2 supplementation on lipid profile, anthropometric indices, blood pressure, and inflammatory and glycemic biomarkers in humans. METHODS: Web of Science, Scopus, PubMed/Medline, and Embase were searched from database inception to July 2024, and the random effects model, according to the DerSimonian and Laird method, was used to generate combined estimates of the intervention's effect on the outcomes. RESULTS: After full-text analysis, 11 eligible articles were included in our meta-analyses. No statistically significant association was observed between vitamin D2 administration and BMI, WC, TC, HDL-C, LDL-C, TG, DBP or SBP; however, a statistically significant decrease in CRP (WMD: -1.92mg/dL, 95% CI: -3.30 to -0.54, P= 0.006) and HbA1c levels (WMD: -0.37%, 95% CI: -0.66 to -0.09, P= 0.009), and a non-statistically significant decrease in FBG (WMD: -4.61mg/dL, 95% CI: -14.71 to 5.47, P= 0.370, I2=90%, P˂0.001) and HOMA-IR (WMD: -0.10, 95% CI: -0.17 to 0.03, P= 0.002) were detected. CONCLUSION: In summary, our systematic review and meta-analysis discovered that vitamin D2 administration was associated with a statistically significant decrease in CRP and HbA1c levels, without a significant correlation with other outcomes.

The effect of vitamin D2 supplementation on vitamin D levels in humans: A time and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Inconsistencies exist regarding the influence of vitamin D2 (ergocalciferol) supplementation on serum vitamin D levels. These inconsistencies could be attributed to numerous factors, such as dosage, baseline vitamin D levels, and duration of intervention. Hence, this dose-response meta-analysis of randomized controlled trials was conducted to assess the efficacy of vitamin D2 supplementation on vitamin D levels. METHODS: Relevant studies were searched in PubMed/Medline, Web of Science, Embase, and Scopus, from their inception to 3 January 2023. Variable alterations were considered to calculate the pooled weighted mean difference (WMD) with 95% confidence interval (CI) using the random effects model. RESULTS: Pooled results from 33 study arms demonstrated that Vitamin D2 treatment significantly increases total vitamin D concentrations (WMD: 11.47 ng/mL, 95 %CI: 9.29 to 13.64, p < 0.001), 25(OH)D2 concentrations (WMD: 11.40 ng/mL, 95 %CI: 4.72 to 18.09, p = 0.001), and 1,25(OH)D concentrations (WMD: 5.61 ng/mL, 95 %CI: 0.74 to 10.48, p = 0.024), but decreases 25(OH)D3 concentrations (WMD: -4.63 ng/mL, 95 %CI: -6.46 to -2.81, p < 0.001). In subgroup analyses, increase in total vitamin D concentrations was more significant in vitamin D2 doses >2000 IU/day (WMD: 13.82 ng/mL), studies with duration ≤12 weeks (WMD: 12.53 ng/mL), participants aged ≥60 years (WMD: 14.40 ng/mL), and trials with basal 25(OH)D concentrations <20 ng/mL (WMD: 11.47 ng/mL). CONCLUSIONS: This meta-analysis indicates that the supplementation of vitamin D2 significantly increases the serum concentrations of total vitamin D, 25(OH)D2, and 1,25(OH)D, but decreases 25(OH)D3 concentrations. Careful consideration of patient characteristics, dosage, and treatment duration is recommended for vitamin D2 supplementation.

The effect of tamoxifen on estradiol, SHBG, IGF-1, and CRP in women with breast cancer or at risk of developing breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The effects of tamoxifen on the serum levels of hormones and acute phase reactants have been studied previously, but study results have been inconsistent, especially in women with breast cancer. Hence, we conducted this meta-analysis of randomized controlled trials (RCTs) to try to clarify the effects of tamoxifen on estradiol, insulin-like growth factor 1 (IGF-1), sex hormone binding globulin (SHBG), and C-reactive protein (CRP) serum levels in women with breast cancer or at risk of developing breast cancer. METHODS: Databases were systematically searched up to December 2023. The meta-analysis was generated through a random-effects model and is presented as the weighted mean difference (WMD) and 95 % confidence intervals (CI). RESULTS: Nine publications were included in the present meta-analysis. The comprehensive findings from the random-effects model revealed an elevation in estradiol (WMD: 13.04 pg/mL, 95 % CI: 0.79, 25.30, p = 0.037) and SHBG levels (WMD: 21.26 nmol/l, 95 % CI: 14.85, 27.68, p = 0.000), as well as a reduction in IGF-1 (WMD: -14.41 µg/L, 95 % CI: -24.23, -4.60, p = 0.004) and CRP concentrations (WMD: -1.17 mg/dL, 95 % CI: -2.29, -0.05, p = 0.039) following treatment with tamoxifen in women with breast cancer or at risk of developing breast cancer, with no impact on IGFBP-3 levels (WMD: 0.11 µg/mL, 95 % CI: -0.07, 0.30, p = 0.240). CONCLUSION: Tamoxifen administration seems to increase estradiol and SHBG levels and reduce CRP and IGF-1 levels in women with breast cancer or at risk of developing breast cancer. Further studies are needed to determine whether these changes have any clinical relevance.

The impact of medroxyprogesterone acetate on lipid profiles in Women: A time and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose-response meta-analysis of randomized controlled trials was conducted to assess the effect of MPA on lipid profiles in women. METHODS: A comprehensive search was conducted in the following databases: Web of Science, Scopus, PubMed/Medline, and Embase, up to October 20, 2023. A random-effects meta-analysis approach based on the DerSimonian and Laird method was used to compute the combined estimates of the intervention's impact on the lipid profile. RESULTS: 35 eligible studies with 58 arms were included in our meta-analyses analysis. Combined effect sizes suggested a significant effect of MPA on total cholesterol (TC) levels (WMD: -3.43 mg/dL, 95 % CI: -5.38 to -1.48, p < 0.001), HDL-C levels (WMD: -3.34 mg/dL, 95 % CI: -3.77 to -2.91, p < 0.001), and triglyceride (TG) levels (WMD: -9.13 mg/dL, 95 % CI: -10.92 to -7.33, p < 0.001). The subgroup meta-analysis revealed a more substantial reduction in TC in studies with dosages > 2.5 mg/day (WMD: -4.10 mg/dL), mean participant age lower than 60 years (WMD: -3.80 mg/dL), mean BMI lower than 25 kg/m2 (WMD: -5.61 mg/dL), duration of intervention of 12 months or more (WMD: -3.98 mg/dL), and when the baseline TC value was equal to or greater than 200 mg/dL (WMD: -4.13 mg/dL). CONCLUSIONS: The current meta-analysis showed a statistically significant decrease in TC, TG, and HDL-C levels and a non-significant increase in LDL-C levels after MPA administration in women.

The effect of subcutaneous Lixisenatide on weight loss in patients with type 2 Diabetes Mellitus: Systematic review and Meta-Analysis of randomized controlled trials.

BACKGROUND: The impacts of subcutaneous Lixisenatide on body weight in patients with type 2 DM, remain inadequately understood; consequently, this systematic review and meta-regression analysis of randomized controlled trials (RCTs) was conducted to evaluate the influence of subcutaneous Lixisenatide administration on BW and BMI values in individuals with Type 2 diabetes. METHODS: A comprehensive literature search was conducted across four databases, spanning from their inception to February 2023. We computed effect sizes employing the random-effects model and reported results in terms of weighted mean differences (WMD) along with their corresponding 95% confidence intervals (CI). RESULTS: 23 articles with 26 RCT arms were included in the meta-analysis. The combined findings from a random-effects model demonstrated a significant reduction in body weight (WMD: -0.97 kg, 95 % CI: -1.10, -0.83, p < 0.001) and BMI (WMD: -0.48 kg/m2, 95 % CI: -0.67, -0.29, P < 0.001) after subcutaneous administration of Lixisenatide. Furthermore, a more pronounced reduction in body weight was discovered in RCTs lasting less than 24 weeks (WMD: -1.56 kg, 95 % CI: -2.91, -0.20, p < 0.001), employing a daily dosage of subcutaneous Lixisenatide lower than 19 Âµg per day (WMD: -1.94 kg, 95 % CI: -2.54, -1.34, p < 0.001) and with a mean participant age of 60 years or more (WMD: -1.86 kg, 95 % CI: -3.16, -0.57, p = 0.005). CONCLUSIONS: Lixisenatide was found to significantly decrease BW and BMI in patients with type 2 DM and could be considered as a therapeutic option for those suffering from weight gain caused by other anti-diabetic agents. However, while prescribing Lixisenatide, careful consideration of patient-specific factors is recommended.