What if you could enjoy the benefits of exogenous testosterone - even if on a limited basis - while minimizing many of the usual side effects?
I was determined to find out through a very unscientific experiment with Natesto, a short-acting nasal testosterone gel discussed numerous times on this forum. Over a 3-month period, I took a single dose (11mg) of Natesto one hour before each workout (5-6 times per week). Feel free to skip my long-winded thought process and go straight to the results at the end.
TESTOSTERONE REPLACEMENT versus SUPPLEMENTATION
Many TRT rookies (including myself) are surprised when they first learn that TRT eventually shuts down the body’s natural production of testosterone, sending the HPTA into hibernation mode. Once you reach that point, you are replacing, not supplementing, your naturally produced testosterone.
But what if there was a way you could supplement your endogenous testosterone without shutting down your HPGA? If so, why would you want to do this?
ROLE OF THE TROUGH IN HPGA SUPPRESSION
Several months ago, I became interested in the idea of “topping off” your natural production instead of replacing it. I had read reports about athletes microdosing T without suppression, but didn’t understand how that could be possible. I posted the following thread and received some very interesting feedback from members far more knowledgeable and experienced than me:
How do athletes microdose without suppressing natural T?
I had initially thought that the body suppressed natural production either because it detected exogenous/synthetic testosterone or because peak testosterone levels had exceeded a pre-determined threshold. Wrong on both counts.
Cataceous explained that such HPGA suppression is driven more by the trough than the peak, pointing to a study done on Natesto, a testosterone gel that is squirted into the nasal cavity. The idea is that a fast acting testosterone like Natesto clears the body so quickly that it allows your testosterone level to return to its baseline (i.e., your natural trough) in between doses so that HPGA suppression is minimal. In the words of Nastesto’s makers, “the release of testosterone with NATESTO is pulsatile - closely matching the bodies natural testosterone release. Consequently, NATESTO does not suppress a man's natural testosterone level, but simply adds to it to achieve a normal, safe level of testosterone.”
Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels
“The unique, pulsatile PK profile is believed to have limited impact on the hypothalamic-pituitary-gonadal (HPG) axis, with substantial trough time preserving LH, FSH, and endogenous testosterone production, and sperm counts, while also limiting excess red blood cell production, estradiol, DHT, and prostate-specific antigen levels in clinical trials.”
POTENTIAL ADVANTAGES OF THE PULSATILE APPROACH
Achieving a ‘steady state’ testosterone level (or something close to it) seems to have become the gold standard in HRT presumably because it enables you to avoid large swings following suppression of natural T production.
So why would anyone want to settle for the highs and lows of the short-acting, ‘pulsatile’ approach of Natesto? The short answer is that a daily return to your natural baseline levels may not be such a bad thing after all. Nelson posted an interesting interview with Dr. Ramasamy in which he explained why such short-acting forms of testosterone fell out of favor over the decades and the potential for “on-demand” fast-acting testosterone forms like Natesto:
New Testosterone Nasal Gel (Natesto) Data- Interview with Dr Ramasamy - ExcelMale
Staying fertile is one obvious reason to favor the pulsatile approach since studies appear to show that sperm production is maintained with Natesto. But there is another less obvious reason to try this approach. It could become a viable alternative for those of us who have quit TRT due to the inability to manage a particular side effect that may have been caused by shutdown of the HPGA.
WHAT ABOUT HCG?
HCG is a far more popular option for maintaining natural production of testosterone, in this case by mimicking LH. So why not simply use HCG with TRT to get the best of both worlds? Many people on this forum have done just that with excellent results. Although there are potential short-term side effects and long-term health implications to consider, all of which which have been hotly debated around here. Another possible downside is that HCG has no effect on TRT’s suppression of GnRH - i.e., it only solves a part of the problem by treating the testes, but not the hypothalamus and its signaling of GnRH.
This may be important because the implications of shutting down GnRH are still not well understood. For example, this recent thread (courtesy Cataceous) raises some very interesting questions about the potential negative effects of GnRH suppression that go beyond LH and FSH production.
Is GnRH suppression hurting us?
By contrast, Natesto appears to maintain release of GnRH by allowing testosterone to return to its natural trough.
LIMITED UPSIDE OF PULSATILE APPROACH
Let’s assume you could eliminate a particular TRT side effect that has plagued you by taking the pulsatile approach to avoid HPTA shutdown. How would the benefits compare to a TRT steady-state approach?
One would expect that the upside to the pulsatile approach would be somewhat limited compared to full-blown TRT considering that you are only enjoying peak levels for several hours per day versus 24 hours per day with steady state. However, even if the upside is limited, something is better than nothing for those of us who have begrudgingly quit TRT.
BACKGROUND ON NATESTO
There have been many informative Natesto posts on this forum. For the uninitiated, Natesto is a testosterone gel with the following ingredients:
Natesto supposedly takes advantage of the nose’s highly vascular environment for rapid absorption of testosterone into the bloodstream. Natesto is fast-acting, peaking at 45 min - 1 hour followed by a return to endogenous, pre-dose baseline levels 4 to 6 hours later. Maximum TT levels are approx 600-800 depending on your starting baseline.
The recommended dosing of 3x times per nostril per day requires 6 total actuations per day (180 actuations per month). There are 60 actuations per bottle, meaning that you would need 3 bottles per month.
The pricing of Natesto is rather confusing. The drugstore price is jaw dropping if your insurance does not cover it and seems to be a moving target. Initially you could get coupon for $211 per bottle, then it increased to $311 per bottle. Now multiple that price x 3 bottles per month! I later discovered that there is a direct-to-home option for $140 per month, which apparently covers the prescribed 3 bottles ($1.50 per dose). Natesto has apparently cut an exclusive deal with one particular pharmacy to offer the steeply discounted price. NATESTO® (testosterone) Nasal Gel CIII | Patient Resources
MY PREVIOUS TRT EXPERIENCE
Before I launch into the details of my Nastesto experiment, here is background on my TRT experience for context. I am a somewhat typical 50-year old secondary hypogonadism case who grew tired of getting weaker (and skinny-fat) despite lifting and eating right. In the 5 years prior to TRT, my TT had consistently tested in low to mid-200s. Thanks to this forum and an open-minded doc, I finally mustered up the courage to try TRT last year.
My protocol was T cypionate shallow IM injections w/ dose of 100mg per week (50mg E3.5). Total TT of 740 (123 - 813) on trough day. No major E2 issues, testing in low 20s (8-35). SBGH of 40 (19.3 - 76.4).
Physical results on cypionate were excellent and definitely exceeded my expectations. Over 8 month period, I put on solid 15lbs, which is a lot for a hard gainer, ectomorph body type like mine even when taking into account water weight. Strength gains of 20-25%. My traps and shoulders finally came back! Unbelievable effect on workout recovery.
Now for the downside. The side effects started to rear their ugly head around the 3-month mark. Libido all but disappeared. Lust was no longer part of my vocabulary. During sex, my shrunken right testicle kept getting stuck up inside my body, making for a very awkward experience. Sensitivity went from great to terrible. On top of that, my emotions were blunted to point where it became a serious problem as a father and husband. (I felt like a Great White Shark with those flat, unfeeling eyes). Sleep apnea hit me out of nowhere. The last straw was that I started experiencing random dizzy spells with ringing in the ears and difficulty concentrating.
Long story short, all of these issues finally convinced me to discontinue TRT after an 8-month run. I went cold turkey for several months before undertaking my Natesto experiment and lost nearly all of my hard-earned TRT gains. The side effects went away except for the flagging libido and curiously, the random dizziness.
MY NASTESTO ‘PRE-WORKOUT’ PROTOCOL
I did not follow Natesto’s recommended 3 doses per day protocol. Instead, I only used a single dose of Natesto (1 pump per nostril for total of 11mg) prior to each of my workouts (5-6 per week). I took this minimalist approach for two reasons. First, I needed to keep my expenses down. Second, I wanted to start with the minimum number of doses per day so I could tritrate later if necessary. Regarding the timing, I experimented a bit and eventually settled on 1 hour prior to the workout (which matches Natesto’s peak).
My experiment has been running for 3 months. In short, the results have been encouraging! While there was inevitably a placebo effect during first 2 weeks, the positive differences have been noticeable. However, there is one major problem aside from the expense. The nasal delivery method is not sustainable on a long-term basis. Just my subjective opinion.
PROS
The skeptic in me would argue that a pre-workout shot of caffeine w/ creatine could achieve similar results to my Natesto routine. That is an exaggeration, but the point is that you are definitely not optimizing exogenous testosterone with the pulsatile approach compared to steady state TRT. But again, if full-blown TRT is no longer an option due to a side effect, you have nothing to lose (other than $$ of course!).
I will definitely continue to explore the pulsatile approach, but not with Natesto. Major kudos to the creators of Natesto for thinking outside the box. However, the daily gel up the nose would drive me nuts over the long haul.
FAST-ACTING ALTERNATIVES TO NATESTO?
If not Natesto, what other fast-acting forms of testosterone might be suitable for the pulsatile approach?
Would Empower’s scrotal cream work? My limited understanding is that the scrotal application peaks around 2 hours, but the tail is longer, with levels staying elevated at 10 hour mark and then finally dissipating at 16 hours.
Let’s assume you applied the scrotal only once in the morning. Would this give your body enough time to return to its natural T trough before the next dose in order to avoid HPGA suppression?
I was determined to find out through a very unscientific experiment with Natesto, a short-acting nasal testosterone gel discussed numerous times on this forum. Over a 3-month period, I took a single dose (11mg) of Natesto one hour before each workout (5-6 times per week). Feel free to skip my long-winded thought process and go straight to the results at the end.
TESTOSTERONE REPLACEMENT versus SUPPLEMENTATION
Many TRT rookies (including myself) are surprised when they first learn that TRT eventually shuts down the body’s natural production of testosterone, sending the HPTA into hibernation mode. Once you reach that point, you are replacing, not supplementing, your naturally produced testosterone.
But what if there was a way you could supplement your endogenous testosterone without shutting down your HPGA? If so, why would you want to do this?
ROLE OF THE TROUGH IN HPGA SUPPRESSION
Several months ago, I became interested in the idea of “topping off” your natural production instead of replacing it. I had read reports about athletes microdosing T without suppression, but didn’t understand how that could be possible. I posted the following thread and received some very interesting feedback from members far more knowledgeable and experienced than me:
How do athletes microdose without suppressing natural T?
I had initially thought that the body suppressed natural production either because it detected exogenous/synthetic testosterone or because peak testosterone levels had exceeded a pre-determined threshold. Wrong on both counts.
Cataceous explained that such HPGA suppression is driven more by the trough than the peak, pointing to a study done on Natesto, a testosterone gel that is squirted into the nasal cavity. The idea is that a fast acting testosterone like Natesto clears the body so quickly that it allows your testosterone level to return to its baseline (i.e., your natural trough) in between doses so that HPGA suppression is minimal. In the words of Nastesto’s makers, “the release of testosterone with NATESTO is pulsatile - closely matching the bodies natural testosterone release. Consequently, NATESTO does not suppress a man's natural testosterone level, but simply adds to it to achieve a normal, safe level of testosterone.”
Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels
“The unique, pulsatile PK profile is believed to have limited impact on the hypothalamic-pituitary-gonadal (HPG) axis, with substantial trough time preserving LH, FSH, and endogenous testosterone production, and sperm counts, while also limiting excess red blood cell production, estradiol, DHT, and prostate-specific antigen levels in clinical trials.”
POTENTIAL ADVANTAGES OF THE PULSATILE APPROACH
Achieving a ‘steady state’ testosterone level (or something close to it) seems to have become the gold standard in HRT presumably because it enables you to avoid large swings following suppression of natural T production.
So why would anyone want to settle for the highs and lows of the short-acting, ‘pulsatile’ approach of Natesto? The short answer is that a daily return to your natural baseline levels may not be such a bad thing after all. Nelson posted an interesting interview with Dr. Ramasamy in which he explained why such short-acting forms of testosterone fell out of favor over the decades and the potential for “on-demand” fast-acting testosterone forms like Natesto:
New Testosterone Nasal Gel (Natesto) Data- Interview with Dr Ramasamy - ExcelMale
Staying fertile is one obvious reason to favor the pulsatile approach since studies appear to show that sperm production is maintained with Natesto. But there is another less obvious reason to try this approach. It could become a viable alternative for those of us who have quit TRT due to the inability to manage a particular side effect that may have been caused by shutdown of the HPGA.
WHAT ABOUT HCG?
HCG is a far more popular option for maintaining natural production of testosterone, in this case by mimicking LH. So why not simply use HCG with TRT to get the best of both worlds? Many people on this forum have done just that with excellent results. Although there are potential short-term side effects and long-term health implications to consider, all of which which have been hotly debated around here. Another possible downside is that HCG has no effect on TRT’s suppression of GnRH - i.e., it only solves a part of the problem by treating the testes, but not the hypothalamus and its signaling of GnRH.
This may be important because the implications of shutting down GnRH are still not well understood. For example, this recent thread (courtesy Cataceous) raises some very interesting questions about the potential negative effects of GnRH suppression that go beyond LH and FSH production.
Is GnRH suppression hurting us?
By contrast, Natesto appears to maintain release of GnRH by allowing testosterone to return to its natural trough.
LIMITED UPSIDE OF PULSATILE APPROACH
Let’s assume you could eliminate a particular TRT side effect that has plagued you by taking the pulsatile approach to avoid HPTA shutdown. How would the benefits compare to a TRT steady-state approach?
One would expect that the upside to the pulsatile approach would be somewhat limited compared to full-blown TRT considering that you are only enjoying peak levels for several hours per day versus 24 hours per day with steady state. However, even if the upside is limited, something is better than nothing for those of us who have begrudgingly quit TRT.
BACKGROUND ON NATESTO
There have been many informative Natesto posts on this forum. For the uninitiated, Natesto is a testosterone gel with the following ingredients:
- Testosterone (4.5% concentration)
- Castor oil (solvent)
- Oleoyl polyoxylglyceride (wetting agent)
- Colloidal silicon dioxide (viscosity increasing agent)
Natesto supposedly takes advantage of the nose’s highly vascular environment for rapid absorption of testosterone into the bloodstream. Natesto is fast-acting, peaking at 45 min - 1 hour followed by a return to endogenous, pre-dose baseline levels 4 to 6 hours later. Maximum TT levels are approx 600-800 depending on your starting baseline.
The recommended dosing of 3x times per nostril per day requires 6 total actuations per day (180 actuations per month). There are 60 actuations per bottle, meaning that you would need 3 bottles per month.
The pricing of Natesto is rather confusing. The drugstore price is jaw dropping if your insurance does not cover it and seems to be a moving target. Initially you could get coupon for $211 per bottle, then it increased to $311 per bottle. Now multiple that price x 3 bottles per month! I later discovered that there is a direct-to-home option for $140 per month, which apparently covers the prescribed 3 bottles ($1.50 per dose). Natesto has apparently cut an exclusive deal with one particular pharmacy to offer the steeply discounted price. NATESTO® (testosterone) Nasal Gel CIII | Patient Resources
MY PREVIOUS TRT EXPERIENCE
Before I launch into the details of my Nastesto experiment, here is background on my TRT experience for context. I am a somewhat typical 50-year old secondary hypogonadism case who grew tired of getting weaker (and skinny-fat) despite lifting and eating right. In the 5 years prior to TRT, my TT had consistently tested in low to mid-200s. Thanks to this forum and an open-minded doc, I finally mustered up the courage to try TRT last year.
My protocol was T cypionate shallow IM injections w/ dose of 100mg per week (50mg E3.5). Total TT of 740 (123 - 813) on trough day. No major E2 issues, testing in low 20s (8-35). SBGH of 40 (19.3 - 76.4).
Physical results on cypionate were excellent and definitely exceeded my expectations. Over 8 month period, I put on solid 15lbs, which is a lot for a hard gainer, ectomorph body type like mine even when taking into account water weight. Strength gains of 20-25%. My traps and shoulders finally came back! Unbelievable effect on workout recovery.
Now for the downside. The side effects started to rear their ugly head around the 3-month mark. Libido all but disappeared. Lust was no longer part of my vocabulary. During sex, my shrunken right testicle kept getting stuck up inside my body, making for a very awkward experience. Sensitivity went from great to terrible. On top of that, my emotions were blunted to point where it became a serious problem as a father and husband. (I felt like a Great White Shark with those flat, unfeeling eyes). Sleep apnea hit me out of nowhere. The last straw was that I started experiencing random dizzy spells with ringing in the ears and difficulty concentrating.
Long story short, all of these issues finally convinced me to discontinue TRT after an 8-month run. I went cold turkey for several months before undertaking my Natesto experiment and lost nearly all of my hard-earned TRT gains. The side effects went away except for the flagging libido and curiously, the random dizziness.
MY NASTESTO ‘PRE-WORKOUT’ PROTOCOL
I did not follow Natesto’s recommended 3 doses per day protocol. Instead, I only used a single dose of Natesto (1 pump per nostril for total of 11mg) prior to each of my workouts (5-6 per week). I took this minimalist approach for two reasons. First, I needed to keep my expenses down. Second, I wanted to start with the minimum number of doses per day so I could tritrate later if necessary. Regarding the timing, I experimented a bit and eventually settled on 1 hour prior to the workout (which matches Natesto’s peak).
My experiment has been running for 3 months. In short, the results have been encouraging! While there was inevitably a placebo effect during first 2 weeks, the positive differences have been noticeable. However, there is one major problem aside from the expense. The nasal delivery method is not sustainable on a long-term basis. Just my subjective opinion.
PROS
- Recaptured about half of my TRT gains relating to strength and muscularity (all relative of course
. If TRT is 9 out of 10 in this category, single dose Natesto is 6-7. A noticeable improvement over my endogenous skinny-fat days throughout my 40s. - Look leaner than T Cyp. Maybe less water retention?
- If you time your dose correctly, you definitely get a rush that lasts throughout a 1-hour workout and beyond.
- Emotionally, I feel like much better than on TRT. Flatness is gone. Sentimental feelings are back. I’m very pleased with this aspect.
- Minimal nut shrinkage
- Sensitivity is back!
- Sleep apnea has not returned
- If you can squirt a vaseline-like substance up your nose every day (let alone 3x per day!), you’re a better man than me. Sometimes I manage not to dwell on it while other times it feels like I’ve got a big snotter up there.
- The gel occasionally runs down back of your throat. Not pleasant. Tastes like something you really shouldn’t ingest.
- Even though I didn’t have any of the nasal-related side effects, you have to wonder about the long-term implications of squirting this stuff into your nasal cavity on a daily basis. Could it affect smell or taste over a period of years??
- Unfortunately, the “on-demand” approach failed to improve libido. This was a major disappointment. I had high hopes that timing a dose 1 hour before sex would do the trick, but no dice. My libido is actually worse than pre-TRT.
- Workout recovery did not come close to matching steady state TRT although its still better than my natural baseline. It would be interesting to see if recovery would improve with a post-workout Natesto dose at night.
- There was no positive or negative impact on mental clarity, alertness, assertiveness, etc. Same for TRT in my case.
- No E2 issues either, but likewise, I never had that problem on TRT.
- HCT impact is to be determined since no blood test yet (sorry Vince!). However, Madman posted recent study indicating that Natesto is less likely to increase HCT so that could be another potential benefit. High hematocrit prevalence with intranasal vs. intramuscular testosterone
The skeptic in me would argue that a pre-workout shot of caffeine w/ creatine could achieve similar results to my Natesto routine. That is an exaggeration, but the point is that you are definitely not optimizing exogenous testosterone with the pulsatile approach compared to steady state TRT. But again, if full-blown TRT is no longer an option due to a side effect, you have nothing to lose (other than $$ of course!).
I will definitely continue to explore the pulsatile approach, but not with Natesto. Major kudos to the creators of Natesto for thinking outside the box. However, the daily gel up the nose would drive me nuts over the long haul.
FAST-ACTING ALTERNATIVES TO NATESTO?
If not Natesto, what other fast-acting forms of testosterone might be suitable for the pulsatile approach?
Would Empower’s scrotal cream work? My limited understanding is that the scrotal application peaks around 2 hours, but the tail is longer, with levels staying elevated at 10 hour mark and then finally dissipating at 16 hours.
Let’s assume you applied the scrotal only once in the morning. Would this give your body enough time to return to its natural T trough before the next dose in order to avoid HPGA suppression?
