Baldness/Prostatitis Treatment, Impotence, Inflammation

Male pattern baldness appears to result from the interaction between enzyme-modified male sex hormones (DHT) and receptors in some hair follicles of the scalp.  Inhibition of the enzyme by topical (Rogaine) or oral administration (Propecia) of an inhibitor, e.g Finasteride, can stop hair loss.  One of the significant side effects of oral use of Finasteride is loss of all sexual functions, which can be temporary and reversible after the drug is stopped, or permanent.  I think that inflammation may play a critical role in both hair loss (and prostatitis) and loss of sexual functions in response to Finasteride and an anti-inflammatory approach my be helpful.

Testosterone is Converted to  Dihydrotestosterone (DHT) by 5-Alpha Reductase

The male hormone, testosterone, is produced in the testes and travels to hair follicle or to other parts of the body via the blood in either a free state, or bound to a carrier protein.  Only the free form interacts with the 5-alpha reductase enzyme in the scalp to produce the DHT that diminishes hair follicles.  Application of the Reductase inhibitor, Finasteride, directly to the scalp stops the production of DHT in the scalp.  Taking oral Finasteride blocks DHT production throughout the body, and unlike topical application, can also result in apparent changes in the brain, which can explain loss of sexual behavior.

DHT Role in Hair Loss and Brain-Based Sexual Behavior is Poorly Understood

Surprisingly, the molecular biology of male pattern baldness (MPB) is not known, even though this is one of the classic examples of a dominant, sex-associated phenotype, i.e. a single copy of the baldness allele in males produces baldness.  Of course, this is not a sex linked gene, since baldness is not inherited from mothers with their X chromosome, and in some cases as many as 80% of the males in a single family exhibit male pattern baldness.  It appears to me that baldness is also likely to have an environmental, e.g. gut flora, heritability similar to obesity.  In fact, metabolic syndrome and type 2 diabetes are substantial risk factors for male pattern baldness.

There is also an association between MPB and polycystic ovary syndrome (PCOS) in females of the same family.  I would also expect that MPB is related to prostatitis, since the prostate is a major processor of testosterone to DHT via 5-alpha reductase and prostatitis can be treated with Finasteride.  PCOS is also treated with Finasteride.  PCOS is also associated with obesity and metabolic syndrome.  Prostatitis, PCOS, obesity and metabolic syndrome can all be treated as inflammatory diseases with significant contribution of dysfunction of gut flora.

  

PMB, Testosterone, 5-Alpha Reductase and Aromatase

In PMB, testosterone levels are lower and 5-alpha reductase is higher.  This suggests that testosterone has been converted into DHT in scalp hair follicles.  In order for DHT levels to make a difference, the hair follicles have to have specific receptors for DHT.  Testosterone/DHT receptors, like all steroid hormone receptors, are proteins in the cytoplasm of cells, which bind the hormone and become activated as transcription factors that migrate to the nucleus and control the expression of particular genes.

Testosterone can also be converted by another enzyme, aromatase, into estrogen.  DHT cannot be converted enzymatically into estrogen.  Estrogen has a separate receptor and controls a different set of genes.  Thus, enhanced conversion of testosterone into DHT in MPB follicles, may shift the balance away from estrogenic in favor of androgenic effects.  Women exposed to aromatase inhibitors, stop converting their limited testosterone into estrogen and more is converted into DHT, resulting in rapid signs of baldness.   All brain estrogen is produced from testosterone via aromatase in the brain and aromatase inhibitors can reduce libido in women.

DHT Activates Inflammatory NFkB (and Block Nerve Apoptosis?)

Prolonged exposure of cerebral blood vessels to DHT has been shown to activate the inflammatory transcription factor NFkB.  Conversion of testosterone to DHT by 5-alpha reductase may amplify the inflammatory impact of testosterone by virtue of the stronger activation of the androgen receptor by DHT.  Activation of NFkB also suppresses apoptosis and may be necessary to maintain some neural cells.  Reducing DHT production by 5-alpha reductase inhibitors, may reduce NFkB activation in the brain and expose androgen-sensitive parts of the brain to apoptosis.  This loss of brain cells may result in loss of sexual behavior.

Vitamin D is also Steroid Hormone/Co-Transcription Factor

It should be remembered that vitamin D also has a cytoplasmic receptor that acts as a transcription factor and that vitamin D deficiency can result in hair loss.  If fact, vitamin D is required for the normal hair growth cycle, as well as intestinal villi development (defensin production).   The vitamin D receptor can also inhibit the inflammatory transcription factor NFkB.

Thus, multiple steroid hormone receptors are involved in hair development, prostate function and brain sexual behavior.  Modification of the conversion of testosterone into DHT or estrogen can have diverse consequences directly or indirectly by modification of inflammation/development signaling.  This is also true of fertility/menstrual cycles, mammary tissue and perhaps intestinal epithelial villi or skin/follicle development in the case of rosacea.  All of these processes are affected by enzymatic interconversion of steroid hormones and interaction of hormone/receptor and NFkB transcription factors.

Questions

The questions that I have about hair loss (or prostatitis), treatment with 5-alpha reductase inhibitors, and subsequent loss of sexual function are:

1. Why are the genetics of MPB so unusual/non-Mendelian?  There are too many males with MPB in the same family.  This points to some hereditary predisposition, but with a major environmental component, e.g. “inherited gut flora.”
2. Why are only a few of the people treated with 5-alpha reductase inhibitors rendered permanently impotent?
3. There is anecdotal evidence that dexamethasone (or prostate message and antibiotics) can reverse some impotence.  Does this indicate that inflammation is involved in hair loss and/or impotence?  Where do the antibiotics act and is their action to kill bacteria?

Treatment for Finasteride-Induced Impotence

Impotence is a severe side effect of a few men using Finasteride to treat baldness or prostatitis.  I doubt that those with induced impotence are genetically predisposed, but rather these individuals probably had an altered immune system.  I suspect two types of alterations:  a compromised blood/brain barrier and a compromised suppressive immune system.  Diet-based chronic inflammation is a typical path to a leaky blood/brain barrier that facilitates the penetration of Finasteride into the brain to alter 5-alpha reductase in the DHT-responsive regions responsible for sexual function.  I presume that the subsequent reduction of DHT also results in inflammation that contributes to loss of function.  Dexamethasone and some antibiotics could attenuate the inflammation and return normal function.

Suppression of attack of normal tissues by the immune system is mediated by development of the suppressive immune system in the gut in response to specific bacteria of the gut flora.  A history of antibiotic treatment can yield a dysfunctional gut flora and a compromised immune system that results in allergies and autoimmunity.  Prostatitis may have an autoimmune component and may result from compromised gut flora.

All of the symptoms discussed from hair loss to prostatitis to impotence should be improved by normal function of the gut and immune system by my anti-inflammatory diet and normal gut flora.  Use of antibiotics will always lead to further side effects by perturbing and limiting the function of gut flora and the immune system that is dependent on the gut flora.

I particularly suspect that vitamin D deficiency is a significant contributor.  Most “anti-inflammatory diets” will lead to chronic inflammation, because they are just high carb diets with a few vegetables.  All of the complex phytochemicals produced by plants will be “antioxidants”.  Adding these antioxidants to an inflammatory diet has no impact.  Look at my anti-inflammatory diet and note that it requires attention to serum vitamin D levels, gets most calories from saturated fat and not carbs (low carb/high saturated fat), no vegetable oils and high omega-3 (EPA, DHA) to 6 ratio.  That means meat/fish/eggs/dairy and lots of fresh vegetables for new gut bacteria.

BPA in Thermal Printer Ink

Bisphenol A Free Bottles, BPA-Free Pacifiers, BPA-Free Receipts

I previously poo-pooed the threat of the estrogen mimetic bisphenol A (BPA) from polycarbonate bottles, cans and pacifiers, because my quick calculations indicated that there was just too little BPA and too many other natural sources of estrogens that haven’t been problems.  But it’s not the water that’s the problem, it’s the other plastic, your credit card.

Some Receipts Are Covered with BPA

In a recent article on the use of BPA for thermal printing it was claimed that some receipts have as much as 100 milligrams of BPA.  I simply didn’t believe this, because 100mg is 0.1 gram, which is what I approximate as the weight of a cash register receipt.  So, I emailed the investigator and he clarified.  He encountered some coupons that were printed on 100 sqare inches of thermal printer paper.  That is one whopping receipt, but even at that size, the coating with BPA was impressive and scary.

Thermal Printing Heats BPA with Second Reagent to Make Pigments

Thermal printing ink, e.g. BPA plus an acid-sensitive dye, smeared over the whole surface of the special thermal paper.  Heating the paper in the printer head causes the BPA, which is a weak acid, to release its protons and react with the dye to produce a colored pigment.  In order to make the printing visible, a lot of initially colorless ink has to be coated on the paper.  That means that perhaps 5% of the weight of the thermal printer paper is BPA and that BPA is all on the surface and able to rub off onto your hands!

Don’t Touch the Receipts

A recent study of BPA exposure during gestation and subsequent stereotypical sex-specific behavior showed that women with higher BPA in their urine during their first trimester of pregnancy gave birth to babies that developed with less than their expected sex-specific behaviors.  In other words, higher BPA in utero meant that boys behaved more like girls and vice versa.  Most of the women tested had about 1 ppm BPA contaminating their urine.  Some had a thousand fold more.  Even if they ate polycarbonate bottles, they could not have had more than 1,000 ppm (1 ppm = one part per million = 1 microgram per gram = 1 milligram per liter, so 1,000 ppm = 1 gram per liter).  This suggests that the women with funny, really average kids, were getting their BPA from some other source than bottles and cans contaminated with BPA.

Wash Your Hands or Wear Gloves When Shopping

I think that the culprit is the cashier.  Why are some of these people so cheerful when they have to deal with so many louts in line?  Maybe it is the BPA soaking into their finger tips from the BPA-soaked receipts that they are handing to you.  You may have wondered why some people become fanatical about coupons.  Maybe they are also taking in too much BPA.  What about the kids playing with credit card receipts?  BPA has been linked with precocious sexual development.  Maybe it would be safer to let the kids play with cigarette butts.

Not All Receipts Have BPA

I have asked a few cashiers if their receipts are printed on thermal paper laced with BPA, but most don’t know or care.  Many receipts are printed with ink, so they aren’t a problem.  Either way, the cashier should know to avoid self-contamination or risks to customers.  May you should ask the next time you hand over the plastic.

I Don’t Believe It ...

There are too many myths in biomedical science. I think that our fears are misplaced and if we just address the real threats, e.g. inflammatory vegetable oils, we can enter the New Year with realistic hopes for good health.

Don’t Worry about Genetic Predispositions to Disease

Mendel was wrong in asserting that there is one gene for each phenotype. Modern clearinghouses of genes reveal the relationships between gene sequences and numerous protein functions. In the Human Protein Reference Database (HPRD), for example, each human gene is listed with all of its synonyms. The synonyms frequently reveal that genes lead multiple, unrelated lives and have sundry tangled relationships with dozens of other proteins. So the idea that there is one gene for each physical trait, phenotype, is a misleading simplification.

The good news is that the complexity would only be a problem, if our individual genetic composition was important to our health. In most cases, I think that our individual genetic predispositions to disease would only be important, if we stress our bodies (usually with an inflammatory diet) to the point of failure. With a healthy diet and lifestyle, I don’t think that most genetic predispositions to disease would ever affect health. To be specific, most people should be able to live until 80 with few physical compromises. This is very hopeful.

Don’t Worry about Drug Side-Effects (avoid the need for drugs)

Drugs have many side effects, simply because we don’t know enough about the interactions of small drug molecules with all of the possible protein targets. Take heparin, for example. Heparin is one of the most commonly used drugs to inhibit blood clotting. There is a clotting assay to measure how well heparin blocks clotting and injecting more heparin makes clotting slower. It appears that heparin binds to a protein involved in clotting. Heparin does bind to anti-thrombin, which in turn inhibits thrombin that is needed for clotting. Heparin also binds to several other proteins required for clotting and also binds to a dozen proteins involved in the complement system needed to kill pathogens or infected cells. Heparin binds to hormones, growth factors and their cell surface receptors. There are hundreds of proteins that use heparin to facilitate attachment to other proteins, to change shape and activity or to enter or leave cells. The point here is that heparin is a vivid example of a drug used to treat blood clotting, while at the same time dozens of other major interactions are ignored.

All drugs have multiple interactions with myriad proteins, but during screening, a drug is identified as having a significant desired affect. All drugs have side effects, because they are not completely specific. The side effects are often exploited as off-label uses for the drugs. Statins, for example, can impact lipid metabolism and change LDL blood levels. Unfortunately, research shows that lowering LDL does not affect heart disease. Fortunately, statins also lower inflammation and inflammation causes heart disease, so statins can be used as very expensive anti-inflammatory drugs.

The hopeful side is that most drugs are not necessary and there are other approaches that are more effective and cheaper to prevent and treat disease.

Don’t Worry about Your Gut Flora

There is a major NIH initiative to identify all of the bacterial species that live in or on the human body. That sounds potentially very useful in the context of all of the hype about pre- and probiotics. Your gut flora are important and people are doing very dumb things by killing off the bacteria that protect their skin from pathogens. The problem is that the concept of species of bacteria is wrong. In your gut, there is so much transfer of DNA between all of the different types of bacteria, that the idea of bacterial species doesn’t work.

Consider the pathogenic, toxin-producing E. coli strain. E. coli gets a bum rap, because we have created a new bacterium by treating cattle with antibiotics. The antibiotics increase fat accumulating in the beef, by altering the gut flora. The antibiotics eliminate some bacteria that normally live by adhering to the rectal areas of the cattle. E. coli can colonize the vacancies, but only if the gut lining releases nutrients and the E. coli is resistant to the antibiotics. The solution comes in the form of a plasmid from another bacterium. The plasmid is a small segment of DNA that carries genes for resistance to several different antibiotics and a toxin that causes intestinal cells to leak. The cattle don’t care much about the new Frankenstein E. coli, but if that plasmid-toting E. coli goes from cowpie to hamburger, and replaces your natural E. coli, it can be deadly.

The point is that the bacteria needed to fill all of the niches in your gut environment are created by approximation from the myriad genes of your whole gut flora community. You are constantly creating new “species” of bacteria. The problem is that you produce your own gut flora based on what you eat and by interactions with your gut. Those interactions can make you healthy or keep you sick. A single bottle of formula, for example, can permanently compromise the gut flora of a breastfed baby. We are learning how to control the development of healthy gut flora, probiotics, by supplements containing particular polysaccharides and oligosaccharides, i.e. prebiotics.

The hopeful side is that diets that have been shown to be healthy also produce healthy gut flora. That isn’t much of a surprise.

Don’t Worry about Toxins

The world is a dangerous place, but people have been there and done that. Plants have been standing around synthesizing a witch’s brew of natural toxins for millions of years. They are so good at it that even the most highly evolved species, bacteria, can’t eat them and survive. You can find a plant toxin that will interact with every human protein. That is why most human drugs are derived from plant toxins.

We know not to eat green potatoes, but pregnant women who make the mistake of eating rotten potatoes will regret the birth defects in their babies. There are so many toxins in plants that we have to be careful to watch what toddlers put in their mouths and every poison control center has to be able to identify plants over the phone to recommend emergency treatment. Pregnant women have a built in system to avoid plant toxins during the embryo’s most vulnerable first trimester. It is called morning sickness. A healthy diet during this time is to avoid vegetables and stick to meat and starch. Women build up baby fat to get through this sensitive time without exposure to plant toxins that their bodies may not be able to detoxify.

The happy thought here is that environmental toxins of human origin are not what make us sick, any more than eating plants generally is not a problem. With a healthy diet, even one modestly contaminated, we will not get sick. With a diet that compromises our health, even natural toxins become a threat.

Don’t Worry about Environmental Estrogens (except to save the rest of the animals)

There is an abundance of synthetic molecules that mimic human sex hormones, but once again, plants have been producing estrogen mimetics for millions of years. The second most abundant biological polymer (macromolecule), after cellulose, is lignin. Lignin is what makes up a large part of plant tissue and is what permits plants to be stiff. Lignin is also the “organic” material in fertile soil. This polymer is black in soil, because it is so complex that it has molecular structural components that can absorb all wavelengths of light. Lignin has no defined structure, but rather it is essentially a combination of thousands of structures.

Now imagine the mucky, black, lignin-laden banks of a forest stream. Tons of complex organic molecules leach into the stream and many of those molecules can mimic the shape of estrogens and bind to human molecules, receptors, that would normally bind to estrogen. It is possible to have excess estrogen leach from a sewage treatment plant, because it is not specifically targeted for removal, and the estrogens could temporarily reach a level to affect sensitive aquatic species, but there are already so many natural sources of estrogenic compounds, that the impact on humans would be expected to be unmeasurably small.

It is certainly possible for humans to pollute streams with other molecules, antimicrobial toothpaste ingredients, for example, that have unusually high environmental stability and bind with unnatural strength to estrogen receptors. Those would be problems like DDT. It would make sense to avoid exotic compounds and use natural plant products where possible, just because biological systems can digest them more readily.

The hopeful perspective here is that we already have ways of avoiding most of the problems with manmade estrogens and although these may be environmental hazards, they probably won’t affect human fertility.

An Anti-Inflammatory Diet and Lifestyle Is the Simple Solution

Prevention is the easiest way to stay healthy and since chronic inflammation is the foundation of degenerative, autoimmune and cancer diseases, an anti-inflammatory diet and lifestyle avoids most of the diseases. These same diseases also provide a modern description of aging, i.e. the consequences of mismanaged chronic inflammation. A healthy body is also the best protection from environmental threats, genetic weaknesses and the dangers of modern medicine.

The hopeful perspective for the New Year is eating and living well can keep you healthy and physically fit into your eighth decade.