In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6. 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.
The general recommendation is that men 50 and older who are candidates for testosterone therapy should have a DRE and a PSA test. If either is abnormal, the man should be evaluated further for prostate cancer, which is what we do with everybody whether they have low testosterone or not. That means a biopsy. But if all of those results are normal, then we can initiate testosterone therapy. The monitoring that needs to happen for men who begin testosterone therapy is really very simple: DRE, PSA, and a blood test for hematocrit or hemoglobin, once or twice in the first year and then yearly after that, which is pretty much what we recommend for most men over age 50 anyway.
“I see people who've been doing things in the gym and they've never been told that it can shut off your own production and it can also irreversibly lower your sperm count,” says Roked. “These are all quite serious issues that even though they may be rare if it happened to you it would cause a big impact on your life, so I'd say it's always best to do things with a specialist, but also for anyone it's not a great idea to take things that aren't needed."
One thing that is often overlooked when it comes to testosterone boosters is the dosing. Test boosters aren’t like other supplements where you can just take the one dosing per day and forget about until the next day. As with any supplement, it only stays in your system for 4-8 hours. This means you need to be taking more than one dose per day. 2 doses are better but it still is not enough. If you want to keep your test levels up all day you will need to be taking at least 3 and preferably 4 doses per day to keep your testosterone levels high throughout the day and to keep them from dropping between doses. You should also be sure to take them every day and try to not miss any doses to get the most out of them.
Unlike women, who experience a rapid drop in hormone levels at menopause, men experience a more gradual decrease of testosterone levels over time. The older the man, the more likely he is to experience below-normal testosterone levels. Men with testosterone levels below 300 ng/dL may experience some degree of low T symptoms. Your doctor can conduct a blood test and recommend treatment if needed. They can discuss the potential benefits and risks of testosterone medication, as well.
When you’re under stress (be it from lack of sleep, workplace stress, emotional stress, stress from a bad diet, overtraining etc.), your body releases cortisol. Cortisol blunts the effects of testosterone (47), which makes sense from an evolutionary point of view – if we were stressed as cavemen chances are it was a life or death situation – not running late to a meeting - in this state (i.e. running from a lion) the body wouldn’t care if you couldn’t get it up, there was more to worry about!
Estrogen is important in men, but too high of a level has all sorts of negative consequences – ranging from heart attacks to prostate cancer (32 & 33). The balance between testosterone and estrogen (or estradiol) is critical for a man. If the ratio is out and estrogen starts to dominate you run into all sorts of issues – such as breast cell growth, prostate enlargement and of course lower testosterone.
Testosterone is observed in most vertebrates. Testosterone and the classical nuclear androgen receptor first appeared in gnathostomes (jawed vertebrates). Agnathans (jawless vertebrates) such as lampreys do not produce testosterone but instead use androstenedione as a male sex hormone. Fish make a slightly different form called 11-ketotestosterone. Its counterpart in insects is ecdysone. The presence of these ubiquitous steroids in a wide range of animals suggest that sex hormones have an ancient evolutionary history.
Testosterone levels generally peak during adolescence and early adulthood. As you get older, your testosterone level gradually declines — typically about 1 percent a year after age 30 or 40. It is important to determine in older men if a low testosterone level is simply due to the decline of normal aging or if it is due to a disease (hypogonadism).