Can a breast cancer drug benefit cattle?
Can a drug that's proved useful for humans be of value to the beef and dairy cow industry?
By Brittany Davis
That's a question Dr. Gregg Adams and a team of researchers at the Western College of Veterinary Medicine (WCVM) are hoping to answer.
Adams and his team are investigating the effects of letrozole, a non-steroidal drug commonly used in human medicine to treat infertility and breast cancer in women. Their research focuses on letrozole's effects on ovarian function and its possible use for synchronizing the reproductive cycles in cattle. Being able to trigger the synchronization of estrus or heat is useful because it means that the females can all be bred at approximately the same time.
Synchronizing reproductive cycles is an important tool in the cattle industry because it allows cattle producers to apply advanced reproductive technologies such as fixed-time artificial insemination and embryo transfer. By using these technologies, they can operate more efficiently and profitably.
Letrozole was commonly used for treating breast cancer, but when researchers discovered that the drug had ovarian effects which improved fertility in women, they developed a bovine model aimed at understanding more about its function. That model led to their realization that letrozole could also benefit the cattle industry.
Letrozole is an aromatase inhibitor; that means it blocks the enzyme responsible for converting testosterone into estrogen. The drug prolongs the lifespan of the dominant follicle in the ovary, resulting in the delay of ovulation.
"It prevents the follicle from producing what it wants to produce and that's estrogen," says Adams, a veterinary professor who specializes in theriogenology. "Due to low levels of estrogen, there is no suppression of luteinizing hormone released from the pituitary gland in the brain so it can continuously feed the dominant follicle, causing it to grow."
Although it's unknown whether the dominant follicle can be maintained this way indefinitely, researchers discovered that they could delay ovulation by administering this drug for a short period of time – making it a useful tool for synchronization in cattle.
Traditionally, synchronization for fixed-time artificial insemination was done using a combination of estrogen and progesterone. Artificial insemination is a technique where semen is collected from a bull and then manually inserted directly into the uterus of a cow.
But less than six per cent of North American beef cattle producers use artificial insemination, and in Adam's view that low rate represents a lost opportunity for the cattle industry.
"Producers are missing out on two important things: condensing the calving season and the opportunity to use high quality genetics," says Adams.
"In the early '90s we developed a steroid approach for synchronization in cattle and it was awesome; it took off across the world, particularly in South America. The South Americans really showed us how well artificial insemination works and how it is an important part of the beef business."
By taking advantage of advanced reproductive technologies, South America can produce high-quality beef more efficiently. The rest of the world has been slower to implement artificial insemination in their cattle herds, partly due to the stricter regulations on the use of steroids in food production animals.
While estradiol is commonly used for synchronization in South America, its use has been banned in the European Union, Australia and New Zealand, and there are increasing restrictions on its use in North America.
These restrictions result from the increasing controversy surrounding the use of hormones in food production animals due to potential health and environmental concerns.
"The residue created by the estradiol synchronization protocol is negligible, but perception rules, and the perception is that there are too many estrogens floating in the environment and we need an alternative," explains Adams.
Alternative, non-steroidal methods for synchronization are available, but none have had great success. However, letrozole has the potential to meet consumer demands. It's a non-steroidal drug that's been proven safe for humans, and it's been approved by the FDA for treatment of breast cancer and infertility in women.
Another benefit of letrozole: it's easy to use. Producers can administer a dose using a minimally invasive intravaginal device that allows for prolonged drug release and reduces animal stress and handling, as opposed to protocols that involve multiple injections. The device also allows for immediate removal of the drug source once the medication period is up.
Letrozole could prove to be a very useful tool for the dairy and beef cattle industries. Right now there's a lack of products that can generate synchronization, and with an expanding market this drug has a lot of potential.
Although letrozole is an exciting advancement for the cattle industry that promises to provide a consumer-friendly, cost-efficient alternative to current synchronization methods, Adams is cautiously optimistic.
"With research you have to be patient and take a step-by-step approach and that's what we are doing," he says.
Brittany Davis of Saskatoon, Sask., is a second-year veterinary student who was part of the WCVM's Undergraduate Summer Research and Leadership program in 2016. Brittany's story is part of a series of articles written by WCVM summer research students.
Adams and his team are investigating the effects of letrozole, a non-steroidal drug commonly used in human medicine to treat infertility and breast cancer in women. Their research focuses on letrozole's effects on ovarian function and its possible use for synchronizing the reproductive cycles in cattle. Being able to trigger the synchronization of estrus or heat is useful because it means that the females can all be bred at approximately the same time.
Synchronizing reproductive cycles is an important tool in the cattle industry because it allows cattle producers to apply advanced reproductive technologies such as fixed-time artificial insemination and embryo transfer. By using these technologies, they can operate more efficiently and profitably.
Letrozole was commonly used for treating breast cancer, but when researchers discovered that the drug had ovarian effects which improved fertility in women, they developed a bovine model aimed at understanding more about its function. That model led to their realization that letrozole could also benefit the cattle industry.
Letrozole is an aromatase inhibitor; that means it blocks the enzyme responsible for converting testosterone into estrogen. The drug prolongs the lifespan of the dominant follicle in the ovary, resulting in the delay of ovulation.
"It prevents the follicle from producing what it wants to produce and that's estrogen," says Adams, a veterinary professor who specializes in theriogenology. "Due to low levels of estrogen, there is no suppression of luteinizing hormone released from the pituitary gland in the brain so it can continuously feed the dominant follicle, causing it to grow."
Although it's unknown whether the dominant follicle can be maintained this way indefinitely, researchers discovered that they could delay ovulation by administering this drug for a short period of time – making it a useful tool for synchronization in cattle.
Traditionally, synchronization for fixed-time artificial insemination was done using a combination of estrogen and progesterone. Artificial insemination is a technique where semen is collected from a bull and then manually inserted directly into the uterus of a cow.
But less than six per cent of North American beef cattle producers use artificial insemination, and in Adam's view that low rate represents a lost opportunity for the cattle industry.
"Producers are missing out on two important things: condensing the calving season and the opportunity to use high quality genetics," says Adams.
"In the early '90s we developed a steroid approach for synchronization in cattle and it was awesome; it took off across the world, particularly in South America. The South Americans really showed us how well artificial insemination works and how it is an important part of the beef business."
By taking advantage of advanced reproductive technologies, South America can produce high-quality beef more efficiently. The rest of the world has been slower to implement artificial insemination in their cattle herds, partly due to the stricter regulations on the use of steroids in food production animals.
While estradiol is commonly used for synchronization in South America, its use has been banned in the European Union, Australia and New Zealand, and there are increasing restrictions on its use in North America.
These restrictions result from the increasing controversy surrounding the use of hormones in food production animals due to potential health and environmental concerns.
"The residue created by the estradiol synchronization protocol is negligible, but perception rules, and the perception is that there are too many estrogens floating in the environment and we need an alternative," explains Adams.
Alternative, non-steroidal methods for synchronization are available, but none have had great success. However, letrozole has the potential to meet consumer demands. It's a non-steroidal drug that's been proven safe for humans, and it's been approved by the FDA for treatment of breast cancer and infertility in women.
Another benefit of letrozole: it's easy to use. Producers can administer a dose using a minimally invasive intravaginal device that allows for prolonged drug release and reduces animal stress and handling, as opposed to protocols that involve multiple injections. The device also allows for immediate removal of the drug source once the medication period is up.
Letrozole could prove to be a very useful tool for the dairy and beef cattle industries. Right now there's a lack of products that can generate synchronization, and with an expanding market this drug has a lot of potential.
Although letrozole is an exciting advancement for the cattle industry that promises to provide a consumer-friendly, cost-efficient alternative to current synchronization methods, Adams is cautiously optimistic.
"With research you have to be patient and take a step-by-step approach and that's what we are doing," he says.
Brittany Davis of Saskatoon, Sask., is a second-year veterinary student who was part of the WCVM's Undergraduate Summer Research and Leadership program in 2016. Brittany's story is part of a series of articles written by WCVM summer research students.