"5α-REDUCTASES IN HUMAN PHYSIOLOGY: AN UNFOLDING STORY"
While the clinical use of 5α-reductases inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs especially on the central nervous systems is still unrecognized, due to lack of knowledge of the various physiological function of this family of enzymes, especially in the central nervous system.
There is an urgent need to better understand the function of 5α -reductases and the role of neuro-active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α-reductases to treat BPH and AGA.
new information suggests that these drugs may impair sexual function including sexual desire, erectile and orgasmic function [Table 3](for review cf. 83, 84). Recent studies in animal models suggested that these agents alter penile tissue histo-architecture and nitric oxide synthase function in penile tissue and thus can contribute to erectile dysfunction
It is particularly important to note that in a subset of patients, the effects of these drugs are long lasting and may be irreversible (84). An association between use of these inhibitors and depression is also noted (88), suggesting potential adverse effect on the brain.
A number of case reports have suggested that 5α-reductase inhibitors therapy is associated with angioedema ( 91); cataract and intraoperative floppy-iris syndrome (92), pseudoporphyria, (93),T cell–mediated acute localized exanthematous pustulosis (94) and gyncomastia and male breast cancer
The recent introduced warnings on the drug labeling also suggests that increased awareness of the potential irreversible side effects of these agents
"DEPRESSIVE SYMPTOMS AND SUICIDAL THOUGHTS AMONG FORMER USERS OF FINASTERIDE WITH PERSISTENT SEXUAL SIDE EFFECTS"AGOSTO 2012
Pharmacovigilance is the science relating to identifying, monitoring, and effectively reducing adverse drug reactions. When a drug comes to market, it is often studied in only a thousand patients or less, as in the case of finasteride. 1,2 Less common adverse effects of a medication may be uncovered only in the postmarketing phase after many thousands of patients have been exposed to the medication.
In April 2012, the US Food and Drug Administration announced changes to the professional labels for Propecia (finasteride 1 mg) to expand the list of persistent sexual adverse events reported.8 ... In December 2010, the product labeling for Propecia in the United States was updated to include the side effect of depression.
In a group of 61 otherwise healthy former users of finasteride who developed persistent sexual side effects, depressive symptoms were present and categorized as mild in 11% of users, moderate in 28% of users, and severe in 36% of users. Suicidal thoughts were present in 39% of former finasteride users, and an additional 5% chose the statement “I would like to kill myself.”
The corresponding rates of depressive symptoms and suicidal thoughts were significantly lower in a control group of young men with male pattern hair loss who had not used finasteride and who did not have any current or past psychiatric conditions or use of psychiatric medications.
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 and that are also transported to the brain from the gonads and adrenal glands.
It turns out that finasteride crosses the blood-brain barrier and blocks the enzyme 5α-reductase, which reduces the concentrations of multiple neuroactive steroids derived not only from testosterone, but also from progesterone and deoxycorticosterone.... reduced concentrations of neuroactive steroids are associated with depression in several human 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. This is the first study to document suicidal thoughts in (former) users of finasteride.
Come possiamo vedere in questi stralci, la ricerca in questi ultimi mesi si sta impegnando a fondo nel cercare di definire tutti le implicazioni patologiche dell'uso di inibitori della 5α-reduttasi.
Purtroppo per ora l'eziologia della sindrome rimane ancora un mistero.
Tuttavia, nuovi studi che sono all'orizzonte promettono di fornire al più presto importanti informazioni.