You must be one of the clowns from the bro forums that hold a grudge.....almost as bad as the manchild who lurks on here!
Let me put it plain and simple numbskull...the metabolites estradiol and DHT are needed in healthy amounts to experience the full spectrum of testosterones beneficial effects.
Mood, energy, libido, erectile function, cardiovascular/brain/bone/immune system health, body composition.
*Considerable evidence exists in the contemporary literature regarding the physiological role of 5a-reductases in the peripheral tissues and CNS and the pathophysiological implication of inhibiting this family of enzymes and blunting biosynthesis of neurosteroids, which are critical biological mediators in the CNS, and contribute to altered mood, cognition, and libido (23–50). Also, significant pre-clinical evidence exists demonstrating that inhibition of 5a-RIs contributes to erectile dysfunction (16–22) and may also contribute to neurological symptoms (Fig. 4 (36).
Let's dig a Lil deeper champ!
DISCUSSION
Until recently, the adverse effects of finasteride and dutasteride therapy on sexual function were not recognized or well understood. However, a body of emerging evidence suggests that the assessment of sexual side effects of finasteride in many clinical studies was not accurately captured or reported (83). In addition, considerable bias and inaccuracies in reporting adverse effects of finasteride or dutasteride in most clinical trials of men AGA (83). An editorial following the report by Belknap (83) highlighted the need to re-think the safety of these drugs (188).
It is not surprising that almost all studies published to date do report increased sexual adverse effects. However, even when such sexual adverse events were reported, many argued that the numbers of subjects afflicted are small and propagated the falsehood that the adverse effects do resolve with continued treatment. This is unfortunately willful blindness and a deceptive method to continue to prescribe these drugs to unsuspecting young men. The number of subjects experiencing adverse events is neither small nor irrelevant, given the persistent nature of adverse events in susceptible individuals. For those individuals afflicted, this constitutes a life sentence of sexual dysfunction, depression, and/or anxiety. To put this in perspective, approximately 30 million young men, worldwide, would be prescribed finasteride or dutasteride treat male pattern hair loss. Even if the incidence of persistent sexual adverse events is 3% to 5%, which may be viewed as a small number, approximately 900,000 to 1.5 million men would suffer persistent sexual and psychiatric adverse events. By no means this would be considered a small number and should not be dismissed or ignored.
The key argument raised by many clinicians remains: What is the level of evidence supporting the persistent nature of the sexual adverse effects and psychological symptoms caused by finasteride?
Considerable evidence exists in the contemporary literature regarding the physiological role of 5a-reductases in the peripheral tissues and CNS and the pathophysiological implication of inhibiting this family of enzymes and blunting biosynthesis of neurosteroids, which are critical biological mediators in the CNS, and contribute to altered mood, cognition, and libido (23–50). Also, significant pre-clinical evidence exists demonstrating that inhibition of 5a-RIs contributes to erectile dysfunction (16–22) and may also contribute to neurological symptoms (Fig. 4 (36).
*Data from several studies as well as from the manufacturer own reporting that some adverse events do not resolve and may persist. A number of studies discussed in this review demonstrated that not all adverse events resolve with drug discontinuation and in some cases, they persist or become irreversible (8,12, 13, 52–54, 83, 84, 88, 67, 68, 115, 127, 129, 130, 170, 186–189). For these reasons, we find the argument that sexual adverse events resolve with continued treatment is outright inaccurate and, at best, deceptive.
The increased reporting of and documentation of persistent side effects in the clinical literature resulted in warnings by the Medicine Health Care Products Regulatory Agency (MHRA) public assessment report on the risk of finasteride published in December of 2009 in Section 4.8 Undesirable Effects, it was stated, ‘‘In addition, the following have been reported in post-marketing use: persistence of ED after discontinuation of treatment with PROPECIA.’’ Clearly, the sexual adverse events do not necessarily resolve completely in all patients, who discontinue use of finasteride, again supporting the premise that in some patients these sexual side effects remain ‘‘persistent.’’ Furthermore, in December 2008, the Swedish Medical Products Agency concluded its safety investigation of Propecia. The Agency's updated safety information now lists as a possible side-effect difficulty in obtaining an erection that persists even after discontinuing Propecia. In addition, in 2011, the USA FDA mandated that labeling of finasteride includes information about potential risks of depression as well as sexual dysfunction and problems and high-grade prostate cancer. In 2017, the European Medical Agency recommended adding depression and suicidal ideation to the finasteride label.
One other argument consistently made in the literature is that the low-quality evidence available does not support a causal link between finasteride and persistent symptoms. Examining the contemporary clinical literature, it appears that almost all studies published to date (Tables 1–3) demonstrated the increased onset of sexual dysfunction and psychiatric dysfunction, irrespective of the assessment method, age, or drug dose. How could such evidence be totally ignored and dismissed as low-quality evidence? Given that considerable level of bias is introduced in many of these studies since a large number of these clinical trials were funded and administered by the drug manufacturers, it is paramount that clinicians do their due diligence and not fall for the slogan, ‘‘these drugs are well-tolerated and safe.’’
It is imperative that we consider how safety reporting of adverse events due to finasteride and dutasteride have been inadequate in most clinical trials (83, 84). Indeed, this inaccurate reporting of harm makes the evidence regarding the adverse events to be limited and may appear of poor quality. Given the level of bias due to conflict of interest, it is not surprising that the level of harm is tampered down significantly. Well-trained and experienced clinicians may see the coexistence of adverse events as a distinct syndrome with its own pathogenesis rather than a simple random or haphazard co-occurrence. Despite the lack of final proofs, the presence of severe and persistent side effects induced by these drugs raises serious concerns for clinicians. Simply, a low estimated prevalence of PFS should not be used as an excuse for non-vigilance, given that these drugs are prescribed for millions of relatively young healthy men.
