5 alpha reductase in inhibitors

[PhilipSZacarias]

There are many on this forum that take Avodart to reduce DHT levels. I perused the NCCN Guidelines Version 1.2020 - Prostate Cancer and searched Pubmed but did not find any guidance or reports that would support using an 5 alpha reductase inhibitor. I would appreciate a discussion on this topic by users and experts on the forum. Cheers, Phil

[LearnAll]

I am aware of only two studies about Finasteride. First one is .an old ,retrospective study which concluded that Off period was prologed from 15 months to 31 months in patients who were on Intermittent ADT.

More recent Second study is a multicentric trial, called AVIAS which did not find any benefit of using Dutastaride (5 alpha reductase inhibitor)

I just could locate the first study (2006) by Scholz et al ..."intermittent use of testosterone inactivating pharmaceuticals using Finasteride prolongs the time off period. (j. Of Urology)

This one is a 9 year long observational, retrospective study very much in favor of use of Finasteride in cases of Intermittent ADT.

[PhilipSZacarias in reply to LearnAll]

Thanks, I found the paper, Cheers, Phil

[Hidden in reply to PhilipSZacarias]

Some more studies and papers:

1. ARTS - AVODART After Radical Therapy for Prostate Cancer Study - Study Results - ClinicalTrials.gov

clinicaltrials.gov/ct2/show...

2. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS) - PubMed

pubmed.ncbi.nlm.nih.gov/231...

3. Feasibility of Hormones and Radiation for Intermediate or High-Risk Prostate Cancer - Study Results - ClinicalTrials.gov

clinicaltrials.gov/ct2/show...

4. Prostate Cancer Study in Men Who Have Failed First-Line Androgen Deprivation Therapy - Study Results - ClinicalTrials.gov

clinicaltrials.gov/ct2/show...

5. Assessment Of Dutasteride (AVODART) In Extending the Time to Progression of Low-Risk, Localized Prostate Cancer In Men - Study Results - ClinicalTrials.gov

clinicaltrials.gov/ct2/show...

6. Early dutasteride monotherapy in men with detectable serum prostate-specific antigen levels following radical prostatectomy: A prospective trial - PMC

ncbi.nlm.nih.gov/pmc/articl...

7. Early Dutasteride Monotherapy in Patients with Elevated Serum Prostate-Specific Antigen Levels Following Robot-Assisted Radical Prostatectomy - PMC

ncbi.nlm.nih.gov/pmc/articl...

8. Effect of dutasteride on castration-resistant prostate cancer - PMC

ncbi.nlm.nih.gov/pmc/articl...

9. "REDUCE" - A Clinical Research Study To Reduce The Incidence Of Prostate Cancer In Men Who Are At Increased Risk - Study Results - ClinicalTrials.gov

clinicaltrials.gov/ct2/show...

10. Prostate cancer patients can benefit from 5-alpha-reductase inhibitor treatment: a meta-analysis

ncbi.nlm.nih.gov/pmc/articl...

11. Possible PSA masking: Association of Treatment With 5α-Reductase Inhibitors with Time to Diagnosis and Mortality in Prostate Cancer | Oncology | JAMA Internal Medicine | JAMA Network

jamanetwork.com/journals/ja...

12. Study was underpowered but has a neutral conclusion: Effect of dutasteride in men receiving intermittent androgen ablation therapy: The AVIAS trial - PMC

ncbi.nlm.nih.gov/pmc/articl...

13. A metanalysis that had neutral conclusions: Prostate cancer specific mortality after 5α-reductase inhibitors medication in benign prostatic hyperplasia patients: systematic review and meta-analysis - PubMed

pubmed.ncbi.nlm.nih.gov/348...

[LowT]

I am most interested in this as well. I trialed a three week period of Dutasteride when my DHT was climbing (81-> 93-> 124) along with uPSA values of (0.014->0.013->0.017->0.024). This resulted in a fall of DHT to 5 and uPSA to 0.010. I stopped the Avodart out of fear I potentially would mask a BCR should one occur and thus delay treatment.

[LearnAll in reply to LowT]

Seems your PSA was being driven up by DHT...so when you lowered DHT ..PSA fell down again.

I see in your details that you are on testosterone off and on...if it is so..how can you know that you are in BCR. ?

Biochemical recurrence means rising PSA and NOT falling PSA.

I do not understand ...falling PSA with Falling DHT ..Whats wrong with that ?

Its PSA which is the biomarker for PCa..its fall means less cancer cells. There are no cells in human body other than normal prostate cells and prostate cancer cell..who can release PSA. None !

[Tall_Allen]

It is a drop in the bucket if you are already using Lupron. When they ran a randomized trial for its use with iADT, they found there was no benefit to adding it.

ncbi.nlm.nih.gov/pmc/articl...

There may be some benefit if you are only using Casodex and not Lupron.

[LearnAll]

I am getting DHT level done in 2 weeks. If it comes high, i will not hesitate using Finasteride to bring DHT in line and hopefully prolong OFF period of IADT.

[LowT in reply to LearnAll]

Be aware of the following from WikiPedia:

Finasteride (brand names Proscar, Propecia) inhibits the function of two of the isoenzymes (types 2 and 3) of 5α-reductase. It decreases circulating DHT levels by up to about 70%. Dutasteride (brand name Avodart) inhibits all three 5α-reductase isoenzymes and can decrease DHT levels by 95%. It can also reduce DHT levels in the prostate by 97 to 99% in men with prostate cancer.

Also Dutasteride hangs around for 4 to 6 months after stopping it.

[Hidden in reply to LowT]

Finasteride isn't nearly as effective as dutasteride but it hangs around for only a couple of days.

half-lifes:

• 5ARI Finasteride: 5-7 hours (max DHT removal action within 8 hours)

• 5ARI Dutasteride: 5 weeks.

[LowT]

Cholesterol and Vitamin D?

[PhilipSZacarias]

Hello Nalakrats, Thank you for your reply. I have to balance the anecdotal, although reliable information regarding the use of Avodart by members of this forum and clinical trials that show that there is no efficacy. The rationale for using 5 alpha reductase is quite logical but logical theories don’t always pan out in clinical trials. It is a bit of a quandary because messing with hormones is serious business, hence my reticence. Cheers, Phil

[Hidden in reply to PhilipSZacarias]

The largest RCT that I have seen (if there are others could someone please point them out?)

clinicaltrials.gov/ct2/show...

and an NIH writeup

pubmed.ncbi.nlm.nih.gov/231...

[PhilipSZacarias]

Wow Nalakrats, that's pretty harsh and unnecessary. I do have an open mind - I think my regimen will attest to that. It reflects the recommendation that you, pjohea and a good many others have made over the last couple of years. I have had many discussions with "closed minded, conservative, SOC doctors" to convince them, but to no avail. I use in vitro, in vivo and Phase I, II and III clinical trial reports to make my assessments as well. I analyze and ruminate over particular adjuvants until I am comfortable with them, which is exactly what I am doing with Avodart. To date doctors have refused to prescribe this drug as well as estradiol, much to my consternation. As an American (you), I am sure you will appreciate the phrase "to have freedom of thought and assembly". I was not challenging you or the other respected members on the forum...just seeking additional information to make sure I don't FU and obtain ammunition for twisting a MOs arm to obtain the GD prescription. To obtain the prescription, I have to convince them. I asked for a discussion not a rant. Cheers, I think, Phil

[pjoshea13]

Hi Phil,

In a vlog post, Dr. Myers expressed surprise that PCa docs do not generally measured the DHT of men on ADT. After all. the true purpose of ADT is to deprive PCa of DHT - not T.

Myers himself was a DHT producer while on ADT. For most men, near zero T translates to near zero DHT, but DHT can be created by pathways that do not depend on T.

While a blood test can identify a DHT producer, it cannot identify cancer that has learned to make DHT without T. Presumably, this is late-stage development, but there are other paths to CRPC.

It makes sense to test the usefulness of 5ARIs during the off-phase of IADT, but there are issues. T levels going into ADT tend to be low & recovery from castrate levels is very slow. It takes a long time for T (& DHT) to plateau. Also, the last Lupron shot doesn't suddenly stop working. Dr. Freedland has said that the off-phase is largely a continuation of castration.

As has been pointed out, it takes a long time for Avodart to clear. The half-life is long. Similarly, it takes a long time to reach the therapeutic level. I think Dr. Myers mentioned months. He suggested doubling up on dosage to shorten the period.

So the benefit of a 5ARI is in:

- independent DHT producers (a small percentage, identifiable via testing)

- PCa DHT producers (no test for those)

- those in the off-phase of ADT who are producing meaningful amounts of DHT. IMO, very few men would meet that criterion for months, if at all.

- men who have reached the therapeutic level of the 5ARI.

Here's Myers on 5ARIs during remission:

askdrmyers.wordpress.com/20...

askdrmyers.wordpress.com/20...

-Patrick

[PhilipSZacarias]

Patrick, this a very thoughtful, thorough and helpful response. It is sincerely appreciated. Now, I will try once again to convince a doctor to write the requisition for DHT assay and the Avodart prescription. Thank you again! Cheers, Phil

[Hidden in reply to PhilipSZacarias]

If your doctor doesn't want to write the Rx but you want to get it there are other ways. One that I have used is pushhealth.com/. If they write the Rx I can get it at my local pharmacy (using my insurance or goodrx.com).

[noahware]

You may find this relevant... I just had a conversation with an MO today, regarding Casodex (anti-androgen) monotherapy. He is not all that keen on men doing it, as compared to standard ADT, but said when he does prescribe it (normally with much older men) he insists on them also using a 5 alpha reductase inhibitor (Proscar) as his alternative SOC.

He said the studies showing the best efficacy for Casodex in a non-ADT protocol (without Lupron, or the like) were not strictly anti-androgen "monotherapy" but rather used a combination of Casodex AND Proscar. I did not ask when or where these studies occurred, but presumably you could do a search for them.

[PhilipSZacarias in reply to noahware]

Much appreciated noahware!

[middlejoel]

I have been using Avodart as well as Lupron for many years now. My MO Tania Dorff at City of Hope from time to time tells me that it doesn't add anything to my treatment but she is ok with me using it and keeps writing prescriptions for it.

joe

[Hidden]

You might want to add prolactin to your list. 0.25 mg cabergoline twice a week got my PRL from 8.0 to undetectable (I'm going to try to let it float up a bit).

1. The Suppression of Prolactin is required for the Treatment of Advanced Prostate Cancer – PMC

ncbi.nlm.nih.gov/labs/pmc/a...

2. Prolactin, stem cells and prostate cancer | ECE2011 | 13th European Congress of Endocrinology | Endocrine Abstracts

endocrine-abstracts.org/ea/...

3. The role of prolactin in prostate cancer

medigraphic.com/cgi-bin/new...

4. Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma - PMC

ncbi.nlm.nih.gov/labs/pmc/a...

5. A Proposed Efficacious Treatment with Clioquinol (Zinc Ionophore) and Cabergoline (Prolactin Dopamine Agonist) for the Treatment of Terminal Androgen-independent Prostate Cancer. Why and how? - PMC

ncbi.nlm.nih.gov/labs/pmc/a...

6. Frontiers | The Relevant Participation of Prolactin in the Genesis and Progression of Gynecological Cancers | Endocrinology

frontiersin.org/articles/10...

7. Prolactin receptor targeting in breast and prostate cancers: new insights into an old challenge - PubMed

pubmed.ncbi.nlm.nih.gov/285...

8. Local prolactin is a target to prevent expansion of basal/stem cells in prostate tumors - PubMed

pubmed.ncbi.nlm.nih.gov/206...

9. Investigative Clinical Study on Prostate Cancer Part VIII: Prolactin Hormone and the Pituitary-Testicular-Prostate Axis at the Time of Initial Diagnosis and Subsequent Cluster Selection of the Patient Population after Radical Prostatectomy | Anticancer Research

ar.iiarjournals.org/content...

10. Randomized Pilot Study of Cabergoline, a Dopamine Receptor Agonist: Effects on Body Weight and Glucose Tolerance in Obese Adults - PMC

ncbi.nlm.nih.gov/labs/pmc/a...

11. Phase I Study of LFA102 in Patients with Advanced Breast Cancer or Castration-resistant Prostate Cancer | Anticancer Research

ar.iiarjournals.org/content...

12. The Survival Effect of Prolactin on PC3 Prostate Cancer Cells - ScienceDirect

sciencedirect.com/science/a...

13. Prolactin and cancer: Has the orphan finally found a home? - PMC

ncbi.nlm.nih.gov/labs/pmc/a...

14. Testosterone, prolactin, and oncogenic regulation of the prostate gland. A new concept: Testosterone-independent malignancy is the development of prolactin-dependent malignancy!

urotoday.com/recent-abstrac...

15. Possible Involvement of Prolactin in Endocrine-Resistant Metastatic Prostate Cancer

journals.sagepub.com/doi/pd...

16. The Survival Effect of Prolactin on PC3 Prostate Cancer Cells - ScienceDirect

sciencedirect.com/science/a...

17. The Role of Prolactin in Men

longdom.org/open-access/the...

18. Development and Potential Clinical Uses of Human Prolactin Receptor Antagonists | Endocrine Reviews | Oxford Academic

academic.oup.com/edrv/artic...