Can 5 Cups of Coffee Boost Testosterone to Estrogen Ratio in Overweight Men Transiently by Almost 200%? Plus: SHBG Its Own Receptor and Its Role in Prostate & Breast Cancer

Testosterone booster in men and estrogen amplifier in women? As if there were not already enough good reasons to get your daily dose of the 'kingly' brew ;-)

You would not have to be a diligent student of the SuppVersity to know: Coffee is a truly remarkable brew. Even mainstream media has gotten wind of the multitude of beneficial effects a moderate intake of the former drink of the kings and popes can have on your health and if it was not for the authors and newscasters blind reliance on whatever the press release guys are telling them, it would probably not even have been necessary for me to broach the beneficial effects coffee can have on your metabolic health and overall well-being in posts like "Coffee - 3 Cups a Day Keep Insulin at Bay", "Pre-Workout Caffeine: Fat Liberator, Substrate Modulator, Trans-Fatty Acid Eliminator & Performance Upregulator!" and many more.

So what is it this time? What else can coffee do for you?

I guess something only few people others than SuppVersity readers will be aware of is the fact that caffeine  and therefore coffee makes a nice testosterone booster (Beavon. 2008; study was discussed briefly as part of a longer post on June 20, 2012 an mentioned previous times in other posts) -- at least if you stick to moderate doses of ~300-400 mg before a workout. So, unless you are a newbie or missed the respective news, you should not be surprised that a recent study from the Harvard School of Public Health (Wedick. 2012), which had actually been designed mainly to investigate the effects of 5x 6-ounze cups caffeinated and decaffeinated coffee (both instant coffees; brand: Nestlé’s Taster’s Choice) on serum levels of sex hormone-binding globulin (SHBG), found that the consumption of both 'real' and 'fake' (=decaffeinated) intant coffee did lead to increases in total and free testosterone and profound decreases in estradiol (bound and free).

Figure 1: Levels of SHBG, testosterone, free testosterone, estradiol, free estrogen, the testosterone to estrogen ratio and DHEA in the male participants of the study expressed relative to a caffeine abstinent control group (based on Wedick. 2012)

As the data in figure 1 goes to show these changes were unfortunately transient and the impressive +189% increase in the testosterone to estrogen ratio which occurred during the first month of treatment totally disappeared within the next four weeks. On the other hand, the effects on SHBG the scientists had expected based on the assumption that both SHBG and caffeine intake have been found to be associated with lower risk of type II diabetes in large epidemiological studies, was non-existent in the first and second 4 weeks of the study... at least in the male subjects who were all overweight, nonsmokers and habitually coffee consumers, who had been required to abstain from caffeine intake for at least 2 weeks before the study was conducted.

Figure 2: Levels of SHBG, testosterone, free testosterone, estradiol, free estrogen, the testosterone to estrogen ratio and DHEA in the female participants of the study expressed relative to a caffeine abstinent control group (based on Wedick. 2012)

If you take a look at the data from the female participants (likewise overweight non-smokers, habitual caffeine consumers and, at the beginning of the study, 'dried out'; see figure 2), a different image emerges, in the women we do in fact see a transient rise in SHBG, which goes hand in hand with a decrease in testosterone, de to which the T/E ratio drops by -36% and -54% in the groups drinking caffeinated and noncaffeinated coffee respectively. Just as in their male counterparts, the levels did go back up in the second part of the study so that all values, including the SHBG levels were back in to normal after 8 weeks (please note changes in the 20% range are irrelevant and could be due to having a meal before the test, bad sleep, whatever).

The relative data tells only part of the story

Figure 4: Absolute values of the testosterone to estrogen ratio after 4 and 8 weeks; baseline levels were 16.2, 15.8, 18.2 in the caffeinated coffee, decaffeinated coffee and control group respectively. The data clearly shows: Coffee needs a PCT ;-)

If we do now take a closer look at the actual data and discard the comparison to the control group the scientists the picture becomes even more complex. After all the data in figure 4 clearly indicates that we are dealing with a combined effect here. It is correct that the ingestion of the caffeinated beverage had pronounced effects on the T/E ratio especially in the male participants, what the data in figure 1 does yet not tell you is the fact that this effect was also so pronounced, because simply stopping to drink caffeine reduced the T/E ratio from 18.1 to 8.4, i.e. by 54%(!).

Now this certainly reduces the effect size, but it does not totally negate the effect. After all the 'real' coffee drinkers (w/ caffeine) did still increase their T/E ratio from 16.2 to 24.2 -- a certainly likewise noteworthy increase of +29% that is however still far away from the exorbitant +189% increase compared to the poor guys who did not just lose their coffee, but also their virility.

So what does this tell use?

How cares about SHBG anyways? You should! After all there is relatively conclusive evidence that normal (not exorbitantly high!) SHGB levels have a protective effect against breast cancer in women and mechanistic evidence that they increase the risk of prostate cancer in men. In both cases SHBG acts independently via the largely ignored SHBG receptor that modulates the action of estrogens. Co-activation of SHBG and estrogen receptor in the prostate induces similar effect on prostate specific antigen secretion as DHT (Nakhla. 1997). Since estrogen alone does not have this effect, it is no wonder that stinging nettle root (Urtica dioica), with its SHGB inhibiting effect is a viable tool in the treatment of benign prostatic hyperplasia (Hryb. 1995). In the female breast, on the other hand, SHBG seems to " trigger a 'biologic' anti-estrogenic pathway" (Fortunati. 1999) and does therefore exert anti-instead of pro-carcinogenic effects.

I guess there are more than just the following three lessons to learn from this study, but at the moment these appear to be the most important ones for me:

1. The beneficial effects habitual coffee intake has on type II diabetes risk are, contrary to the scientists hypothesis, not mediated by its effect on SHBG.
2. In overweight men caffeine has a very shortlived beneficial effect on testosterone and the testosterone to estrogen ratio. After 4 weeks the levels do yet return to baseline, so this cannot explain the long-term benefits of habitual caffeine consumption either (maybe you should cycle caffeine instead of testosterone booster < I am just kidding ;-).
3. In overweight women, there is a similar, yet negative effect on testosterone levels, which is likewise transient and lasts less than 8 weeks. 
4. The caffeine ads to the 'pro-testosterone' effects, but even decaffeinated coffee has some effects.
5. Stopping "cold turkey" is not a good idea, when you are "on caffeine"

Now, what is important here is that we are dealing with overweight individuals, in whom the endocrine millieu is usually off. In particular, men tend to have reduced, women tend to have increased androgen levels (think PCOS). The effects we see after short-term withdrawal and the subsequent consumption of a non-negligible amount of 5 cups of coffee everyday could actually have corrective effects on the endocrine milieu, of which both, men and women could benefit, if they would last for more than 4-6 weeks. The detrimental effects of stopping, on the other hand, could be due to the sudden absence of the benefits of caffeine.

Regardless of whether you stop or start drinking coffeine, the endocrine "disturbances" are relatively short-lived and only further testimony to the fact that our bodies will always try to find a new "steady state" in what they consider normal.

Bottom line: There are a myriad of good reasons to drink coffee, getting more manly or more feminine is yet not one of them. Disappointed? Well, on the other hand this means coffee is no endocrine disruptor - and at least in this overweight population it seems to have a marginally beneficial baseline effects (thus the detrimental effects of abstinence).

References:

• Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41. 
• Fortunati N, Becchis M, Catalano MG, Comba A, Ferrera P, Raineri M, Berta L, Frairia R. Sex hormone-binding globulin, its membrane receptor, and breast cancer: a new approach to the modulation of estradiol action in neoplastic cells. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):473-9.
• Hryb DJ, Khan MS, Romas NA, Rosner W. The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes. Planta Med. 1995 Feb;61(1):31-2.
• Nakhla AM, Romas NA, Rosner W. Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone-binding globulin. J Biol Chem. 1997 Mar 14;272(11):6838-41.
• Wedick NM, Mantzoros CS, Ding EL, Brennan AM, Rosner B, Rimm EB, Hu FB, van Dam RM. The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial. Nutr J. 2012 Oct 19;11(1):86.