The effect of menopausal hormone therapy on the risk of melanoma and keratinocyte skin cancer: A systematic review and meta-analysis of observational studies.

BACKGROUND: Whether menopausal hormone therapy (MHT) increases the risk of skin cancer is controversial. AIM: To systematically review and meta-analyze evidence regarding the association of MHT with the risk of melanoma and keratinocyte cancer (KC). MATERIAL AND METHODS: A comprehensive literature search was conducted of the PubMed, Scopus and Cochrane databases, through to 30 October 2021. Skin neoplasms were divided into melanoma and KC. In the latter category, both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were considered. The results are presented as hazard ratios (HR) with 95 % confidence intervals (CI). The I2 index was used to assess heterogeneity. Subgroup analysis and sensitivity analysis were also conducted in order to explore potential differences among studies. RESULTS: Twenty-seven studies were included in the qualitative and 23 in the quantitative analysis, with a total of 2,612,712 menopausal women (25,126 with skin cancer; 20,150 with melanoma). MHT was associated with an increased risk of melanoma (HR 1.11; 95 % CI 1.05-1.19; I2 45%). With regard to MHT type, both estrogen monotherapy (HR 1.22, 95 % CI 1.16-1.29; I2 0%) and estrogen in combination with progestogen (HR 1.11, 95 % CI 1.05-1.18, I2 26%) significantly increased that risk. Regarding melanoma subtype, superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) were the only histologic subtypes associated with MHT use. MHT was also associated with an increased risk of KC (HR 1.17, 95 % CI 1.04-1.31, I2 83%), specifically BCC (HR 1.22, 95 % CI 1.12-1.32; I2 29%). Longer duration (>5 years) of MHT, current use and estrogen monotherapy were associated with an increased KC risk compared with no use. CONCLUSION: The use of MHT by postmenopausal women was associated with an increased risk of melanoma and KC. This risk was higher for current MHT users and those treated for over 5 years.

Association of systemic lupus erythematosus with hearing loss: a systemic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect virtually any organ, including middle and/or inner ear. The objective of the current systematic review and meta-analysis was to investigate the association of SLE with the different subtypes of hearing loss. This systematic review and meta-analysis was conducted in agreement with the PRISMA guidelines. The review protocol was registered in the PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=216353 ). A random effects model meta-analysis was carried out while heterogeneity was appraised by I2. Subgroup analysis and sensitivity analysis were also performed. Nine studies comprising 7,654 SLE patients and 37,244 controls were included in this systematic review. Four of them were rated to a moderate rate of bias, while five of them were rated to a low rate of bias. SLE patients had significantly increased odds of sensorineural hearing loss (SNHL) compared with controls (OR 2.31; 95%CI 1.48-3.60; I2 = 0). SLE patients did not have significantly increased odds of Conductive Hearing Loss (CHL) (OR 1.30; 95% CI 0.23-7.45; I2 = 0). Only one study reported on the outcome of Mixed Hearing Loss (MHL) (3 events in SLE group vs. 0 events in control group). Subgroup analysis, based on study design and detection method of hearing loss also showed significantly increased odds of SNHL in SLE patients. The significantly increased odds of SNHL in SLE persisted even after sensitivity analysis. In conclusion, SLE is significantly associated with SNHL; SLE is not associated with CHL, while, due to lack of data, we could not reach a conclusion regarding the odds of MHL in SLE patients. Pure tone audiometry as a screening test and follow-up test in SLE patients could be of essence. Management and prognosis of hearing loss in SLE patients should be discussed.

Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials.

OBJECTIVE: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART. METHODS: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I2 0%). CONCLUSIONS: Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.

Association of rheumatoid arthritis with hearing loss: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the worldwide population. RA is associated with multiple extra-articular manifestations (EAMs). Middle ear, cochlea and the auditory nerve are suspected sites of RA activity and hearing loss is a possible novel EAM of RA. Objective was to investigate the association of RA with the different subtypes of hearing loss. This systematic review was performed according to the PRISMA guidelines. A random effects model meta-analysis was conducted and the I2 was used to assess heterogeneity. Twelve studies comprising 20,022 RA patients and 79,244 controls were included in this systematic review. All studies were observational and were rated to a moderate rate of bias. RA patients had nearly fourfold increased odds of sensorineural hearing loss (SNHL) compared with controls (OR 3.42; 95% CI 2.50-4.69; I2 = 13). RA patients also had a significantly increased risk of SNHL (RR 2.28; 95% CI 1.88-2.76; I2 = 0). RA patients did not have increased odds of conductive hearing loss (CHL) and mixed hearing loss (MHL) (OR 1.36; 95% CI 0.52-3.55; I2 = 22); (OR 2.73; 95% CI 0.78-9.58; I2 = 0%). RA is significantly associated with SNHL. RA is not associated with CHL and MHL. Early screening of RA patients with pure tone audiometry should be considered.

Early menopause is associated with increased risk of arterial hypertension: A systematic review and meta-analysis.

OBJECTIVE: Menopausal transition has been associated with an increased risk of cardiovascular disease (CVD), mainly attributed to atherogenic dyslipidaemia, central obesity and insulin resistance. Whether arterial hypertension (AH) also contributes to menopause-associated CVD is currently unknown. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the association between early menopause (EM) and AH risk. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases, up to January 20th, 2020. Data were expressed as odds ratio (OR) with 95 % confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Ten studies were included in the quantitative analysis (273,994 postmenopausal women, 76853 cases with AH). Women with EM (age at menopause <45 years) were at higher AH risk compared with those of normal age at menopause (>45 years) (OR 1.10, 95 % CI 1.01-1.19, p = 0.03; I2 79 %). The direction or the magnitude of this association remained significant when the analysis was restricted to studies including groups matched for potential confounders, such as age, BMI, smoking or the use of menopausal hormone therapy or oral contraceptives. CONCLUSIONS: Women with EM have an increased risk for AH compared with those of normal age at menopause.