Estrogen and Progesterone in Waterways

In the last post, I was speculating about how estrogens from effluent might end up in way water ways and end up increasing the incidence of prostate cancer. I wondered if the problem (if it there is anything more than a chance association) might be progesterone from birth control pills rather than estrogen. Progesterone is markedly non-soluble in water so it seemed unlikely at first thought. Poking around a little, progesterone might end up in sewage effluent after all. The three studies below report on fecal and/or urinary progesterone, conjugated progesterone or "progesterone metabolites" in animals. So . . . maybe progesterone contamination of water might be relevant. And, not all sewage is filtered and treated. I recently watched someone emptying a truckload of portapotties into one of our local creeks. (Yes, I called the police, who told me it was not their problem.) Don't know if anyone has looked at this or not. If you know, please have at it in comments.

deCatanzaro D, Muir C, Beaton EA, & Jetha M (2004). Non-invasive repeated measurement of urinary progesterone, 17beta-estradiol, and testosterone in developing, cycling, pregnant, and postpartum female mice. Steroids, 69 (10), 687-96 PMID: 15465115Kinoshita K, Inada S, Seki K, Sasaki A, Hama N, & Kusunoki H (2011). Long-term monitoring of fecal steroid hormones in female snow leopards (Panthera uncia) during pregnancy or pseudopregnancy. PloS one, 6 (5) PMID: 21559303Brown JL, Wasser SK, Wildt DE, & Graham LH (1994). Comparative aspects of steroid hormone metabolism and ovarian activity in felids, measured noninvasively in feces. Biology of reproduction, 51 (4), 776-86 PMID: 7819459google-site-verification: googleaa234ad89e44d776.html

Response to a friend on significance of Triclosan in drinking water

Sorry Friend. That was a poor response to your question about the significance of Triclosan following news of the chemical as an androgen blocker in water.

Triclosan is a thyroid disruptor and according to recent reports, an androgen blocker. As an anti-androgen, exposure could be important to male fetuses, since it could potentially interfere with development of the genito-urinary system, which could mean birth defects like hypospadias, small phallus, or non-obvious problems like changes in numbers and proportions of cells that would, later in life, produce sperm and testosterone. Thyoid inhibition has its own effects on development of the male reproductive system as well. So there might be some interesting interactive effects if both thyroid hormones and androgens are impacted. If that would occur you'd see reduced fertility. In an adult lowered testosterone would lead to other problems.

Blocking androgens, on the upside, might lead to less prostate cancer. It would be interesting to see if Dial Soap or other triclosan-containing products use this as a marketing point. "protects against body odor, gingivitis AND prostate cancer" Let's guess not.

Lastly, there was also an article out recently that associates rates of prostate cancer with presumed levels of estrogen (presumably from urine from women on birth control) in water supplies (Margel & Fleshner 2011). This was unexpected to me, until I thought about the pathway through which testosterone is produced. Testosterone can be synthesized from Progesterone, which is also present in birth control pills. So, it may be the progesterone, rather than estrogen, that is causing the problem. Progesterone is not water soluble, so its unlikely to be found in water systems unless conjugated to something else or incorporated in something else, so this is just speculation on my part.

Back to Triclosan. You can find some basic information on what kinds of products contain Triclosan at the Environmental Working Group Website. Its dated 2008, but the basic information may be useful.

For all of this, note that, for Triclosan, the picture is far from clear, as recent papers also report Triclosan enhancing androgenic activity in vitro (Christen et al. 2010) and as having estrogenic activity (Jung et al. 2011). Neither of those qualities is desirable in an environmental contaminant.
Best wishes,

Margel, D., & Fleshner, N. (2011). Oral contraceptive use is associated with prostate cancer: an ecological study BMJ Open, 1 (2) DOI: 10.1136/bmjopen-2011-000311

Christen V, Crettaz P, Oberli-Schrämmli A, & Fent K (2010). Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere, 81 (10), 1245-52 PMID: 20943248

Jung EM, An BS, Choi KC, & Jeung EB (2011). Potential estrogenic activity of triclosan in the uterus of immature rats and rat pituitary GH3 cells. Toxicology letters PMID: 22062131

Rostkowski, P., Horwood, J., Shears, J., Lange, A., Oladapo, F., Besselink, H., Tyler, C., & Hill, E. (2011). Bioassay- directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. Environmental Science & Technology DOI: 10.1021/es202966c

Selenium, Brazil Nuts and Testosterone

There seems to be a lot out in the popular press or online material that incresing selenium intake will increase a healthy man's testosterone production (example and example II from Forbes Magazine: what were they thinking?), but little, if anything, in the scientific literature to support that idea. (I like the scientificky approach used by that website, especially the graph that shows no effect, and no indication of variability in the data points). However, elevated testosterone, long term, will increase risk of testicular and prostate cancer. There has also been recent emphasis on consumption of brazil nuts as a natural source of selenium that will boost testosterone and increase virility.

Selenium is protective against prostate cancer, and good for testicular development (fetal period . . . sorry guys) and possibly protective against other oxidative-stress-induced ailments, testicular or not. On the other hand, selenium, at high concentrations can result in DNA damage, and thus increase risk of cancer. The problem with supplementing, either through tablets, or through consumption of a natural product high in selenium, is that we do not know where the lines of good and evil cross.

As for Brazil nuts, selenium concentrations in any plant should be dependent on the concentration of selenium in the soil in which it grows, therefore, the concentration of selenium in Brazil nuts probably varies. This turns out to be the case, with nuts grown in Manaus-Belem more than ten times higher in selenium than those grown in Acre-Rondia. Someone consuming Brazil nuts may or may not be making a significant increase in selenium intake.
Chang, J. (1995). Selenium content of Brazil nuts from two geographic locations in Brazil Chemosphere, 30 (4), 801-802 DOI: 10.1016/0045-6535(94)00409-N

ATIF, F., YOUSUF, S., & AGRAWAL, S. (2008). Restraint stress-induced oxidative damage and its amelioration with selenium European Journal of Pharmacology, 600 (1-3), 59-63 DOI: 10.1016/j.ejphar.2008.09.029

Brozmanová J, Mániková D, Vlčková V, & Chovanec M (2010). Selenium: a double-edged sword for defense and offence in cancer. Archives of toxicology, 84 (12), 919-38 PMID: 20871980
Henderson, B. (2000). Hormonal carcinogenesis Carcinogenesis, 21 (3), 427-433 DOI: 10.1093/carcin/21.3.427

Schistosomiasis may be protective against Auto-Immune Disease

Following up here on the associations between parasite infection and reduced incidence of autoimmune diseases such as diabetes, thyroid disorders, arthritis and possibly asthma, this time with a specific focus on Schistosome infection. Schistosomias is a common infection in many areas of the developing world, and is thought to be the second most important human parasite after malaria. Infection may be sub-clinical with little or no indication of infection.

Osada et al. (2009) reported on lower inflammation and less arthritic response in infected mice. Arthritis can be induced in mice by injecting them with Collagen II. A recent publication by Xiao-Ping Chen's group (He et al. 2010) further report that the inhibitory effect of schistosomiasis is dependent on the life stage of the schistosomes. Schistosomes have a very complex life cycle and apparently some phases are more protective or induce different physiological responses in the host than others. Acute infection and egg-laying by the parasite are associated with less response to the collegen injections. Very interesting.

However, it is not advised that people run out and attempt to infect themselves, which can be pretty horrible and disfiguring. Malnutrition, anemia and lowered IQ have been observed in infected children, and increased incidence of bladder cancer is seen among infected adults. Still, it will be interesting to see where this work goes, and what treatments may be eventually developed. Thank you Osada et al. and He et al.

He, Y., Li, J., Zhuang, W., Yin, L., Chen, C., Li, J., Chi, F., Bai, Y., & Chen, X. (2010). The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent BMC Immunology, 11 (1) DOI: 10.1186/1471-2172-11-28

Araújo, M., Hoppe, B., Medeiros Jr, M., & Carvalho, E. (2004). Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases Memórias do Instituto Oswaldo Cruz, 99 DOI: 10.1590/S0074-02762004000900005

OSADA, Y., SHIMIZU, S., KUMAGAI, T., YAMADA, S., & KANAZAWA, T. (2009). Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators International Journal for Parasitology, 39 (4), 457-464 DOI: 10.1016/j.ijpara.2008.08.007

Did Intestinal parasites and poor hygiene protect us from autoimmune diseases?

Autoimmune diseases are troubling, and often frustrating and painful for health care practitioners and patients. As far as I know, celiac disease is the only autoimmune disorder with a specific and identified trigger: the protein gluten. It has also been pointed out that the incidence of Celiac Disease, the formal name for gluten-triggered autoimmune reactions in the bowel, appears to have been increasing. Some have claimed that humans are not adapted to consumption of plant proteins like gluten, and that inflammatory bowel disorders are the result of the development of agriculture. However, there are a few other possibilities. One is that autoimmune disorders in general have been increasing and that Celiac disease is not increasing at a uniquely faster rate.

A major hypothesis in the development of allergies (inappropriate immune responses to non-pathogens, such as glutten or pollen or dog hair) is lack of exposure to potential allergens early in life. This, perhaps, is the root of the problem: soap, lysol, and a generally high level of cleanliness. Also, a huge change in human habit is the widespread introduction of infant formula to replace breast milk, and early introduction of other foods into infant diets. The ideal window of exposure to gluten is now considered to be between 4 and 7 months and that exposure should be concurrent with continuing breast milk consumption. Introduction to wheat cereals during this period is thought to be protective against celiac disease. Those raising their young children on gluten-free diets in the hope of protecting them from celiac disease, or the adverse effects of inflammation in general, may be taking the wrong route. (See Pinier et al. 2010 and Lopez-Serrano et al. 2010). Let them get a little dirty

Another possiblity, proposed by Elliot and Weinstock (2009) is the current rarity of helminth infection in the Western World. These authors propose that helminth infection was protective against autoimmune diseases like celiac disease by stimulating immune circuits that lower inflammation. I suppose if one were to choose between a gluten-free diet and helminth infection, most would go with the gluten-free diet. However, before you consider loss of bread as the price some pay for the protection of all against intestinal parasites, note that Elliot and Weinstock also propose exploration of the use of helminths for clinical treatment of auto-immune disease.

Elliott, DE and Weinstock JV (2009). Inflammatory bowel disease and the hygiene hypothesis: an argument for the role of helminths Progress in Inflammation Research, 149-178 DOI: 10.1007/978-3-7643-8903-1_9

Pinier M, Fuhrmann G, Verdu E, & Leroux JC (2010). Prevention measures and exploratory pharmacological treatments of celiac disease. The American journal of gastroenterology, 105 (12) PMID: 20877349

López-Serrano P, Pérez-Calle JL, Pérez-Fernández MT, Fernández-Font JM, Boixeda de Miguel D, & Fernández-Rodríguez CM (2010). Environmental risk factors in inflammatory bowel diseases. Investigating the hygiene hypothesis: a Spanish case-control study. Scandinavian journal of gastroenterology, 45 (12), 1464-71 PMID: 20704469

Ketogenic Diets

I would advocate moderation in just about everything. Ketogenic diets have proven helpful to people with uncontrolled epilepsy and may be of benefit to epileptics in general, to victims of stroke and other forms of brain injury and possibly cancer. They come with other effects that may not be worth the discomfort or unintended risks to healthy people. This includes kidney stones and, in women and girls, amenorrhea. Amenorrhea is associated with bone loss, increasing risk of osteoporosis, and indicates problems in hormone balance. Supplementation with calcium may help with this, but then again, it might not. Physiology can be quite complex, and consumption does not necessarily indicate absorption is occurring. It is quite possible that something that causes hormonal imbalance in women may also cause hormonal imbalance in men. Playing with one’s physiology, when we don’t know the unintended outcomes of such play, may be inadvisable, especially long-term.

I have been a vegetarian for 30 years and an athlete all my life. I have excellent bone density, low blood pressure, low resting heart rate, low fasting blood sugar, excellent blood lipid profile and great strength to body weight ratio. I'm happy and healthy, even though I thoroughly understand I represent but a single data point. I do get a lot of advice from well-meaning friends that I need to eat meat and would be much healthier if I followed a ketogenic diet.  Vegetarians, as described in some current diet books, are weak and "skinny-fat". I will leave it at this: The "optimal diet" for one person may not be the "optimal diet" for another, nor the optimal diet for all conditions. Humans are omnivores and physiologically polymorphic and adaptable. This has given us tremendous abilitity to survive in wildly different climes and environments, and has made us such a resilient species. It is also quite possible, that our individual resilience allows our bodies to adjust to dietary and environmental change.

The current state of research indicates no harm though, from short-term ketogenic diets. I have not found much in the way of research on the risks and benefits of long-term ketogenic diets in healthy adults. Anyone who wishes to add a citation, please feel free.


Kossoff, E., Zupec-Kania, B., & Rho, J. (2009). Ketogenic Diets: An Update for Child Neurologists Journal of Child Neurology, 24 (8), 979-988 DOI: 10.1177/0883073809337162

Bergqvist AG, Chee CM, Lutchka L, Rychik J, & Stallings VA (2003). Selenium deficiency associated with cardiomyopathy: a complication of the ketogenic diet. Epilepsia, 44 (4), 618-20 PMID: 12681013

Brinkworth GD, Buckley JD, Noakes M, Clifton PM, & Wilson CJ (2009). Long-term effects of a very low-carbohydrate diet and a low-fat diet on mood and cognitive function. Archives of internal medicine, 169 (20), 1873-80 PMID: 19901139

Role of Hormones, Genes, Hybrid Cars and Environmental Factors in Human Cryptorchidism

Undescended testicles (Cryptorchidism) appear to be of complex origin . . . one of those cases where there are genetic and environmental components, and therefore difficult to figure out. You can consider genetics, exposures to environmental estrogens and anti-androgens and the relations among risk factors. You will not be bored trying to figure this one out. Added to this mix is a previously unconsidered variable: Hybrid Cars.

I teach a course called "Introduction to Research" which is somewhat like boot camp for aspiring academics.  I would now only encourage people to go into academia if they are so driven by love or fascination for a subject that they are willing to sacrifice a signifant amount material comfort in its pursuit.  I described my 16 year old minivan as dented and rusty, with an interior re-upholstered piece-meal with green fluorescent duct-tape.  The starstruck response: a breathless and drawn out "cool . . . "  I went on to describe my leaky roof and deceased dishwasher, and received this: "Dr. K, I will come to your house and fix your dishwasher" followed by "and I will drape my body over the hole in your roof next time it rains" from yet another.  Undergraduates can be absolutely amazing. 

So, to the hybrid part of the cryptorchidism story.  The minivan leaks oil, gets not-so-good mileage and I drive about 120 miles a day to commute to the University.  This is horrible for the environment, and costs about 1/7th of my income in gasonline alone.  It suddenly struck me, during a quiet conversation with a good friend, and sometimes nemesis, that I could get a used Prius and maybe come out ahead financially on the reduction in gas expenditures.  "Oh No!  I'm Emasculating!" (that wasn't exactly how it was phrased, but you get the point: he has just become cryptorchidic).   I only struck up a conversation with him in the first place because he looked like a hippie and a good environmentalist.  Just another reminder not to speak to strangers even if they look "nice". 

So what's the deal with hybrids and environmentalism that threatens the masculinity of men in Texas?  A simple question, that could be answered with a simple "beats the hell out of me" until I started considering bumper stickers:

This is a question that should be posed to an historian, psychologist and/or poli sci person.


Foresta, C., Zuccarello, D., Garolla, A., & Ferlin, A. (2008). Role of Hormones, Genes, and Environment in Human Cryptorchidism Endocrine Reviews, 29 (5), 560-580 DOI: 10.1210/er.2007-0042

Hearing, Reading Disabilities and PCB exposures

I found this article very exciting. Serum PCB Concentrations and Cochlear Function in 12-Year-Old Children. by Trnovec et al. 2010, in which they describe associations between hearing function and PCB exposures in Slovakian kids. (In regular terms: PCB exposure in children probably causes hearing deficits). My forebears were deaf, graduated from the American School for the Deaf, were members of Deaf Baseball and Football teams, and from all the old pictures we have, seem to have had absolutely fun and wonderful lives, so I've never really considered Deafness a disability. However, hearing deficits make it hard for children to learn to read, and they do not get the full range of information available to children without hearing deficits. This can be a problem that may put them at a disadvantage in terms of conventional measures of school and life success. See Banai et al. 2009 for some recent interesting work in this area.

Trnovec et al. also observed differences between ears (no, not that some kids heads were filled with Kapok and some weren't) with the left ear showing a stronger deficit than the right. This does lead one to wonder if people are left earred or right-earred and that the same effect might not be seen if they had recruited only right-handed or left-handed children. This is also more complex than it seems because you can be right handed and "goofy footed" i.e. left foot dominant. I am goofy footed, but its only apparent when I'm out surfing.

Here is a link for understanding the systems through which Trnovec are evaluating correlations of PCB exposure with hearing. http://www.est-med.com/OAE/understanding-using_OAE%20von%20Kemp.pdf

Trnovec, T., Šovčíková, E., Pavlovčinová, G., Jakubíková, J., Jusko, T., Husťák, M., Jurečková, D., Palkovičová, L., Kočan, A., Drobná, B., Lancz, K., & Wimmerová, S. (2010). Serum PCB Concentrations and Cochlear Function in 12-Year-Old Children Environmental Science & Technology, 44 (8), 2884-2889 DOI: 10.1021/es901918h