Switched to Scrotal T Cream - Crazy Results

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Ya good point. @osirisrisen have you considered just splitting your dose into one click in am and one click in pm instead of dropping down to one click?

@osirisrisen have you ever tried twice a day dosing with the cream?



True.....but the main advantage when using testosterone gels/creams or even the older patch (which is rarely used now) is that they are the only methods of treatment which have the benefit of most closely mimicking the daily 24 hr diurnal circadian rhythm.

This can only be achieved when the testosterone is applied once daily!

In healthy young men there is significant diurnal variation in testosterone.....levels peak and are highest in the early morning with nadir levels in the evening hours.

Unfortunately many are using gels/creams whether standard body/scrotal application twice daily (am/pm) so you are in no way no how mimicking the natural 24 hr circadian rhythm of a healthy young male.

Let alone many are using very high doses so not only are you achieving a high peak in the early am but also again in the early evening.

Many end up with amped up levels of T in the evening/later hours when in fact naturally levels would be declining.

Healthy DHT levels definitely plays a role in libido/erectile function but I would say the true benefit of transdermal testosterone whether standard body application/scrotal is that when applied once daily in the am it will allow one to achieve the benefits of the daily fluctuations of T with levels highest in the am and lower in the evening/night.

Testosterone has a tonic effect and can amp up the CNS.....having very high levels in the evening/later hours goes against the natural 24 hr circadian rhythm where peak levels are highest in the am only to later decline in the early afternoon/late evening.

On average there will be a 20-25% (25-40% in some) difference in peak--->trough levels.

Many put too much weight on feeling the need to have to keep T levels elevated 24/7 in order to benefit from trt.

Sure if one were to use the once daily am application you would definitely want to make sure T levels are not too low in the evening but again highly doubtful that having lower (reasonable) levels in the evening is going to make or break the effectiveness of a protocol.

Top it off that most healthy young males have TT levels of 600-800 ng/dL at peak only to be followed by on average a 20-25% (25-40% in some) decline--->trough in the late afternoon/early evening.
 
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I sent an email to Defy asking about switching to cream.

This is probably my last ditch effort as I am over TRT at this point. The emotional and sexual sides are wearing me down again.
 
I sent an email to Defy asking about switching to cream.

This is probably my last ditch effort as I am over TRT at this point. The emotional and sexual sides are wearing me down again.

I hope the cream gives you the TRT results that you’ve been looking for. I have an appt with defy in a couple weeks, and I’m also going to request to switch to scrotal cream.
 
Top it off that most healthy young males have TT levels of 600-800 ng/dL at peak only to be followed by a 25-40% decline--->trough in the late afternoon/early evening.
I've always been curious about this. Do you know of any studies on health young men that show this ? To mimic the pulsatile nature of T is quite a challenge - would something like natesto may come closer than cream perhaps when dosed multiple times a day.
 
https://www.excelmale.com/forum/threads/efficacy-of-nasal-testosterone-gel-natesto®-stratified-by-baseline-endogenous-testosterone-levels.19080/





The 24-hour pharmacokinetic profile of testosterone for patients on TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur on average every 2 hours. A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h). The nadir (trough) between doses correlates well with pre-treatment endogenous levels at diagnosis.

The unique, pulsatile, pharmacokinetic profile is believed to have limited impact on the HPG axis with significant trough time preserving luteinizing hormone (LH), follicle stimulating hormone (FSH), endogenous testosterone production and sperm counts, while also limiting excess RBC production, estradiol, DHT and PSA in clinical trials.


Conclusions
Testosterone nasal gel treatment restores TT levels while preserving significant aspects of HPG function, including continued release of gonadotropins and production of endogenous testosterone, which allows maintenance of baseline levels. Both modest TDS (TT 250-300 ng/dL; (8.7 – 10.4 nmol/L)) and more severe TDS patients (TT 0-100 ng/dL (0 – 3.5 nmol/L), when treated with TNG, achieve max TT levels around 800 ng/dL (27.7 nmol/L). Efficacy, as measured by erectile function and mood were significantly improved to similar levels in both groups. The unique, ultradian, pulsatile nature of TNG, which does not depress endogenous testosterone production means that a wide range of testosterone deficient patients can effectively be treated with it.
 
“The pharmacology of NATESTO® is unique from other testosterone products that treat low testosterone or hypogonadism”, said Dr. Ethan Grober, Associate Professor, Division of Urology, University of Toronto and one of the new study’s authors. “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. Furthermore, NATESTO® has been shown to work even in severely testosterone deficient patients, suggesting that a wide range of testosterone deficient patients can be effectively treated.





Take home points:

*In between NATESTO® doses, all patients in the phase 3 study maintained their natural testosterone at the same levels they had prior to entry into the study, indicating that NATESTO® does not suppress natural testosterone production.


*Based on the data, Acerus believes that the mechanism of action of NATESTO® is unique whereby the peaks in testosterone generated by NATESTO® dosing provide efficacy and improvement of symptoms, while the time between doses (4-8 hours) allows for the maintenance of testicular testosterone production and sperm production.


*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.


*Furthermore, NATESTO® has been shown to work even in severely testosterone deficient patients, suggesting that a wide range of testosterone deficient patients can be effectively treated.


Acerus Announces Publication of Study Results Demonstrating Effectiveness of NATESTO® Regardless of Baseline Symptom Severity

 
Take home points:

*In between NATESTO® doses, all patients in the phase 3 study maintained their natural testosterone at the same levels they had prior to entry into the study, indicating that NATESTO® does not suppress natural testosterone production.


*Based on the data, Acerus believes that the mechanism of action of NATESTO® is unique whereby the peaks in testosterone generated by NATESTO® dosing provide efficacy and improvement of symptoms, while the time between doses (4-8 hours) allows for the maintenance of testicular testosterone production and sperm production.


*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.


*Furthermore, NATESTO® has been shown to work even in severely testosterone deficient patients, suggesting that a wide range of testosterone deficient patients can be effectively treated.

awesome, now lets wait for a nasal irritation free ,cheaper compounded version of this lol ! Probably 5-10 years later, people on new forms of trt may look back with pity on us for what we had available.
 
awesome, now lets wait for a nasal irritation free ,cheaper compounded version of this lol ! Probably 5-10 years later, people on new forms of trt may look back with pity on us for what we had available.


So true!

I had a co-worker of mine who started on androgel and although he felt ok it was doubtful his levels were ever where they truly needed to be as his treating doc was one of those "we will just test TT" and not even blink an eye when it came to SHBG/FT/estradiol..... he eventually moved to injections (mind you his doctor had him injecting 200 mg every 2 weeks.....shame full to say the least).

I had to convince him to at least change over to 100 mg once weekly mind you I would have had him inject 50 mg every 3.5 days over once weekly and even than his SHBG was never tested and I had to convince him the significance of this let alone he may very well end up being one who needs to inject lower doses of T more frequently as in EOD or daily.

Finally he switched over to Natesto when it first became available in Canada and when he first started he felt great but again he was only dosing once daily and I again had to explain to him that the proper dosing protocol is 3 times daily.

Unfortunately due to his doctors ignorance let alone his stubborn headedness he eventually quit and stopped trt!

He never had a chance to succeed!
 
I’m curious if the cream when it works is more from DHT raising so high or the super short half life.

With injections you really have to wait out sides for weeks to really see where you are at. With the creams you spend some time at very high T levels, but you are back into a normal range same day.

Glad it’s working for people. Has me curious but not enough to leave a working protocol.
As Madman pointed out, most are using the cream twice a day so levels are kept pretty high throughout. After 12 hrs there is about a 25% decrease so with the next application near that time levels are not dropping significantly.
 
Pharmacokinetics of testosterone cream applied to scrotal skin



True that the absorption is fast and the 25 mg dose was shown to maintain physiological levels for 16 hrs.






Pharmacokinetics of testosterone cream applied to scrotal skin




Transdermal delivery of testosterone was first reported in the late 1980s (Findlay et al., 1987). Transdermal absorption depends on testosterone forming a local depot in the stratum corneum, the dead skin cell layer which limits permeability of small molecules through the skin, to allow for prolonged testosterone delivery (Barry, 1983).



. The first transdermal testosterone product, an adhesive scrotal patch (Findlay et al., 1987; Behre et al., 1999), was discontinued because of poor acceptability arising from the need for scrotal shaving, dermal irritation and poor adhesion when wet and elevated circulating DHT. Subsequently, non-scrotal patches were developed for application to truncal skin (Meikle et al., 1996; Arver et al., 1997), but they feature a generic limitation of application site irritation (as a result of necessary inclusion of absorption enhancers) leading to a high rate of skin reactions (Jordan et al., 1998) including even severe burn-like skin reactions (Bennett, 1998). Transdermal testosterone gels are intended for application to truncal but not genital skin and feature low rates of dermal irritation (Handelsman, 2012), but risk topical transfer to women (de Ronde, 2009) and children (Martinez-Pajares et al., 2012) in intimate contact with the patient. Yet, scrotal skin is advantageous for transdermal testosterone delivery as it has the thinnest stratum corneum (Smith et al., 1961; Ya-Xian et al., 1999), high steroid permeability (Wester & Maibach, 1989) many times greater than non-scrotal skin (Lin et al., 1999), and minimizes the risk of passive topical transfer to others. The present dose ranging study aimed to determine the pharmacokinetics of testosterone in an alcohol-free cream formulation (Wittert et al., 2016) when administered to the scrotal skin.






MATERIALS AND METHODS
This was a single-center, three-phase cross-over pharmacokinetic study of three single doses in random sequence of testosterone cream [AndroForte 5, 5% w/v (50 mg/mL) testosterone cream; Lawley Pharmaceuticals, West Leederville, Australia] administered to healthy volunteers. To evaluate the pharmacokinetics of exogenous testosterone in eugonadal volunteers, endogenous testosterone production was suppressed throughout the study by injection of nandrolone decanoate. Healthy male volunteers aged 18–50 years were recruited by advertising and reimbursed for their time and travel costs to participate in the study.

The primary endpoint was serum testosterone concentrations over 16 h measured by liquid chromatography, tandem mass spectrometry (LC-MS). The secondary endpoints were serum dihydrotestosterone (DHT) and estradiol (LC-MS) as well as tolerability

Each eligible, consenting participant was administered three single doses of testosterone cream in random sequence on different study days with at least 2 days wash-out period between studies. The testosterone doses were 50 mg (1 mL cream), 25 mg (0.5 mL cream) and 12.5 mg (0.25 mL cream) each drawn from the same tube for each participant with the volume (dose) of testosterone cream measured using 1 mL insulin syringe and verified by a separate investigator. A venous cannula was inserted to obtain three pre-dose baseline blood samples at 15, 5 min and immediately prior to application of the testosterone cream which was applied at 08:00 to the scrotum by the participant using a gloved hand. Blood sampling was then further undertaken at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, and 16 h post-cream application. Serum was stored frozen (20 °C) until assay in a single batch. In addition, venous and finger-prick blood samples were spotted onto filter paper at 0, 4, 8, 12, 16, and 24 h and stored at room temperature in sealed plastic bags. To convert ng/mL to ng/dL, multiply ng/mL by 100. To convert ng/mL to SI units (nM) multiply by 3.47 for testosterone and 3.45 for DHT and to convert pg/mL to SI units (pM) multiply by 3.68 for estradiol.






RESULTS
Administration of testosterone to the scrotal skin produced a swift increase in serum testosterone with significant effects of dose (p < 0.0001), time (p = 0.003) and the time x dose interaction (p = 0.04) (Fig. 1). After administration of testosterone, serum DHT concentrations demonstrated significant effects of time (p < 0.0001) but neither the dose (p = 0.35) nor the time x dose interaction (p = 0.08) had statistically significant effects on serum DHT. For serum estradiol, there was no significant effects of testosterone administration on dose (p = 0.057), time (p = 0.057) or their interaction (p = 0.60) (Fig. 2).


After testosterone administration, the peak concentration of serum testosterone was dose dependent with the time of peak being between 1.9 to 2.8 h after doses (Table 2). Serum DHT rose to a peak concentration between 1.0 and 1.4 ng/mL (3.5–4.8 nM) between 4.1 and 5.6 h after testosterone administration, but the peak times and concentrations were not dose dependent. Using data from pooling the three testosterone doses, the estimated peak serum DHT concentration was 1.2 ng/mL (4.1 nM) and occurred at 4.9 h. When time of peak was determined empirically, there were similar trends to later time of peak concentration of serum DHT compared with serum testosterone (Table 2). Serum estradiol did not display any significant changes in time of peak or of peak concentrations with testosterone dose (Fig. 3).

All doses were well tolerated without complaint of skin irritation or discomfort






DISCUSSION
This study provides a pharmacokinetic profile of three doses of testosterone administered to the scrotal skin in a cream formulation. Application of the testosterone cream produced a rapid rise in serum testosterone peaking around 2 h after administration with a dose-dependent peak concentration, but not any consistent relationship between time of peak and testosterone dose. At the lowest dose (12.5 mg), the serum testosterone concentrations were maintained in physiological range for at least 12 hr and with the 25 mg dose maintained serum testosterone concentrations within the physiological range for nearly 24 h concentration.






SUMMARY
Scrotal skin is thin and has high steroid permeability,
but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9–2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nM) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route



Figure 1 Serum testosterone following three doses (12.5, 25, 50 mg) of testosterone cream applied to the scrotal skin at time zero with sequential blood sampling at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 16 h. Each participant underwent scheduled blood sampling after administration of each of the three doses with at least 2 days between administration and sampling periods. S1 and S2 are two screening blood samples taken prior to the study and P1 and P2 are two blood samples taken 15 and 5 min prior to the application of the testosterone cream. Data are plotted as mean and standard error of the mean. Biexponential curves are fitted to all the data for each dose. For further details see the text. Note conversion factors: to ng/dL multiple ng/mL by 100; to SI units multiply ng/mL by 3.47. [Colour figure can be viewed at wileyonlinelibrary.com].
Screenshot (537).png
 
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Case Study: Absorption of Testosterone Cream via Scrotal Delivery



In this case study it was shown that after application (200 mg dose) that therapeutic levels with concentrations of 1204.7 ng/dL were reached within 2 hrs and consistent concentrations of 1320.6 remained beyond 6 hrs.



Case Study: Absorption of Testosterone Cream via Scrotal Delivery.


Abstract

Transdermal testosterone has been used for years to treat patients with low testosterone symptoms. Clinically, we have monitored patients to evaluate results of testosterone absorption via blood serum concentrations. The data on multiple time points to determine trough and peak concentrations is lacking in the literature. In this case study, we demonstrate the absorption of testosterone cream via scrotal delivery. The data suggests that after application therapeutic levels are reached with concentrations of (1204.7 ng/dL) within two hours. Additionally, consistent concentrations (1320.6 ng/dL) remain beyond six hours. To our knowledge, this is the first study to collect and measure multiple time points for testosterone via transdermal delivery. The research indicates that testosterone via transdermal delivery is an excellent method to achieve therapeutic concentrations of testosterone. Most importantly, the patient's symptoms resolved without side effects.

PMID: 30384346
 
Crisler was known for treating many with once daily application of transdermal testosterone!

Many men do and have done fine using the standard once daily application regarding transdermal testosterone.

As we know the ones frequenting the forums are in many cases not doing well and it could just as easily be said that there are many men who do not seek out a forum for advice as they are doing just fine!
Screenshot (538).png
 
How’s that work anyway? I was under the impression there was no ester, and the body absorbs it very fast through the scrotum.

When once daily was the norm it was EXTREMELY rare you’d find someone on a forum telling you cream was working out great.
Yes, it does (as Madman pointed out).

I still don't think that once daily is going to be very optimal as you still would drop pretty dramatically by the next application the next day (24hrs). Then a big/fast increase again (to me) creates a rollercoaster effect again. I would imagine that it would be much more doable on scrotum application as you are getting levels higher/absorbing more then with the various other application methods (so you aren't starting at 500ng/dl and ending at 100ng/dl).

I'm not a big believer in mimicking the bodies "natural" process in this regard anyway. I would rather feel great all of the time (provided bloodwork is not showing any issues).
 
I can see the theoretical benefits of both having variations in blood levels, and having steady levels of testosterone. Dr. Nichols said the majority of his patients apply testosterone cream to their scrotum twice a day, so I’m assuming having steadier levels is what he has found to be a little more optimal.
 
True.....but the main advantage when using testosterone gels/creams or even the older patch (which is rarely used now) is that they are the only methods of treatment which have the benefit of most closely mimicking the daily 24 hr diurnal circadian rhythm.

This can only be achieved when the testosterone is applied once daily!

In healthy young men there is significant diurnal variation in testosterone.....levels peak and are highest in the early morning with nadir levels in the evening hours.

Unfortunately many are using gels/creams whether standard body/scrotal application twice daily (am/pm) so you are in no way no how mimicking the natural 24 hr circadian rhythm of a healthy young male.

Let alone many are using very high doses so not only are you achieving a high peak in the early am but also again in the early evening.

Many end up with amped up levels of T in the evening/later hours when in fact naturally levels would be declining.

Healthy DHT levels definitely plays a role in libido/erectile function but I would say the true benefit of transdermal testosterone whether standard body application/scrotal is that when applied once daily in the am it will allow one to achieve the benefits of the daily fluctuations of T with levels highest in the am and lower in the evening/night.

Testosterone has a tonic effect and can amp up the CNS.....having very high levels in the evening/later hours goes against the natural 24 hr circadian rhythm where peak levels are highest in the am only to later decline in the early afternoon/late evening.

On average there will be a 20-25% (25-40% in some) difference in peak--->trough levels.

Many put too much weight on feeling the need to have to keep T levels elevated 24/7 in order to benefit from trt.

Sure if one were to use the once daily am application you would definitely want to make sure T levels are not too low in the evening but again highly doubtful that having lower (reasonable) levels in the evening is going to make or break the effectiveness of a protocol.

Top it off that most healthy young males have TT levels of 600-800 ng/dL at peak only to be followed by on average a 20-25% (25-40% in some) decline--->trough in the late afternoon/early evening.


I agree with what you are saying. I might try one click twice a day, but I have noticed sleep/mood issues when doing 2x a day dosing. On top of that, it is a real PITA. Once in the morning getting a high peak and then slowly tapering off over the day seems to work best for me.

I think that is a big reason I always felt off using shots. It was max T, all day, every day, no break. Shots have never felt good for me.

Plus I don't think it drops out of our systems in some super dramatic way. It's not like I'm going from 1500 at 2pm to 100 at 9pm. At least it doesn't feel like it.
 
I agree with what you are saying. I might try one click twice a day, but I have noticed sleep/mood issues when doing 2x a day dosing. On top of that, it is a real PITA. Once in the morning getting a high peak and then slowly tapering off over the day seems to work best for me.

I think that is a big reason I always felt off using shots. It was max T, all day, every day, no break. Shots have never felt good for me.

Plus I don't think it drops out of our systems in some super dramatic way. It's not like I'm going from 1500 at 2pm to 100 at 9pm. At least it doesn't feel like it.

Do you know what your SHBG level is?
 
How long after you apply the cream do you wait to put on underwear?

I put it on right after I dry off, so the time it takes me to put on deodorant and brush my teeth. As far as the other stuff, it's all fine and dandy.

Osirisrisen - Great to hear you're doing well with the cream. I have the same question as Gman86 about putting on underwear. Do you wait for the cream to dry first? Sorry if that's what you were answering...sounded like you were saying when you apply the cream.

Also, with the click applicator, do you rub the cream in with your fingers, or do you use the rounded top of the applicator to rub it in?
 
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