ABSTRACT
Hypothyroidism is a widespread condition in the United States, affecting approximately 5% of the adult population. Although the clinical use of levothyroxine is well understood, its effect on preventing dementia is not well established. While the exact role of thyroid hormones in the adult brain is unknown, it is apparent that poor thyroid function can lead to mood swings, cognitive impairment, and other psychiatric symptoms. Most studies demonstrate an association between thyroid health and cognition, specifically slow processing of information, decreased effectiveness of executive functions, and lack of learning. This study aims to review the effect of levothyroxine on dementia. We searched electronic databases such as PubMed, Google Scholar, Science Direct, Cochrane, gray literature, and the references of included articles to find relevant articles. Two investigators independently identified eligible studies, screened title/abstract, and extracted data. We identified a total of 319 citations through a database search with six studies (case-control, longitudinal, cross-sectional, randomized controlled trials) meeting the inclusion criteria. Studies with moderate to low risk of bias were evaluated using their respective quality check tools. Five of six studies showed a positive impact of levothyroxine (LT-4) on dementia. According to these studies, the plausible rationale behind the reversal of memory with LT-4 treatment is restoring thyroid-stimulating hormone (TSH), thyroxine (T4) levels, and gamma-aminobutyric acid (GABA) concentrations. People with abnormal thyroid function should be screened for cognitive dysfunction using specific neurocognitive tests and start treatment with LT-4 regardless of symptom presentation. Multi-dose randomized placebo-controlled intervention studies are recommended to assess the effect of LT-4 on lowering the risk of dementia in hypothyroid patients.
ABSTRACT
Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels <300ng/mL were included in the analysis. The intervention group received testosterone in various routes including transdermal patches, gels, mouth patches, testosterone injections, and deposits. The incidence of MI was taken to be the primary measure outcomes. The pooled data from eight studies showed MI incidence in 249 out of 11,720 (2.1%) in the TRT group and 1420 out of 33,086 (4.3%) in the control group. The pooled OD showed no statistically significant association of TRT and MI compared to the control group (OR = 0.76, 95% CI 0.36-1.31; p=0.48). The model revealed high heterogeneity with I2 =79%. With sensitivity analysis and, excluding two studies out of the eight, the pooled data was able to achieve low heterogeneity with I2 = 0%. The newly pooled data from six studies showed MI incidence in 226 out of 10,137 (2.2%) in the TRT group and 969 out of 36,304 (2.7%) in the control group. The pooled OD shows no statistical significance in the association between TRT treatment and MI compared to the control group. (OR =0.87, 95% CI 0.75-1.01; P =0.08). It appears that TRT does not increase the risk of MI as compared to the non-intervention group. Further RCTs with greater population size are needed that could produce more solid results, allowing more definitive conclusions to be made on this topic.
ABSTRACT
Hydroxyurea (HU) or hydroxycarbamide is a cytotoxic antimetabolite widely used to treat Philadelphia chromosome-negative Myeloproliferative Neoplasms (Ph-MPN) like Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF). Patients with Ph-MPN are at an increased risk of Non-melanoma skin cancers (NMSC). The cause of this finding remains uncertain. In this systematic review, we would like to know if chronic use of HU in this population is responsible for the sudden onset of NMSC. The results obtained will help the patients and clinicians with early diagnosis of cutaneous lesions and in optimizing the current treatment options for MPN. We conducted a multi-database literature search, applied eligibility criteria and quality assessment tools to the studies extracted, with an intention to include only fair to high-quality articles. We analyzed six observational studies and four traditional reviews. Two out of 10 studies concluded that no relationship exists between the incidence of NMSC and HU. The remaining eight studies indicated the association. According to these studies, the possible risk factors include old age, excessive exposure to sunlight, higher doses, and prolonged HU therapy duration. Ultraviolet (UV) radiation and HU play a combined role in carcinogenesis. Periodic dermatologic screening is essential in these patients. Prompt biopsy and accurate diagnosis can prevent the progression of cancer and decrease the associated morbidity and mortality. True incidence and causation cannot be ascertained due to the scarcity of research on this topic. Multi-center prospective studies in large groups of Ph-MPN patients are recommended to determine the temporal relationship between NMSC and HU treatment.
