(not written by me; references in next post)
"""Testosterone
Finally, we get to the good part -- or bad, if you like to hit the sauce with regularity. Acute ingestion of ethanol has been fairly consistently shown to significantly suppress testosterone production in both animals and humans, adults and adolescents. We will first look at the mechanisms involved, then turn to studies looking at actual testosterone levels.
Ethanol exerts its hypogonadic effects through several direct and indirect mechanisms. The primary mechanism is through direct suppression of leydig cell functions, either through a direct toxic effect (including reduction of LH receptors) ( 47,48 ), free radical activity -- selenium was found to ameliorate ethanol induced testosterone suppression ( 49 ), through reductions of 3beta-HSD (this is the enzyme that converts androstenediol to testosterone as well as DHEA to androstenedione) ( 50 ), 17beta-HSD (converts androstenedione to testosterone) ( 51 ), and 17,20 lysase (converts progesterone to androstenedione) ( 50 ), and through depletion of NADPH generating enzymes -- NADPH is a cofactor utilized in many steps of steroidogenesis ( 52 ), and ethanol administration has been shown to result in a decrease in the enzymes responsible for the generation of NADPH ( 53, 54 ).
Ethanol has also been shown to decrease LH releasing hormone at the hypothalamus ( 55 ), to decrease LH release at the pituitary ( 56 ), as well as to inhibit betaLH mRNA in vitro ( 57 ). This could be mediated by endogenous opiates as they are known to be increased by ethanol, and opiate antagonists have been shown to increase LH release as well as to block ethanol induced testosterone suppression at the testicular level ( 58 ).
Nitric oxide (NO) has also been implicated in this suppression (remember that next time you pop some Viagra or a tribulus product). While NO stimulates LH releasing hormone in the hypothalamus ( 59 ) and LH release in the pituitary ( 60 ), its overall effect o-n testosterone is negative due to its effects at the gonadal level ( 61 ). Substances that increase NO levels have been shown to inhibit testosterone secretion ( 61 ), as well as possibly inhibiting steroidogenic enzymes ( 62 ). Concomitant use of L-NAME, L-NA, or 7Ni (nitric oxide synthase inhibitors) with ethanol completely prevented the fall in testosterone seen with 3g/kg ethanol ( 63,64 ).
Another interesting possibility is a mechanism involving a neural connection between the brain and the gonads via adrenergic receptors. It has been shown that direct injection of adrenergic agonists into the hypothalamus decreased testosterone production at the testes, without a change in LH levels ( 65 ). As we saw in part 1, ethanol is known to increase catecholamine levels in the CNS. And, indeed injection of both phentolamine (alpha adrenergic antagonist) and propranolol (beta antagonist) were found to partially overcome ethanol's suppressive effect o-n HCG stimulated testosterone production ( 66 ).
Before you go out and get these drugs, remember that adrenergic stimulation, PERIPHERALLY, has a positive effect o-n testosterone levels. However, if anyone knows of adrenergic antagonists that o-nly act centrally, not peripherally, feel free to let us know.
Let's now turn to some studies that looked directly at testosterone levels following acute alcohol administration. In adult males, 1.3g/kg of ethanol (about 10 drinks for a 200 lb person), caused a significant decrease vs. basal levels at the 60 minute mark. Differences for the next two hours were not significant, though the researches did not utilize a control group, so the natural morning rise in testosterone could have masked any effects ( 38 ). 1.5g/kg lowered levels by an average of 23% over a 24 hour period ( 28 ). 1.75g/kg lowered levels by 27% and 16% at 12 and 24 hours, respectively ( 34 ). Adolescent males admitted to the hospital for alcohol intoxication were found to have 21% lower testosterone levels than controls (36).
A couple of studies have looked at alcohol and exercise. 1.5g/kg depressed testosterone by more than 20% by 1 hour and was still depressed by the same margin at hour 10 ( 37 ). Interestingly, when the same ethanol dose was preceded by an exercise session, the suppressive effect continued for 22 hours -- and when exercise was performed during a hangover, significant suppression ( 21-32% ) vs. ethanol alone continued for 26 hours. Compared to control, both ethanol groups had significantly lower testosterone levels for 42 hours - this is almost 2 full days. A much smaller intake (.83g/kg) did not result in a significant decrease ( 35 ).
All of this is at what are fairly moderate doses. Let's take a look at binge drinking doses.
Probably for ethical reasons, doses equating to 20+ drinks have not been studied in humans, so we must settle for rat data, but considering the effects at lower doses seem quite similar, these studies are likely quite relevant -- and could actually underestimate the effect, since, as we mentioned, these doses resulted in much lower blood alcohol levels in rats than humans.
3g/kg caused massive suppression of testosterone ( 67 ). Between hours 1.5 and 96 (yes, 4 days later), testosterone was reduced between 50-75% and, even a full week later, it was still down 40%. By week two, it was finally back to control level. 3g/kg also reduced HCG stimulated testosterone secretion by 75% ( 66 ). In male macaque monkeys, 2.5 and 3.5g/kg reduced testosterone levels by 63 and 70%, respectively ( 68 )
One study in adolescent rats found that testosterone levels doubled for the first 3 of weeks of ethanol ingestion ( 69 ) -- however, this was with an intake equal to 90 drinks per day for a 200 lb person. If anyone tries this, please report back with your results.
On the other hand, levels below 1g/kg seem to have no deleritous effects ( 35, 70 ).
Another interesting tidbit -- increased testosterone levels were found to correlate with decreased symptoms of withdrawal in alcoholics -- and the authors recommended supplemental testosterone as a possible treatment strategy ( 71 ). Wonder if a doctor would buy this??
Alcohol and Estrogen
Chronic alcoholics, in addition to being hypogonadal, exhibit sign of overt feminization ( 72 ). There is some evidence to suggest that ethanol might also increase the aromatization of testosterone to estradiol. Consumption of .9 - 2.1g/kg of beer or wine significantly (P <0.05 to P< 0.001) increased estradiol levels in healthy adult humans (73). A study in rats found levels of estradiol increased by 60% (to go along with 55% lower test levels) - however, this was with the equivalent of about 13 drinks/day for 1-2 months ( 74 ).
In addition, alcohol administration has been shown to increase estrogen receptor density ( 75, 76 ) and to decrease levels of a estradiol binding protein ( 77, 78 ) -- as well as to lower androgen receptor numbers ( 76 ). However, this has primarily been found in conjunction with alcoholic liver disease, so its relevance to acute consumption in questionable.
Another possibility is the existence of phytoestrogens in alcoholic beverages. Hops, used as a flavoring agent and preservative in beer, contains several powerful phytoestrogens, including 8-prenylnaringenin, genistein, and daidzein ( 79, 80 ). And, congeners, which are found primarily in dark liquors such as bourbon and wines have been found to contain biochanin A, beta-sitosterol ( 72, 80 )
Testosterone and Females
Ethanol's effects o-n the female bodybuilder, however, are not so bleak. Because female testosterone production occurs primarily outside the gonadal structures ( 81 ), ethanol's effect o-n LH is not as relevant -- and its effects o-n Leydig cells obviously are not at all relevant. In addition, ethanol is known to stimulate adrenal activity ( 82 ) -- 25% of female testosterone production is produced as an intermediate in the production of cortisol in the adrenals ( 81 ).
This results in INCREASED testosterone levels in women after ethanol consumption. As little as .4g/kg caused a significant increase in testosterone levels ( 83 ),and 1.2g/kg and 2g/kg caused increases of 25% and 54% respectively ( 84 ).
Interestingly, serum epitestosterone is not proportionally increased, nor are urinary levels, thus the testosterone to epitestosterone ratio (T:Ep) used in athletic drug screenings is skewed. The same study mentioned above resulted in a T:Ep ratio of around 4.5 compared to 1.5 before drinking. Individual increases ranged from 1.9 to 8.7 times baseline ( 84 ). Given that the testing cutoff is 6:1, it is easy to see that this could result in a false positive (or perhaps be used as a handy excuse for a true positive).
Protein Synthesis
Both ethanol and its metabolic byproduct, aldehyde, have been shown to reduce protein synthesis in skeletal muscle ( 85, 86, 87, 88 ). To make matters worse, it is predominately Type II, fast-twitch fibers that are affected, with type IIB being hit the hardest ( 85, 86, 87 ). This is not a good thing for bodybuilders, and it is a very bad thing for athletes.
With acute administration of real-world doses (.8 - 2.0g/kg) of ethanol, reductions in protein synthesis of 20-30% have been seen within about o-ne to two hours of administration, this is before the previously reviewed hormonal changes occur, indicating that alcohol is exerting a direct effect ( 85, 86, 88 ). Within 24 hours, decreases of as high as 63% have been shown to occur ( 86 ), which likely reflects the added contribution of negative hormonal changes.
The mechanism behind this is not fully characterized. Reduction in both mRNA ( 86 ) and translational efficiency ( 87 ) have been observed. The generation of free-radicals, which are known to be increased by ethanol ( 89, 90 ), could be involved ( 91 ). Low levels of selenium and alpha-tocopherol (vitamin E) are found in alcoholics with myopathy (muscle wasting) ( 92 ). However, there is also evidence that does not support this theory ( 93 ). Another possibility is direct ischemic damage ( 94 ).
Given alcohol's hormonal effects and its direct effects o-n protein synthesis, if you are going to indulge in fairly heavy alcohol consumption, it would probably be a very good idea to utilize a topical prohormone formulation (or a short-acting injectable ester of the real thing) the evening of drinking and the next day in order to minimize the damage to your hard earned muscle.
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