Less than 1 yr to almost 14 yrs after finasteride discontinuation, symptoms both psychological and levels in the brain and blood persist.
J Steroid Biochem Mol Biol. 2015 Feb;146:74-9.
"Patients also developed depression during finasteride treatment [10] and [11] that still persisted despite treatment withdrawal [12]. Depression after finasteride treatment might be due to impairment in the levels of neuroactive steroids. This steroid family, which includes both steroid hormones produced in peripheral glands and steroids directly synthesized in the nervous system (i.e., neurosteroids), has an important role in the control of nervous function, affecting mood, behavior, reproduction and cognition, as well as being protective agents in models of injury and neurodegenerative diseases [13], [14], [15] and [16]. Indeed, finasteride is not only able to block 5α-reductase (5α-R) enzyme, which converts testosterone (T) into dihydrotestosterone (DHT), but also the conversion of progesterone (PROG) into dihydroprogesterone (DHP) [16]. In this context, it is also important to highlight that these neuroactive steroids are then converted by the action of the 3α- or 3β-hydroxysteroid dehydrogenase into 5α-androstane-3α,17β-diol (3α-diol) or 5α-androstane-3β,17β diol (3β-diol) in case of DHT and into tetrahydroprogesterone (THP), also known as allopregnanolone, or into isopregnanolone in case of DHP [16]. It is interesting to note that THP, as well as the 3α-diol (i.e., a metabolite of DHT), are known as ligands of GABA-A receptor [17]. Moreover, isopregnanolone does not bind directly to the GABA-A receptor [18], but it antagonizes the effect of THP on the GABA-A receptor [19] and [20]. Changes in GABA as well as in neuroactive steroid levels in plasma and cerebrospinal fluid (CSF) are associated with depression in several human studies [21]."
"Interestingly, our recent preliminary observations obtained in three male patients who received finasteride for the treatment of androgenic alopecia and that after drug discontinuation still had long-term sexual side effects as well as anxious/depressive symptomatology showed altered neuroactive steroid levels in plasma and CSF vs. those assessed in 5 healthy patients [22]. A further link with neuroactive steroids may be supported by recent observations. Indeed, as reported in a subset of post-finasteride patients with persistent symptomatology, a decline in their alcohol consumption was also observed [23]. This is very interesting, because a relationship between GABAergic neuroactive steroids and ethanol consumption is well documented [24]."
"Mean age of these patients was 38 years old; mean of treatment duration was 727 days. The interval between finasteride withdrawal and CSF sampling was very wide (range 171–5000 days, median 1635 days). "
"Although the severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. The most frequently reported symptoms were: reduction in self-confidence, decreased initiative and difficulty in concentration (71%), forgetfulness or loss of short-term memory (43%), irritability or easily flying into a rage (57%), depression and feelings of worthlessness (86%), suicidal thoughts (14%), anxiety (57%) panic attacks (14%) and sleep problems (86%)."
"Furthermore, all these patients reported at the moment of clinical and laboratory assessment muscular stiffness and cramps (43%), tremors (57%), chronic fatigue (86%) as well as joint pain and muscular ache (86%) in the absence of clinical evidence of any muscular disorder or strength reduction. It is important to highlight that, with the exception of sleep problems already reported by two patients, all these symptoms were not present before treatment with finasteride"
"Indeed, DHP, THP and isopregnanolone were significantly decreased in CSF of post-finasteride patients with levels under detection limit. DHP and THP were also significantly decreased in plasma, with the levels of THP that were under detection limit."
"on the contrary, both in CSF and plasma of post-finasteride patients the levels of T were significantly increased. While the levels of the first metabolite of T, DHT, were significantly decreased in CSF but unchanged in plasma"
"Levels of 17β-E were significantly increased in plasma and unchanged in CSF."
