Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro and in vivo evidence.

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Toxicology of arsenate, arsenite, cadmium, lead, chromium, and nickel in testes of adult Swiss mice after chronic exposure by intraperitoneal route.

BACKGROUND: Some residues such as the heavy metals cadmium (Cd), lead (Pb), chromium (Cr VI), nickel (Ni), and arsenic (As), this last one in its oxidized forms + 5 (arsenate) and + 3 (arsenite), can cause injuries to human health, so they are currently considered environmental health emergencies. In the testis, heavy metals can cause morphological and functional damage due to constant exposure acting chronically in individuals. Thus, we aimed to determine the toxicological mechanism of As+5, As+3, Cd, Cr VI, and Ni that leads to testicular damage and establish for the first time an order of toxicity among these studied heavy metals. METHODS: Forty-two Swiss mice at reproductive age (140 days) were used, randomly distributed into seven experimental groups (n = 6). Exposure to heavy metals was weekly performed, by intraperitoneal route. Group 1 received 0.7 mL 0.9% saline (control), and the other groups received 1.5 mg/ kg of As+5, As+3, Cd, Pb, Cr VI, or Ni, for six weeks. RESULTS: These studied heavy metals did not accumulate in the testis tissue. However, exposure to Ni induced moderate pathologies in the seminiferous tubules, plus changes in the tunica propria, blood vessels, lymphatic space, and carbonyl protein levels. Cd exposure caused moderate tubular histopathologies and changes in the blood vessels and lymphatic space. Cr VI induced slight tubular histopathologies, changes in the lymphatic space, blood vessels, and SOD activity. Pb and As+3 exposure triggered moderate tubular pathologies and changes in the SOD activity and carbonyl protein levels, respectively. Finally, As+5 induced only slight tubular pathologies. CONCLUSION: The testicular histopathologies caused by the studied heavy metals are mainly triggered by changes in testicular oxidative balance. Based on our findings of histomorphological alterations, the toxicity order among the heavy metals is Ni>Cd>Cr(VI)>PbAs+3 >As+5. However, considering oxidative stress results, we propose the following testicular toxicity order for these heavy metals: Ni>As+3 > Cd>Cr(VI)>Pb>As+5. Ni exposure shows the most harmful among the heavy metals to the testis.