I’ve gave in and started a cycle after lots of TRT frustration. Can I PCT off altogether or back on TRT

[Spartan1985]

So after a long frustrating process with TRT and managing side affects with little benefits I found a kind of tolerable middle ground after some kind advice from members on here. Was doing 10mg test prop subQ daily with 250iu hcg. This made the side effects of worsening ED issues etc a little more manageable, felt a little more emotionally stable. Libido woke up but very minimal. Did seem to put a fair amount of weight on round the mid section and training recovery went to almost nothing as hit a kind of burnout feeling ( I was training very intensely so not sure this is linked) anyway as I’ve been losing the battle of trying to get my physique into shape and not feeling any benefits from TRT in terms of energy, libido, ED, or pretty much any area in which made me start I decided I would do a 10week cycle to try get into some sort of shape for summer to help me feel a little better about myself. Question is, could I use a long PCT after this to just not return to TRT? Been on TRT around 5years and it’s been a disaster, started after nearly dying due to excessive oral use but haven’t found any of the results other people seem to claim. Is it possible now to just PCT back to normality after this cycle just to see what ‘normal’ would be like at this stage? Could always return to TRT with a blank canvas afterwards if it works out another disaster

 

[madman]

So after a long frustrating process with TRT and managing side affects with little benefits I found a kind of tolerable middle ground after some kind advice from members on here. Was doing 10mg test prop subQ daily with 250iu hcg. This made the side effects of worsening ED issues etc a little more manageable, felt a little more emotionally stable. Libido woke up but very minimal. Did seem to put a fair amount of weight on round the mid section and training recovery went to almost nothing as hit a kind of burnout feeling ( I was training very intensely so not sure this is linked) anyway as I’ve been losing the battle of trying to get my physique into shape and not feeling any benefits from TRT in terms of energy, libido, ED, or pretty much any area in which made me start I decided I would do a 10week cycle to try get into some sort of shape for summer to help me feel a little better about myself. Question is, could I use a long PCT after this to just not return to TRT? Been on TRT around 5years and it’s been a disaster, started after nearly dying due to excessive oral use but haven’t found any of the results other people seem to claim. Is it possible now to just PCT back to normality after this cycle just to see what ‘normal’ would be like at this stage? Could always return to TRT with a blank canvas afterwards if it works out another disaster

Even when implementing PCT you are still going to experience a crash it will just soften the blow and allow you to get back to your baseline much quicker but even then your fertility can take a big hit and much longer to recover than natty T levels.

If you have been abusing T/AAS whether blasting/cruising or cycling especially long-term let alone if you are older chances are your baseline TT and more importantly FT will be dismal.

The only way to know where your baseline truly sits is to come off everything and give it time then get a thorough panel which will include LH/FSH, TT, FT, SHBG, and estradiol.

Would need to have an SA done to see where your fertility markers sit.

 

[Spartan1985]

Even when implementing PCT you are still going to experience a crash it will just soften the blow and allow you to get back to your baseline much quicker but even then your fertility can take a big hit and much longer to recover than natty T levels.

Chances are if you have been abusing T/AAS whether blasting/cruising or cycling especially long-term let alone if you are older chances are your baseline TT and more importantly FT will be dismal.

The only way to know where your baseline truly sits is to come off everything and give it time then get a thorough panel which will include LH/FSH, TT, FT, SHBG, and estradiol.

Would need to have an SA done to see where your fertility markers sit.

Hi Madman thanks for taking the reply, it was actually your advice that allowed me find a balance with previous issues so thanks again for that.

I’ve got 3 kids and no intentions of adding any more under any circumstances so fertility has no bearing on my life thankfully. I was essentially just looking for guidance on if it would be possible to PCT off this cycle to find what baseline would look and feel like to allow a comparison to TRT. As I said I’ve not really found TRT to be of any real benefit whatsoever and have considered many times whether it’s worth continuing. It may be that due to previous AAS abuse as opposed to use the benefits are limited but essential when compared to natty or it may make no real difference either way in which case the daily jabs etc are pointless.

So yes the idea would be to PCT off and find baseline then do bloodwork and also compare general symptoms plus overall how do I actually feel with no TRT, just a question of how do I do that? I assume PCT duration would be much longer than just the usual 3-4 weeks post cycle?

 

[madman]

Hi Madman thanks for taking the reply, it was actually your advice that allowed me find a balance with previous issues so thanks again for that.

I’ve got 3 kids and no intentions of adding any more under any circumstances so fertility has no bearing on my life thankfully. I was essentially just looking for guidance on if it would be possible to PCT off this cycle to find what baseline would look and feel like to allow a comparison to TRT. As I said I’ve not really found TRT to be of any real benefit whatsoever and have considered many times whether it’s worth continuing. It may be that due to previous AAS abuse as opposed to use the benefits are limited but essential when compared to natty or it may make no real difference either way in which case the daily jabs etc are pointless.

So yes the idea would be to PCT off and find baseline then do bloodwork and also compare general symptoms plus overall how do I actually feel with no TRT, just a question of how do I do that? I assume PCT duration would be much longer than just the usual 3-4 weeks post cycle?

Thread 'Fertility maintenance or restoration in men before, during, and after TRT or AAS'

Sep 25, 2022

Fertility Preservation in Hypogonadal Men (2018)
Robert J. Carrasquillo and Ranjith Ramasamy


Introduction

Testicular failure is defined as the impairment or loss of both the endocrine functions of the testis (production of testosterone, or T) and exocrine function (production of spermatozoa). Testicular failure can result from the pathology of the testis itself or disorder at any point in the hypothalamic-pituitary-gonadal axis. Primary testicular failure is characterized by normal/low T in the presence of the elevated follicle-stimulating hormone...

• madman
• fertility/spermatogenesis; tth/aas; hypogonadism
• Replies: 25
• Forum: hCG, Clomid & Others for Fertility, PCT or Low T

• 

 

[Spartan1985]

Thread 'Fertility maintenance or restoration in men before, during, and after TRT or AAS'

Sep 25, 2022

Fertility Preservation in Hypogonadal Men (2018)
Robert J. Carrasquillo and Ranjith Ramasamy


Introduction

Testicular failure is defined as the impairment or loss of both the endocrine functions of the testis (production of testosterone, or T) and exocrine function (production of spermatozoa). Testicular failure can result from the pathology of the testis itself or disorder at any point in the hypothalamic-pituitary-gonadal axis. Primary testicular failure is characterized by normal/low T in the presence of the elevated follicle-stimulating hormone...

• madman
• fertility/spermatogenesis; tth/aas; hypogonadism
• Replies: 25
• Forum: hCG, Clomid & Others for Fertility, PCT or Low T

• 

I’ve read through that but again the focus seems to be mostly in regaining fertility. I’m essentially looking to see if the end of this cycle would be a good time to just come off TRT and how that could be done safely and effectively. As per the end of any cycle there is always an expected crash so it may be more tolerable psychologically to come off TRT at that time. I am looking for PCT protocol advice given the duration of the cycle when coupled with the duration of time on TRT plus history of AAS abuse. It may end up that I feel worse overall and have to restart TRT with a blank canvas and accept that I despite the fact I get little to no benefits when compared to others it’s better than how I would feel without it.

 

[Guided_by_Voices]

I used to come off of TRT for two months out of the year. Some things I learned that might be relevant for you. Don't expect to recover as quickly as you do on AAS. I would adopt a training protocol where you never do max effort reps and you may also want to go to a 9 day week for your training schedule in order to have more time to recover between body parts. TRT and AAS mask overtraining. You will likely recover faster if you have been doing HCG. Weight around the mid-section screams excess cortisol so you may want to look into protocols that normalize cortisol. Once you are a few month into your PCT, you can reassess and see what remaining issues you have as well as do blood work, and then focus on the remaining issues. For example if libido is an issue, PT-141 or MT2 is worth trying and is not suppressive.

 

[Spartan1985]

I used to come off of TRT for two months out of the year. Some things I learned that might be relevant for you. Don't expect to recover as quickly as you do on AAS. I would adopt a training protocol where you never do max effort reps and you may also want to go to a 9 day week for your training schedule in order to have more time to recover between body parts. TRT and AAS mask overtraining. You will likely recover faster if you have been doing HCG. Weight around the mid-section screams excess cortisol so you may want to look into protocols that normalize cortisol. Once you are a few month into your PCT, you can reassess and see what remaining issues you have as well as do blood work, and then focus on the remaining issues. For example if libido is an issue, PT-141 or MT2 is worth trying and is not suppressive.

Why did you do the 2 months off? Was that just to restore some normal function? I think I’ve been over training as was on a mission to try be in good shape for turning 40 in a few weeks but hit burnout which set the whole process back around 2 months. Aside from that though I’ve had a poor experience of TRT so looking to try life without it and recover to whatever baseline I may be able to reach then decide from there. Would you have any guidance on PCT protocol? I used to do 100mg clomid EOD twice then 75mg EOD twice then drop to 50mg EOD for around 3 weeks. 20mg nolvadex throughout with large blast of 5000iu twice in first week. This was in my 20s after 12-16week cycles but in those days being young and naive no blood work was done and used to adopt the bro science “equal time off as on cycle” before starting again. Would I just run similar to the above for 4 weeks and do bloods or would it be expected to take 8-10weeks or longer before any recovery given the duration of TRT?

 

[madman]

I’ve read through that but again the focus seems to be mostly in regaining fertility. I’m essentially looking to see if the end of this cycle would be a good time to just come off TRT and how that could be done safely and effectively. As per the end of any cycle there is always an expected crash so it may be more tolerable psychologically to come off TRT at that time. I am looking for PCT protocol advice given the duration of the cycle when coupled with the duration of time on TRT plus history of AAS abuse. It may end up that I feel worse overall and have to restart TRT with a blank canvas and accept that I despite the fact I get little to no benefits when compared to others it’s better than how I would feel without it.

Standard protocol is typically hCG/clomid.

The main purpose of hCG which mimics LH is to kickstart the testes/ITT especially if hCG was not used during T-therapy or abuse of T/AAS (cycling/blast n cruise).

Need to be mindful of how long you stay on as the hpta will still be depressed.

Clomid will increase LH/FSH which will aid in restoring/preserving intra-testicular testosterone/fertility without further suppression hpta.

You do not need to use really high doses of clomid!

Depending on the protocol chosen various doses/weeks implemented are used.




More recent paper.

Thread 'Endocrine therapy to restore endogenous T levels and alleviate ASIH symptoms in AAS dependent men'

Jun 10, 2024

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

Long-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment ta…

www.sciencedirect.com

ABSTRACT

Introduction

Long-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men.


Methods

In this...

• madman
• aas; hypogonadism; pct; serm/hcg
• Replies: 6
• Forum: hCG, Clomid & Others for Fertility, PCT or Low T

Many people who use AAS tend to self-monitor symptoms of androgen deficiency that follows AAS cessation through a practice called “post-cycle therapy” (PCT) (Bulut et al., 2023; Griffiths et al., 2017). PCT comprises hormonal agents such as selective estrogen receptor modulators (SERMs), human chorionic gonadotropin (hCG) and aromatase inhibitors (Rahnema et al., 2014). These drugs are normally prescribed for treatment of infertility or breast cancer in women (Bonnecaze et al.,2021). In men, hCG acts as a LH-analogue with longer half-life on Leydig cells in the testicles, by stimulating the synthesis and release of endogenous testosterone (Lee & Ramasamy, 2018). Clomiphene citrate (CC) belongs to the drug class SERM (Rahnema et al., 2014), and has previously been used in treating male hypogonadism unrelated to AAS use (Guo et al., 2020; Wheeler et al., 2019). CC‘s mechanism of action is to increase the release of pituitary LH and FSH, thus restoring and preserving testicular testosterone production and spermatogenesis, without further suppressing the HPG axis (Krzastek et al., 2019). While there has been limited research on the safety profile of CC use in men, previous literature has indicated mild side effects such as weight gain, mood changes, breast tenderness and hot flushes (Huijben et al., 2023; Huijbenet al., 2022; Krzastek et al., 2019). Moreover, there have been single case reports of more severe adverse events such as liver injury (Zhang et al.,2018), suicidal behavior and psychotic episodes (Knight et al., 2015), thromboembolic events (Solipuram et al., 2021), and visual disturbances (Purvin, 1995)

A combination of CC and hCG has previously demonstrated to be an effective therapeutic approach in promoting a sufficient HPG axis response to recover spermatogenesis after exogenous testosterone exposure (Wenker et al., 2015), and has been proposed as a treatment option among infertile men with former AAS use (Tatem et al., 2020). Additionally, the use of off-label PCT protocols has widespread accessibility among people who use AAS (Westerman et al., 2016). Despite this, no previous experimental study has evaluated their efficacies in treating or preventing the development of ASIH. There is an urgent need to gain more knowledge on the safety and usefulness of PCT and whether endocrine therapies of similar nature should be implemented during or after AAS discontinuation in clinical settings. In this pilot study, we aimed to obtain insights into the potential utility of endocrine therapy with CC, transdermal testosterone, and hCG for AAS dependent men withdrawing from prolonged continuous AAS use. A key aspect of AAS dependence involves the difficulty in discontinuing use due to substantial discomfort. Recognizing this challenge, we initiated this treatment to assess its feasibility in guiding individuals through the most challenging phase following AAS cessation.




2.4. The intervention

In this proof-of-concept study, we tested an adapted version of a 16-week hormone therapy model with CC as main component, as initially proposed by Rahnema et al. (2014). Based on previous clinical and user experience with AAS dependence, we considered it highly likely that men with years-long continuous use would become symptomatically hypogonadal shortly after discontinuing AAS, even with a total testosterone (TT) levels within the normal reference (range 9–30 nmol/l) due to accustomed supraphysiological endogenous androgen levels over many years. Therefore, we chose to initiate treatment when TT levels dropped below 25 nmol/l, which according to our observations occurred relatively quickly after they had ceased AAS, depending on their recent cycle interval. Subsequently, 25 mg CC were administered every second day for a continuous period of 16 weeks, and 50 mg transdermal testosterone gel were added daily during the first four weeks to avoid symptoms of ASIH. Upon cessation of gel treatment, serum testosterone concentrations typically start to decline after 24 h, returning to baseline levels within 48 h following the administration of the final dose (Marbury et al., 2003). Consequently, to ensure that the recent dermal application did not interfere with blood tests, participants were instructed to abstain from using testosterone gel for 48 h before undergoing the first blood test during the intervention phase, which occurred after four weeks of CC treatment. hCG injections (Ovitrelle 250µg/0.5 ml prefilled pen = choriogonadotropin alfa/recombinant hCG equivalent to approximately 6500 international units (IU)) were then added in the treatment scheme in cases of inadequate endogenous TT response below 10 nmol/l. An initial dose of 1500 IU hCG was given twice per week during week 4–8, and if insufficient testicular response persisted at week 8, the dosages were increased to 1500 IU 3x per week during week 8–12 (i.e. maximum eight weeks of hCG injections). Of note, participants presenting with low levels of both TT and sex hormone binding globulin (SHBG), giving a concurrent high free testosterone index (FTI or also called free androgen index), were not given hCG. See Fig. 1 for a detailed illustration of the treatment model. The original treatment protocol as proposed in Rahnema et al. (2014) suggested to halve the CC dose from 25 to 12.5 mg in weeks 10–16. However, drawing from the existing literature concerning the safety and efficacy of treatments for men with hypogonadism not stemming from ASIH (Huijben et al., 2022), the lowest dose of CC used was 25 mg every other day. Hence, we regarded a dosage of 25 mg every second day for a duration of 16 weeks as a safe and feasible alternative option. Nonetheless, since this intervention had not been scientifically tested previously, we were still uncertain about the outcomes. All modifications to the original endocrine model, as well as the decision on whether to include hCG in the individual protocol or terminate the intervention,were made after thorough evaluations among a team of three physicians,including a senior endocrinologist. Furthermore, Rahnema et al. (2014) did not specify a particular target TT level. However, we presumed that achieving a TT level of 20 nmol/l during the intervention or a TT level within the normal physiological TT range (9–30 nmol/l) at the conclusion of intervention would be a reasonable target. The midrange TT level of 20 nmol/l during intervention was specifically chosen to avoid setting it too low, which might have lead participants to experience symptoms of hypogonadism before the HPG axis was normalized. Consequently, participants reaching TT levels of ≥20 nmol/l before week 16 would conclude the intervention. The treatment would be considered potentially low-responsive if the target was not reached or in cases of TT levels below 9 nmol/l by week 16.

Frontiers | Prolonged post-androgen abuse hypogonadism: potential mechanisms and a proposed standardized diagnosis

Androgen abuse, which is increasingly prevalent, inevitably leads to suppression of the hypothalamic-pituitary-gonadal axis (HPGA). While most individuals re...

www.frontiersin.org

 

[Guided_by_Voices]

Why did you do the 2 months off? Was that just to restore some normal function? I think I’ve been over training as was on a mission to try be in good shape for turning 40 in a few weeks but hit burnout which set the whole process back around 2 months. Aside from that though I’ve had a poor experience of TRT so looking to try life without it and recover to whatever baseline I may be able to reach then decide from there. Would you have any guidance on PCT protocol? I used to do 100mg clomid EOD twice then 75mg EOD twice then drop to 50mg EOD for around 3 weeks. 20mg nolvadex throughout with large blast of 5000iu twice in first week. This was in my 20s after 12-16week cycles but in those days being young and naive no blood work was done and used to adopt the bro science “equal time off as on cycle” before starting again. Would I just run similar to the above for 4 weeks and do bloods or would it be expected to take 8-10weeks or longer before any recovery given the duration of TRT?

Regarding training, overtraining and short-term extreme goals are very stressful in themselves and can cause a lot of problems because the body is in a constant state of stress. I also think 18 months of consistency toward any goal is a good timeframe and mindset to have. I say 18 months because you have to pursue something long enough to work through setbacks and things like vacations/holidays. None of what you're planning will work if you are overtraining or under-eating. Something as simple as walking can be a big benefit if done consistently. I'm a huge believer in only doing things that are maintainable long-term so that you develop a mentality of consistency.

Regarding why I came off, I had a life situation at the time where I could do it and I just wanted the peace of mind knowing that I could come off if I had to. I also like to experiment, but I wouldn't recommend that for most people.

Regarding Clomid and PCT in general, I did Clomid mono-therapy before I ever got on TRT, and the highest dose I could use without an "off" feeling was either 12mg every other day or 25mg twice per week, which put my LH and T in a decent place. I am not a fan of the huge doses used by many since Clomid can have negative emotional side effects for some people and take a long time to clear out of the body. Also, you have been putting your body through extreme hormonal gyrations, so, for your current goals, the closer you can stay to a single maintainable steady state the better. If you did the doses above and then did bloods including LH after 3 months or so, that seems like it would be a reasonable plan. Enclomiphene was not available when I was using Clomid so you might have better results with it if you can get it. Ideally you can come off of the Clomid completely but some people need it long-term. Some years I also did HCG mono-therapy for my "off" time but that would suppress you natural LH production.

Something I did not do them but would do now is to supplement with one of the Bull Testicle extract products. I have used the Grazin brand and the product from Heart and Soil. I used to think they would be broken down into their amino acids and do nothing, but there is theory that (apparently like collagen) they have some sort of signaling affect, and they seem to very anecdotally have a benefit for me even on TRT.

As an aside, the time on equals time off guideline is not really valid IMO and is one of the problems with the cycling mentality because you are not in a hormonal steady-state for much of the time "off". Most gym bros should not IMO be cycling but, if they are truly near their genetic maximum (which few are due to lack of sufficient training volume and overall conditioning) should only add in either a GH secretagouge and/or a microdose of a minimally suppressive compound like oxandrolone.

In your case, if you are not back to a good place in a few months, there are non-hormonal options to try once you have your natural production re-established, and depending on what your issues are at that time.

 

[Spartan1985]

Regarding training, overtraining and short-term extreme goals are very stressful in themselves and can cause a lot of problems because the body is in a constant state of stress. I also think 18 months of consistency toward any goal is a good timeframe and mindset to have. I say 18 months because you have to pursue something long enough to work through setbacks and things like vacations/holidays. None of what you're planning will work if you are overtraining or under-eating. Something as simple as walking can be a big benefit if done consistently. I'm a huge believer in only doing things that are maintainable long-term so that you develop a mentality of consistency.

Regarding why I came off, I had a life situation at the time where I could do it and I just wanted the peace of mind knowing that I could come off if I had to. I also like to experiment, but I wouldn't recommend that for most people.

Regarding Clomid and PCT in general, I did Clomid mono-therapy before I ever got on TRT, and the highest dose I could use without an "off" feeling was either 12mg every other day or 25mg twice per week, which put my LH and T in a decent place. I am not a fan of the huge doses used by many since Clomid can have negative emotional side effects for some people and take a long time to clear out of the body. Also, you have been putting your body through extreme hormonal gyrations, so, for your current goals, the closer you can stay to a single maintainable steady state the better. If you did the doses above and then did bloods including LH after 3 months or so, that seems like it would be a reasonable plan. Enclomiphene was not available when I was using Clomid so you might have better results with it if you can get it. Ideally you can come off of the Clomid completely but some people need it long-term. Some years I also did HCG mono-therapy for my "off" time but that would suppress you natural LH production.

Something I did not do them but would do now is to supplement with one of the Bull Testicle extract products. I have used the Grazin brand and the product from Heart and Soil. I used to think they would be broken down into their amino acids and do nothing, but there is theory that (apparently like collagen) they have some sort of signaling affect, and they seem to very anecdotally have a benefit for me even on TRT.

As an aside, the time on equals time off guideline is not really valid IMO and is one of the problems with the cycling mentality because you are not in a hormonal steady-state for much of the time "off". Most gym bros should not IMO be cycling but, if they are truly near their genetic maximum (which few are due to lack of sufficient training volume and overall conditioning) should only add in either a GH secretagouge and/or a microdose of a minimally suppressive compound like oxandrolone.

In your case, if you are not back to a good place in a few months, there are non-hormonal options to try once you have your natural production re-established, and depending on what your issues are at that time.

Thanks for the reply. Sounds positive and that there may be life after TRT as a possibility I often wonder whether my HPTA is just fried altogether. I’m finishing this cycle around 3rd week in August then going to attempt PCT to achieve a natural baseline and re-evaluate after a few months at that level. Madman has sent a detailed study regarding PCT so have plenty of info to work with. You guys have been great again so many thanks. Will update on the process as it goes along. I think you may be right with the cortisol also so ordered some cortibloc to assist with the short term issues.

 

[Spartan1985]

Standard protocol is typically hCG/clomid.

The main purpose of hCG which mimics LH is to kickstart the testes/ITT especially if hCG was not used during T-therapy or abuse of T/AAS (cycling/blast n cruise).

Need to be mindful of how long you stay on as the hpta will still be depressed.

Clomid will increase LH/FSH which will aid in restoring/preserving intra-testicular testosterone/fertility without further suppression hpta.

You do not need to use really high doses of clomid!

Depending on the protocol chosen various doses/weeks implemented are used.




More recent paper.

Thread 'Endocrine therapy to restore endogenous T levels and alleviate ASIH symptoms in AAS dependent men'

Jun 10, 2024

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

Long-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment ta…

www.sciencedirect.com

ABSTRACT

Introduction

Long-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men.


Methods

In this...

• madman
• aas; hypogonadism; pct; serm/hcg
• Replies: 6
• Forum: hCG, Clomid & Others for Fertility, PCT or Low T

Many people who use AAS tend to self-monitor symptoms of androgen deficiency that follows AAS cessation through a practice called “post-cycle therapy” (PCT) (Bulut et al., 2023; Griffiths et al., 2017). PCT comprises hormonal agents such as selective estrogen receptor modulators (SERMs), human chorionic gonadotropin (hCG) and aromatase inhibitors (Rahnema et al., 2014). These drugs are normally prescribed for treatment of infertility or breast cancer in women (Bonnecaze et al.,2021). In men, hCG acts as a LH-analogue with longer half-life on Leydig cells in the testicles, by stimulating the synthesis and release of endogenous testosterone (Lee & Ramasamy, 2018). Clomiphene citrate (CC) belongs to the drug class SERM (Rahnema et al., 2014), and has previously been used in treating male hypogonadism unrelated to AAS use (Guo et al., 2020; Wheeler et al., 2019). CC‘s mechanism of action is to increase the release of pituitary LH and FSH, thus restoring and preserving testicular testosterone production and spermatogenesis, without further suppressing the HPG axis (Krzastek et al., 2019). While there has been limited research on the safety profile of CC use in men, previous literature has indicated mild side effects such as weight gain, mood changes, breast tenderness and hot flushes (Huijben et al., 2023; Huijbenet al., 2022; Krzastek et al., 2019). Moreover, there have been single case reports of more severe adverse events such as liver injury (Zhang et al.,2018), suicidal behavior and psychotic episodes (Knight et al., 2015), thromboembolic events (Solipuram et al., 2021), and visual disturbances (Purvin, 1995)

A combination of CC and hCG has previously demonstrated to be an effective therapeutic approach in promoting a sufficient HPG axis response to recover spermatogenesis after exogenous testosterone exposure (Wenker et al., 2015), and has been proposed as a treatment option among infertile men with former AAS use (Tatem et al., 2020). Additionally, the use of off-label PCT protocols has widespread accessibility among people who use AAS (Westerman et al., 2016). Despite this, no previous experimental study has evaluated their efficacies in treating or preventing the development of ASIH. There is an urgent need to gain more knowledge on the safety and usefulness of PCT and whether endocrine therapies of similar nature should be implemented during or after AAS discontinuation in clinical settings. In this pilot study, we aimed to obtain insights into the potential utility of endocrine therapy with CC, transdermal testosterone, and hCG for AAS dependent men withdrawing from prolonged continuous AAS use. A key aspect of AAS dependence involves the difficulty in discontinuing use due to substantial discomfort. Recognizing this challenge, we initiated this treatment to assess its feasibility in guiding individuals through the most challenging phase following AAS cessation.




2.4. The intervention

In this proof-of-concept study, we tested an adapted version of a 16-week hormone therapy model with CC as main component, as initially proposed by Rahnema et al. (2014). Based on previous clinical and user experience with AAS dependence, we considered it highly likely that men with years-long continuous use would become symptomatically hypogonadal shortly after discontinuing AAS, even with a total testosterone (TT) levels within the normal reference (range 9–30 nmol/l) due to accustomed supraphysiological endogenous androgen levels over many years. Therefore, we chose to initiate treatment when TT levels dropped below 25 nmol/l, which according to our observations occurred relatively quickly after they had ceased AAS, depending on their recent cycle interval. Subsequently, 25 mg CC were administered every second day for a continuous period of 16 weeks, and 50 mg transdermal testosterone gel were added daily during the first four weeks to avoid symptoms of ASIH. Upon cessation of gel treatment, serum testosterone concentrations typically start to decline after 24 h, returning to baseline levels within 48 h following the administration of the final dose (Marbury et al., 2003). Consequently, to ensure that the recent dermal application did not interfere with blood tests, participants were instructed to abstain from using testosterone gel for 48 h before undergoing the first blood test during the intervention phase, which occurred after four weeks of CC treatment. hCG injections (Ovitrelle 250µg/0.5 ml prefilled pen = choriogonadotropin alfa/recombinant hCG equivalent to approximately 6500 international units (IU)) were then added in the treatment scheme in cases of inadequate endogenous TT response below 10 nmol/l. An initial dose of 1500 IU hCG was given twice per week during week 4–8, and if insufficient testicular response persisted at week 8, the dosages were increased to 1500 IU 3x per week during week 8–12 (i.e. maximum eight weeks of hCG injections). Of note, participants presenting with low levels of both TT and sex hormone binding globulin (SHBG), giving a concurrent high free testosterone index (FTI or also called free androgen index), were not given hCG. See Fig. 1 for a detailed illustration of the treatment model. The original treatment protocol as proposed in Rahnema et al. (2014) suggested to halve the CC dose from 25 to 12.5 mg in weeks 10–16. However, drawing from the existing literature concerning the safety and efficacy of treatments for men with hypogonadism not stemming from ASIH (Huijben et al., 2022), the lowest dose of CC used was 25 mg every other day. Hence, we regarded a dosage of 25 mg every second day for a duration of 16 weeks as a safe and feasible alternative option. Nonetheless, since this intervention had not been scientifically tested previously, we were still uncertain about the outcomes. All modifications to the original endocrine model, as well as the decision on whether to include hCG in the individual protocol or terminate the intervention,were made after thorough evaluations among a team of three physicians,including a senior endocrinologist. Furthermore, Rahnema et al. (2014) did not specify a particular target TT level. However, we presumed that achieving a TT level of 20 nmol/l during the intervention or a TT level within the normal physiological TT range (9–30 nmol/l) at the conclusion of intervention would be a reasonable target. The midrange TT level of 20 nmol/l during intervention was specifically chosen to avoid setting it too low, which might have lead participants to experience symptoms of hypogonadism before the HPG axis was normalized. Consequently, participants reaching TT levels of ≥20 nmol/l before week 16 would conclude the intervention. The treatment would be considered potentially low-responsive if the target was not reached or in cases of TT levels below 9 nmol/l by week 16.

Frontiers | Prolonged post-androgen abuse hypogonadism: potential mechanisms and a proposed standardized diagnosis

Androgen abuse, which is increasingly prevalent, inevitably leads to suppression of the hypothalamic-pituitary-gonadal axis (HPGA). While most individuals re...

www.frontiersin.org

Thanks madman yet again for a very comprehensive answer. It’s very much appreciated. Judging by the paper you sent the idea of a 4/5week PCT won’t be very likely so plan will be to follow the timeline in that study with bloodwork around week 12. Not sure if there’s test gel available without prescription here though so might not be able to include that part. I’ll update on how the process goes once PCT is started. Thanks again you always seem to be able to offer clarity when there’s so much confusion

 

[Willyt]

Did seem to put a fair amount of weight on round the mid section and training recovery went to almost nothing as hit a kind of burnout feeling ( I was training very intensely so not sure this is linked)

You've already identified a potential culprit other than TRT that could be contributing to your issues.
Overtraining can hit you hard - shitty sleep, general malaise, wired but exhausted feeling, etc.

I have been guilty of this many times. As you get older, its very easy to overdo it especially with heavy lifting and/or excessive cardio. Respect those rest days!