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7β-hydroxy-epiandrosterone (7β-OH-EpiA) is an endogenous androgen metabolite that has been shown to exert neuroprotective, anti-inflammatory and anti-estrogenic effects. However, to the best of our knowledge no information is available about this androgen steroid in relation to sperm quality. We analyzed 7β-OH-EpiA in plasma and seminal plasma using a newly developed isotope dilution ultra-high performance liquid chromatography – mass spectrometry method. Validation met the requirements of FDA guidelines. Levels of 7β-OH-EpiA were measured in 191 men with different degrees of infertility. One-way analysis of variance followed by multiple comparison and correlation analysis adjusted for age, BMI and abstinence time were performed to evaluate the relationships between this steroid and sperm quality. Concentrations of 7β-OH-EpiA in seminal plasma were significantly higher in severely infertile men in comparison with healthy men and slightly infertile men. The same trend was found when blood plasma was evaluated. Furthermore, plasma 7β-OH-EpiA negatively correlated with sperm concentration (-0.215; p<0.01) and total count (-0.15; p<0.05). Seminal 7β-OH-EpiA was negatively associated with motility (-0.26; p<0.01), progressively motile spermatozoa (-0.233; p<0.01) and nonprogressively motile spermatozoa (-0.188; p<0.05). 7β-OH-EpiA is associated with lower sperm quality and deserves more research in that respect.

In order to develop an immunoassay of 7β-hydroxy-epiandrosterone, a stereoselective synthesis of a specific hapten, 7β-hydroxy-19-oxo-androstan 19-(O-carboxymethyl)oxime (17), was performed. This synthesis was achieved in 16% overall yield starting from the well-known 3β-acetoxy-19-hydroxy-5-androsten-17-one (1). After coupling of the alkyl oxime moiety, an allylic oxidation of the C-7 carbon under mild conditions followed by two selective reductions established all the functionalities of the final compound 17.