Testosterone up-regulation, a tricky issue
There is ample evidence that a sufficiently high testosterone level is absolutely essential to a sexualized lifestyle. Testosterone, the hormone primarily synthesized in the testicles (though also in smaller amounts in the adrenal glands), is necessary both for sexual appetite and performance (e.g., achieving a reliable erection). Men whose testosterone levels are low will often be lacking in both.
There are oral testosterone medications. The best-known historical example is Andriol. Andriol contains testosterone undecanoate, a chemical modification of testosterone, a small percentage of which bypasses first-pass liver metabolism and enters the bloodstream via the lymphatic system.
Animal testicles have a reputation as aphrodisiacs, but this is based on overly simplistic logic. Any benefit is highly limited, similar to how eating liver helps anemic patients. Iron is a major mineral in blood, and anemia is often caused by iron deficiency. Consuming iron-rich foods like liver provides the body with additional iron for blood synthesis, provided that a malabsorption issue is not the root cause of the anemia.
For many years, oral testosterone undecanoate was not licensed in the US, though newer formulations (such as Jatenzo) have recently gained FDA approval. For the treatment of hypogonadism, oral formulations have historically been considered a second-line choice globally. It is difficult to predict how much of the 40 milligrams of testosterone undecanoate in each capsule actually reaches the bloodstream. Estimates range from 2 to 3 milligrams (about 5-7% bioavailability). Furthermore, absorption varies from person to person, and even within a single person from day to day, depending on the fat content of the meal consumed alongside the medication.
However, even in subjects for whom oral testosterone medications are effective, they do not act as an immediate aphrodisiac like yohimbine. Assuming the capsules successfully raise blood levels of free testosterone, the user will not feel a sudden increase in libido an hour or so after ingestion. If raising testosterone levels works, it seldom does so immediately. There is a good measure of unpredictability. For men on testosterone replacement therapy, the sexualizing effects often arrive sporadically. The exact reason for this delayed and fluctuating onset of sexual benefits is not entirely understood, though it likely relates to the time required for neurological adaptations and androgen receptor modulation.
As mentioned, testosterone is not a medication whose psychological effects are felt within an hour—unless it is massively overdosed. And the effect of an overdose is not just a potentiation of the desired effects of a normal dose.
The desired psychological effects of a normal physiological dose include increased sexual appetite, reliable erections, and satisfying orgasms. Testosterone-deficient men will be lacking in all three. Testosterone supplementation in these men will restore these functions. However, desire, performance, and orgasms are not enhanced immediately after taking an oral dose. It may take days or weeks for the effects to set in initially. Increased desire may arrive rather surprisingly, not at a planned moment. It is not as direct an effect as taking aspirin or yohimbine.
Increased desire also does not correlate directly with acute spikes in plasma testosterone levels. The endocrine system is highly complex. Furthermore, peak plasma levels occur a long time after an oral dose is absorbed. For older formulations of oral testosterone undecanoate, peak plasma levels occur roughly four to five hours after ingestion when taken with a fatty meal.
While the supplementation of regular or even high physiological dosages will not be felt within hours, the story changes with massive overdoses. Observations in women provide a clear indication of this.
Of course, Andriol and similar testosterone products are not intended for use in women. However, testosterone is the hormone for sexual appetite in women as well, albeit at much lower physiological levels than in men.
Though not intended for female use, some women take testosterone medications, usually to raise performance levels in sports.
Women using anabolic steroids often exhibit an increased libido, but this is a result of chronic use, not a single dose. The idea that a single overdose causes immediate "extreme anger" or "roid rage" is a myth; acute behavioral changes from a single dose are not scientifically supported, though chronic supraphysiological use can cause mood instability.
Contrary to the bad reputation of testosterone in this regard, high but physiological levels of this hormone are not associated with an anger-prone personality. In fact, optimal plasma levels of testosterone usually give men a positive outlook, making them friendly and confident. Abnormally low levels, conversely, go hand-in-hand with bad moods and depression. Only extreme, chronic supraphysiological abuse may result in severe mood swings or aggression.
As pointed out above, endocrine matters are complicated because the system relies on multiple feedback loops and balances.
Because of this, total blood testosterone levels are only an indicator of limited value when judging whether there is enough active testosterone in the organism to optimize sexual function.
The bioavailability of testosterone is regulated by a blood protein called sex hormone-binding globulin (SHBG). Testosterone molecules bound to SHBG are rendered biologically inactive until they are eventually cleared from the body.
Many men who undergo a standard testosterone test are getting an incomplete picture. These tests often measure total testosterone, which includes both the inactive SHBG-bound testosterone and the active free testosterone.
Relying solely on total testosterone can be incomplete when assessing whether a man needs testosterone replacement therapy. The determining factor is often whether a man has sufficient free, bioavailable testosterone.
Compared to relying solely on total testosterone lab results, evaluating clinical symptoms is a smarter approach to deciding on replacement therapy. For all men, aging is accompanied by a decline in testosterone synthesis.
Not only does production decline, but the amount of bioavailable testosterone is further reduced because older men typically experience increased levels of SHBG.
The decline in bioavailable testosterone is largely proportional to other symptoms of aging, such as bones becoming brittle, sagging skin, loss of lean body mass, decreased muscle tone, increased body fat, and a decline in sexual desire and performance.
This looks like an evolutionary mechanism to phase out older specimens of the species Homo sapiens by genetically programming a decline in testosterone availability.
Indeed, there is little doubt in the scientific literature that testosterone supplementation can mitigate or improve many of these aging events.
Older men undergoing properly monitored testosterone replacement therapy will practically always develop stronger bones and exhibit more lean body mass while carrying less fat. They will usually have a more active and satisfying sex life, though this is harder to quantify than lean body mass.
So, why do doctors not recommend that all men from their mid-40s undergo testosterone replacement therapy?
There are several reasons why physicians have been cautious in prescribing it.
Testosterone has substantial potential as a doping drug in sports. Supplementation during training periods leads to increased muscle mass and enhanced performance, which is why strict doping controls are undertaken at major events.
The tendency among those who abuse testosterone or synthetic anabolic steroids is to use massive overdoses, which are undeniably unhealthy. Therefore, sports and healthcare administrations have run public awareness campaigns warning that anabolic steroids pose a serious health risk. Testosterone is the endogenous prototype of all anabolic-androgenic steroids (AAS); it possesses both strong androgenic and anabolic properties.
While mice given massive, lifelong overdoses of testosterone have shorter lifespans, we are not talking about massive overdoses in clinical therapy. We are talking about restoring high-normal, youthful levels. A good number of studies have shown that testosterone supplementation to achieve physiological levels carries minimal long-term health risks when properly monitored.
Horror stories about dreadful consequences of synthetic steroid abuse are good copy but bad science when applied to clinical testosterone replacement aiming for physiological levels.
Apart from the doping issue, testosterone has long been associated with two health risks: heart attacks and prostate cancer.
Historically, it was thought that men with reduced testosterone levels were less prone to heart attacks. Conversely, modern cardiology shows that men with *low* testosterone levels are actually at a *higher* risk for cardiovascular events and metabolic syndrome. Maintaining physiological (normal) testosterone levels is generally cardioprotective or neutral, whereas supraphysiological (abused) levels are cardiotoxic. I favor maintaining healthy testosterone levels, but I use this cardiovascular data as a reminder to avoid other heart attack risks, such as smoking or obesity.
Regarding the second health risk, testosterone was the wrong suspect for many years. It was long considered the main culprit in prostate cancer.
Current urological consensus shows that physiological testosterone levels do not cause prostate cancer. Furthermore, while dihydrotestosterone (DHT) is the primary androgen responsible for prostate growth (and benign prostatic hyperplasia), it is not the sole driver of sexual function. Both testosterone itself and its conversion to estradiol in the brain are crucial for libido, while erectile function relies on a complex interplay of testosterone, DHT, and nitric oxide pathways.
If one has decided to undergo testosterone replacement therapy, one must decide by which means to supplement it. Most people would feel most comfortable with an oral drug. While historically unavailable in the US, oral testosterone undecanoate is now available under specific brand names.
Unlike older 17-alpha-alkylated oral steroids which are hepatotoxic, testosterone undecanoate is absorbed via the lymphatic system and largely bypasses first-pass liver metabolism. However, it must be taken with a high-fat meal for proper absorption, which can be impractical. Consequently, injections and transdermal gels remain the applications of choice in the US.
A practical shortcoming of the original Andriol formulation was that it required strict refrigeration (between 2 and 8 degrees Celsius).
Having lived in various countries of Southeast Asia for about 20 years, I have observed that in some regions, prescription medications are easily accessible without strict oversight.
Some individuals travel to these regions to purchase large supplies of medications.
Unfortunately, when purchasing oral testosterone products in unregulated markets, buyers often end up with degraded, ineffective medication. Because professional pharmaceutical standards are sometimes lacking, sellers may not understand that certain medications require strict refrigeration.
In many unregulated or non-air-conditioned pharmacies, oral testosterone products may sit in cabinets at 30 degrees Celsius or higher for months on end. The package may still bear the brand name, but the active testosterone undecanoate inside the capsules has likely broken down due to heat exposure. The reputation that oral testosterone undecanoate is "worthless" among some users often stems from purchasing these degraded products on the black market or in regions where appropriate cold-chain storage is not guaranteed.