Inhibition of 5α-reductase alters pregnane metabolism in the late pregnant mare.

The research studies the effects of the 5α-reductase inhibitor, dutasteride, on the metabolism of pregnane, a group of hormones, during late pregnancy in mares. The study found that dutasteride increases progesterone concentration but does not significantly affect other hormones or gestational parameters.

Objective of the Study and Methodologies Used

• The primary aim of this research was to study the impact of a 5α-reductase inhibitor, dutasteride, on pregnane metabolism. This includes pregnenolone, progesterone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol, and allopregnanolone.
• The secondary objectives of this study were to measure circulating dutasteride concentrations and examine the effects of dutasteride treatment on certain gestational parameters.
• The researchers studied five pregnant mares that received dutasteride and four control mares that received a placebo from day 300 to 320 of their gestation or until they gave birth.
• They evaluated the concentrations of dutasteride, pregnenolone, progesterone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol, and allopregnanolone through liquid chromatography-tandem mass spectrometry.
• They analysed the data both as the number of days post-treatment and the number of days before parturition.

Findings of the Study

• No significant effects were detected in pregnenolone, 5α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, 5α-pregnane-3β,20α-diol or allopregnanolone for either of the analyses.
• However, progesterone concentrations increased sixfold in mares treated with dutasteride as compared to the control mares.
• Treated mares showed increased dutasteride concentrations, with a significant correlation between dutasteride concentrations and concentrations of pregnenolone or progesterone.
• The gestational length and neonatal outcomes were not significantly changed in the mares treated with dutasteride.

Impact and Conclusion

• Even though 5α-reduced metabolites were unchanged, the data suggest an accumulation of precursor progesterone with the inhibition of 5α-reductase.
• This indicates that dutasteride has the potential to alter progesterone metabolism. Altered progesterone metabolism has the ability to influence pregnancy maintenance or fetal quiescence in mares.
• Despite the apparent increase in progesterone levels, the study didn’t find any significant alteration in the gestational parameters or neonatal outcomes. This suggests that increased levels of progesterone do not necessarily impact the gestation period or neonatal health.