LACK OF FOLYLPOLYGLUTAMATE SYNTHETASE ACTIVITY AND METHOTREXATE POLYGLUTAMYLATION AS UNDERLYING MECHANISMS EXPLAINING WHY METHOTREXATE DOES NOT IMPAIR SPERM QUALITY.
Authors: L. F. Perez-Garcia et al.
The safety of methotrexate (MTX) in male patients is debated. These authors measured the bioactive form of MTX, MTX-polyglutamate (MTX-PG), which was detectable in the semen in male patients taking MTX. They found that MTX-PG accumulation in spermatozoa was markedly lower than in blood cells for example. Indeed, hardly any bioactive forms of MTX (MTX-PG) was detected in spermatozoa. This appears to be due to a lack of FPGS activity in spematozoa, the enzyme that transforms MTX in its bioactive form (MTX-PG).
Currently the Swiss compendium still recommends using a long wash out period for men on MTX wanting to become father, although several studies have already established that MTX does not increase sperm DNA damage. These results support that MTX can be safely prescribed to men who wish to become a father. Interestingly this seems to be due to the fact that spermatozoa are not transforming MTX into its bioactive form.