Any theories on the crash when we quit this drug? Most of us had mild sides while on the drug, but when we quit, all hell broke loose. Any ideas on why this happens?
Well, in addition to Hypo, I believe Galapagos summed up what likely happened to some of us while on the drug, in terms of hormones:
propeciahelp.com/forum/viewt … ight=#3002
My guess is the issue of being “fixed” in a certain mode of homeostasis either occurs while on, or shortly after discontinuing the drug for many.
When you quit, there is a surge of DHT that comes back into the body within 1-2 weeks, as the 5AR enzyme is no longer inhibited.
It is also known that while on Finasteride, T/LH/FSH/Estradiol rise as follows:
merckfrosst.ca/assets/en/pdf … 2_06-E.pdf
PAGE 11:
“Circulating levels of testosterone were increased by approximately 10-20% yet remained within the physiologic range.”
“An increase of approximately 15% in luteinizing hormone (LH) and 9% in follicle-stimulating hormone (FSH) was observed in patients treated for 12 months; however, these levels remained well within the physiologic range.”
propecia.com/finasteride/pro … drogen.jsp
“Clinical studies showed men treated with PROPECIA® (finasteride) had increased mean testosterone and estradiol levels (approximately 15%), but these levels were within normal physiologic range.”
So to recap, while on Fin:
T increased up to 20%
E2 increased up to 15%
LH increased up to 15%
FSH increased up to 9%
What happens to the HTPA when you discontinue the drug and a flood of DHT is re-introduced BACK into this equation of elevated T, LH, FSH and E2? Therein lies the big question.
According to this study (The Effects of Transdermal Dihydrotestosterone in the Aging Male: A Prospective, Randomized, Double Blind Study)…
jcem.endojournals.org/cgi/content/full/87/4/1467
“As expected and observed previously (15), serum FSH and LH concentrations decreased during DHT treatment as a result of the negative feedback effect.”
… so a high level of DHT apparently inhibits LH, and thus T production… in other words, the HTPA reduced T because it thought there was too high of a level of DHT in the blood (since DHT comes from T).
So perhaps for some men, the rapid return of DHT in the body, coupled with a high level of E2 (and possibly SHBG, since elevated Estradiol can also lead to elevated SHBG, which can bind up Free Testosterone) caused this downregulation of T production – and those high levels of rebounding DHT/E2/SHBG (possibly) were enough to keep T down long enough to set a new “homeostasis level” (Hypo, care to comment? Possible?)
The question is why wouldn’t the HTPA “correct itself” after discontinuing the drug and re-establish its original Pre-Finasteride hormonal balance. I don’t know, I’m not an endocrinologist, just a common joe trying to piece this together best I can.
Some other thoughts (worst-case, and no I’m not being pessimistic, I’m just trying to think of potential ways the drug could have messed things up… if this is even possible):
For those with normal levels since quitting, could it be androgen deprivation thanks to Fin caused either significant downregulation and expression of the androgen receptor, or alternatively caused an androgen receptor mutation which brought on a form of “androgen insensitivity”, such that even if levels return to normal, we wouldn’t be able to “feel it”?
For example: propeciahelp.com/forum/viewtopic.php?t=512
It is known that in Prostate Cancer, when deprived of androgens for a long period of time, the androgen receptor can potentially mutate to achieve an “androgen-independent” state. This allows the Prostate Cancer to continue.
In our cases, perhaps a lack of androgens caused the androgen receptor to mutate in such a way that it can no longer bind correctly with DHT and thus, even when DHT returns, we can’t “feel it” the way we used to before the drug. Just a thought… albeit not one I’m too fond of.
These are just some theories thrown around this forum, worst-case scenario thinking of course. But it needs to be thought of, so we might have another avenue to investigate.
Hopefully the medical community will find the answers to this problem… seems Dr. Shippen has had success in helping a number of patients, so we know this isn’t irreversible for some.
Frankly I don’t buy the fact that my receptors could have mutated because of androgen deprivation.
I had side effects while I was on the drug, when I quit the drug the side effects went away and I felt totally normal, after about 2 weeks things started going downhill again…
So the fact that I felt normal after quitting the drug proves that my receptors still work, and also proves that there is a way that I can return to normal.
Yea I hear you, pretty much the same thing happened to me. Within 2 weeks I felt like my old self for about 5 days, then things started going downhill again.
For the most part, I agree. I was just throwing that theory out there to see what people thought of it.
I do believe this is primarily a hormonal issue for many, since the majority describe the same pattern of brief recovery/side effects returning and downhill trend since quitting… seems something happened when the DHT returned … maybe it increased too rapidly and downregulated T production (as I described in my initial post), or caused things to go haywire in a way we don’t know of yet (but an endocrinologist might, if they’d actually investigate this deeper with us!!). What do you think happened?
Since I quit cold turkey, I’ll never know if weening off could have made a difference. Anyone here ween off and still experience problems?
I weaned off over an significant amount of time (I think about 4 months) and still followed the same pattern as you guys, right after the last dose. Maybe smaller levels of fin still have a significant effect on whatever our problem is, so weaning doesn’t change much.
Anyway, does the bounce back after quitting really discount your “androgen insensitivity” theory? If there really was a desensitivity, wouldn’t the bounce back phase/increase in levels kind of balance the insensitivity, making us seem normal until the levels normalized? Is there any possibility in testing these receptors?
You may be right that weaning off may not have made a difference – and the only reason I say that is because Finasteride has a flat dose response rate, as seen here (Study of the FDA Files on Propecia): physics.upenn.edu/facultyinf … index.html
Unless we were able to obtain doses of under 0.05mg (impossible), we basically inhibited nearly the same amount of DHT wether we took 0.25mg, 1mg or 1.25mg. So it would make sense that no matter how you quit – even if reducing dosage to 0.125mg (8th of a Propecia pill), it wouldn’t make much of a difference. The only thing that might make a difference is increasing the days between dosing, since it can take up to a week for DHT to return to baseline from a single dose.
Yea, that is pretty much what I was thinking… perhaps the receptors were downregulated/reduced expression to the point that it requires MUCH HIGHER levels of DHT for us to “feel normal” – and that high point only came about after we quit, briefly.
Then when DHT settled down, DHT levels weren’t high enough to stimulate the androgen receptor fully (although, based on my own bloodwork, I have high DHT yet don’t feel “normal”, “full of vitality” or “horny” the way I used to – which leads me to the last point, androgen receptor mutation preventing me from harnessing the effects of DHT like I’m supposed to).
Yes, you’d need to get genetic testing done at a lab to measure your 5AR enzymes and their chromosomes/DNA. They can check for mutations.
Although, I’ve heard that Dr. Crisler tests 5AR activity via a 24-hr Urine Panel… can anyone who’s seen him confirm?
This is interesting, and something that really needs to be elaborated upon…
T and E increase, so presumably GnRH decreases, which has a negative effect on LH and FSH release. Yet, LH and FSH actually increase, presumably because of lower DHT, as you point out. Is DHT a more potent modulator of the pituitary than GnRH? Or is it just that the size of the change in DHT has more impact than the smaller change in T and E?
So how can we create a model of fin-HPTA interaction that accounts for the range of observed symptoms? Is it indeed the case that onset of hypogonadal symptoms occurs primarily either soon after beginning or soon after quitting?
If so then maybe this interaction between DHT and the pituitary could in fact play a very large role.
Anyways, no time to think about this now, but I do think it’s fundamentally important that we figure out the mechanism here, so I hope people keep thinking and writing about this.
Mew you say you do have a lot of DHT but lets not forget that there are in fact 2 types of DHT.
I wonder if maybe finasteride caused there to be an imbalance between the two different types of DHT and you have more of one type than you need to and not enough of the other?
Just a thought.