Absence of Adverse Reactions When PDE5's Lose Efficacy

[Cozpgh]

Just curious if others have experienced this. I've seen many times here that PDE5's worked great for many men for a certain time frame and then lost effectiveness even at higher dosages. I was first prescribed Viagra in 1999 at 25 years old. For about 18 years, a 25mg dosage would pretty much guarantee a red faced facial flush within 15 minutes to a half hour followed by a stuffed up nose and what I'd call "throat gurgles." Presumably either acid reflux or drainage from my stuffed up nose. My erections were usually rock hard through completion although there'd be some misses here and there.

In maybe 2017, I started adding L Arginine and L Citrulline supplements to the mix. Expecting that enhancing the NO production in my body would further boost the effectiveness of the Viagra/Sildenafil. It was also helping with my white coat hypertension at the doctor's office. My doctor at one time would have to take my BP several times throughout the appointment because the initial reading would be high. It would always come down the further the appointment went along and he attributed the higher readings it to anxiety. I'd go from like a 145/85 reading at first to a 118/70 by the end of the appointment. Once I started the Arginine/Citrulline, that high initial reading would lessen substantially. There would be still be a spike but the spike was more like 130/70 and would subsequently go down as he rechecked it.

However, this also coincided with my divorce and Viagra losing its effectiveness in encounters with new women for the first time in 20 years. Dosages as high as 100mg to 200mg would sometimes fail. Usually producing an erection that would soften 5 or so minutes into intercourse. And one common thing I noticed was the complete absence of that once always reliable facial flush and stuffed up nose. To some degree, this was welcome as I'd often have to explain the redness in my face - often attributing it to taking a niacin supplement or remarking that strippers used to love teasing me because I'd blush when turned on. At the same time, it was always that particular adverse reaction that would be my indicator that the medication was kicking in and I'd be ready with an erection with stimulation. Without feeling that any longer, I found myself less confident going into sexual encounters.

I've since transitioned to Trimix but still take a daily 5mg dose of Cialis and an as needed 100mg to 200mg dose of Sildenafil on days between injections. Sometimes the Sildenafil doses may not come all at once. I might take a 50mg dose at lunchtime, another 50mg dose two hours later, and a 100mg dose an hour before bed if my girlfriend's staying over. But there's still no facial flush - and just licking a little bit of powder from a Viagra tablet in a pill cutter used to give me that reaction) - no more stuffy nose, no more headache, etc. The only AE that remains is indigestion and acid reflux if taken too close to bedtime.

I guess I'm wondering if I've just experienced the same loss of efficacy of PDE5's over time that many men here have also experienced, perhaps coupled with some performance anxiety in new sexual experiences post-divorce, or did I mess up my body's own NO production adding the Arginine/Citrulline supplements to the mix? I don't expect anyone to have an answer to this but I'm curious if those failing now on PDE5's that once worked are also not feeling those same side effects they once experienced when it worked?

[Stenlie_]

Hello. The same thing happened to me. I reacted very well for several months. Then the side effects disappeared and with them - the erection. It happened almost suddenly. I reacted great the day before, but not the next day. Check your testosterone. You may have a problem with this. I have low testosterone and doctors say I may not react for this reason. I also don't have any libido. I masturbate to see what kind of erection I can achieve, rather than wanting to.

[Stenlie_]

I saw that you did a gainswave. For me, PDE5 stopped working after that. Think about whether there is a connection with you.

[BrokenPiston]

Sorry for a tangential question: why would you space out dosing of sildenafil like that when sildenafil has such a short half-life? It seems to me that your 200mg dosing really wasn't 200mg if you're going 50 (wait two hours) 50 (wait a few hours) 100. I ask because I have a new girlfriend an am thinking eventually I'll try 120mg on an occasion (empty stomach and no alcohol for full effect). I haven't been that impressed with sildenafil so far, but also haven't had good situations where I take it in the perfect setting.

[Cozpgh]

Sorry for a tangential question: why would you space out dosing of sildenafil like that when sildenafil has such a short half-life? It seems to me that your 200mg dosing really wasn't 200mg if you're going 50 (wait two hours) 50 (wait a few hours) 100. I ask because I have a new girlfriend an am thinking eventually I'll try 120mg on an occasion (empty stomach and no alcohol for full effect). I haven't been that impressed with sildenafil so far, but also haven't had good situations where I take it in the perfect setting.

I've gone as high as 200mg in one dose, on top of my daily low dose Cialis. In fact, when Sildenafil still works beautifully for me, it's usually when I do a 125mg to 200mg dose at once and have sex within an hour to hour and a half. No adverse reaction at all - not even the slightest facial flush or stuffy nose - but the occasional acid reflux/indigestion if it's close to bedtime.

The spacing out the doses I mentioned tends to be on days where I'm not sure sex will happen or not. Like if my girlfriend comes over on Friday night, we're pretty much going to have sex as soon as we see each other. I can do the larger as needed dose then. Although these past few weeks I've replaced that large dose with a Trimix injection to good results. If she's staying here through Monday morning, I'm not sure when the next time something's going to go down will be.

So I might take 50mg when we wake up, another 50mg around lunchtime or in the afternoon, and then the larger 100mg dose at bedtime since we're likely to fool around then if we haven't throughout the day. It tends to be these times where it doesn't work as well for me. I'll get an erection and penetrate but will lose it before I can ejaculate. Thankfully, this is always after she's orgasmed multiple times so I just write it off as some sort of sexual exhaustion. Especially if I came twice the previous night.

Have you tried experimenting with the Sildenafil dosing when alone and masturbating? One thing I've discovered is Sildenafil and the PDE5s in general aren't enough to overcome performance anxiety or that erection killing adrenaline rush you get in a sexual situation with a new partner. And I think that's a huge part of the problem I've experienced with their loss of efficacy since my divorce. The 25mg dose probably worked so well when I was married because sex was predictable and routine but also comfortable without nerves. Even though I've been with my girlfriend for a year, the fact that she's 17 years younger than me, makes money from Only Fans content, polyamorous, and in the "lifestyle", still makes me fixate on performance or worry about failures with my ED whether medicated or not.

[Cozpgh]

I saw that you did a gainswave. For me, PDE5 stopped working after that. Think about whether there is a connection with you.

Interesting. I didn't notice it as much after the Gainswave as much as I did after my P Shot. I had several all out failures on Sildenafil, we're talking no lift off at all, a few times in the weeks after my P Shot. When I mentioned this to the clinic I went to for these procedures, his response was I probably needed at least two more P Shots I felt like I was experiencing some progress and even requiring lower dosages after my Gainswave that all went to shit after my P Shot. Now I'm basically back to where I was before dropping the $3500 for both of those procedures.

[slipnslider]

Pills slowly worked less for me over 15 years of use. I tried all the different kinds of pills.

Problem was, the side effects were getting worse and the desired effects were getting smaller.
Less reliable erections, and worse headaches. Moved on to injections and they work much better with zero side effects, even if they're far less convenient.

Plus with pills, you're not supposed to eat food or drink alcohol with them. Excuse me, but aren't those like the main activities people usually do on a date before they have sex?

[Cozpgh]

Hello. The same thing happened to me. I reacted very well for several months. Then the side effects disappeared and with them - the erection. It happened almost suddenly. I reacted great the day before, but not the next day. Check your testosterone. You may have a problem with this. I have low testosterone and doctors say I may not react for this reason. I also don't have any libido. I masturbate to see what kind of erection I can achieve, rather than wanting to.

Sorry to hear that. I at least had a good 18 year run with the Sildenafil being mostly effective minus some failures here and there either too soon after eating or after a night of drinking. I've been on TRT since February of this year. .25 cc twice weekly. Total T has gone from 330 to 850 and Free T from 69 to 109. However, I'm still not feeling much improvement in regards to libido, physical strength/endurance, sleep, mood, and exercise recovery, and erection quality. Another testosterone doctor is telling me I'd feel better if I did 1ml once every week or two. But he also scared me away because he said, "I don't care about numbers. I mean, I'm going to look at your lab results and red flag anything concerning but I care more about how you feel day to day and quality of life than your total testosterone number. That twice a week low dose isn't doing shit for you."

I can also relate to what you're saying about masturbation becoming more on an erection quality barometer for you than horniness or libido. It's been that way for me for maybe the past 5 years.

[ScrewedbyDoctors]

Years ago Cialis was working great for me, then at 35 I got the vasectomy, around two months after the vasectomy the Cialis didn't work as well, I went to check my hormones and they were really bad. I went the the MDF who did the vasectomy and asked him why the vasectomy affected my hormones? He said it wasn't the vasectomy but because I was 4 months older!!!!!!!!!!!!!WTF......Cialis or Viagra won't work the same if your hormones are not balanced.

[Simbarn]

Sorry to hear that. I at least had a good 18 year run with the Sildenafil being mostly effective minus some failures here and there either too soon after eating or after a night of drinking. I've been on TRT since February of this year. .25 cc twice weekly. Total T has gone from 330 to 850 and Free T from 69 to 109. However, I'm still not feeling much improvement in regards to libido, physical strength/endurance, sleep, mood, and exercise recovery, and erection quality. Another testosterone doctor is telling me I'd feel better if I did 1ml once every week or two. But he also scared me away because he said, "I don't care about numbers. I mean, I'm going to look at your lab results and red flag anything concerning but I care more about how you feel day to day and quality of life than your total testosterone number. That twice a week low dose isn't doing shit for you."

I can also relate to what you're saying about masturbation becoming more on an erection quality barometer for you than horniness or libido. It's been that way for me for maybe the past 5 years.

I agree with you that performance anxiety is most probably overriding the effect that PDE5i are having. Sympathetic influence can be all powerful in the penis, hence why Trimix injections work best as they deliver phentolamine directly to the penis and supress the inhibitive influence, the other two ingredients are strong direct relaxers of smooth muscle in the erectile tissues which by pass the NO pathway, the pathway PDE5i affect.
I also think that TRT can in many men exacerbate the influence of the inhibitive sympathetic pathway in the penis and sometimes in the whole body. I feel this is due to the way testosterone is delivered into the body artificially, it does not mimic the way we produce it naturally. The other issue with TRT is that is shuts down most of the upstream hormones with regard to testicular function and this can have far reaching effects on sexual function, specifically the loss of LH, FSH and GNRH. The ill effects of this take time to be felt. Are you at least using HCG in your protocol? This can for some men help to replace a portion of this in a crude manner. Taking more testosterone in order to try and combat this loss of upstream hormones usually only causes more problems with excessive E2, desensitisation of the androgen receptors and further increase in sympathetic function in the body. TRT can cause ED if the dose is too high. The loss of LH can cause anxiety to develop in many men. This anxiety can interfere with erectile function as well.

I now think that it is possible that PDE5i do lose effectiveness over time, I was opposed to this possibility, but if one utilises high doses of these drugs frequently, and these effects are changing how the enzyme PDE5 is working in the body, it make sense that the body may upregulate this enzyme over time to correct what it sees as a malfunction at a cellular level.