The steroidal compounds used for anabolic purposes in food animals are estradiol, progesterone, and testosterone. Gender and maturity of an animal influences its growth rate and body composition. Bulls grow 8-12% faster than steers, have better feed efficiencies, and produce leaner carcasses. Superior performance of bulls is due to the steroids produced in the testes (mainly testosterone but also estradiol, which in ruminants is also anabolic and is produced in relatively large quantities). Testosterone, or one of its physiologically active metabolites, binds to receptors in muscle and stimulates increased incorporation of amino acids into protein, thereby increasing muscle mass without a concomitant increase in adipose tissue. Estradiol, on the other hand, may act by stimulation of the somatotropic axis to increase growth hormone and thus IGF-1 production and availability by modulation of the IGF binding proteins. Naturally produced endogenous steroids are not orally active, require picogram concentrations of estradiol and nanogram concentrations of testosterone in blood for physiologic effects, and can transiently affect the behavior of treated animals
Estradiol:
| A potent anabolic agent in ruminants at blood concentrations of 5-100 pg/mL, estradiol is administered as an ear implant, either as compressed tablets or silastic rubber implants. When estradiol is formulated as compressed tablets, a second steroid (usually testosterone or progesterone) is typically present, in a ratio of ~1 part estradiol to 10 parts of the other steroid. The purpose of the second steroid is to reduce the release rate of estradiol and thereby prolong the effective life span of the implant to 100-120 days. The release of hormones from compressed pellets is relatively rapid within 2-4 days after insertion (50-100 times higher than baseline), followed by a slower rate of release for the next 30-50 days (5-10 times higher than baseline). Hormone concentrations gradually decline up to day 80-100, when concentrations are no different from those in control animals. |
| Estradiol formulated in silastic rubber enhances the effective life span of the implant relative to pelleted formulations. The pattern of release includes a short-lived spike in plasma estrogen concentration for 2-5 days after insertion, followed by a stable but modest increase (5-10 times greater than baseline). Toward the end of the effective life span of the implant, there is a gradual decline to estradial concentrations found in control animals. |
| Estradiol, on its own, increases nitrogen retention, growth rate by 10-20% in steers, lean meat content by 1-3%, and feed efficiency by 5-8%. It can be used in steers to best advantage, but it has some anabolic effects in heifers and veal calves. It works best in lambs in conjunction with androgens. It is not effective as an anabolic agent in pigs. |
Testosterone:
| A potent anabolic agent at the relatively high concentrations of 1-5 ng/mL in peripheral circulation, testosterone is not used on its own as an anabolic agent in farm animals, because it is very difficult to achieve the effective physiologic concentrations for long periods (up to 100 days) with current delivery systems. It is generally used as a propionate formulation in conjunction with 20 mg estradiol benzoate (EB) in a compressed tablet implant; its major role in the compressed pellet may be to slow down the release rate of estradiol. In high concentrations in blood, testosterone induces male sexual behavior (eg, aggression and mounting), but this is not observed with the concentrations delivered by compressed pellets in the ear (1 ng/mL). Behavior resulting from use of 20 mg EB and 200 mg progesterone is not different from that observed after the use of 20 mg EB and 200 mg testosterone propionate. |
Progesterone:
Unambiguous data suggesting progesterone is anabolic in farm animals does not exist. Its major use is to slow the release of estradiol from compressed pellet implants.
| Synthetic Steroids: |
Synthetic steroids are commercially available in some countries because of their efficacy, their relatively mild androgenicity, and because they cause few behavioral anomalies
| . Commercial synthetic steroids are androgenic, (TBA), or progestogenic (melengestrol acetate, MGA). |
| Synthetic steroidal androgens are not commonly used as anabolic agents except for TBA. TBA is currently the only synthetic androgen approved for use for growth promotion in cattle; it is used to a lesser extent in sheep and not in pigs or horses. It has weak androgenic activity but has greater anabolic activity than testosterone. There are no obvious side effects in males. TBA has significant anabolic effects on its own in female cattle and sheep, but in castrated males, it gives maximal response when used in conjunction with estrogens. It is administered as a pellet-type implant containing 140-300 mg TBA for heifers and cull cows, and it can be used with estradiol in doses ranging from 140-200 mg TBA as either combined or separate implants. |
Melengestrol acetate is an orally active synthetic progestagen. It is fed at doses of 0.25-0.5 mg per heifer per day in the feed. It suppresses recurrent estrus in feedlot heifers and increases growth rate and feed efficiency . It is not effective in pregnant or spayed heifers or in steers. Its mode of action is to suppress ovulation presumably by suppressing luteinizing hormone (LH) pulse frequency; however, large follicles develop, which can increase concentrations of estradiol and growth hormone, and hence growth. There is generally a 48-hr withdrawl period prior to slaughter. Melengestrol is permitted for use in the USA but not in the EU.
| Synthetic Nonsteroidal Estrogens: |
| Two major classes of synthetic nonsteroidal estrogens have been used as production enhancers in food animals. Stilbene estrogens (either diethylstilbestrol [DES] or hexestrol) have been banned in most countries as anabolic agents because of residue and food safety concerns. |
The discovery of a naturally occurring estrogen, zearalenone (produced by the fungi Fusarium spp ), led to the development of the synthetic analog zeranol. Zeranol is estrogenic and has a weak affinity for the uterine estradiol receptor. It is used in animal production as a SC ear implant at a dose of 36 mg for cattle and 12 mg for sheep, with a duration of activity of 90-120 days. In steers, zeranol increases nitrogen retention, growth rate by 12-15% and feed conversion by 6-10%. However, lower responses are seen in heifers. Its effects are additive to those of androgens (generally TBA).
| Use in Cattle: |
| Calves have a high conversion of feed into animal tissue. Therefore, their responses to anabolic agents are variable. Responses of 0-10% have been obtained when zeranol was given to 3-mo-old castrated male calves. No significant response has been obtained from TBA. Bull calves in an intensive bull beef system can be given an estrogen implant at 1-2 mo of age to suppress testicular development, which may lead to subsequent reduction in mounting and aggression. A growth response of ~5-8% is also sometimes obtained from this implant. Reimplantation every 100 days is necessary if compressed pellet implants are used. The value of implanting heifer calves is doubtful because of the low and variable responses obtained. |
| A major limitation to the use of anabolic agents in weanlings is the low liveweight gain they may achieve because of poor feeding. Hence, anabolic agents should be considered only if the weanlings are expected to gain >0.5 kg/day. Zeranol can be used in male castrates. Dairy heifer replacements cannot be given steroid implants as weanlings. |
| Higher and more consistent responses are obtained in yearling and older cattle than in calves or weanlings. This is partly related to age and partly to the higher plane of nutrition. In the case of pellet-type implants with effectiveness of 90-100 days, consideration can be given to reimplanting cattle in midsummer, provided gains >0.5 kg/day are maintained. Silastic implants of estradiol are effective for 200-400 days, depending on dose used. Daily gains have increased 20-30% after implantation of male castrates with an estrogen and an androgen. Less research has been done in yearling beef heifers, so a definite recommendation cannot be given. However, TBA could be considered for use in these animals. |
| The choice of implant to use in finishing beef cattle is governed to some extent by which implants, if any, have been previously used. Responses are good when animals are on a high plane of nutrition. Feed conversion efficiency is improved, and lean meat content of the carcass is generally increased. Feed additives do not affect carcass composition. Although less clear, conformation of implanted cattle tends to improve, but repeated use of implants in older cattle can decrease the percentage of choice and prime carcasses produced. |
| In steers, an androgen plus an estrogen hormone combination can be used. Pellet-type implants are effective for 90-100 days; in a 4- to 5-mo finishing period, a silastic implant or reimplanting cattle after 70-80 days should be considered due to decreased response from the pellet-type implants. In a prolonged finishing phase, long-acting implants obviate the need to reimplant the estrogen component of the combination treatment. The other major alternative is to use a hormonal implant and a feed additive. |
| Heifers should be given TBA or a feed additive. They can be given estradiol, but 20-40% of the heifers so treated show mammary development and can be classified as “cow heifers” after slaughter. Cull cows can be given TBA, estradiol, or a feed additive, as mammary development is of no concern. TBA may play some role in drying off cull cows still in milk. |
In some studies in which bulls were treated with estrogens, growth rate increased by 2-10%, and testicular growth was suppressed with a consequent reduction in mounting and aggression. This would make the bulls easier to manage on the farm and less subject to “dark cutting” after slaughter. The mechanism involved appears to be the reduction of gonadotropic hormones LH and follicle-stimulating hormone (FSH) from the pituitary gland by estrogen, which has a strong negative feedback effect on LH and FSH secretion. This reduction in LH and FSH results in decreased testicular size and lower testosterone levels, with a consequent reduction in aggressive behavior. However, there appears to be sufficient testosterone secreted to maintain an anabolic effect. Therefore, the repeated use of estrogens in bulls beginning at 1-3 mo of age may lead to a hormonal castration effect with increased growth rate.
| Use in Horses: |
The use of anabolic agents in horses is not recommended because of adverse effects on the reproductive system. Administration of a steroid hormonal androgen analog decreases testicular size in stallions. Decreased hormonal concentrations, especially LH, testosterone, and inhibin, adversely affect testicular histology and spermatogenesis and transiently decrease sperm output and quality. One of the most commonly used compounds is 19-nortestosterone for therapy in debilitated and anemic horses. However, use of these compounds is contraindicated, and longterm treatment or large doses have serious side effects on reproductive tract function.
| Use in Other Species: |
| In pigs, the growth responses from the use of estradiol, progesterone, and zeranol are variable but generally low. TBA seems to increase lean meat content of pig carcasses. |
| In sheep, the responses to anabolic agents parallel those obtained in cattle. The most consistent responses have been obtained in lambs finished on high-concentrate diets; a 10-15% increase in daily gain can be expected. Anabolic steroids should not be used in lambs to be retained for breeding. Also, implantation with zeranol reduces testicular development in ram lambs and delays the onset of puberty and reduces the ovulation rate in female sheep. Moreover, the short finishing period and the extensive nature of some production systems militate against widespread practical use of growth promotants in sheep on economic grounds. |
| In poultry, responses to estrogens include increased fat deposition. Androgens, however, have given conflicting responses. Hence, their use is of no practical significance at this time. |
In fish, methyl testosterone can induce sex reversal in rainbow trout, thereby promoting growth and improved feed conversion efficiency.
| Possible Complications: |
| Any hormonal implant has a negative feedback effect on pituitary gonadotropins, thereby reducing LH and FSH secretion. Therefore, they can affect the onset of puberty and the regularity of estrous cycles, as well as reduce conception rate in females and testicular development (and thus sperm output) in males. Hormonal growth promotants should never be used in animals that are or may be used for breeding purposes; nor should they be used before puberty to increase growth in yearling thoroughbreds or young pedigree bulls for show purposes. If given to pregnant heifers, TBA results in increased incidence of severe dystocia, masculinization of female genitalia of the fetus, increased calf mortality, and reduced milk yield in the subsequent lactation. |
In general, no undue behavioral side effects have been reported after the use of either zeranol or TBA alone or in combination in cattle. However, cattle that have implants may succumb to stress more easily than cattle that do not. The major problem arises from the use of estradiol as a growth promotant. Its use in various implants has been associated with transient increased mounting behavior and aggression. These effects generally last for 1-10 days after implantation and then subside. In some cases, the size of rudimentary teats can be increased. However, there have been a few reports of undesirable behavior in steers that lasted for 4-10 wk. The cause of this unpredictable adverse behavior is not clear, but it is generally more severe in dairy cattle used for beef production. To minimize the adverse behavior after implantation, it is important to avoid crushing the pellet-type implants during insertion and to not mix new cattle with those that have implants. If the problem is severe, the buller steers should be identified and removed; if very severe, removal of the implants or administration of 50-100 mg progesterone in oil for a number of days to suppress behavior should be considered.
| Factors Affecting Response: |
| A number of factors affect the response, including genetic make-up, plane of nutrition, the sex and age of the animal, and prior implantation. |
| Animals should be gaining a minimum of 0.5 kg/day before an economic response is obtained. Implants are best used in animals on a high plane of nutrition and under good husbandry conditions. They are an aid to, but not a substitute for, good husbandry. Consequently, there is no point in implanting cattle destined for a 3- to 4-mo “store period.” Responses are also lower in animals of high genetic merit (eg, growth rate >1.4 kg/day). The quality of the diet may influence the growth response, with higher crude protein (up to 18% of diet) yielding improved responses. |
| Steers show the maximal response. Responses are reduced in calves, and responses are good in yearlings and older animals. Maximal responses are probably obtained in older beef cattle at the beginning of an intensive winter finishing period. Females do respond, probably better to androgens such as TBA. |
| Prior implantation does not affect the response to the next implantation. Also, once the implant effect has ceased, the rate of gain reverts back to the rate that was obtained before implantation, assuming the level of feeding has not changed. Also, extra weight induced by implants in early life is transferred through to extra carcass weight at slaughter. |
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