Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients
Melcangi et al., 2017
“finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.”
Melcangi et al. Performed case-controlled clinical evaluations of 16 PFS patients aged 22-44 with a strong focus on the neurological component of the syndrome. He determined important physiological findings of altered neuroactive steroid levels as well as markers of pudendal neuropathy.
Mean treatment duration was 1037 days with a range of 451–4697 days between cessation of finasteride and clinical evaluation. 50% of PFS patients were deemed to suffer from major depressive disorder per screening with the Mini-International Neuropsychiatric Interview. Scores of Beck Depression Inventory and Beck Anxiety Inventory were significantly higher in those with MDD.
Ten patients experienced severe erectile dysfunction per the IIEF15 evaluation, while the remaining 6 exhibited mild to moderate erectile dysfunction. Ultrasound determination of testicular volume was calculated to be normal in patients.
Objective markers of neuropathy were identified in 25% of patients via sensory evoked potentials of the pudendal nerve. No evidence of metabolic, toxic, or inherited disease that could account for peripheral nervous system damage was detected.
Interestingly, depression results were not related to the severity of erectile dysfunction. Rather, severity of sexual dysfunction correlated to abnormal PN_SEP measurements.
The cerebrospinal fluid of 14 patients was analysed with comparison to 25 healthy age-matched controls. Significant differences were determined. Pregnenolone, isopregnanolone, progesterone and dihydroprogesterone were significantly decreased, while levels of dehydroepiandrosterone (DHEA), testosterone and 3α-diol were increased. Additionally, 17β-estradiol and DHT were decreased.
Plasma determination showed differences to the CSF findings. In serum, pregnenolone, tetrahydroprogesterone, DHEA and T were significantly increased, while dihydroprogesterone was significantly decreased.
The authors conclude that this disruption in neuroactive steroids adds a piece of information regarding the condition, but there is yet to be a clear demonstration of the pathogenic mechanism underlying PFS.
