I was reading an article the other day lamenting that men in the US are being all feminized due to the politically correct environment in which we apparently exist. But is this the issue? Can we blame politics for hypogonadism? I think not. However, I do agree wholeheartedly that there is a change occurring.
I tell you folks, the feminization of men is biochemically, not politically, mediated.
I am serious. It’s tragic. And as a red-blooded woman who appreciates men being men, I am not happy about it. But if the obesity, cardiovascular disease, diabetes, cancer and autoimmune epidemics aren’t arousing you to action, maybe the terrible and sad fate of testosterone in this inflammatory soup of modern life will.
Superlatives and hyperbole. But it’s all true.
Let’s take a look at that Big Gulp Coke that Sarah Palin promoted so heavily last year as a natural-born right of all Americans. Let’s track the main Coke ingredient, sugar, down through a primary biochemical pathway in the body and see what happens to it.
The short view: Sugar trashes testosterone. Period.
The slightly longer view: The mechanism by which this happens underlies all chronic inflammatory diseases; from the ubiquitous metabolic syndrome to cancer, autoimmunity and cardiovascular disease.
The Soapbox: In the US, more than 70% of us eat TOO MUCH SUGAR. And men, you consume more than the ladies.
Some behind-the-scenes biochemistry. And a couple of cases outlining what to do about it:
Sugar stimulates insulin (and chronic sugar ingestion keeps this going and going and going). Insulin promotes the genetic upregulation of the desaturase enzymes that convert the too-highly-abundant-in-the-American-diet linoleic acid (vegetable oils — think fried foods, potato chips) to arachidonic acid (AA). Arachidonic acid is the parent compound of the exquisitely potent pro-inflammatory molecules called 2- and 4-series eicosanoids. These AA-derived eicosanoids are the most fundamental drivers of all things inflammation in the body. Aracidonic acid is cleaved from the lipid membrane for metabolism to eicosanoids by the enzyme phospholipase A2 (PLA2). A main end-product of this cascade of events is prostaglandin E2 (PGE2). PGE2 promotes genetic upregulation of aromatase (CYP19), the enzyme that converts testosterone to estrogen.
So, high sugar = low testosterone= high estrogen: The feminization of men
What we can do about it. A couple patient cases.
George is a 57 year old male patient of mine who I’ve been seeing for six years. In fact, we just met last week, hence this blog topic. I began to treat George when I was working at Advanced Diagnostic Pain Treatment Center. He arrived on seven heavy-hitting medications ranging from Fentanyl and oxycodone to atenolol and Avodart (BPH). A handful of NSAIDs were thrown in for good measure. We effectively addressed his complaints, including BPH, hypertension, hyperlipidemia and inflammatory arthritis. He tapered off all of his medications. He quit smoking. He lost weight. He’s been doing well for years, except he’s complained of difficulty with abdominal adiposity and poor muscle mass, despite regular weight and cardio workouts. (He just ran a ½ marathon.) His free and total testosterone levels were actually within normal limits, but his total estrogen level was high. So for George, his good lifestyle (and tapering off opioids- which lower T) has kept his T within normal limits, but he’s still converting too much testosterone to estrogen. George lamented that this was due to genetics. That all the men in his family were cursed with the dreaded “man boobs.”
For George, one of the key findings — despite general good health — was a consistently slightly elevated blood sugar.
He also had high total estrogen.
And a love of beer.
We started a fairly straight forward plan. We got extra serious about the diet: very low/no grains (sadly, beer is gone right now); high veg and fiber, with good proteins. He periodically achieves ketosis, which he measures himself in urine. We increased his fish oil intake to inhibit desaturase conversion of linoleic acid to arachidonic acid. (We’re trying to stop production of AA-derived PGE2> aromatase> testosterone> estrogen). I added zinc, chrysin and a natural hops-derived aromatase inhibitor. We started a relatively modest dosage of 50mg DHEA per day. His blood sugar tends to run around 100, so I added berberine 500mg daily. (I know this is lower than the 1500mg/day recommended amount for type II diabetes, but we’re fine-tuning here.) His baseline total estrogen was high at 132. After ten weeks of this protocol, his estrogen was 109; fasting blood sugar 93. A nice drop!
Most importantly is that George is reaping the benefits. He reports more muscle definition (he’s now getting compliments from his gym buddies), better energy, reduced body fat and improved libido and performance. He’s gained muscle weight but his clothes fit better. And the dreaded man boobs? Gone. George is thrilled with his results and wants to continue on the plan. He’s empowered. He’s no longer a victim of his genetics.
On the extra-cautious side, we’ve watched his PSA (free and total), and they’re both consistently low.
George’s baseline total estrogen and free testosterone:
George’s follow-up total estrogen (testosterone pending, but it will be higher based on his clinical response):
One more quick case. With George, we had to really get in there with some fine-tuning to drop his total estrogen. On the other hand, Bill (46 years old, normal weight-for-height) came to my office with complaints of inflammatory arthritis, severe seasonal allergies and GI issues (all inflammatory-driven). Secondary issues included fatigue and loss of muscle mass and definition, despite pushing himself through regular work-outs.
Bill’s treatment plan was relatively straightforward. We focused on his chief complaints with the goal of reducing total body inflammation (which drives up PGE2 and increases estrogens; even allergies contribute here). We did so through a hypoallergenic, lower carbohydrate diet; high dose fish oils, gut repair nutrients (including glutamine, licorice, slippery elm); and a few antimicrobial and anti-inflammatory botanicals (which further inhibit production of PGE2). I also added a hops-derived aromatase modulator and a modest 25mg DHEA/daily. Sublingual immunotherapy was used for allergies. Needed nutrients included B12, B complex, vitamin D and magnesium.
Like George, Bill had normal baseline total and free testosterone. This is really important. While you will commonly see low testosterone in your patients, sometimes values are within normal limits, thus it’s essential to look at total estrogen to get the full picture of what’s happening on the inflammatory front.
As you can see from Bill’s baseline and follow-up labs, his estrogen is dropping nicely with the protocol. This result correlated with better muscle mass and exercise tolerance. He also shed a few extra pounds, noticeable in the abdominal region. By reducing total inflammation through a number of mechanisms, including lower carbs and sugar, we achieved a significant drop in estrogens.
The caveats
As clinicians treating the “Low T” hypogonadal epidemic, we need to take a full systems approach. Endocrine disruption happens from all sides. Yes, diet is our greatest leverage point in virtually all disease. But stress will increase testosterone’s conversion to estrogen and reduce total sex hormone availability. And remember- glucocorticoids are diabetogenic. Toxins- especially plastics and all of the “cides”-pesticides, herbicides, insecticides are xenoestrogens. Think about the sexually ambiguous salmon swimming in polluted waters… Of course, numerous medications will deplete testosterone- opioids, statins. Nutrient depletions will contribute and complicate matters- vitamin D repletion alone has been shown to increase testosterone. Gut and liver health: Can your patients’ biotransform and eliminate estrogens?
Finally, testosterone replacement therapy for hypogonadism is all the rage. Lots of media promotion for treating “Low T” but I’ll tell you this: if you do NOT address the underlying inflammation, then a portion of that nice large pool of exogenous testosterone will indeed be driven on to estrogen.
Links for further reading.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2012.04401.x/abstract;jsessionid=39FE5839B989B83E037C9DA2BF0C6A1F.f03t04?deniedAccessCustomisedMessage=&userIsAuthenticated=false (low grade inflammation and hypogonadism)
http://care.diabetesjournals.org/content/28/7/1636.long (testosterone, blood glucose, mitochondria)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173509/ (BPH, testosterone, blood glucose)
http://atvb.ahajournals.org/content/27/6/1411.full.pdf (metsyn PLA)
http://www.lipidworld.com/content/13/1/6 (GGT, ALT, AST, obesity, CVD CHD DM PLA)
http://www.medscape.com/viewarticle/589222_4 (metsyn ferritin CVD PLA)
http://tae.sagepub.com/content/1/5/207.abstract (low T and metsyn, abnormal lipids)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150075/#R12 (CHD stroke subclinical inflammation and Lp-PLA2)
http://www.ncbi.nlm.nih.gov/pubmed/20362028 (PLA2 cancer)
http://www.ncbi.nlm.nih.gov/pubmed/15670148 (PLA autoimmune)
http://www.ncbi.nlm.nih.gov/pubmed/15670148 (A lot about PGE2)