The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason G

[Grammaton Cleric]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/

 

[bushbush]

A nice review that anyone considering (or already) taking finasteride should read.

 

[Ptrt]

Nothing new.

 

[JZA70]

Nothing new.

Nope.

 

[cthulhu2.0]

I'm a finasteride user and although this information is useful, I do not find it all that convincing to make me quit he drug. So I've been taking finasteride for over 3 months now with very good results in terms of hair regrowth. I started out taking .5mg but then dropped my dose to .25mg because of some mild physical fatigue, which seemed to go away once I dropped the dose. My concern with many of these studies is that they are not well controlled. I have not seen a well controlled study with finasteride users, demonstrating which percentage of those users experienced persistent side effects compared to those who didn't and to those who acted as controls. It would also be interesting to see a study that comparing brain levels of neurosteroids for people taking lower doses of finasteride like in my case to people taking the normal dose of 1mg and the side effect profile for the different doses. Since I haven't really had any side effects besides the physical fatigue that seemed to diminish after dropping the dose, I see no reason to quit the drug unless something better comes along, perhaps cb in a few years.

 

[JZA70]

It would also be interesting to see a study that comparing brain levels of neurosteroids for people taking lower doses of finasteride like in my case to people taking the normal dose of 1mg and the side effect profile for the different doses.

0.2mg inhibits nearly the same amount of DHT as 5mg.

 

[cthulhu2.0]

[h=1]Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone.[/h]Vaughan C1, Goldstein FC, Tenover JL.
[h=3]Author information[/h]

[h=3]Abstract[/h]Testosterone (T) levels decline as men age, but it is unclear whether this has an effect on cognition. Some studies indicate that lower T levels are associated with memory loss; thus, maintaining a higher T level could have positive effects on aspects of cognitive function. Concerns exist, however, about the effect of T therapy on the prostate in older men. We hypothesized that T replacement in older men with low T levels would improve aspects of cognitive function and that the addition of finasteride would not affect the T-induced cognitive improvements. Healthy men, 65 to 83 years of age, with baseline total T below 350 ng/dL and no evidence of cognitive impairment were randomly assigned to 1 of 3 regimens: 200 mg of T every 2 weeks by intramuscular injection with placebo pill daily (T-only), 200 mg of T every 2 weeks by intramuscular injection with 5 mg of finasteride daily (T+F), or placebo injections and pills (placebo). Sixty-nine men completed baseline cognitive testing; 65 completed at least 4 months, and 46 completed all 36 months of the study. Participants were given a battery of cognitive evaluations at baseline, 4 months, and 36 months, along with measurement of serum hormone levels. Serum total T, bioavailable T, and estradiol levels in the T-only and T+F groups significantly increased throughout the treatment period, whereas these hormone levels did not change in the placebo group. Only minimally significant differences were seen among the 3 groups in any evaluation of cognitive performance, either in the short-term (4 months) or the long-term (36 months) analysis. These results indicate that T replacement, whether given alone or in combination with finasteride, for 36 months in healthy older men without cognitive impairment at baseline has no clinically significant effect on tests of cognitive function. Further studies are warranted to determine whether hormone replacement in men with preexisting cognitive impairment is beneficial.

Well it doesn't appear that finasteride affects cognition by the above study, just a fleeting thought. I wonder why a small percentage get depressive and sexual side effects on the drug while the majority do not. Perhaps they already have very low levels of these neurosteroids?

 

[Armando Jose]

Other factor to take into account is the huge decline of pregnanolone 300%.
Also with Epieticholanolone, ups more than 600%.

 

[xRedStaRx]

0.2mg inhibits nearly the same amount of DHT as 5mg.

A little unfair comparison.

5 mg ED should inhibit more DHT than 0.2 mg, and thus more neurosteroids. Serum DHT is just a proxy for 5-AR II inhibition.

 

[JZA70]

A little unfair comparison.

5 mg ED should inhibit more DHT than 0.2 mg, and thus more neurosteroids.

That's why I said nearly the same amount of DHT, not the exact same.

Look what else is in the news today - https://uk.tv.yahoo.com/morning-hair-loss-pills-made-penis-shrink-111800904.html

 

[cthulhu2.0]

Other factor to take into account is the huge decline of pregnanolone 300%.
Also with Epieticholanolone, ups more than 600%.

What interests me the most is the variability with those two steroids. Epieticholanolone is inhibited at a lower quartile of 161 and at a high of 1106 while pregnanolone is inhibited at a low of 13 and a high of 876. This could explain why many experience significant side effects while others experience no side effects whatsoever.

And yes, steroid reduction may not align exactly with dht inhibition

 

[xRedStaRx]

That's why I said nearly the same amount of DHT, not the exact same.

That's not what I meant.

Serum DHT levels do not measure the level of inhibition of finasteride using different doses properly.

 

[cthulhu2.0]

At the end of the day, we have clinical trials of finasteride that included roughly 18,000 participants in total from the studies and found that roughly 2% more of people taking finasteride compared to placebo had sexual side effects. Many people blame finasteride for sexual disfunction but the reality is most men who take finasteride(45+) are prone to experience these symptoms anyway and are simply the product of aging. At the age of 50, you can't expect to have the same sex drive as someone who is 25.

 

[bushbush]

At the end of the day, we have clinical trials of finasteride that included roughly 18,000 participants in total from the studies and found that roughly 2% more of people taking finasteride compared to placebo had sexual side effects. Many people blame finasteride for sexual disfunction but the reality is most men who take finasteride(45+) are prone to experience these symptoms anyway and are simply the product of aging. At the age of 50, you can't expect to have the same sex drive as someone who is 25.

The placebo effect is a very real phenomenon, but it would be overly dismissive to say that it is solely responsible for what many men experience when taking this drug in the face of mounting evidence.

 

[Ventures]

That's not what I meant.

Serum DHT levels do not measure the level of inhibition of finasteride using different doses properly.

What do you want to say ? Serum DHT level doesn't represent level of 5-ard-II inhibition ? Because serum consists mostly of DHT type I, not II, and finasteride inhibits type II.

 

[xRedStaRx]

What do you want to say ? Serum DHT level doesn't represent level of 5-ard-II inhibition ? Because serum consists mostly of DHT type I, not II, and finasteride inhibits type II.

No.

Serum DHT levels mostly consist of Type II 5-AR. But serum DHT levels do not represent the percentage of inhibition based on the percentage drop in serum levels, because serum levels of DHT are excess waste, more or less, of tissue concentrations.

 

[isishearmyplea]

Other factor to take into account is the huge decline of pregnanolone 300%.
Also with Epieticholanolone, ups more than 600%.

300 % decline?? what do you reduce beyond 100% ?

 

[zzzzz]

No.

Serum DHT levels mostly consist of Type II 5-AR. But serum DHT levels do not represent the percentage of inhibition based on the percentage drop in serum levels, because serum levels of DHT are excess waste, more or less, of tissue concentrations.

Do you know the levels inhibition of tissue/scalp type 2 DHT in different meds and doses? For ex: .2mg vs 1mg finasteride, .5mg dutasteride

 

[isishearmyplea]

Do you know the levels inhibition of tissue/scalp type 2 DHT in different meds and doses? For ex: .2mg vs 1mg finasteride, .5mg dutasteride

+1

 

[IDW2BB]

At the end of the day, we have clinical trials of finasteride that included roughly 18,000 participants in total from the studies and found that roughly 2% more of people taking finasteride compared to placebo had sexual side effects. Many people blame finasteride for sexual disfunction but the reality is most men who take finasteride(45+) are prone to experience these symptoms anyway and are simply the product of aging. At the age of 50, you can't expect to have the same sex drive as someone who is 25.

Molecular difference in males taking finasteride:

Abstract
Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (Androgenetic Alopecia). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against Androgenetic Alopecia. Cases were 8 males (aged 29-43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23-49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.