New Study: Long Term Dutasteride Is Associated With Metabolic Alterations

[NSix]

Michael, what's the purpose of loading dutasteride?

Have you had any bloodwork done to see what your hormone levels are as well as your cholesterol? Ty

 

[Michael1986]

Michael, what's the purpose of loading dutasteride?

Have you had any bloodwork done to see what your hormone levels are as well as your cholesterol? Ty

Dutasteride takes a long time to build up in your system because it has a long half-life of five weeks. By starting out with a loading dose, you are enabling it to build up your system and to begin potently inhibiting your DHT much more quickly than if you were not to start with a loading dose.

I've not had any bloodwork done. I don't see the necessity of it, at least in my case.

 

[Stating facts]

Good for you if you are taking it for more than 5 years without sides. For me it brought unnecessary weight gain, difficulty in organizing my thoughts, ED, and way longer to get aroused. I started it in my early 20's, continued it for 2 years and stopped due to migrating into a different country where it was not prescribed for hair loss.

I have no doubt that it works but between those 2 years on duta, I never got morning wood. Also no strong erections which I get now, and before starting duta.

 

[stejames]

20+ on finasteride. started losing effectivness 1+yrs ago. Starting incorporating dutasteride
1st 4 months - 1 .5Dut + 6 Fins - shed for 6 weeks no regrowth/or results still probably slowly lost
2nd 4 months - 2 .5 duts + 5 finasteride - no shed but no regrowth
Last 2 months - 3 duts and starting to wean off finasteride. too soon to tell IMP if upped dosage helps.

My derm thinks 3-4 a week is all you need. wont max intake (7 days or even 5days)

 

[Feelsbadman.jpg]

Just bumping this thread for an update. I've been on dutasteride for 3 years now. No side effects that I'm aware of. I had lab tests and liver enzymes were fine, fasting blood sugar was ok despite being sedentary and poor diet at the time. The only risk with 5AR inhibitors in my opinion is the reduced glucocorticoid clearance. I don't believe the absence of DHT causes any negatives, only positives.

To reduce glucocorticoid exposure while taking a 5AR inhibitor, I think it is important to inhibit 11 beta HSD1 as this enzyme is really the only reason I think 5AR would be needed to metabolize cortisol. Ideally, we would have a drug that inhibits this in a proportional manner to the reduction in 5AR1 (and possibly 5beta-reductase) but no such drugs exist to my knowledge. EGCG is a natural compound that is a competitive inhibitor of 11 beta HSD1 and is cheap and easily obtainable. I would recommend taking the daily equivalent of drinking 5 cups of green tea. I would not recommend using green tea or green tea extract as the other catechins have less desirable effects (antagonize thyroid, increase 5ar).

 

[losingbattle88]

Just bumping this thread for an update. I've been on dutasteride for 3 years now. No side effects that I'm aware of. I had lab tests and liver enzymes were fine, fasting blood sugar was ok despite being sedentary and poor diet at the time. The only risk with 5AR inhibitors in my opinion is the reduced glucocorticoid clearance. I don't believe the absence of DHT causes any negatives, only positives.

To reduce glucocorticoid exposure while taking a 5AR inhibitor, I think it is important to inhibit 11 beta HSD1 as this enzyme is really the only reason I think 5AR would be needed to metabolize cortisol. Ideally, we would have a drug that inhibits this in a proportional manner to the reduction in 5AR1 (and possibly 5beta-reductase) but no such drugs exist to my knowledge. EGCG is a natural compound that is a competitive inhibitor of 11 beta HSD1 and is cheap and easily obtainable. I would recommend taking the daily equivalent of drinking 5 cups of green tea. I would not recommend using green tea or green tea extract as the other catechins have less desirable effects (antagonize thyroid, increase 5ar).

Damn no sides? Christ. That sh*t made me produce 1 drop of semen. And worsened my hair.

 

[Feelsbadman.jpg]

Damn no sides? Christ. That sh*t made me produce 1 drop of semen. And worsened my hair.

No, only benefits. I was on finasteride for 4 years prior though. I initially had watery semen on finasteride but it went away over time. That is what the studies seem to show. Any legitimate side effects that do appear tend to decrease over time on 5ARIs.

 

[losingbattle88]

No, only benefits. I was on finasteride for 4 years prior though. I initially had watery semen on finasteride but it went away over time. That is what the studies seem to show. Any legitimate side effects that do appear tend to decrease over time on 5ARIs.

No, only benefits. I was on finasteride for 4 years prior though. I initially had watery semen on finasteride but it went away over time. That is what the studies seem to show. Any legitimate side effects that do appear tend to decrease over time on 5ARIs.

Why u quit finasteride after 4 years? Dutasteride made my semen super thick. But reduced my semen like mad and no force upon ejaculation.

 

[darsith]

Why u quit finasteride after 4 years? Dutasteride made my semen super thick. But reduced my semen like mad and no force upon ejaculation.

I got a solution, eat raw meat, raw woa liver , raw cow calf heart, it will boost your hormones .
That is what I do, I still consume carbs but moslty meat.

 

[losingbattle88]

I got a solution, eat raw meat, raw woa liver , raw cow calf heart, it will boost your hormones .
That is what I do, I still consume but moslty meat.

Tbh dutasteride made hair worse after 1.5 years anyway. Doing better after dropping it and starting finasteride. It boost testosterone too much in me. I felt like the hulk on it.

 

[norwood_spotter]

Just bumping this thread for an update. I've been on dutasteride for 3 years now. No side effects that I'm aware of. I had lab tests and liver enzymes were fine, fasting blood sugar was ok despite being sedentary and poor diet at the time. The only risk with 5AR inhibitors in my opinion is the reduced glucocorticoid clearance. I don't believe the absence of DHT causes any negatives, only positives.

To reduce glucocorticoid exposure while taking a 5AR inhibitor, I think it is important to inhibit 11 beta HSD1 as this enzyme is really the only reason I think 5AR would be needed to metabolize cortisol. Ideally, we would have a drug that inhibits this in a proportional manner to the reduction in 5AR1 (and possibly 5beta-reductase) but no such drugs exist to my knowledge. EGCG is a natural compound that is a competitive inhibitor of 11 beta HSD1 and is cheap and easily obtainable. I would recommend taking the daily equivalent of drinking 5 cups of green tea. I would not recommend using green tea or green tea extract as the other catechins have less desirable effects (antagonize thyroid, increase 5ar).

can you elaborate on egcg a bit? i never read about this in regard to finasteride anywhere else

 

[norwood_spotter]

bump for egcg

 

[Feelsbadman.jpg]

can you elaborate on egcg a bit? i never read about this in regard to finasteride anywhere else

Well this whole thread is talking about the potential increased risk for diabetes and NAFLD from finasteride/dutasteride. There are multiple studies in the thread that hint at this and some that contradict. From my understanding, this increased risk is due to peripheral tissues having increased exposure to glucocorticoids due to 5AR and 5BR inhibition as these enzymes can metabolize and deactivate cortisol (though they are not the only enzymes that do this). To mitigate this, you would want to inhibit the 11 beta HSD1 enzyme as this enzyme converts inactive cortisone into active cortisol in peripheral tissue and high levels of 11 beta HSD1 would lead to increase glucocorticoid exposure.

With low 11 beta HSD1 activity, 5AR 5BR would not be needed at high levels. This is was demonstrated in a study that shows that losing weight lowers both 5AR1 and 11 beta HSD1. My conclusion is pretty straight forward. If you inhibit 5AR/5BR, you should also seek to inhibit/lower 11 beta HSD1 to preserve a non insulin resistant phenotype in peripheral tissues. EGCG is an 11 beta HSD1 inhibitor.

 

[Feelsbadman.jpg]

Name one function that DHT performs that is beneficial that can't also be performed by Testosterone.

 

[Feelsbadman.jpg]

Is Dihydrotestosterone a Classic Hormone?

In 1968, Brochovsky and Wilson (1, 2) published the first two papers describing dihydrotestosterone (DHT). Wilson and colleagues (3) subsequently demonstrated t

academic.oup.com

View attachment 181227

Wow way to cherry pick that quote and take the negation of it's actual meaning. Here is the full quote:

but the evidence is insufficient to conclude that DHT has clinically significant specific effects (that are unique to DHT vs testosterone) on a variety of outcomes and functions, including cardiovascular health, cognitive function, immune function, erythropoiesis, and glucose and lipid metabolism.

Also from your study:

As noted by the authors, it is not possible to examine the effects of DHT in isolation because of the interaction between testosterone, estradiol, and DHT. Administration of DHT results in suppression of testosterone and estradiol (via feedback on the hypothalamopituitary/gonadal axis), and suppression of endogenous DHT production also affects testosterone and estradiol production.

Way out of context and disingenuous on your part.

Some quick reading for you if you are interested.

DHT cardiovascular health. Sure.

Dihydrotestosterone—a culprit in left ventricular hypertrophy

Independent clinical studies have demonstrated a relationship between testosterone and cardiac mass with Hayward et al. being the first to report the idea that sex hormones are involved in cardiac hypertrophy [1]. There is clear evidence to suggest testosterone to induce cardiac hypertrophy and...

www.internationaljournalofcardiology.com

Cognitive Function. Not likely.

Androgens Induce Dopaminergic Neurotoxicity via Caspase-3-Dependent Activation of Protein Kinase Cδ

Aged men have a greater incidence of Parkinson’s disease (PD) than women. PD is a neurodegenerative condition associated with the loss of dopamine neurons in the nigrostriatal pathway. This study examined the neurotoxic effects of androgens in ...

www.ncbi.nlm.nih.gov

The 5α-reductase inhibitor Dutasteride but not Finasteride protects dopamine neurons in the MPTP mouse model of Parkinson's disease - PubMed

Finasteride and Dutasteride are 5α-reductase inhibitors used in the clinic to treat endocrine conditions and were recently found to modulate brain dopamine (DA) neurotransmission and motor behavior. We investigated if Finasteride and Dutasteride have a neuroprotective effect in...

pubmed.ncbi.nlm.nih.gov

There are studies showing a direct correlation with older men having high DHT and not having diabetes.

Testosterone, Dihydrotestosterone, Sex Hormone–Binding Globulin, and Incident Diabetes Among Older Men: The Cardiovascular Health Study

Although sex hormone–binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, in older adults, whose glycemic pathophysiology ...

www.ncbi.nlm.nih.gov

Among older men, higher levels of DHT were inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, whereas levels of T were not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.

But as the study concludes, this is most likely due to SHBG interaction. Older men have lower T and having high DHT will bind to SHBG creating more free testosterone. studies with T replacement therapy combined with dutasteride show increased insulin sensitivity.

 

[Feelsbadman.jpg]

Study from 2020:

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onlinelibrary.wiley.com

Dihydrotestosterone in Amyotrophic lateral sclerosis—The missing link?


Conclusions:


DHT is probably integral to survival of motor neurons. In patients predisposed to develop ALS, there is possibly a sort of “testosterone resistance” at level of blood–brain barrier [BBB] existing right from birth and is likely the result of dysfunctional transport protein involved in testosterone transfer across the BBB. In these patients, lesser amount of testosterone is able to breach the BBB and enter the central neural axis. Lesser amount of testosterone is available to 5 α reductase in the anterior pituitary to be converted to DHT and lesser amount of DHT is generated. There is inadequate negative feedback suppression of LH at the level of anterior pituitary by DHT. As a result of higher LH levels, testosterone levels rise in the peripheral testosterone fraction [the fraction outside the BBB] and this explains the various physical attributes of ALS patients like lower Ratio of the index and ring finger lengths (2D:4D ratio), increased incidence of early onset alopecia etc. This deficiency of DHT leads to motor neuron death causing ALS.

Amyotrophic lateral sclerosis is very rare. The authors are only hypothesizing DHT being integral because testosterone can't cross the blood brain barrier. This is an extremely small subset of the population. How is this even an argument?

For people who don't have ALS (almost everyone), DHT is not preferential over T as DHT will lead to faster apoptosis of dopamine neurons than T.

 

[Feelsbadman.jpg]

You're right about that pic, I had that from some twitter account. But still, insufficient doesn't mean DHT has no unique properties, And you left out this part too "Broadly speaking, the evidence suggests that DHT may directly modulate sexual function".

As the study says, we just don't know much about DHT but more and more evidence is coming out that it does have unique properties compared to testosterone.

I left it out because of what immediately follows it. Also, this from the same study:

administration of high-dosage DHT maintains most androgenic effects of exogenous testosterone in men with androgen insufficiency with the notable exception of libido and bone mineral density

Testosterone is responsible for libido. One way DHT might modulate it is by suppressing Testosterone.

 

[Feelsbadman.jpg]

Of course it matters, just because ALS is rare doesn't mean this new information is not important.

No this is a special case. From what I have briefly read, people with ALS have an abnormal transport protein which prevents T from crossing the blood brain barrier.

And 5ar inhibitors have an effect on many neurosteroids,

Right and this being shown to be beneficial.

In regards to allopregnanolone

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion ...

www.ncbi.nlm.nih.gov

I commented on this on the first page.

 

[Feelsbadman.jpg]

And estrogen is important for libido too in men, a balance of test, dht and estrogen are important for libido, they all interact with eachother. Balance is key, something the bodybuilding community has known for a long time.

The role of estradiol in male reproductive function - PubMed

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and...

pubmed.ncbi.nlm.nih.gov

The vast majority of men can take dutasteride, nuke their DHT, and still have their libido remain the same or better. The same can not be said for letrozole I don't think (although I don't know of any studies that tested this specifically). Testosterone and Estradiol have vital roles in the adult male. I don't believe DHT does and from what I've seen, most research agrees with this.

I believe androgenic stimulation has a pro-aging effect via mTOR activation and DHT is the most androgenic androgen with an androgenic to anabolic ratio of 5:1 where as Testosterone is 1:1.

DHT and mTOR

Antiandrogenic Therapy With Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction

Background—In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testos

www.ahajournals.org

Although Akt and ERK were not
influenced by finasteride at this time point, the phosphorylation
of p70S6K as mTOR target was induced by FBS treatment, but
not in the cells that were pretreated with finasteride. However,
this effect was rescued, at least in part, when DHT was added in
abundance to the culture medium, indicating that the reduction
of DHT was required for finasteride-triggered mTOR inhibition.

Antiandrogenic Therapy With Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction

Background—In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testos

www.ahajournals.org

DHT treatment increased mTOR activity as assessed by phosphorylation of the downstream targets p70 S6 kinase and 4E-BP1, and mTOR inhibition with rapamycin blocked the DHT-stimulated increase in cyclin D proteins. Significantly, DHT stimulation of mTOR was not mediated through activation of the PI3K/Akt or mitogen-activated protein kinase/p90 ribosomal S6 kinase pathways and subsequent tuberous sclerosis complex 2/tuberin inactivation or by suppression of AMP-activated protein kinase. In contrast, mTOR activation by DHT was dependent on AR-stimulated mRNA synthesis.

Eunuchs live much longer than intact men. Women live longer than men and this is clearly due to sex hormone differences. If you are interested in longevity to any extent, short of becoming a eunuch, then you want to minimize androgenic hormones while optimizing more anabolic ones. If not, then go blast high levels of DHT and see how it goes. It would be interesting to measure such people's rate of aging with epigenetic clocks (Horvath) compared to 5AR users.

 

[jamesbooker1975]

Still surprise me that, in 2022, some people think that can eliminate a NATURAL in range enzyme in their body ( 5-alpha-reductase ) and no side effect will happen. And, worst part, inhibiting in the whole body cause you only need to block it in the scalp ( contrary to what Mercks propaganda told us in the 90s )