Quote from: Paige on April 08, 2016, 06:20:17 PM
Allopregnanolone production seems to continue to be blocked after cessation? Is that in all or just some of the people who discontinued finasteride?
Yes, it continues to remain low in brain and in plasma. In some people.
QuoteIt didn't seem to suggest the DHT would continue to be blocked after cessation? I wonder what the difference is?
DHT remained low in brain but not in plasma.
More details...
J Steroid Biochem Mol Biol. 2015 Feb;146:74-9."Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3α-diol was detected. Changes in neuroactive steroid levels also occurred in plasma."
"The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment."
From full study:
"The seven post-finasteride patients we have considered in our study had taken (...). 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)."
"The levels of neuroactive steroids in CSF and plasma of the seven post-finasteride patients were compared with those of twelve male, age-matched healthy controls. In comparison to the healthy controls, the post-finasteride patients presented a quite different neuroactive steroid pattern both in CSF and in plasma."
"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."
THP is also called allopregnanolone.
"While the levels of the first metabolite of T, DHT, were significantly decreased in CSF but unchanged in plasma"
"The present results show that persistent sexual side effects as well as anxious/depressive symptoms are associated with changes of neuroactive steroid levels in CSF and plasma of seven male patients with male pattern hair loss despite discontinuation of finasteride. These results extend our previous preliminary observations that were obtained comparing three post-finasteride patients vs. five control subjects [22]."
"In our preliminary observations we observed a decrease of metabolites of PROG and T, such as THP, isopregnanolone and DHT, associated with an increase of T and 17β-E in CSF. "
"Observations here presented show in CSF a decrease of metabolites of PROG, such as DHP and THP, as well as of PROG itself."
"Indeed, a significant decrease of DHT associated with an increase of T as well as of 3α-diol was detected."
"The few observations so far present in the literature have mainly focused the attention on the role of 3α-reduced metabolites of PROG and particularly of THP in anxious/depressive symptomatology."
"A relationship between T levels and depression has also been demonstrated [32]. Indeed, young hypogonadal as well as aged men, showing decreased levels of T, exhibit a high prevalence of anxiety disorders and major depressive disorder [33], [34], [35] and [36]. In our study, we observed an increase in the CSF and plasma levels of T. However, the active metabolite of T, DHT was significantly decreased in CSF of post-finasteride patients. Indeed, finasteride blocks the conversion of T into DHT [37], which is able, in comparison to T, to interact with the androgen receptor with a higher affinity [16]."
"Recently, it has been demonstrated that treatment with finasteride induces a decreased of DHT levels in brain of mice associated with a decrease of hippocampal neurogenesis [39] and [40]. Interestingly, adult neurogenesis has been related to depression [41]. Indeed, depressed patients show a reduced hippocampal volume related with a reduced dendritic complexity, decreased neuronal soma size, as well as reduced hippocampal neurogenesis [42] and [43]. In this context it is important to highlight that GABA has crucial roles in regulating different steps of adult neurogenesis, including proliferation of neural progenitors, migration and differentiation of neuroblasts, and synaptic integration of newborn neurons [44]. As here demonstrated the levels of PROG and T, and particularly those of their metabolites which, like for instance THP and 3α-diol are also to modulate GABA transmission through GABA-A receptors [17], are affected in post-finasteride patients and reported to modulate adult neurogenesis [41] and [45]."
"Indeed, as here demonstrated, after discontinuation of the finasteride treatment a subset of patients that was treated for male pattern hair loss show sexual dysfunction as well as anxious/depressive symptomatology associated with altered levels of PREG, PROG, DHP, THP T, DHT and 3α-diol in CSF and of PREG, DHP, THP, T, 3α-diol, 3β-diol and 17β-E in plasma."
J Clin Psychiatry. 2012 Sep;73(9):1220-3."Rates of depressive symptoms (BDI-II score ≥ 14) were significantly higher in the former finasteride users (75%; 46/61) as compared to the controls (10%; 3/29) (P < .0001). Moderate or severe depressive symptoms (BDI-II score ≥ 20) were present in 64% (39/61) of the finasteride group and 0% of the controls. Suicidal thoughts were present in 44% (27/61) of the former finasteride users and in 3% (1/29) of the controls (P < .0001)."
"A plausible biological mechanism to explain the association between finasteride and depression lies with neuroactive steroids, neuromodulators that are synthesized in the central nervous system itself"
"Reduced concentrations of neuroactive steroids are associated with depression in several human studies. Depressed adults have lower concentrations of allopregnanolone in their cerebrospinal fluid as compared to nondepressed subjects.22 Similarly, serum levels of allopregnanolone were lower in men with a first episode of unipolar major depressive disorder as compared to a control group.23 Even women who had been in remission from depression for several years had lower serum levels of 4 progesterone-derived GABAergic neuroactive steroids as compared to controls.24"
"Interventional studies in rodents provide further support for the links among finasteride, neuroactive steroids, and depression. Administering finasteride into the amygdalae of rats attenuated antianxiety and antidepressive behavior.25 Systemic and intrahippocampal finasteride had the same effect on anxiolytic and depressive behaviors as assessed through the forced swim test, open field test, and elevated plus maze test.26,27 Likewise, rats that received finasteride had lower levels of plasma and hippocampal allopregnanolone and increased depression as measured with the forced swim test.28"
"While sexual dysfunction may lead to depression, another independent and plausible hypothesis is that finasteride lowers the concentrations of neuroactive steroids linked to depression, which has been demonstrated in both human and rodent studies. Although the effects of finasteride in the human brain are poorly understood, clinicians, as well as potential finasteride users, should be aware of the serious potential risks of this medication, especially as it is being used cosmetically to alter a normal age-related process."
In another study, men without sexual dysfunction problems and women also reported depression.
