More on Transdermal gels

One of my Greek friends asked me to try to develop an improved Thiomucase gel. After I had read about some experiments someone performed on himself and I discussed this with my Greek friend, we decided to do some “in vivo” research. I mixed some different active ingredients (aminophylline and glycyrrhetinic acid).

After I finished the first batch of “Improved Thiomucase” and sent it to be tested, I started to make some alcohol-based gels. I had read some reviews on new methods to improve bioavailability and wanted to make some new experimental transdermal compounds.

There is an everlasting attempt to find ways to deliver pharmaceutical active ingredients successfully and convenient to patients. One of those ways is the transdermal gel. Everyone that follows my experiments knows I love to do lab-scale experiments and also developed gels, lotions, sub-q injectables etc, for clients.

I still had some purified and micronized Testosterone Base. Plus I had some powders from sildenafil (Viagra) and tadelafil (Cialis). After reading the many threads about Testim on bodybuilding forums. I became curious about Pentadecalactone, a naturally-occurring scent chemical of male humans which serves to attract females (pheromone). Pentadecalactone is produced by the apocrine glands of the male armpit. It is not only naturally-occurring but can also be artificially synthesized. Later more about pheromones. Pentadecalactone is not used in Testim as a sexual attractant, as most people on the forum seems to think, but it improves bioavailability (absorption).

Elitefitness.com: Dear Friend and Fellow Athlete,

Have you ever dreamed of having insanely high testosterone levels, combined with a muscular explosion and amazing sexual performance? Well a topical testosterone gel called Testim could be the answer to your dreams. You’d be hard-pressed to find a guy who doesn’t want increased muscle gains, unparalleled sexual performance, and improved cognitive functions. Seeing as how testosterone helps boost all of these qualities, it’s no wonder why many people do whatever it takes to increase their testosterone levels. And one of the most popular ways to do this is through a topical testosterone gel called Testim.

What is Testim?

Doctors often prescribe Testim to patients who have low levels of testosterone because this gel provides an infusion of testosterone into the body. So when this manufactured product is used, it helps increase sexual desire/ability, muscle-building capabilities, motivation, and one’s overall sense of well-being. The nice thing about Testim is that you don’t have to use needles because it’s a topical testosterone gel. In other words, you apply the product directly to your skin, and it will absorb into your dermis. As for the packaging, you can get Testim in either a packet or pump bottle – the latter of which works like a lotion bottle. The packaging normally gives instructions for how much of the product to use on your skin, and the best places to apply Testim are your shoulders and upper arms. If you’re familiar with AndroGel, you may have noticed that Testim is very similar to this topical testosterone gel. However, there are some slight differences in the products, with one of the most notable being that you should avoid applying Testim to your abdomen (which is fine for AndroGel). Another difference you should note in the Testim vs. AndroGel comparison is that the latter takes longer to absorb into the skin; in fact, it takes 5-6 hours to settle in, while Testim is absorbed in around 2 hours. Finally, keep in mind that Testim is stickier and has more of an odor than AndroGel does.

Bioavailability

Compounded Testosterone Gels: A Guide for Clinicians and Pharmacists. Cutter C. 2000:

“However, results demonstrated great intra- and interpatient variation in response to therapy, so monitoring serum hormone levels was essential for proper titration of the dose. An estimated absorption efficiency of the gels was from 6% to 50% of the applied amount.”

Despite of these huge differences in bioavailability Testim® claims to deliver 10% testosterone into the body.

Not only the carriers but also the application sites (just as with injectables) seem to be important for the bioavalability.

Application sites: Twenty-one hypogonadal men (age 56.9 +/- 9.0) naïve to prior testosterone therapy and otherwise in good health participated. Three groups of seven applied Testim to three distinct anatomical sites for 1 month per site: arms/shoulders, chest/abdomen, and calves/legs. Overall Total Testosterone and free Testosterone increased significantly over pretreatment levels into the normal range. Testim Gel 1% applied to various anatomical sites increases Total Testosterone and free Testosterone into the normal range; the best levels are achieved with arms/shoulder application. Flexibility in the application site of Testim is possible. Anemia, possibly associated with testosterone deficiency, was an incidental finding in several men and was corrected with topical testosterone replacement(Hb < 13.5 g/dL). Guay et al 2009

Why Viagra or Cialis

Greco et al 2006: “Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil might have a role in the regulation of erectile function.”

Spitzer et al 2013: Phosphodiesterase-5-inhibitors, such as sildenafil increases serum testosterone levels by a direct action on the testes. It causes a 40% increase in Total Testosterone and a 50% Increase in Free Testosterone.

Cialis has a longer half-life (17.50 hours) compared to Viagra (4.0–5.0 hours)

Changing testosterone gel preparations (Testim or Androgel)

Prior to substitution, among patients initially treated with Androgel, the mean total and free testosterone levels were 311 ng dl⁻¹ and 10.4 pg ml⁻¹, respectively. Total testosterone levels were below 300 ng dl⁻¹ in 58% of these patients. Following a change to Testim, mean total and free testosterone levels increased to 484 ng dl⁻¹ (P<0.001) and 14.6 pg ml⁻¹ (P=0.01), respectively. Total testosterone levels remained below 300 ng dl⁻¹ in only 17% of these patients. The enhanced absorption of Testim is attributed to pentadecalactone.

The main reason for gel substitution from Testim to Androgel was secondary to specific properties (scent) of Testim gel.

pentadecalactone sexual attractant

As I said earlier Pentadecalactone is used in Testim to improve permeability, but (concerning attraction) what for some is only a myth, is true for others.

Just read the bodybuilding forums and gay forums, if you use Google you can find an enormous amount of interesting, enjoyable comments. Either way I will use this compound in my experimental tests. I could easily fill this entire blogpost with comments from bb-fora, but this will give you an idea:

**This is incredible to me, but I've been on Testim 1% gel now for about a month, and women are actually stopping me walking by and asking what I'm wearing. They absolutely love the scent, and can only describe it as a "clean and crisp" type smell. WTF? My question: Is anybody else out there experiencing this with this product?

**just started using Testim 1% two months ago...I apply it every nite before bedtime. **This morning when i went to the lab to have blood work done the female lab technician kept going on and on how good i smelled; she asked what kind of cologne i used. I just got out of bed and went straight to the lab to have my blood work done i didn't apply any cologne..I rarely use cologne..She said it was a nice musk smell :). First time this ever happen to me.

**I've heard of this of this phenomena from a few other sources. Not sure what the cause is, but you're not the first person to say that.** I'm about to get some just to smear on my clothes. I always wondered why I loved that scent so much.

** Weird but fascinating stuff...if anyone has gotten similar feedback, I'm very curious to hear your experience(s) with this product is.

** I have so much extra testosterone, I have to sweat it out, drives woman nuts. That our I'm so confident it makes me irresistible. Either way I feel great!

**The smell drove me crazy, too. My wife didn't mind, and I had several women hit on me (different for me.)

** To me, it smells like alcohol. However, when I did use it, there was a lady in the office that would walk past me and smell me and ask me over & over what cologne I used. I thought it was a fluke, but apparently there must be something special about Testim.

**I've heard of this of this phenomena from a few other sources. Not sure what the cause is, but you're not the first person to say that.**Pentadecalactone is the sexual attractant pheromone (musk) produced in the male armpit that makes females PUSSYBOYS desperate to get fucked… isn’t the male body fucking amazing.

What is the purpose of my experiments?

I liked to find out if I would be able to improve existing compounds like Testim. After all Testim is developed for TRT/HRT. I could easily increase the amount of Testosterone base and by adding a synergistically working PDE5 inhibitor like Cialis the effects would only be enhanced. There is increasing body of knowledge on how to increase drug solubility by means of binary mixtures of solvents. The transdermal drug delivery from binary mixtures is synergistic rather than additive, according a study on transdermal delivery of Tadalafil.

Future treatments for erectile dysfunction are being developed at the moment. Bodybuilders are well-known with Caverject (alprostadil), a compound that was meant to inject in the penis but bodybuilders soon found an off-label use .

Now a cream is being developed that should be applied to the penis called Topiglan, it uses the same drug (alprostadil) as in Caverject. In this case everyone will agree with me that a cream is a far better solution than injection. Also in TRT/HRT a transdermal cream is often preferred over injectables. To be continued…