What to do if a conventional post-cycle therapy (PCT) fails you [2025 Research]

So guys, I thought I’d do a post about what the next options are if conventional PCT fails. I’ve heard from and spoken to many guys across the world on this, and I’d say in 70-75% of cases I can help get them relatively close to their pre-cycle or pre-TRT levels. Obviously, this is not a perfect science and this process can be complicated by a number of things: generally older guys and those who have used 19-nortestosterone derivatives/progestins (that are more suppressive than non-19-nortestosterone derivatives) are going to have a harder time to recover their HPT axis function. Another big variable is dosage and time on - obviously the guy who has been on 100mg TRT for 3 months and wants to come off is going to have a much easier time than the guy who has B&Ced for 10 years.

Now, in most cases, the big 3 usually suffice:

• Time
• Initial hCG stimulation (but removing this quickly - hCG is suppressive in its own right)
• SERM to modulate estrogen receptors to increase T

However, men who have had significant suppression of their HPT axis over a long period of time for whatever reason just cannot seem to break past say 200-250 Total T levels, and may still feel terrible. I do have some theories around why this is the case, including damage to the Leydig and Sertoli cells (death, apoptosis) - however, what is interesting that even in these men, clomid or enclomiphene actually boosts their LH level to often double or triple reference range - and their body responds. Some men get some solid testosterone readings on enclomiphene, but here’s the issue: once the stimulus is removed, they often go right back down to hypogonadal levels of androgens. In other words, it’s almost as if the brain signalling just isn’t there (gonadotropin release: LH, FSH) to support their natural pre-anything baseline levels of testosterone.

In my opinion, with these men, if the fact that a SERM can raise their LH and they get a significant increase in testosterone as a result, only to go hypogonadal once removed, it’s not actually an issue at the Sertoli/Leydig cell level - this infrastructure is working well with the stimulus of enclomiphene. It’s actually, the brain isn’t pumping out enough gonadotropins. In other words, it’s a brain signalling issue higher up in the HPT axis.

PCT Options for Men after Cycle (Post-Cycle Therapy):

So, there is another option for these kind of men. And it’s in the form of an analogue of GnRH called Triptorelin (acts in the same way that GnRH does). Now, way up in the cascade of the entire HPT axis, GnRH is released from the hypothalamus to stimulate your anterior pituitary to release LH/FSH. So the idea is this - if you can introduce a single, potent dose of GnRH, the idea is you can ‘kickstart’ your HPT axis back into life:

Initially, you might be confused, because if you search Triptorelin online, you get the following:

Triptorelin is a gonadotropin releasing hormone (GnRH) agonist that is a potent inhibitor of the synthesis of testosterone (in men) and estrogen (in women) and is used to treat advanced prostate cancer.

A potent inhibitor of testosterone? Isn’t that the exact opposite of what we want? Well, triptorelin is a double-edged sword.

1. Initially (first injection): Triptorelin, like other GnRH agonists, initially stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This initial phase leads to a temporary increase in the production of sex hormones, like testosterone in men and estrogen in women.
2. Continued Use: With continued administration, triptorelin downregulates GnRH receptors in the pituitary gland as the receptors are fully saturated, thus desensitised and downregulated. This downregulation leads to a significant reduction in the secretion of LH and FSH. As a result, the production of sex hormones (testosterone in men and estrogen in women) by the gonads is greatly reduced. In men, this effect is sometimes referred to as chemical castration. This is precisely why long-term and esterified triptorelin administration (to increase its half-life significantly) is used in men with prostate cancer to suppress androgens to basically castrate levels.

But, there is an opportunity to manipulate step 1 to try and kickstart your HPT axis. In fact, although it's hard to find any evidence of this in the research (mainly because most studies are designed to investigate how well triptorelin suppresses androgens), there is some evidence that the first injection of triptorelin can significantly increase LH and androgens.

According to this study, which administered patients 11.25mg triptorelin pamoate Sub-Q, there was an initial increase in luteinizing hormone (LH) concentrations at week 1 after the first triptorelin injection. Specifically, the mean serum LH values increased by 37.6% at week 1 compared to baseline. However, from week 2 until the end of the study, LH levels were reduced (as expected with continued use). Now, regarding testosterone levels, there was a short-lived “flare-up” (not sure how that got passed as scientific language but anyway) of testosterone levels after the first injection of triptorelin, which is obviously an expected response with GnRH agonists. However again, as expected, after this initial increase, the testosterone levels decreased as intended by the treatment:

Now, to be completely honest, testosterone levels only rose around 50 ng/dL in the study above. Not exactly a great result. And you may be thinking, surely this isn’t going to fix my 10 year B&C-induced hypogonadism to any significant degree. Well, just wait.

In this next study, where rats were given intramuscular injections of triptorelin acetate biodegradable microspheres (0.6 mg/kg) every 28 days, for three cycles, there was a huge spike in total testosterone in the following fashion:

• Initial Testosterone Spike: Following the first injection of triptorelin, there was an initial big surge in testosterone levels. The peak concentration of testosterone (Cmax) reached 22.8 ng/mL at 1 hour after the injection (graph below). This initial increase is consistent with an initial stimulation of the pituitary gland to produce LH and thus increase testosterone.
• Subsequent Testosterone Suppression: After this initial spike, the testosterone levels showed a rapid and sustained decrease. The castration level of testosterone was reached within 5 days after the injection and was maintained below this level until day 28.
• Repeated Doses: For the second and third injections (on days 28 and 56), there was a transient escape of testosterone above castration levels, with peak concentrations (Cmax) of 0.83 ng/mL and 1.27 ng/mL, respectively, observed on day 28 and day 56.

• The second spike (0.83 ng/mL) was 22.8 ng/mL - 0.83 ng/mL = 21.97 ng/mL lower than the initial spike.
• The third spike (1.27 ng/mL) was 22.8 ng/mL - 1.27 ng/mL = 21.53 ng/mL lower than the initial spike.

But that first spike, the first dose was 27x higher than baseline levels. That’s a huge spike in testosterone and perhaps proof that if you could manipulate the pharmacokinetics of an initial dose of triptorelin, you could potentially ‘kickstart’ a sluggish HPT axis into life by forcing a concomitant increase in LH.

So, where does this leave us?

Well, the theoretical idea behind using triptorelin is as follows:

1. Utilising the Initial Stimulatory Effect from known Phamacokinetic Studies: A single small dose of triptorelin may act as a powerful stimulant of the pituitary gland, leading to a surge in LH and FSH. This surge could, in theory, "kickstart" the testes into producing testosterone again.
2. Cautions with Dosage: It's crucial to use a very small dose. A typical dose used for prostate cancer treatment would be far too high and could actually cause further suppression of the HPT axis. The dose intended to stimulate the HPT axis would be significantly lower, often referred to as a "micro-dose."

Take this with a grain of salt and obviously not medical advice, but something like a once off 100mcg shot of triptorelin could be an option here, as a micro-dose to kickstart the HPT axis again.

In summary, this post was mainly for the guys where conventional PCT has failed or they have had such an aggressive and sustained suppression of their HPT axis for such a long time that once the stimulatory effect of a SERM/PCT is removed their HPT axis just cannot return to their natural baseline levels. Using triptorelin is highly controversial and there really is limited information on using it in the context of HPT restarts (as opposed to androgen suppression), but my goal is to get as much information out there as possible so you can be informed in the fitness industry. Groundbreaking research and new theories are often deemed crazy and unrealistic at the start, but can lead to some interesting scientific discoveries.

To have men out there going to their doctor, complaining about low/borderline-low testosterone levels to only be brushed aside and told “you’re fine”, or worse shamed for their usage, is unacceptable to me - these men need help just as much as anyone else.

Thanks so much for reading guys, I’ll see you in the next one!