Pubmed is my friend. It is obvious that GnRH agonists act far beyond their suggested efficacy at maintaining sex hormone suppression. In a 1999 study, a single 3-month LH-RH agonist injection was shown to maintain castration levels of testosterone for 6 months. And it took 13.6 months for the men to return to base line levels! (
281040]
http://www.ncbi.nlm.nih.gov/pubmed/
[/quote]
9783932 ) In a second study which looked at cessation of a GnRH agonist after 6 months, it took an average of 13 week to reach 50 ng/dL, which use to be the old standard for castrate levels. And it took 16.6 weeks for testosterone levels to get into the normal range at 212 ng/dL. I did not have access to read the full article and the latter abstract did not mention whether levels
were restored. (
5821487?log$=activity ).
If I stop right now, how long will it take for me to reach
for an adult mal
back to *my* normal level of testosterone, which is about 2/3rds into the normal range? The other question is how long does this normalization take compared to the depo provera that I have taken in the past for one and four month trials, respectively?
Can I answer any of those questions? The answer may lie in whether the time to normalization after taking a GnRH agonist for only 28 days is comparable to taking a GnRH agonist for 3 and 6 months in the above referenced studies. I don't know. I can't find any studies that looked at a shorter time frame. GnRH agonists are typically prescribed on much longer time frames, such as for prostate cancer, precocious puberty, etc. The one exception is GnRH agonists used for 14 days during IVF (in vitro fertilization). It isn't too surprising I can't find studies looking at shorter time periods on a GnRH agonist and subsequent normalization of sex hormones upon discontinuation.
I had my blood work drawn up yesterday to look at testosterone levels. I had to prod my doctor to do it as he thought it was unnecessary. I strongly feel that if we are going to run an experiment there should be at least some hard numbers to correlate perceived changes physiologically and psychologically. In all likelihood, my numbers should be at or around 20ng/dL. Based on other studies there is at least a 10-15% chance that I have not responded fully and have not reached below 50 ng/dL. Some men don't respond fully to leuprolide acetate and it is unclear what factors may be at play. It would be helpful to know for sure how well I responded to the leuprolide acetate. I am going to ask to have my blood work drawn up periodically until I reach my normal level of testosterone. The information may be of some benefit to others to make an informed decision on whether they would like to use leuprolide acetate as a short trial to suppress testosterone or whether to use depo provera or androcur instead. One data point is better than nothing. At the minimum it will help me make a more informed decision in the future on whether to go this route or not.
I have had a ridiculous amount of fear and preoccupation the last few days about the cessation of the leuprolide acetate. I am diagnosed with bipolar type 2 and I don't respond well to mood stabilizers. This presents a challenging situation to say the least. I have taken depo provera twice unsupervised by professionals. The first trial was a single injection. The second trial consisted of two injections followed by a single injection every month for a total of 5 injections. In both cases my mood was hypomanic before starting each trial. My mood became stable and normal while on the depo provera. However after one to two months upon cessation of the depo provera, my mood switched into ultra rapid cycling. This cycling took approximately 6 months in each case to run its course without much if any remediation with mood stabilizers. As the depo provera wore off, I experienced an indescribable feeling of puberty. It was uncomfortable, irritating, and ultimately a very bad experience given the excruciating pain of ultra rapid cycling that seemed to last far longer than the time needed to return to base line testosterone levels.
I have a lot of fear becauseI feel that there is an extremely high probability of entering rapid cycling again for the third time. This feels like deja vu all over again in the worst possible case. It appears that the slow gradual rise in testosterone somehow creates the perfect condition to enter rapid cycling. I have never encountered rapid cycling under any other circumstance; it has ONLY been in response to stopping androgen deprivation. I would love to know why, but I can only provide a conjecture on why this might be the case.
This is quite a conjecture, so bear with me. There is some evidence to suggest that hormones play a role in mood disorders. They are not the cause of the problem, but they may have pronounced effects on the underlying condition as hormone levels change. For instance it is speculated that during mania, levels of norepinephrine and dopamine surge. This could explain why I feel extreme levels of excitement and energy with evaluated levels of norepinephrine and why I experience euphoria with excessive amounts of dopamine in the synapses. To be clear, norepinephrine is both a hormone and neurotransmitter while dopamine is strictly a neurotransmitter.
Continuing with the conjecture… The body has three feed back loops when it comes to regulating sex hormones in the body. Levels of GnRH (gonadotropin-releasing hormone) are produced by the hypothalamus, which is affected by the amount of sex hormones in the blood stream. This sex hormone is obviously testosterone in men. Levels of GnRH effect the amount of LH (luteinizing hormone) released by the pituitary. And levels of LH affect the amount of sex hormones produced by the testicles in men. Both depo provera (medroxyprogesterone acetate) and lueprolide acetate monkey with these feedback loops in different ways to cause a net reduction in sex hormones. Once both of these prescription medications clear the system, the body recognizes that sex hormone levels are very low. The hypothalamus will begin pumping out supranormal levels of GnRH. This in turn triggers the supranormal levels of LH. It is likely that the supra levels are not pulsed in constant frequency, but in surges in an attempt to restart the production of sex hormones. LH surges are partially implicated in the phenomenon of hot flashes. LH and norepinephrine are somewhat linked together. With a surge in LH, norepinephrine in the hypothalamus rises. If norepinephrine does not fall during the night or surges during sleep, it may interfere to varying degrees with a person's ability to enter and maintain REM sleep. And changes in sleep are strongly associated with mood disorders; sleep deprivation can trigger changes in mood for those diagnosed with bipolar.
Last year as I entered rapid cycling, I documented the progression of changes in a lot of detail. What I noticed is that a couple of months after the last injection of depo provera, something indescribable changed. I knew that it was bad and yet there wasn't anything I could do about it. My mood initially remained stable, but slowly the oscillations in mood grew larger and larger until I was clearly experiencing ultra rapid cycling. Sleep problems led the initial onset of mood changes by about 2 to 3 weeks. The most notable problem was waking up from nightmares. There are two places in the sleep cycles where dreams may take place. Nightmares will almost always be found during REM sleep. It is plausible that a LH surge during the nighttime was the trigger for changes in sleep that cascaded into extreme mood instability.
Because I took a GnRH agonist, it will take some time for the pituitary to up-regulate the number of GnRH receptors. If the 3 and 6 month studies referenced above are relevant and offer any clue, FH surges will likely happen three months from now. I cannot find any studies as a reference and comparison for the depo provera that I have taken in the past. It would be helpful to find a study looking at changes in testosterone for men given medroxyprogesterone acetate (depo provera) and their subsequent discontinuation. But my intuition is that the FH surge happens sooner with medroxyprogesterone acetate compared to leuprolide acetate--around 2 months from the last injection of medroxyprogesterone acetate compared to 3 months from the last daily injection of leuprolide acetate. Anyone want to volunteer for this study? LoL
If you recall from an earlier writing, leuprolide acetate is a GnRH agonist. Initially it stimulates the pituitary into releasing extra LH which causes an overall surge in testosterone levels for the first week or so. You might think that these LH surges would cause notable problems with my mood. They didn't and I have an idea on why that might be the case. I definitely noticed a surge of something following the initial injections of leuprolide acetate. It was a very strong sensation at first and diminished over one and half weeks. The sensation began approximately 2 hours after the injection and lasted about 5 to 6 hours afterward. It is possible that the LH surge happened quickly after each injection and went away after several hours. The LH surge was gone well before I attempted to sleep in the evening hours. This is mostly likely why the daily injections are recommended to be given in the morning. Sleep problems are a known side effect of luprolide acetate. I also feel that the extra testosterone provided a stabilizing effect on my mood. It was dramatic and surprising how much my mood improved. I felt normal for the first time in years. My levels may have ventured some into the supranormal range, but not by gross amounts. (My back of the envelope calculation suggests that I peaked at 113% of the maximum point of the normal adult male testosterone range. I started out at 75% of base line. You can multiple by 1.5 to get a rough idea of where you peaked in testosterone levels during the initial exposure to leuprolide acetate. I would give a reference to this, but that would take some searching.)
Part of my fear is founded on experience with the cessation of androgen deprivation. The other part is founded on plausible conjecture. Rapid cycling is no joke. I'm serious when I say I'd rather have my fingernails pulled out than to go through that again for another 6 months. The price to pay for taking leurpolide acetate is looking to be extremely high--much higher than the money I paid for it.
If LH surges during the night are what ultimately set off ultra rapid cycling, I feel my options are limited from a theoretical perspective.
Taking a mood stabilizer for 3 to 4 months and letting my hormone levels return to normal would seem like the best course of action, but I have yet to find any mood stabilizer that I can tolerate longer than a week let alone on the scale of months. And starting and stopping a mood stabilizer can result in even more damage, so this doesn't seem like a great candidate to even try.
I could taper off of the leuprolide acetate. This will almost certain require a LH surge to start the leydig cells up again with normal production of testosterone. At best, tapering off the leuprolide acetate would only delay what would be the enviable course of ultra rapid cycling.
I proposed to my doctor that I be given testosterone cypronate at levels representative of 50 to 75% of my previous testosterone levels. Then over several months the testosterone cypronate would be slowly dialed back until I am off of it completely. The hope is that it would avoid the slow and gradual rise in testosterone levels. As the exogenous testosterone would be lowered, my body would make up for the slack. The goal would be to minimize the gradual rise in testosterone. However, if my leydig cells are nearly shutdown, it is likely that I will still experience some LH surge initially as my body attempts to start things back up again. The hope would be that the LH surges would quickly be minimized. But honestly I have no idea if these LH surges would be the same or less in intensity and frequency compared to doing nothing. At a minimum, having extra testosterone available during significant increases in LH may be enough to stop the initiation of rapid cycling. It is conjecture, but is there anything better to go off of at this point?
Another option is to forego being on my own internal production of testosterone and start TRT indefinitely at my previous levels. I am driven to gain control over my testosterone levels, so this may eliminate the drive toward castration without the need for any periodic break in testosterone. This option would allow me to periodically take a break from testosterone if it were still needed. This could be accomplished by stoping the exogenous testosterone and, if necessary, resuming the leuprolide acetate or depo provera ahead of time. Once I achieved the necessary reprieve due to psychological reasons, I could immediately start back on TRT to previous levels. Even with the possibility of start and stops, this would disconnect the the hypothalamic-pituitary-gonadal axis and most likely avoid rapid cycling all together.
Being at a minimum of testosterone currently gives me access to a kind of clarity and a minimum of bias. I am okay with how I feel on a day to day basis with androgen deprivation. I feel complete relief from the incongruity that exists with normal levels of testosterone. However, the long term side effects of androgen deprivation are completely and unequivocally unacceptable. So while it is something that I seemingly need to experience from time to time, it is not a physiological state I should endure for long periods of time. If I do not experience androgen deprivation from time to time in my life from normal endogenic levels of testosterone, I have no doubt that I will eventually act out on the drive toward castration. I have fought against this for years and have yet to find any other reasonable alternative to manage and reduce the castration fixation. The million dollar question is how to take a testosterone break without rapid cycling upon discontinuation? Secondarily, how do I minimize the amount of time spent in testosterone deprivation?
If this experiment once again sends me into ultra rapid cycling, I will consider this an overall failure. I cannot and must not be allowed to enter ultra rapid cycling again and again. Any solution that repeatedly results in that is inherently a non-solution. The question is obviously what alternative is there? If this fails, it increases the likelihood that I will eventually act out on the castration fixation, especially if there are no alternatives. This experiment has likely bought me a year or two at best and I value that, but it is obviously a temporary solution. It may not be reasonable to repeat if it produces rapid cycling. Prolonging this experiment as my doctor suggests, likely won't noticeably delay the day when all of this comes to a head again. And if it is inevitable that I'm going to enter rapid cycling, I want to get it over with as soon as possible and move on in life.
In an optimal situation, I would discontinue the leuprolide acetate, in several months I would be back within normal levels of testosterone, and my mood would remain stable. Unfortunately, that is likely a fantasy. The idea of ultra rapid cycling is frankly terrifying and it's even worse that I largely don't have any control over whether it happens or not.
At this point it appears that I get to choose from stoping immediately or slowly tapering off the leuprolide acetate. I feel that both carry nearly the same risk of rapid cycling. Thus given the choice between the two, it is an obvious choice to me to stop now. I feel that doing nothing will almost certainly result in rapid cycling. And I feel that tapering down on leuprolide acetate will only marginally reduce the risk of rapid cycling, I will have
y take MUCH longer to
ne levels.
I feel that taking exogenous testosterone and cycling down over 3 to 4 months would provide a significantly reduced chance of rapid cycling and is the most reasonable option. This probably won't be given as an option. My therapist didn't seem overly supportive of this idea either.
The most likely idea to avoid rapid cycling is to skip any idea of returning to normal levels of endogenous testosterone and take exogenous testosterone indefinitely. I'm not excited about this idea, but my therapist is very supportive of this option. In fact, he would like to see me put at the very high end of the normal range unless there is some physiological reason not to do so. Self administered intramuscular injections on a weekly basis would not be cost prohibitive, but it seems somehow wrong. It only seems somewhat reasonable given that I'm likely to cause a permanent infarction of the leydig cells anyway in the next few years. And it is the most likely to avoid the rapid cycling.
G
g down of weekly injections of testosterone cypionate over 4 months is the best course of action. Start with 80mg/week. Hold that level for 2.5 months. Then reduce the dosage by an average of 10mg/week.
If given the option to taper down or just stop the leuprolide acetate, I will simply stop. There seems to be little if any benefit to be gained. If there is some physiological reason why this should not be done, I am all ears. I have yet to see any evidence to suggest that this is the case.
If I am given the option to just start and stay on a normal amount of exogenous testosterone, I would have to give it some serious thought. It somehow seems wrong. But it might provide the most straight forward way to give me control in the long run without inducing ultra rapid cycling. And I would have a much better informed decision on whether it is a bad idea to follow through with the castration fixation.
If I am given the option to try mood stabilizers, I will say no. Given my past experience with them, I feel that it actually raises the chance of cycling. The likelihood of needing to start and stop is astronomically high, so I can't imagine why it would even be recommended.
If I am given the option of staying on the leuprolide acetate at current levels indefinitely, the answer is no. My therapist and I are in concurrent that this is unacceptable. The long term side effects of androgen deprivation are not reasonable.
If I am given the option of staying on the leuprolide acetate indefinitely but at much lower levels that allow my testosterone levels to stay within the lower normal range, I will still say no. For one thing, it is predicated on the idea that the desire won't persist if my testosterone levels are left in the lower range. I don't know if that is true or not. And secondly, it is way too expensive and I'm not for sure there is a low enough level that permits some reduction of testosterone but a reduction within the normal adult range. It would have to be an extremely small amount… maybe on the order of .2 to .4mg/day. Or maybe even spreading a fraction of a partial dose to every few days. It would still require frequent injections to allow some kind of titration. This was the original plan. But now that the castration drive has been eliminated, the desire to do this indefinitely has dropped to zero. The fact that it is extremely expensive makes this a definite no. I cognitively knew that this would happen, but it is easy to ignore when you are on the verge of castrating yourself.
And although the option is not on the table, it is worth at least pondering. If there were ever a clear headed moment to critically think about this option, now would be the time while I am at castrate levels. What about the idea of following through on actual castration in a sa[quote="g
nner? This would be done with every intention
[/quote]
of going on TRT (testosterone replacement therapy) afterward. And it would require getting silicon replacements for my other half's sake. The appearance is important to him. This is a really bad idea since I don't know with any certainty how I will feel on exogenous testosterone. It is possible that exogenous testosterone will interact with my mood in unpredictable ways or maybe there will be some aspect of TRT that is undesirable compared to my natural production of testosterone. I won't know this until I have explored this option first hand. And I refuse to use illicit sources to explore it. Maybe this is a good reason to trial it now anyway for a short period of time? What is the worst that could happen? I enter rapid cycling? There is already a high probability of that as it stands. It's possible that I could have some regret about the actual physical loss of my testicles. Even with the drive completely eliminated, I safely feel that this will not be the case. But I will never be 100% certain until I'm actually faced with it. Because of this struggle, I have never felt that my identity is tied to whether or not I have testicles.
In short, the idea of castration should really be the last option of resort and it should only be remotely considered after experiencing exogenous testosterone. The real advantage to this solution is I would absolutely have control over my level of testosterone. So long as it didn't create a physiological problem, such as too high of red blood count and I stayed within the normal range, I would have control of where I stood in the range.
In conclusion, I strongly feel that now is the time to restore androgen levels to the normal range. Taking leuprolide acetate was ultimately predicated on the risk of following through with castration. As was expected and based on previous experience with depo provera, that drive has been entirely eliminated with androgen deprivation.
The internal drive for castration generally rises over time largely independent of my mood. The drive for castration can and does reach critical levels with hypersexuality during periods of hypomania. How well I am able to deal with the sudden increase in the fixation depends on where the base line levels started out. Once the period of hypersexuality is over with, the level generally returns to its prior base line or slightly above where they were before the episode of hypomania. The most recent trial of leuprolide acetate has not permanently eliminated the drive toward castration. It is likely that it will resolve the castration fixation to manageable levels for the next year or two.
The trick is to return to
without entering rapid cycling.
If someone, anyone, has better information that is relevant, I am eager to hear what you have to say. As it has always been, I am stuck between a rock and a hard place. And right now I'm simply struck with fear.
