(4) Decreased 17-hydroxy-pregnane levels after treatment with anti-MS drugs in FP indicate a decreasing trend of CYP17A1 activity, suggesting a weakening of one of the steps of the cortisol pathway and, together with the analysis for individual anti-MS drugs, a strengthening of the step toward immunomodulatory adrenal androgens.
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Progesterone and Its Metabolites As expected, P and its C21 Δ 4 metabolites strongly correlated with PMC but did not exhibit a pronounced trend in changes after anti-MS treatment.
For a total of 79 investigated steroids, a significant trend toward a decrease in their levels after treatment was found.
The results from our previous study suggested an overall trend toward impaired adrenal activity in patients, which may affect the synthesis of most steroids (including active steroid hormones and neuroactive, neuroprotective, and immunoprotective steroids) found downstream in the metabolic pathway [ 33 ].
Concerning our current data, although the levels of 7α/β- and 16α-hydroxy-steroids did not show a significant trend toward changes after treatment with anti-MS drugs, the SMRs of 7α/β- and 16α-hydroxy-steroids to the parent steroids suggested a reduction in the activities of the enzymes catalyzing their synthesis (CYP7B1, CYP3A4, and CYP3A7) of borderline significance despite the low number of corresponding SMRs ( n = 8).
Also, the SMRs that may reflect the balance between reductive AKR1C1 on one hand and oxidative HSD17B2 enzymes showed a trend toward a shift to the latter one.