Healthcare for who? How our current system is putting profits over people.

It has become very clear that our for-profit healthcare system is biased to only providing cures for the rich. Sovalti is a lifesaving drug used to treat hepatitis C (HCV) with great success and minimal side effects in comparison to the previous drug it replaced. This groundbreaking drug was developed by a small biotech company called Pharmasset which was partially funded by the federal government before it was bought by the pharmaceutical company Gilead for a massive $11 billion (Henry, 2018).

Where the story starts getting messy is how Gilead decided how much to charge for the drug as well as why. Gilead priced Sovalti at a massive $84,000 or about $1000 per pill, making Sovalti inaccessible to the majority of the population who need it the most (Henry, 2018). This sounds ridiculous, but unless you can afford to buy the drug directly from the company, you have to wait until you are at the end stages of liver disease in order to qualify for the treatment through Medicaid (Khazan, 2015). This isn’t Medicaid’s fault, public health agencies like Medicaid cannot afford the $3.2 billion it would take to treat all of those suffering from HCV (“Column,” 2017). We have to ask ourselves, why are these drug prices so high?  

The high cost for research and development that goes into producing a drug like Sovalti is usually the excuse used for why companies like Gilead price their treatment so high, but let’s not forget who paid for that initial cost. Sovalti was partially funded using tax payer money, yet Gilead is trying to sell it back to you at an exorbitant amount (Americans for Tax Fairness, 2016). The treatment Sovalti replaced was priced at around $70,000 and Gilead used that price as a reference for pricing their new and improved drug, regardless of how much it is actually worth. The manufacturing price for Sovalti is estimated at about $134 per pill, yet is being sold at $1000 per pill (“This Is Why Hepatitis C Drugs Are So Expensive,” 2015). Pharmaceutical companies like Gilead are not in the business of helping people, they solely care about the bottom line, even if that means withholding treatment for those less fortunate.

The federal government is legally not allowed to negotiate drug prices due to massive lobbying by drug companies (Henry, 2018). Sovalti was partially funded using tax payer money, yet is bankrupting those who paid for that drugs development in the first place. This is indicative of a much bigger problem, one that that all of us as a society are facing. The healthcare system and primarily pharmaceutical companies are unethical and unjust by putting profits over people. Unraveling the health care system is too ambitious for a blog post but with the 2020 elections right around the corner we have a responsibility to educate ourselves as well as exercise our civic duty by voting. The constant debate is overwhelming but fixing our healthcare system is worth the growing pain of overhauling our current one.

References:

Column: Gilead says drug profits must stay high to pay for “innovation,” but 100% of its profits went to shareholders. (2017, October 23). Retrieved November 18, 2019, from Los Angeles Times website: https://www.latimes.com/business/hiltzik/la-fi-hiltzik-gilead-profits-20171023-story.html

Henry, B. (2018). DRUG PRICING & CHALLENGES TO HEPATITIS C TREATMENT ACCESS. Journal of Health & Biomedical Law, 14, 265–283.

Khazan, O. (2015, September 25). Prescription Drugs Are So Expensive That People Die Waiting to Get Them. Retrieved November 18, 2019, from The Atlantic website: https://www.theatlantic.com/health/archive/2015/09/an-expensive-medications-human-cost/407299/

This Is Why Hepatitis C Drugs Are So Expensive. (2015, November 12). Retrieved November 18, 2019, from HuffPost website: https://www.huffpost.com/entry/why-hepatitis-c-drugs-are-expensive_n_5642840be4b08cda34868c8a

GILEAD SCIENCES - Americans For Tax Fairness. (2016). Retrieved from https://americansfortaxfairness.org/wp-content/uploads/ATF-Gilead-Report-Finalv3-for-Web.pdf.

What Is The Cost of Those Pearly-Whites?

Since the 1940s community water fluoridation has implemented to promote dental nationwide oral health (National Cancer Institue [NIH]). Currently, 74% of the United States population relies on fluoridated water provided by public water systems (Malin et al., 2019). Over the years there have been numerous speculations surrounding the repercussions of water fluoridation. Specifically, research into whether fluoridation causes cancer was conducted in 1991, 1999, and 2011 and each time the conclusion was the same: there is no evidence to support that water fluoridation causes cancer (National Cancer Institute [NIH]). Other investigations have suggested that it may have a role in Alzheimer's disease and the neurodegeneration it brings about (Goshorska et al., 2018). Some even believe that water fluoridation is a mind control method employed by the government to pacify the masses, but let us not go down that road. Please?

Despite the mixed reviews, some new research has come about that may finally have the water fluoridation neigh-sayers telling the rest of us, "I told you so." A cross-sectional study performed by Malin et al. just this year claims that children and adolescents are at risk of suffering kidney and liver damage from long term, low-level, fluoride exposure. What they found was that just a 1µmol/L increase in plasma fluoride levels was associated with an average estimated glomerular filtration rate (eGFR) decrease of 10.36 mL/min/1.73 m^2. Since children and adolescents excrete roughly 45% of the ingested fluoride through the kidneys, while adults can excrete about 60%, it makes sense that individuals in these age groups are more susceptible. These researches also tested blood urea nitrogen levels (BUN) and found that these individuals had a lower BUN than expected implying that the liver may also be affected.

What exactly does this mean? First, it is important to note that the study is not claiming that we are causing kidney and liver disease in our children and teens, but it does appear that the addition of fluoride to our water is affecting kidney and liver function, and metabolism. Second, because of the less effective filtration and excretion of fluoride in children and teens, these researchers believe it possible that as more fluoride is ingested, more will bioaccumulate, sequentially causing more glomerular damage. It is important to note that, although most water sources follow suggested fluoride level guidelines, there are still some that contain well above safe levels causing fluoride toxicity characterized by poor bone formation (including teeth), gastrointestinal issues, and kidney/liver damage (Malin et al., 2019).

The question is, do the benefits of fluoridating our water for cavity prevention and oral health continue to outweigh the damage (even if it is small) that we appear to be doing, especially when vulnerable populations seem to be at the most risk? Or are we doing more harm than good, when we could just as easily promote better oral hygiene and cut out forced intervention all together?

Citations and original article:
https://www.sciencedirect.com/science/article/pii/S0160412019309274?via%3Dihub

Ashley J. Malin, Corina Lesseur, Stefanie A. Busgang, Paul Curtin, Robert O. Wright, Alison P. Sanders,
Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013–2016,
Environment International, Volume 132, 2019, 105012, ISSN 0160-4120, https://doi.org/10.1016/j.envint.2019.105012.

Goschorska, M., Baranowska-Bosiacka, I., Gutowska, I., Metryka, E., Skórka-Majewicz, M., & Chlubek, D. (2018). Potential Role of Fluoride in the Etiopathogenesis of Alzheimer's Disease. International journal of molecular sciences, 19(12), 3965. doi:10.3390/ijms19123965

Corruption in Healthcare: A Quick Glance at Overbilling

              In conversation with my optometrist regarding ethical concerns in healthcare, he encouraged me to explore instances where practitioners overbill government health care programs, such as Medicare. For background, I will explain the concept of overbilling as he explained to me. At the optometry office I work at, we have different billing codes for eye exams which range from Level 1-Level 5, depending essentially on if the patient is new or established and how much time the patient spends with the doctor. Level 1 may be where the patient never sees the doctor while Level 5 would be a much more severe and time-consuming case. The higher the level, the higher the price insurance reimburses the doctor. Overbilling here could be billing for a Level 4 exam when it was actually a Level 2 exam in order to earn more money.

               One example noted in ProPublica was Dr. Mark Roberts, a family practitioner in Alabama, who billed for the most complex and expensive type of visit 4,765 times a year (Ornstein & Grochowski, 2017). This amount was greater than any other U.S. doctor, providing him approximately $450,000 in revenue from Medicare (Ornstein & Grochowski, 2017). For comparison, he essentially billed at this rate 95% of the time while other family practitioners in Alabama only billed this code 5% of the time (Ornstein & Grochowski, 2017).

               Ornstein & Grochowski (2017) note this problem exists among numerous doctors: in 2012, 1,807 practitioners billed for the most expensive visits at least 90% of the time, while in 2015, 1,825 practitioners billed at this high level (Ornstein & Grochowski, 2017).  Dwayne Grant, the regional inspector general for evaluation and inspections in Atlanta, notes that while some physicians may truly only see the sickest patients who require these high-level services, it is unlikely all 1,800+ of these physicians are doing so (Ornstein & Grochowski, 2017). Alternatively, Cyndee Weston, the executive director of the American Medical Billing Association, notes that electronic medical record systems can automatically assign billing codes depending on doctor’s input, and the codes selected tend to be of higher cost (Ornstein & Grochowski, 2017).

               I think for most of us, it is clearly unethical for a practitioner to bill for services they did not provide for financial gain due to justice. While something should be changed to electronic records to prevent this, how should we handle these practitioners with poor ethical choices?
                

References:

Ornstein, C., & Grochowski, R. (2017, December 27). Some Doctors Still Billing Medicare for the Most Complicated, Expensive Office Visits. ProPublica. Retrieved from https://www.propublica.org/article/some-doctors-still-billing-medicare-for-the-most-complicated-expensive-office-visits

Blood Pressure Reductions in Black Barbershops

Last year I read an NPR story about management of blood pressure promoted by barbers in the Los Angeles area led by certified pharmacists of the American Society of Hypertension. In January of this year, the study was published with the results of the research.

                Hypertension is among the highest in African American males, with death rates being 3x higher in black males than white males of the same age (Victor et al., 2019). Barbershops are a known place of comfort and gathering for African American males, a place where trust and companionship is created. Given the high instances of hypertension in black males, Dr. Ronald Victor with a grant from the National Institute of Health trained 52 barbershops from around the city to take patients blood pressure. An enrolled cohort of 319 black male patrons were recruited with a systolic blood pressure of >140 mmHG and were assigned to either the control group, where barbers promoted follow up with primary care providers and life style changes, or the intervention group, where barbers followed up with a pharmacist who then prescribed blood pressure medication under collaboration with the patrons primary care doctor. Results were significant; Over 12 months, barbers who promoted this implementation saw a sustained reduction in blood pressure. In the intervention group, the baseline systolic blood pressure was 152.4 mmHG and after 12 months fell to 123.8 mmHG while the control group baseline was 154.6 mmHG and after 12 months fell to 147.4 mmHG.

                Clearly the intervention group vastly improved, by working in conjunction with the barber, pharmacist, and primary care doctor. Though there was improvement in the control group, which is important, it goes to show how holistic care can be broadened to impact a patient’s healthcare choices.

                Given the success of this research, is it ethical for someone such as a barber, nail tech, or esthetician to try to impart a health intervention, especially since places like this are “safe places for talking”?  Since the health promotion by these barbers showed a reduced and sustained blood pressure in the patrons/patients treated, it has shown that people who we encounter on a daily basis can greatly aid in our health care decisions, however to what extent is there a line crossed in such intervention, if any?

             What factors must be present for you as a patient to get on board with their recommendations? Since the National Institute of Health heavily funded this research, there was much care in choosing the patients who qualified as well as sufficiently training the barbers and having the patients cooperate with the study. Do you see any violations in ethical principles and or what principles did the barbers as well as the pharmacists/primary care doctors impart on these patrons?

               

Victor et al., 2019. Sustainability of Blood Pressure Reduction in Black Barbershops. Circulation.           139. 10-19. DOI:  10.1161/CIRCULATIONAHA.118.038165

NPR Story Link: https://www.npr.org/sections/codeswitch/2014/06/22/324347600/shape-up-and-check-up-la-barbers-to-start-testing-blood-pressure

Splits not gains- Muscle hypertrophy

As a trainer, weight loss was often the main focus for many of my clients. I would often have non-obese women come to me with this goal and I had to explain that they didn't necessarily need lose weight they and they instead should shift their goal to lose fat. Education on this became especially important when these clients started to increase weight due to muscle mass.  My biggest selling point was the fact that increasing muscle mass, increases metabolic rate. In fact, skeletal muscle uses on average 13.0 kcal/kg body weight per day, where as adipose tissue uses only 4.5 kcal/kg of body weight per day (Heymsfield et al., 2002). 

If humans are good at hypertrophy (myofibril splitting), but not so good at hyperplasia (generating new myofibrils), how does muscle mass actually increase under hypertrophic conditions? Is it the contractile proteins that are attributing completely to this muscle mass or is it something else?

To start, hypertrophy is a complex process that contributes to muscle growth through myofibril splitting rather than generation of new muscle fibers (hyperplasia). Activities such as resistance exercise overload can induce hypertrophy though mild trauma or damage to the muscle itself. Satellite cells reside on the outer surface of muscle fibers. They are usually inactive but upon muscle trauma or damage, become activated. Once activated, satellite cells multiple and fuse to existing muscle fibers. Satellite cells donate their nuclei and allow the damaged muscle fiber to regenerate (Hawke & Garry, 2001). This process increases the size of the muscle fiber and also increases the amount of contractile proteins within them. Various growth factors also contribute to hypertrophy. For example, insulin-like growth factor (IGF) stimulates protein synthesis as well as satellite cell proliferation and differentiation (Hawke & Garry, 2001). 

Many factors contribute to an increase in muscle mass after hypertrophic conditions. Increased muscle fiber size allows for space available for glycogen storage, and a larger area for water volume. Additionally, contractile proteins such as myosin and actin proliferate and contribute to some of the mass gain. While exercise may result in weight gain in certain situations this weight gain is due to non-lipid sources and even contribute to increase metabolic rate and subsequent fat loss.

Hawke, T. J., & Garry, D. J. (2001). Myogenic satellite cells: Physiology to molecular biology. Journal of Applied Physiology, 91(2), 534–551. https://doi.org/10.1152/jappl.2001.91.2.534

Heymsfield, S. B., Gallagher, D., Kotler, D. P., Wang, Z., Allison, D. B., & Heshka, S. (2002). Body-size dependence of resting energy expenditure can be attributed to nonenergetic homogeneity of fat-free mass. American Journal of Physiology. Endocrinology and Metabolism, 282(1), NaN-NaN. https://doi.org/10.1152/ajpendo.2002.282.1.E132

High Altitude Drinking

We've all heard drinking alcohol at high altitudes makes you intoxicated quicker. However, one study showed that after drinking 1 L of beer at various altitudes, subjects had the same blood alcohol content (1). So how does this apparent accelerated intoxication really work?

There is less oxygen availability at higher elevations, therefore one of the ways our bodies initially adapt to high elevation is through hyperventilation.This increase in respiratory rate helps supply adequate amounts of oxygen and release excess CO2.  The same study mentioned above, shows that alcohol initially inhibits this respiratory response and could lead to hypoxia (1). Therefore, there is no actual increase in intoxication but rather exacerbated altitude sickness which may in some ways feel similar to alcohol intoxication.

Additionally, alcohol inhibits the effects of anti diuretic hormone (ADH) on the kidney, causing less water reabsorption and subsequently dehydration (2). Higher altitudes tend to have dryer climates which in combination with alcohol, could increase risk for dehydration and exacerbate the effects of alcohol intoxication.  Again, instead of enhanced intoxication, it seems that drier climates may just increase rate of dehydration.

These studies are old and have limitations. It is apparent more research needs to be done on this topic. Who wouldn't volunteer to drink free beer in the mountains?

1. Roeggla, G., Roeggla, M. H., Roeggla, M., Binder, M. M., & Laggner, A. N. (n.d.). Effect of Alcohol on Acute Ventilatory Adaptation to Mild Hypoxia at Moderate Altitude.

2. Wiese, J. G., Shlipak, M. G., & Browner, W. S. (2000). The Alcohol Hangover. Annals of Internal Medicine, 132(11), 897. https://doi.org/10.7326/0003-4819-132-11-200006060-00008

Male Birth Control- a new option in preventing unwanted pregnancy

Important news was recently released in India in regards to male birth control. According to The Hindustan Times, the Indian Council of Medical research finally completed a clinical trial on injectable male contraceptive (Kaul, 2019). This injection prevents pregnancy for 13 years. The birth control requires one single injection of a polymer into the vas deferens of a male. This new method is called reversible inhibition of sperm under guidance or RISUG for short (Jha et al., 2019).  RISUG is made of  styrene maleic anhydride and is reported to a multitude of things. The US patent states that the mechanism by which this contraceptive option works is still ambigous (Lohyia et al., 2014), but research has shown that it causes partial occlusion and lowers pH which affects sperm motility (Carr, 1985). Researchers in India ensure that there are no side effects, despite side effects being seen in previous research studies in the U.K. and the U.S. (Sharma et al., 2019).

For years, birth control has been the responsibility of the females in relationships. Side effects of one female birth control (nexplanon) are outlined here: weight gain,  increased risk for serious blood clot, cyst development, abnormal bleeding, vaginitis, acne, breast pain, dizziness, etc. (“Important Safety Information for NEXPLANON® (etonogestrel implant) 68 mg Radiopaque,” n.d.). This is just one of the many birth controls! With the biomedical principle of non-malfeasance in mind, I as a future medical professional would be very hesitant to prescribe this to a patient, if I knew that there was a safer option out there for the opposing sex.  I am aware that RISUG is not yet legal in the United States, but based on the bioethical principle of justice, I believe the United States has a responsibility to investigate this as a future option because society should not exclusively put the responsibility of preventing unwanted pregnancies on females.  Males who are not intending to have sex result in pregnancy should also carry this burden. 

What are your thoughts on male contraceptives? If it truly is a safe option do medical professionals have obligations to encourage usage, knowing that many women suffer from side effects from their birth control options? 

Carr, D. W. (1985). Effects of pH, Lactate, and Viscoelastic Drag on Sperm Motility: A Species Comparison1 | Biology of Reproduction | Oxford Academic. Retrieved November 29, 2019, from https://academic.oup.com/biolreprod/article/33/3/588/2764005

Important Safety Information for NEXPLANON® (etonogestrel implant) 68 mg Radiopaque. (n.d.). Retrieved November 29, 2019, from https://www.nexplanon.com/safety-information/?src=google&med=cpc&camp=Nexplanon_Brand_BRND_NA_ENGM_EXCT_TEXT_FEMALE&adgrp=Safety+Info+V2&kw=nexplanon+side+effects&utm_kxconfid=sgaizzyx0&gclid=EAIaIQobChMIlu2osqqQ5gIVlLfsCh1N2glwEAAYASAAEgK6dvD_BwE&gclsrc=aw.ds

Kaul, R. (n.d.). India closer to world’s first male contraceptive injection—India news—Hindustan Times. Retrieved November 29, 2019, from https://www.hindustantimes.com/india-news/india-closer-to-world-s-first-male-contraceptive-injection/story-o3lTFLnCkKHpuEDNNqrEnO.html

Jha, P., Jha, R., Gupta, B. L., & Guha, S. (n.d.). Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive—ScienceDirect. Retrieved November 29, 2019, from https://www.sciencedirect.com/science/article/abs/pii/S0969806X09005544

Lohiya, N. K., Alam, I., Hussain, M., Khan, S. R., & Ansari, A. S. (2014). RISUG: An intravasal injectable male contraceptive. Retrieved November 29, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345756/

Sharma, R., Mathur, A. K., Singh, R., Das, H. C., Singh, G. J., Singh Toor, D. P., & Guha, S. K. (2019). Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): A clinical experience Sharma RS, Mathur AK, Singh R, Das HC, Singh GJ, Toor DP, Guha SK - Indian J Med Res. Retrieved November 29, 2019, from http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2019;volume=150;issue=1;spage=81;epage=86;aulast=Sharma

Rx: Hip Hop!

Self proclaimed doctor and dance instructor, Dr. Winters, has taken it upon himself to battle juvenile diabetes from one of its causes: “Part of weight management is not focusing on weight, because it’s not the best way to counsel patients. Our goals are not to promote weight loss, but to promote healthier lifestyles.” He focuses on a cause of obesity, inactivity, and not obesity itself in order to help the children in his practice (Foston, 2018). By doing so, he emphasizes the whole patient. He takes into account the social, socioeconomic, and health interdependent relationships that play into childhood obesity and diabetes. 

As a child who lived with obesity and a diabetes diagnosis, Dr. Winters took it upon himself to make lifestyle changes to beat his diabetes (Foston, 2018). He also found the inspiration as an osteopathic physician to help children do the same. He teaches and prescribes hip hop dance classes to his patients in order to inspire long lasting healthy changes. By doing so he became more relatable as a doctor, which improved the outcomes of his patients. After reading this story, I noticed how it is not only important for a doctor to be able to relate to their patient, but it is equally as important for the patient to be able to relate to their doctor.

Dr. Winters also found it important to "lead by example" (Boston, 2018). He gave his community in Ohio a hand up not a hand out. One of his former students actually took on the leadership role at 16 years old to teach the class when Dr. Winters moved to New Jersey. 

It is pretty cool to acknowledge doctors making lasting differences in their communities. We too can use our experiences to establish our empathetic style of practice and philosophy in medicine. I think that this is very important because in order to treat a patient as a whole unit, doctors too need to see themselves as whole. Yay osteopathy! 


References

Foston, N. (2018, January 4). A hip-hop doc who rocks, as doctor and dance instructor. Retrieved from https://thedo.osteopathic.org/2018/01/hip-hop-doc-rocks-doctor-dance-instructor/.

Doctors That DO - Doctors That DO: Doctors of Osteopathic Medicine. (n.d.). Retrieved from https://doctorsthatdo.org/doctors-that-do.

The DO Difference - Doctors That DO: Doctors of Osteopathic Medicine. (n.d.). Retrieved from https://doctorsthatdo.org/difference.

Downstream Effects of Hormonal Contraceptives

When we wash dishes in the kitchen sink, take a shower, or flush the toilet, we don't generally think about where that water goes; out of sight out of mind. We are fortunate to have the luxury of clean water and not worrying about how our water waste will again become clean, all thanks to water waste treatment plants (WWTP). With all of the different things that we put into our bodies and eventually into the water system, is our treated waste water really as clean as we think it is when it returns to the streams or rivers?

Unfortunately, some endocrine-active chemicals (EAC) still manage to make their way into WWTP effluent, and with the increasing availability of hormonal-based contraceptives and normalization of their use, we aren't the only species experiencing their reproductive effects. Vajda et al. (2008) looked into white sucker fish in Boulder Creek and found some of the population to be intersex. More specifically, samplings of white sucker fish were taken from a site approximately 2km upstream of the Boulder WWTP, and approximately 200m downstream of the WWTP effluent site, but only found intersex fish in the sample taken below the effluent site (Vajda et al., 2008).  Fish were considered to be intersex if both ovarian and testicular tissue were present during histological examination (Vajda et al., 2008). Of several steroidal estrogens that were observed in Boulder Creek, a couple of the more commonly recognized estrogens that were found in a higher relative concentrations were 17β-estradiol (E2) and ethinylestradiol, two chemicals used in common forms of contraceptives (Vajda et al., 2008). Colorado is a relatively arid-state, meaning that during low-flow conditions, the effluent from WWTP can make up a large amount of the creek's water flow, increasing the EAC concentration in the creek water (Vajda et al., 2008). This is of importance because the period of time that white sucker fish undergo sexual differentiation after hatching falls at the same time that Boulder Creek experiences these low-flow conditions where EAC concentration is highest (Vajda et al., 2008). This is a significant threat to this population since EACs are able to interfere with estrogen signaling pathways at even low concentrations, hence the emergence of intersex fish (Vajda et al., 2008). 

The region of Boulder Creek located below the effluent site had a female to male ratio with a significant female bias (Vajda et al., 2008). This has significant ethical implications when it comes to the future of the white sucker population in Boulder Creek. The efficiency of WWTPs ought to be improved in order to rid effluent water from EACs on the basis of beneficence and non-maleficence. Non-maleficence applies here, because although this study doesn't necessarily represent the entire population of white sucker fish, there have been other incidences where EAC contamination has led to the collapse of fish populations (Kidd et al., 2007). We should not be causing any harm, intended or unintended, to other populations as a result of our own chemical use. Beneficence is also important here, because by removing harmful EACs from natural water sources like Boulder Creek, we would help to promote normal reproductive processes in these fish populations. Fortunately, upgrades to the Boulder WWTP have been made slowing the feminization of male fish, but there is still a long way to go (CU Boulder Today, 2010).

References:

Gender-Bending Fish Problem in Colorado Creek Mitigated by Treatment Plant Upgrade. (2010, June 21). Retrieved November 29, 2019, from CU Boulder Today website: https://www.colorado.edu/today/2010/06/21/gender-bending-fish-problem-colorado-creek-mitigated-treatment-plant-upgrade

Kidd, K. A., Blanchfield, P. J., Mills, K. H., Palace, V. P., Evans, R. E., Lazorchak, J. M., & Flick, R. W. (2007). Collapse of a fish population after exposure to a synthetic estrogen. Proceedings of the National Academy of Sciences, 104(21), 8897–8901. https://doi.org/10.1073/pnas.0609568104

Vajda, A. M., Barber, L. B., Gray, J. L., Lopez, E. M., Woodling, J. D., & Norris, D. O. (2008). Reproductive Disruption in Fish Downstream from an Estrogenic Wastewater Effluent. Environmental Science & Technology, 42(9), 3407–3414. https://doi.org/10.1021/es0720661