Get Your Mojo Back!
A Guide to Testosterone Replacement
by Cy Willson

Have You Lost Your Mojo, Baby?

In that classic piece of celluloid, Austin Powers: The Spy Who Shagged Me, Dr. Evil almost defeats our hero by stealing his mojo. Luckily, Austin was able to get his mojo back, defeat Dr. Evil, and shag Heather Graham.

I don't know exactly what "mojo" is in the movie, but in the real world it can be only one thing: Testosterone. If a man's "T" level is low, he'll have a tougher time building and maintaining muscle, losing fat, and performing sexually. Basically, he just won't feel like a man should feel: virile and vigorous.

Luckily, for those who have a Testosterone level that falls below the normal range, there are medical options. For those with low-normal or normal T levels who just want a boost into the high-normal range – where muscle and strength gains will come easier – there are supplemental options. Below, I'll look at the drug options in detail and touch briefly on the supplement choices.

In my best text-based Austin Powers impersonation: Does that make you horny... baby? (Well, it should!)

Hypogonadal: Somethin' Just Ain't Right

If you go to the doctor suffering from symptoms of low Testosterone, the doctor will give you a blood test. If it comes back below normal, then you'll be diagnosed as hypogonadal, which is derived from a Latin word meaning "kicked in the nuts by an angry woman."

No, I'm kidding. What it means is that you'll be qualified to receive exogenous Testosterone by prescription. ("Exogenous" means originating from outside the body.  "Endogenous" means produced inside the body. Got it? Good.)

The following is a list of choices for Testosterone supplementation. Before I begin however, let me make it clear that the following info is provided mostly for those wishing to achieve normal physiological Testosterone levels, not get "hyooooge." I'll address those who wish to get into the high-normal range later.

When choosing a system of T replacement, what you want is something that'll closely mimic natural, endogenous production. Also, you want to minimize the risk of side effects when it comes to achieving supraphysiological (above normal) levels.

Finally, you want to avoid subphysiological or below normal levels because that just won't work worth a flip. Ideally, the "perfect" product wouldn't cause supraphysiological levels for a significant period of time, or subphysiological levels prior to the next dose.

Going beyond that, it would also mimic the normal circadian rhythm seen where peak concentrations of endogenous Testosterone are reached around 8 AM and nadir (the lowest point) around 10 PM. Last but not least, the perfect product would be something that doesn't cost the person an unacceptable amount of pain and time, and allows him to easily adhere to the dosing instructions.

Okay, let's go T shoppin'!

Striant

This product utilizes the buccal (or cheek) route of administration. By placing a mucoadhesive tablet containing Testosterone against the gum, just above the incisor tooth (essentially in between the gum and cheek), the subject's saliva will begin to hydrate it and form a gel of sorts that contains Testosterone.

The Testosterone then crosses the buccal mucosal membrane that lines the oral cavity, eventually reaching small vessels and capillaries. These flow into the internal jugular vein, thereby reaching systemic circulation while avoiding first-pass hepatic metabolism.

Benefits: Average peak plasma concentrations generally don't exceed the physiological range, while steady-state concentrations are also respectable (i.e. 520-570 ng/dl). There's also no pain or discomfort associated with administration via intramuscular injection. Finally, there's no worry of transferring the Testosterone to loved ones, which might be an issue with certain creams or gels applied to the skin.

Drawbacks: You have to apply a tablet twice per day, once in the morning and once in the evening, which is kind of a nuisance. The tablets could also irritate your gums. Lastly, the pharmacokinetic properties don't exactly mimic the normal circadian rhythm.

Testoderm and Androderm

These products are essentially transdermal patches applied to the scrotum (known to us scientist-types as the "chicken sack") and non-scrotal skin respectively. As you'd expect, they allow Testosterone to permeate through the skin and into the bloodstream.

Benefits: Average peak and steady-state concentrations are within the physiological range. When applied either at night or early in the morning, depending on time to reach peak plasma concentrations, they can closely mimic the normal circadian rhythm seen in eugonadal (normal) men. Other benefits include lack of discomfort associated with injections and no risk of accidental transfer to other people.  

Drawbacks: Testoderm, specifically, can result in supraphysiological DHT levels, whereas the Androderm doesn't, due to the placement of the patch. (Androderm isn't applied to the nutsack, but to other areas of the body.) However, both patches may cause skin irritation where the patch is applied. Lastly, having a patch on your nutsack is kind of embarrassing if your date isn't prepared for it. Of course, you could always paint it black and tell her you're playing "pirate".

Testoderm requires shaven scrotal skin for application, but hey, doesn't everyone do that anyway? These patches must be applied daily, or nightly in the case of Androderm.

Androgel and Testim

These are both topical gel formulations containing Testosterone which, when applied, provide a reservoir of T which permeates through the skin and into the bloodstream, allowing a relatively sustained and controlled amount to enter systemic circulation over time.

Benefits: Average peak concentration and steady-state are generally within the physiological range with the usual dosage employed. Skin irritation isn't as much of a concern compared to the patches, and of course there's no need to have an unsightly patch on the skin. You don't have to shave your sack either. Finally, there are regimens available that can possibly mimic circadian rhythm.

Drawbacks: Skin irritation, while not as frequent as that seen with patches, can still occur. Gels require daily application and some men may not like the smell or "feel" of the gel. It's also possible to transfer significant amounts of Testosterone to loved ones when engaged in vigorous skin-skin contact. Lastly, you must wait 2-6 hours after application before sweating, swimming, or washing.

Side Note: While one pharmacokinetic study during short-term administration found that Testim produced approximately 30% and 38% higher peak plasma concentrations for total and free Testosterone as compared to Androgel, more long-term studies (i.e. 30 days) haven't found this to be true. In fact, Androgel had the higher average steady-state concentration.

Delatestryl and Depot-Testosterone (Or compounded products)

These are the esterfied derivatives of Testosterone, Testosterone enanthate and cypionate respectively, administered via intramuscular injection. Testosterone enanthate is the most popularly prescribed form of T for Testosterone replacement therapy.

The lipophilic derivatives are injected deep into the muscle where they're slowly released or absorbed into circulation. There, the esters are effectively cleaved, leaving the free Testosterone molecule to exert its biological effects.

Benefits: Doesn't require daily administration, relatively cheap, and generally lacks the main issues associated with transdermal and topical administration.

Drawbacks: Possible pain or irritation at injection site, plus there's the possibility of infection with improper injection technique. If you can't poke yourself with a needle, then you'll need to make frequent visits to your physician.

There's also a possibility of allergic reaction to sesame or cottonseed oil (solvents/vehicle) and supraphysiological peak concentrations, generally followed by subphysiological Testosterone levels prior to the next administration when 200-400 mg is administered every 2-4 weeks*. Once again, pharmacokinetic properties aren't conducive to mimicking the normal circadian rhythm.

*100 mg/week improves unfavorable pharmacokinetics.

Nebido (Not yet approved for use in the U.S.)

This is another esterfied derivative of Testosterone, in this case, using the undecanoate ester. The use of the much longer carbon-chained ester provides much greater lipophilicity and a much slower release of the molecule from the site of injection in the muscle to systemic circulation as compared to the enanthate and cypionate esters.

Benefits: Average peak and steady-state concentrations don't rise in to the supraphysiological range. A 1,000 mg dose had a half-life of approximately 34 days and allowed for 12 week dosing intervals, obviously making it the most advantageous in terms of frequency of administration.

Drawbacks: If adverse effects are noted, the long half-life is disadvantageous as you have to simply wait until enough half-lives have passed to reach baseline. Also, it's not conducive to mimicking the normal circadian rhythm and, of course, still requires injection.

Side Note: New Drug Application submission or filing is supposed to occur in 2006, so it's possible that Nebido may be on the market within the next few years.

High-Normal Utopia

As I stated earlier, there may be those who wish to achieve steady-state Testosterone concentrations, which allow them to be in the high-normal range. For those who wish to do so, 10 grams per day of either Androgel or Testim should suffice. However, this should be confirmed via blood draw over time.

SERM's and Aromatase Inhibitors

Drugs like clomiphene (Clomid) and tamoxifen (Nolvadex), in addition to aromatase inhibitors such as anastrozole (Arimidex) should be avoided unless supraphysiological estradiol levels are found over the course of therapy and/or symptoms of excess estradiol formation locally is found (e.g., gynecomastia).

It's important that we not unnecessarily antagonize estrogen receptors or decrease estrogen levels. Estrogens plays some very important roles in terms of cardiovascular function, libido, cognitive function, body composition, etc., not to mention the physiological effects which have yet to be elucidated.

5 Alpha-Reductase Inhibitors

Drugs such as dutasteride (Avodart) and finasteride (Proscar and Propecia) should also be avoided unless androgenic alopecia (hair loss) or prostate issues manifest, or perhaps if supraphysiological DHT concentrations are reached.

As a side note, I'd like to help dispel a common myth I hear from guys who really do need to use these drugs concurrently with exogenous Testosterone and are worried about them making the Testosterone less effective due to the inhibition of 5 alpha-reduction to DHT.

The fact is that skeletal muscle possesses little to no 5 alpha-reductase activity, and as would be expected when finasteride was administered concurrently with Testosterone, the positive effects on lean body mass weren't decreased or negated.

Normal Guys, Higher T Levels

For those who have normal Testosterone levels and/or don't qualify for Testosterone replacement, a supplement such as Alpha Male is a good choice.  Alpha Male packs a potent one-two punch as one ingredient prompts the pituitary into pumping out more LH, which in turn causes the testes to produce more Testosterone, while another ingredient promotes the Leydig cells in the testes to start producing more Test without the urging of LH.

You could also consider using drugs which possess estrogen antagonistic effects, such as clomiphene or tamoxifen. Anastrozole, while decreasing estrogen levels enough to where an increase in endogenous Testosterone levels are seen, yet still allowing for estradiol to remain within the physiological range, is also a choice.

However, you need to be cautious when it comes to long-term use, as even that moderate decrease in estrogen can negatively affect endothelial function.

Technically, you should also avoid long-term use of the estrogen antagonists as well. As mentioned, while being receptor subtype selective, the long-term effects in men just aren't known.

Wrap-up

If you think you have low Testosterone, go to your doc and get tested. If you qualify, hopefully this article will guide you in selecting the best product for your needs. If you don't qualify, but feel you could benefit from a boost to high-normal, Austin Powers T-levels, consider the supplemental options.

Whatever you do, never lose your mojo, baby!

References

1. Lew R, et al. "Endogenous estrogens influence endothelial function in young men." Circ Res. 2003 Nov 28;93(11):1127-33.

2. Product Insert (Striant). Columbia Laboratories. Livingston, NJ, 2003.

3. Product Insert (Androderm). Watson Pharmaceuticals, Inc. Corona, CA, 1999.

4. Product Insert (Testoderm). ALZA Pharmaceuticals. Palo Alto, California, 1998.

5. Product Insert (Androgel). Unimed Pharmaceuticals. Marietta, GA, 2003.

6. Product Insert (Testim). Auxilium Pharmaceuticals, Inc. Norristown, PA, 2003.

7. Bouloux P. "Testim 1% Testosterone gel for the treatment of male hypogonadism." Clin Ther. 2005 Mar;27(3):286-98.

8. Product Insert (Delatestryl). BTG Pharmaceuticals. Iselin, NJ, 1996.

9. Product Insert (Depo-Testosterone). Pharmacia & Upjohn Company. Kalamazoo, MI, 2002.

10. Korbonits M, et al. "A comparison of a novel Testosterone bioadhesive buccal system, striant, with a Testosterone adhesive patch in hypogonadal males." JCEM. 2004 May;89(5):2039-43.

11. Schubert M, et al. "Intramuscular Testosterone undecanoate: pharmacokinetic aspects of a novel Testosterone formulation during long-term treatment of men with hypogonadism." JCEM. 2004 Nov;89(11):5429-34.

12. Jockenhovel F. "Testosterone therapy--what, when and to whom?" Aging Male. 2004 Dec;7(4):319-24.

13. Borst SE, et al. "Inhibition of 5alpha-reductase blocks prostate effects of Testosterone without blocking anabolic effects." Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E222-7.

14. Page ST, et al. "Exogenous Testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T." JCEM. 2005 Mar;90(3):1502-10.

15. Longcope C, Fineberg SE. "Production and metabolism of dihydroTestosterone in peripheral tissues." J Steroid Biochem. 1985 Oct;23(4):415-9.

16. Kumar N, et al. "The biological activity of 7 alpha-methyl-19-norTestosterone is not amplified in male reproductive tract as is that of Testosterone." Endocrinology. 1992 Jun;130(6):3677-83.

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