Hormones: Here’s the Beef

Each year, U.S. farmers raise some 36 million beef cattle. Farmers fatten up two-thirds of these animals by using hormones.

Many cattle are fed the same muscle-building androgens–usually testosterone surrogates–that some athletes consume. Other animals receive estrogens, the primary female sex hormones, or progestins, semiandrogenic agents that shut down a female’s estrus cycle. Progestins fuel meat-building by freeing up resources that would have gone into the reproductive cycle.

While federal law prohibits people from self-medicating with most steroids, administering these drugs to U.S. cattle is not only permissible but de rigueur.

So far, almost all concern about this practice has focused on whether trace residues of these hormones in the meat have human-health consequences. But there’s another way that these powerful agents can find their way into people and other animals. A substantial portion of the hormones literally passes through the cattle into their feces and ends up in the environment, where it can get into other food and drinking water.

Some scientists say that it’s time to better manage livestock’s hormone-laced waste stream, which has flowed unabated in North America for decades.

Cancer threat

As much as anyone, John A. McLachlan knows what’s been happening. He first became interested in livestock hormones in the early 1970s, when he learned that farmers were giving the synthetic hormone diethylstilbestrol (DES) to chickens and cattle. This synthetic estrogen chemically castrates male animals, enabling them to grow faster. At the time, McLachlan’s own studies at the National

Institute of Environmental Health Sciences (NIEHS) used animal models to investigate why DES fostered the development of cancer in daughters of women treated to avoid miscarriages.

While McLachlan wasn’t worried about any cancer threat that DES might pose to animals destined for the slaughterhouse, he recalls being very concerned that the animals’ excretions were releasing “something like 13 tons of DES a year into the environment.” He and others began fearing that the hormones might pose chronic risks to wildlife and people.

Although the Food and Drug Administration (FDA) outlawed veterinary use of DES by the mid-1970s, the provision of other hormones to livestock continued to bother McLachlan. So, he convened a 1980 symposium to explore this and related issues.

For the meeting, he coauthored a paper with the late David P. Rall, then director of NIEHS. “We were prescient,” McLachlan now says. He and Rall reasoned that with all the steroid hormones being prescribed not only to livestock but also to people–such as to women for birth control or postmenopausal therapy–excretions of these drugs must be substantial. The economic incentive for farmers to use the hormones–it can amount to a 40-fold return on their investment–is compelling (see The Financial Lure of Hormones,below) and will probably fuel the practice for some time.

“We said we wouldn’t be surprised if significant amounts of pharmaceutical [including veterinary] estrogens end up in water,” remembers McLachlan, now director of the Center for Bioenvironmental Research, which is administered jointly by Tulane and Xavier Universities, both in New Orleans. Recent data have confirmed that human hormonal drugs do taint rivers and streams–sometimes in amounts that adversely affect fish (SN: 6/17/00, p. 388: Excreted Drugs: Something Looks Fishy).

Soon after the 1980 meeting, interest in the environmental fate of livestock hormones faded as researchers got caught up in the discovery that pesticides and other industrial chemicals could mimic and disrupt normal hormone and endocrine action in people and other animals (SN: 7/3/93, p. 10).

Indeed, although he is a biologist specializing in reproduction and hormonelike substances, Bernard Jegou notes that until 3 years ago, he had never heard people discuss excreted livestock hormones.

“Considering that the weakest of these [steroid] growth promoters is probably 100 to 1,000 times stronger in biological activity than the most potent of the [industrial] endocrine disrupters gaining interest, I figured these drugs could pose a real environmental threat,” says Jegou, who’s the director of research at INSERM (the French Institute of Health and Medical Research) in Rennes.

Shared concerns

At a May 2000 meeting in Copenhagen, Jegou finally encountered other researchers who shared his concerns. A host of speakers at the meeting described steroid data that they were beginning to acquire as part of studies in the United States and Europe funded under a new European Union (EU) research program.

Since 1988, concerns about the potential health risks of drug residues has led the EU to ban importation of the meat of hormone-treated animals. The United States and Canada, which produce such meat, have vigorously fought the ban through both punitive tariffs on various imports from Europe and appeals to the World Trade Organization. The EU has expressed hope that new research will provide scientific grounds to rebut these challenges to its ban.

In one of the EU-funded studies, research teams led by Louis J. Guillette Jr. of the University of Florida and Ana M. Soto of Tufts University School of Medicine in Boston collaboratively investigated the environmental fate of hormones running off feedlots in Nebraska.

Soto compared the hormonal activity of water sites downstream of feedlots with that of water collected upstream. In her tests, she added water samples to cells that react in various ways to steroids. In one assay, estrogen turns on cell growth; in another, androgens inhibit cell growth.

At the Copenhagen meeting, Soto reported finding that concentrations of estrogenic pollutants at two of the downstream sites were sometimes almost double those at the upstream site. And water from all three downstream sites was significantly more androgenic than the samples collected upstream. One downstream sample exhibited nearly four times the androgenicity of the upstream water.

Toxicologist L. Earl Gray Jr. with the Environmental Protection Agency in Research Triangle Park, N.C., has also analyzed water from those Nebraska sites. He uses a different assay for androgenicity, but like Soto, he finds evidence of masculinizing steroids.

The steroids may not be just sitting benignly in the water. In a report that he has just sent to the EU, Guillette reports adverse hormonal changes in fathead minnows.

Males just downstream of the feedlots “had a significantly reduced testis size”–which, he says, appears to explain why they also produced less testosterone than males upstream. He also found that the heads of these fathead minnows weren’t all that fat–which also makes sense, he notes, since testosterone helps determine skull size.

What appears to be happening, he says, is that the waterborne androgens provide some signal that tells the males’ bodies to produce less testosterone.

In females, the researchers observed a significant increase in the ratio of androgenic to estrogenic hormone concentrations in blood. The biological significance remains unknown.

These observations indicate that wild fish “are being nailed by polluting hormones,” Guillette told Science News–with males becoming somewhat feminized and females somewhat masculinized.

He says that he’d wanted to compare feedlots that use hormones and those that don’t, but he couldn’t find any operations that don’t take advantage of the drugs. Moreover, because Soto has not yet identified the particular steroids in down-stream waters, Guillette notes, “we can’t rule out that these effects are due to natural androgens and estrogens in manure.” Even untreated cattle, horses, and chickens excrete natural estrogens, testosterone, and other steroids (SN: 11/3/01, p. 285: Available to subscribers at Kitchen tap may offer drugs and more).

However, Guillette adds, when one considers new German data on how long steroidal growth-promoting drugs can persist in the environment, “it’s highly likely that what we’re seeing in these wild fish is a pharmaceutical effect” derived from the farm use of these agents.

Hormonal Holsteins

Much of the German data to which Guillette refers appears in the November 2001 Environmental Health Perspectives. It comes from EU-funded studies at the Technical University of Munich in Freising-Weihenstephan.

Scientists there experimentally treated Holsteins with two growth-promoting steroids commonly used at U.S. feedlots. Andreas Daxenberger and his colleagues inserted implants of trenbolone acetate–an androgen–into the ears of 41 males and females and gave feed laced with melengestrol acetate, a progestin, to another 12 females that had never been pregnant. Then, the researchers had the dirty work of collecting and analyzing all of the manure that these animals produced–some 100 tons–over the next 2 months.

Their trenbolone data showed that by the end of the study, 10 percent of the androgen had passed right through the animals into feces, Daxenberger says. The animals shed similar amounts of the progestin feed additive.

The Munich scientists then looked at how well the steroids survived in manure. During storage of the manure, both drugs resisted bacterial breakdown, each showing a half-life of some 260 days. Once spread on fields, however, the hormones’ degradation rate skyrocketed.

For instance, once liquefied manure was applied to fields, the trenbolone disappeared within a little more than a week. The androgen in dried-dung fertilizer disappeared in about 2 months. However, Daxenberger notes, what share of the drugs’ disappearance might be the result of runoff–versus microbial breakdown–remains an open question.

Scientists at two Environmental Protection Agency laboratories have just begun investigating what trenbolone-laced runoff might do.

In castrated male rats, Gray finds, trenbolone stimulates the growth of androgen-dependent tissues. However, he says, “it didn’t behave exactly like testosterone,” the primary natural androgen. For instance, while trenbolone stimulated muscle development, it had relatively little impact on prostate growth.

He says the unexpected differences “mean that we can’t predict exactly what the drug would do in [wildlife]–especially during their development.” Gray reported his findings in November 2001 at the annual meeting in Baltimore of the Society of Environmental Toxicology and Chemistry.

At that meeting, Gerald T. Ankley of EPA’s lab in Duluth, Minn., described preliminary data on fish exposed to trenbolone for 21 days in the lab. The most visible change, he noted, was the development of head bumps, known as tubercles, on female fathead minnows. These bumps ordinarily show up only on breeding males. The exposed females also produced fewer eggs than unexposed females do.

His lab is now looking for more subtle changes.

Even the excretion of natural steroids by livestock that are raised without artificial hormones can have negative impacts on aquatic animals, observes Eva Oberdrster of Southern Methodist University in Dallas. For example, while at Clemson (S.C.) University, she and her colleagues analyzed field runoff of estrogen-laced manure from a small herd of pregnant and lactating cows that had not received any hormones. Samples of the runoff boosted blood concentrations of the egg-yolk protein vitellogenin in female turtles at nearby ponds.

Inducing these turtles to become “superfemales” could prove harmful, she worries, if they divert unhealthy amounts of energy into egg production.

One of Oberdrster’s students, Lisa K. Irwin, found that the ponds’ enrichment with bovine estrogen also prompted juvenile sunfish to make egg-yolk protein–even though these males and females were all well below an age when even females normally do so.

Useful studies

With a European ban on the use of steroid drugs in livestock, why does the EU fund studies on environmental impacts of such use? One answer comes from data amassed by Rainer Stephany of the National Institute of Public Health and the Environment in Bilthoven, the Netherlands.

Though Europe’s beef industry maintains that no steroids are used, Stephany says that his lab and others have demonstrated by analyzing meat samples that the continent hosts an “illegal–black market–use of growth promoters.”

A “defensible overall estimate for the use of these compounds in the European Union, based on results from annual regulatory residue-testing programs, could be in the range of 5 to 15 percent” of beef cattle, he reported in the proceedings of the Copenhagen conference, published last summer as a special, 571-page issue of APMIS (formerly Acta Pathologica, Microbiologica et Immunologica Scandinavica).

Moreover, he notes, because all such drug treatment in Europe is illegal, illicit users tend to employ whatever is available and affordable. Residues of at least 35 such drugs have been found in meat samples. This complicates screening, Stephany observes, since an investigator never knows quite what to look for and each assay can cost as much as a cow’s entire carcass is worth.

This situation contrasts sharply with that in the United States, where drug residues in meat invariably consist of one or more of only six FDA-approved growth promoters, he says.

Though the EU is clearly concerned about the impacts of livestock steroids, what about U.S. regulators? At the Copenhagen meeting, Stephen F. Sundlof, director of FDA’s Center for Veterinary Medicine in Rockville, Md., noted that although “it is my role to regulate these substances . . . I was only made aware at this workshop that we may be having some environmental issues to consider.”

That was nearly 2 years ago. In the interim, Soto and Guillette have briefed Sundlof on their studies. Sundlof has also learned of the German findings. From these, he now concludes that the environmental fate of livestock-steroid use “is something that we [at FDA] are definitely concerned about.”

“My sense,” he told Science News, “is that right now [FDA is] going to be looking into the whole issue of pharmaceuticals getting into water–and that’s not just steroids, but it’s also antibiotics and some other potent chemicals.”

If soon-to-be-published analyses of stream-sampling data by the U.S. Geological Survey confirm that livestock drugs are getting into the environment, Sundlof says, new regulations may be called for. He doesn’t envision a phase-out of livestock steroids, but he says that farmers might be asked to assume greater diligence in managing the animals’ wastes.

For now, he cautions, plenty of unanswered questions remain about whether and how much livestock wastes contribute to pharmaceutical pollution in U.S. waters (SN: 4/1/00, p. 213: More Waters Test Positive for Drugs).

Indeed, notes Rigshospitalet endocrinologist Niels Skakkabk, an organizer of the Copenhagen meeting, when it comes to the environmental fate of livestock steroids,

“the most frightening thing is that we still know so little.”

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The Financial Lure of Hormones

Each year, U.S. farmers send 30 million head of cattle to feedlots. This is where animals get beefed up on high-protein chow. To enhance the animals’ production of muscle–that is, meat–livestock producers treat 80 percent of all feedlot cattle with steroid hormones.

Some cows get steroids in their feed. Others receive one or more hormones via a controlled-release implant in their ears. Economically, these hormones offer a bonanza.

It costs farmers about $1 to $3 per head to treat their livestock with either procedure, notes animal scientist Michael J. Fields of the University of Florida in Gainesville. Treatment increases animals’ growth by 20 percent, so each cow in a feedlot typically gains 3 pounds per day, he says. Moreover, for each pound that it gains, it consumes 15 percent less feed than an untreated animal does.

“This feed efficiency works out to a cost savings of about $40 per head–so you get more protein at a cheaper cost,” Fields says.

The Center for Veterinary Medicine at the Food and Drug Administration has approved the use of these hormones because they tend to leave only small concentrations–ones believed to be harmless–in meat. However, the regulators haven’t considered what effects the hormones might have after being excreted into the environment.–J.R.

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