The only detected adverse effects of testosterone were oedema and a modest lowering of HDL cholesterol. We established a collaborative group of investigators of all identified trials (35 trials) and collected individual patient data (IPD) from 17 trials (3431 participants in total). Testosterone treatment is most often given to men aged 40–65 years. Long-term data are needed to fully evaluate the safety of testosterone. 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening.
The Research Ethics Committee of King Faisal Specialist Hospital and Research Center (KFSHRC) approved the study. Testosterone, d3-testosterone, as well as ammonium acetate, acetonitrile, and methyl tert-butyl ether were purchased from Sigma-Aldrich MO, USA; IsoScience, PA, USA; and Fisher Scientific, NJ, USA, respectively. The stability of testosterone in extracted and unextracted plasma and salivary samples was tested under common clinical laboratory conditions. We report a specific, sensitive, and fast ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for determining clinically relevant testosterone level in human plasma and saliva.
The decline in testosterone serum levels across years of observation was also confirmed when considering variables related to population change (Chi-squared 177.0, p 2 48.9%). Similarly, a decrease in LH serum levels was confirmed in three out of six groups (Table 5 and supplementary material, page 17–19). Considering the limited number of studies, the analysis of testosterone trend measured by MS requires more data over a longer observation period. Additional confounders, such as the laboratory methodology used to measure serum testosterone levels and the country of origin of the study population, were also extracted.
The databases also do not include testosterone formulations administered in a clinic setting, so our results underrepresent the scope of the observed TT prescribing practices. Our study’s main strength is the utilization of state PDMP databases with mandatory inclusion of all dispensed prescriptions regardless of payor, in contrast to commercial databases and is the first to report new TT prescribing data since 2018. While TT did not show an increased risk of major adverse cardiac events (MACE) in a high-risk population , most research has been limited to topical gels and not the more widely used injectable formulations that have shown a higher incidence of MACE, hospitalizations, and death .
Finally, in order to evaluate the possible influence of environmental and social factors on hormones’ trend across years, we used in-house python code to look up such data for the geographic region and year of each sampled study (data obtained as described above). Data analysis first provide a qualitative and quantitative description of data collected. Moreover, aggregated data for other variables extracted were added as mean and SD for each study, when available. For each study, the number of subjects enrolled was reported, together with the years in which the blood samples were collected for hormone measurement. The data from individual studies were synthesised considering the aggregated data extracted as means and SD after conversion to the same unit of measurement (i.e. nmol/L). After data extraction, an additional round of data editing and quality control of all studies was conducted by D.S. A team of four reviewers performed the data extraction from the final pool of selected studies (C.F., V.G., D.S., and G.S.).
We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and CENTRAL), clinical trial registries, and contacted clinical experts. Searches were restricted to reports published in English from 1992. Risk of bias was judged to be low in most IPD studies (71%). The risk of bias was assessed using the Cochrane Risk of Bias tool. Their authorization to release this information does not imply endorsement of this study or its findings by either the prescription monitoring program or the Department of Health and Environmental Control. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. The Maryland PDMP data provided is considered preliminary and subject to change, pending finalization of PDMP data by data owners.