19 months on finasteride/9 months dutasteride combination and still losing ground. Is testosterone the culprit?

[loner67]

Hello guys, I've been a long time lurker around here and I have 2 previous topics posted before.

I've been battling hair loss for about 3 full years now. Started propecia for 7 months in february 2019. My hairline worsened during the time and I had a huge shed. After slowly recovering from it I wasn't really happy with what the drug was doing as it was barely slowing my hairloss. I quit for about 4 months, realised I needed to go back on it as my hair loss was accelerating. Did blood tests, both DHT and Test were over the top after 4 months with no Finasteride.
I've been on propecia for 19 full months, but I switched to proscar in May 2020 due to price. Not sure if a coincidence, but during this period my scalp started itching very bad all of a sudden, and it became extremely oily. Among other things I had:

Spoiler

-forehead acne
-severe itching around the hairline, temples, and behind it
-itching all over the head, including donor zone and hairs that are deemed safe from DHT
-in some days my libido was over the top
-constant shedding every other day(roughly 300 hairs each time without counting shower hairs). This was no regular propecia shed but instead I was continuing to lose ground.
-painful scalp whenever touching or styling my hair
-itchy scalp whenever I used any shampoo. Nizoral didn't really help I think, but it made my forehead and skin very red when I used it.

I rode this shed and constant itch for the whole summer and in August 2020 I did a blood test to see my DHT. Apparently, finasteride does work, but it only inhibited 67% of my DHT, like it claims. Maybe I needed to inhibit more DHT?
In late autumn I thought that finasteride on its own wasn't enough and I added Dutasteride every Sunday. The itch went on and on and in December I decided to shave my head to see what my scalp looks like. Bad decision, I didn't like the look. The itch was gone for a couple of days until my hair started growing again. I've also used nizoral cream until my hair started getting longer; don't think it did anything for me...

I looked deeper into hair loss topics and came to the conclusion that hair is sensible to all androgens. Seeing that I use propecia, and later added Dutasteride, could a spike in Testosterone be the culprit for still losing ground, constant shedding and itching all over my head? I've been losing my hairline slowly but steady despite using finasteride and later adding duta.

I'm slowly becoming hopeless, and I don't want to become bald, I hated my shaved look, and it doesn't suit me. I wore caps and hats for 4 months till my hair grew back so that I can style it.

 

[Georgi]

Hey how is it going now?

 

[Mr. Slap Head]

It is likely not testosterone, but rather an upregulation of androgen receptors which is causing the increased sensitivity and pronounced androgenic side effects. I think a lot of people get on dutasteride only to realize that it can actually make this upregulation even more intense. Upgrading to dutasteride is something that a lot of people are too hasty with IMO and it should be only considered when most of your other options are exhausted. Those who are not getting the results they want on finasteride should first consider upgrading to oral minoxidil and/or a topical antiandrogen before dutasteride.

 

[Jonah]

It is likely not testosterone, but rather an upregulation of androgen receptors which is causing the increased sensitivity and pronounced androgenic side effects. I think a lot of people get on dutasteride only to realize that it can actually make this upregulation even more intense. Upgrading to dutasteride is something that a lot of people are too hasty with IMO and it should be only considered when most of your other options are exhausted. Those who are not getting the results they want on finasteride should first consider upgrading to oral minoxidil and/or a topical antiandrogen before dutasteride.

Very true. This is know as reflex hyperandrogenicity. It is rare but does happen and it has been posted in the forums. Have you had experience with it?

 

[GRme11]

@loner67 Same here, OP: https://www.hairlosstalk.com/intera...ding-up-tolerance-or-what-blood-tests.133078/
I mentioned my situation many many times. All went downhill when my DHT got back to my baseline levels after being on Oral Finasteride for over a year:
August 2019: Started Topical Finasteride:Baseline levels of DHT: 541 pg/ml
Otober 2019: DHT levels:302 pg/ml
January 2020: DHT levels:298 pg/ml-After starting Oral Finasteride as well ( I was already on it for about 3 weeks-0.5mg 3 times/week)
May 2020: DHT levels:313 pg/ml-I jumped into 1mg daily from 31st of March. I jumped to 0.5mg everyday from mid February
June 2020: DHT levels:283 pg/ml- I even tested 3a-Diol-G which is far a strongest indicator than DHT alone. 3a-Diol-G is a major DHT metabolite and it can converts back to DHT as well. It came low at 1.3 ng/ml while the range is: 3.4-22.
September 2020: DHT levels: 383 pg/ml
January 2021: DHT levels: 550 pg/ml !!! Back to baseline!-I checked as well my PSA levels and it was 0.23 ng/ml but I don't have baseline levels unfortunately.
May 2021 (Latest): I skipped DHT this time and tested only 3a-Diol-G. I got a result of: 16.1 this time!!! It makes sense, doesn't it? Higher DHT->Higher metabolite->Higher Androgenicity overall. I assume that my DHT is still high!

I mentioned my situation many, many times. All went downhill when my DHT got back to my baseline levels after being on Oral Finasteride for over a year. I got pretty good results! The thing is that I was losing ground steadily without changing my treatment. Now, I lost so much ground, and my hair quality is very sickly! Even my donor and sides, who got way thicker on Finasteride, are thinning rapidly. Something got triggered. I started using topical dutasteride for about 2.5 months with zero improvements. I am now taking oral Dutasteride once a week alongside my Finasteride. Two weeks in, and I don't know if I see hope! As much as I am losing ground, I am losing my sanity and my mental health more and more. It's crazy! I don't know if DHT is coming through the Backdoor pathway. I know that Ketoconazole, Dutasteride, Abiraterone Acetate, and Tretinoin (not quite sure) are helping with the backdoor pathway. I will try to do a DHT blood test again. It's like I am taking a sugar pill now. It is horrendous! I didn't experience symptoms like oily scalp and such that you have mentioned.

@Mr. Slap Head What do you recommend? RU, Fluridil, Topical spironolactone, etc?

 

[Mr. Slap Head]

@loner67 Same here, OP: https://www.hairlosstalk.com/intera...ding-up-tolerance-or-what-blood-tests.133078/
I mentioned my situation many many times. All went downhill when my DHT got back to my baseline levels after being on Oral Finasteride for over a year:
August 2019: Started Topical Finasteride:Baseline levels of DHT: 541 pg/ml
Otober 2019: DHT levels:302 pg/ml
January 2020: DHT levels:298 pg/ml-After starting Oral Finasteride as well ( I was already on it for about 3 weeks-0.5mg 3 times/week)
May 2020: DHT levels:313 pg/ml-I jumped into 1mg daily from 31st of March. I jumped to 0.5mg everyday from mid February
June 2020: DHT levels:283 pg/ml- I even tested 3a-Diol-G which is far a strongest indicator than DHT alone. 3a-Diol-G is a major DHT metabolite and it can converts back to DHT as well. It came low at 1.3 ng/ml while the range is: 3.4-22.
September 2020: DHT levels: 383 pg/ml
January 2021: DHT levels: 550 pg/ml !!! Back to baseline!-I checked as well my PSA levels and it was 0.23 ng/ml but I don't have baseline levels unfortunately.
May 2021 (Latest): I skipped DHT this time and tested only 3a-Diol-G. I got a result of: 16.1 this time!!! It makes sense, doesn't it? Higher DHT->Higher metabolite->Higher Androgenicity overall. I assume that my DHT is still high!

I mentioned my situation many, many times. All went downhill when my DHT got back to my baseline levels after being on Oral Finasteride for over a year. I got pretty good results! The thing is that I was losing ground steadily without changing my treatment. Now, I lost so much ground, and my hair quality is very sickly! Even my donor and sides, who got way thicker on Finasteride, are thinning rapidly. Something got triggered. I started using topical dutasteride for about 2.5 months with zero improvements. I am now taking oral Dutasteride once a week alongside my Finasteride. Two weeks in, and I don't know if I see hope! As much as I am losing ground, I am losing my sanity and my mental health more and more. It's crazy! I don't know if DHT is coming through the Backdoor pathway. I know that Ketoconazole, Dutasteride, Abiraterone Acetate, and Tretinoin (not quite sure) are helping with the backdoor pathway. I will try to do a DHT blood test again. It's like I am taking a sugar pill now. It is horrendous! I didn't experience symptoms like oily scalp and such that you have mentioned.

@Mr. Slap Head What do you recommend? RU, Fluridil, Topical spironolactone, etc?

I understand trying out dutasteride in your situation since DHT is still high. However, keep in mind that androgens are also produced from the adrenal glands and it appears that some people just don't respond to 5AR inhibitors. A couple months in on dutasteride you should get bloods done again to see what it is doing.

RU should be helpful but it has a lot of drawbacks. Expensive, and must be applied twice daily for optimal results. I mean, if you have the cash and don't mind the inconvenience then go for it. Personally I would experiment with topical bicalutamide if I were you. It has a long half life and so you save a lot of money, it only needs applied once or twice a week and the dose can be adjusted easily. Fluridil and spironolactone are not strong enough to hold ground if you are losing ground IMO.

 

[Mr. Slap Head]

Oh and don't forget oral minoxidil of course

 

[300]

Oh and don't forget oral minoxidil of course

What do you think adding one duta 0.5 mg once a week for better dht inhibition?

 

[Mr. Slap Head]

What do you think adding one duta 0.5 mg once a week for better dht inhibition?

It's worth trying if you are losing ground and have exhausted other options (or have blood work showing finasteride has become less effective). I personally believe that a lot of people move to dutasteride too soon and it ends up either causing upregulation or just doesn't work. They are enticed by the 90+% inhibition versus 70% inhibition at most from finasteride. But that is SERUM. What most people fail to understand though is that both are pretty similar at inhibiting scalp DHT (around 50%). But no doubt worth trying if you are aggressively balding. Dutasteride's ridiculous half-life allows you to easily adjust the dose, so that is also nice. You can go twice a week, three times a week, daily, etc. and find your sweet spot.

 

[Mr. Slap Head]

Very true. This is know as reflex hyperandrogenicity. It is rare but does happen and it has been posted in the forums. Have you had experience with it?

Sorry, I missed your post. Yes, I have. I thought dutasteride would give me more gains, but it ended up making my hair worse.

I think that possible solutions to reflex hyper are to either quit finasteride (and do so GRADUALLY to prevent DHT from binding to receptors that have been upregulated) and focus on oral minoxidil as the main treatment, or simply reduce finasteride dosage, and/or adding a topical antiandrogen to downregulate the receptors.

 

[losingbattle88]

Just take duta daily and dont mix it with fina. Ur probably causing hormonal imbalance or something.

 

[GRme11]

I understand trying out dutasteride in your situation since DHT is still high. However, keep in mind that androgens are also produced from the adrenal glands and it appears that some people just don't respond to 5AR inhibitors. A couple months in on dutasteride you should get bloods done again to see what it is doing.

RU should be helpful but it has a lot of drawbacks. Expensive, and must be applied twice daily for optimal results. I mean, if you have the cash and don't mind the inconvenience then go for it. Personally I would experiment with topical bicalutamide if I were you. It has a long half life and so you save a lot of money, it only needs applied once or twice a week and the dose can be adjusted easily. Fluridil and spironolactone are not strong enough to hold ground if you are losing ground IMO.

Thanks for the response. I appreciate it.
I got solid results with the combination of topical Finasteride and oral Finasteride. I'm using, of course, topical Minoxidil as well for three years. I definitely can say to you that I responded to 5ARis. Then, as I mentioned above, the downhill started later. I even performed the TrichoTest thing from Fagron to get some further opinions. My DHEA-S last time I checked them was low, as my E2 levels. I am underweight, thus low body fat, lower aromatization, etc. It was one way to eliminate the mild gyno finasteride gave me. All in all, it's a messed-up mix. Even though these, I was still having great hair results! I'm thinking to increase my topical Finasteride dosage and enhance Minoxidil with Tretinoin for better absorption. Everything goes out of favor!

 

[GRme11]

It's worth trying if you are losing ground and have exhausted other options (or have blood work showing finasteride has become less effective). I personally believe that a lot of people move to dutasteride too soon and it ends up either causing upregulation or just doesn't work. They are enticed by the 90+% inhibition versus 70% inhibition at most from finasteride. But that is SERUM. What most people fail to understand though is that both are pretty similar at inhibiting scalp DHT (around 50%). But no doubt worth trying if you are aggressively balding. Dutasteride's ridiculous half-life allows you to easily adjust the dose, so that is also nice. You can go twice a week, three times a week, daily, etc. and find your sweet spot.

That's what I am doing right now.

 

[GRme11]

Just take duta daily and dont mix it with fina. Ur probably causing hormonal imbalance or something.

Yeah, might be possible. It's crazy that even my donor and my sides are getting rapidly thinner.

 

[PRIMEN]

Just take duta daily and dont mix it with fina. Ur probably causing hormonal imbalance or something.

You're already causing hormonal imbalance while using duta, it kills all your DHT and lots of other stuff 5AR responsible for.

 

[losingbattle88]

You're already causing hormonal imbalance while using duta, it kills all your DHT and lots of other stuff 5AR responsible for.

I get a new balance. Not normal balance thats true but by not taking it regularly your hormonal balance may bounce up and down all the time. Keep conistent with the dosage and use at the same time.

 

[Mr. Slap Head]

Did you know that minoxidil supress androgen related functions.

Cmon man just get on oral minoxidill. Im using 12.5mg orally with no side effects.

Yeah, however I believe minoxidil's "anti-androgenic" effect is about the same as ketoconazole - pretty negligible.

If he doesn't want to use OM then he needs to use foam minoxidil twice daily, tretinoin, needle. Could also use 10 or 15% concentrations. But OM is superior because it will increase the sulfotransferase enzymes, allowing for a higher conversion rate to minoxidil sulfate (which is its active form), and of course you can't beat the convenience and not having to deal with topicals effects on hair texture.

 

[GRme11]

Yeah, however I believe minoxidil's "anti-androgenic" effect is about the same as ketoconazole - pretty negligible.

If he doesn't want to use OM then he needs to use foam minoxidil twice daily, tretinoin, needle. Could also use 10 or 15% concentrations. But OM is superior because it will increase the sulfotransferase enzymes, allowing for a higher conversion rate to minoxidil sulfate (which is its active form), and of course you can't beat the convenience and not having to deal with topicals effects on hair texture.

Fagron test showed me that my SULT1A1 enzymes are great, and thus minoxidil will work, and indeed worked. It worked pretty well when I started using it three years ago.

Test results:
PGD2: Mildly Elevated
SULT1A1: Response to Minoxidil: Positive
5AR1: Activity Normal
5AR2: Mildly Elevated
Aromatase Activity: Mildly Reduced
IGF-1 Activity: Mildly Reduced
ACE Acitivity: Mildly Elevated (More Vasoconstriction-Vasodilation Needed: Arginine, Carnitine, etc.)
CRABP2: Mildly Reduced (Vitamin A not properly absorbed into the cells. Noteworthy: Vitamin A was in the low-end levels when I checked it before the test.)
PTGFR-1,-2,-3: 1,3: Mildly Reduced->Latanoprost can act-2: Negative Response to Latanoprost. So, here it's a bit of a mix.

Suggestions that would help:
Finasteride, Saw Palmetto (They mention this but not Duta? There are studies indicating that Saw Palmetto inhibits both isoforms.), 17a-Estradiol, Tretinoin, Vitamin A, Minoxidil, Arginine, Ginko Biloba, Igrantine-F1( Contains Cepharanthine which is meant to increase IGF-1 topically: https://www.longdom.org/open-access...leandrogenetic-alopecia-2167-0951-1000145.pdf), Cetirizine, and Latanoprost.

 

[GRme11]

I believe that they considered this great study as well, for the test:

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia

Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic ...

www.ncbi.nlm.nih.gov

In our study, the most significant exonic variant was rs72623193 located in DHRS9, that was ranked the highest in the gene-based tests. DHRS9 (dehydrogenase/reductase SDR family member 9) has been identified as a 3α-hydroxysteroid dehydrogenase (3α-HSD) [29]. It is a microsomal enzyme whereas other 3α-HSDs in the aldoketoreductase gene superfamily (AKR1C1–AKR1C4) are cytosolic enzymes. This enzyme is expressed in the human epidermis, hair follicles, and sebaceous glands [30, 31]. Since DHRS9 is involved in the synthesis of DHT from 3α-androstanediol [29], upregulation would facilitate the backdoor pathway to DHT in the scalp tissue even when 5AR is inhibited by dutasteride (S6(A) Fig). A previous study showed that there was negative correlation between the change in hair count and the percent change of scalp DHT after treatment with the 5AR inhibitor [16].

Additionally, DHRS9 possesses retinol dehydrogenase (RolDH) activity [32, 33], which converts retinol to retinal in retinoid acid (RA) synthesis (S6(B) Fig). Because DHRS9 can oxidize retinol that is bound to the cellular retinol-binding protein while many other RolDHs cannot [34, 35], it is regarded as a physiological enzyme [35]. Its expression changes during hair cycling in mice and increases in hair follicles of C57BL/6J mice that frequently develop dorsal skin alopecia. DHRS9 also increased in the hair follicles of patients with central centrifugal cicatricial alopecia [30]. Previous studies demonstrated that RA synthesis and the RA signalling system are related to hair growth and cycling [35, 36]. Furthermore, RA was reported to regulate bone morphogenetic protein and Wnt signalling pathways, which are involved in hair growth [37].

This is why I keep mentioning 3a-Diol-G, etc.

We also found that response to dutasteride may be associated with variants of genes involved in steroid hormone metabolism, such as SRD5A1, ESR1, and CYP19A1 (S6(A) Fig). The product of SRD5A1 is type I 5AR, which is a target of dutasteride. Dutasteride inhibits both type I and II 5ARs, while finasteride selectively inhibits type II 5AR. Therefore, a variation in SRD5A1 might affect the subject’s response to dutasteride during treatment for MPHL. However, SRD5A2 encoding type II 5AR was not associated with response to dutasteride.

In addition to androgens, it has long been known that oestrogen also effects hair follicle growth by binding locally expressed oestrogen receptors (ERs) [43]. ESR1 encodes ERα, which is 1 of 2 distinct isoforms of ERs. CYP19A1 converts androstenedione to estrone (E1) and testosterone to 17β-estradiol (E2). It has been reported that ERα is maximally expressed during telogen, and E2 inhibits hair growth [44, 45]. Moreover, E2 modifies androgen metabolism in pilosebaceous units [43].

 

[loner67]

Hey how is it going now?

Still losing ground unfortunately. I still have that crawling itch, and it's not only on my scalp, but sometimes other parts of the body. What's worrying me is that I know that if I don't get rid of this itch then I will still lose ground.

It is likely not testosterone, but rather an upregulation of androgen receptors which is causing the increased sensitivity and pronounced androgenic side effects. I think a lot of people get on dutasteride only to realize that it can actually make this upregulation even more intense. Upgrading to dutasteride is something that a lot of people are too hasty with IMO and it should be only considered when most of your other options are exhausted. Those who are not getting the results they want on finasteride should first consider upgrading to oral minoxidil and/or a topical antiandrogen before dutasteride.

I've thought about reflex hyperandrogenicity as a possible issue since late August 2019(when I quit Proscar for 4 months just to reuse it after). I've wrote in my older topic about this. However, I'm not quite sure yet if this is the main issue. I've read a lot on these forums and to be honest I don't know what to believe anymore, everyone has a different story. I know for a fact that propecia/duta have slowed my hair loss, but ever since the summer of 2020 I got this crazy itch on my scalp, even donor areas and I'm shedding more than normal.

I base my theory about test also being the culprit after closely following Derrick's channel. I'm not sure if you're familiar about this video:

He said that he was blocking his DHT with Duta to almost non-existent levels and yet he was still losing hair. He claims that RU fixed his problem while also switching back to finasteride. I don't know how much is true about RU though, but it's one of the remaining solutions. I don't want to use oral minoxidil since I've heard about its heart related risks, I'm having heart palpitations sometimes so I wouldn't risk it.

Very true. This is know as reflex hyperandrogenicity. It is rare but does happen and it has been posted in the forums. Have you had experience with it?

It could be a cause.

Just take duta daily and dont mix it with fina. Ur probably causing hormonal imbalance or something.

I already dropped finasteride for now. I've been experting with dutasteride for the last 7 months but I'm still losing ground. I used it once a week for about 3 months. If I remember correctly my itching was subsised a bit. I then upgraded to twice a week since I was still losing some hairs every other day. But I'm not sure if I made the right decision. I don't want to take it everyday since I've heard that 2 times should be sufficient given its half life. I'm already having side effects and not happy.