Introduction
Estradiol cypionate is a synthetic estrogen medication used in veterinary medicine. It is an esterified derivative of the endogenous sex hormone estradiol and contains an ester side chain called cypionate. Estradiol cypionate has estrogenic activity when administered to animals, meaning it exerts effects via activation of estrogen receptors throughout the body.
Estradiol cypionate has been used in veterinary medicine since the 1950s to treat certain conditions in animals. Some of its main uses are for hormone replacement therapy and as an estrus suppressant. By providing supplemental estrogen, estradiol cypionate can help regulate important biological processes in female animals that depend on appropriate estrogen levels.
Chemical Structure
Estradiol cypionate is a synthetic ester of estradiol. Its chemical formula is C26H36O3 and molecular weight is 396.6 g/mol. It has the following chemical structure:
Estradiol cypionate contains estradiol, which is a naturally occurring estrogen hormone in humans. The only difference is that it has a cypionate ester attached at the 17β position. This gives it a longer duration of action compared to estradiol itself when administered.
Estradiol is chemically described as estra-1,3,5(10)-triene-3,17β-diol. It has a phenolic A ring that is responsible for its estrogenic activity by binding to estrogen receptors in the body. The addition of the cypionate ester increases its fat solubility and slows its absorption rate.
Mechanism of Action
Estradiol cypionate is an estrogen that acts primarily by binding to estrogen receptors in target tissues (DrugBank). Like other estrogens, it has several mechanisms of action in the body:
1. Estradiol cypionate binds to estrogen receptors, which causes a conformational change in the receptor. This allows the receptor to bind to estrogen response elements on DNA. This increases the transcription of certain genes, resulting in increased synthesis of proteins, DNA, and RNA in target tissues.
2. Estradiol cypionate decreases gonadotropin-releasing hormone secretion from the hypothalamus, which decreases secretion of follicle stimulating hormone and luteinizing hormone from the pituitary gland. This reduces stimulation of estrogen production in the ovaries.
3. Estradiol cypionate causes the maturation of vaginal cells, growth of the uterus, and proliferation of epithelial tissues, among other morphologic changes in the reproductive tract. It plays an important role in female reproductive health and development.
4. Estradiol cypionate has effects on liver protein production, bone growth, and regulation of cholesterol levels. It helps maintain bone density and reduce risk of cardiovascular disease when dosed appropriately.
In summary, estradiol cypionate is a potent estrogen receptor agonist. It produces widespread effects on development, reproduction, and metabolism in both females and males.
Uses in Veterinary Medicine
Estradiol cypionate is primarily used in veterinary medicine for the treatment of hormone-responsive diseases in dogs and cats. It is most commonly used for reproductive purposes such as pregnancy termination, prevention of estrus, management of abnormal estrus cycles, and treatment of vaginitis, prostatitis, and benign prostatic hyperplasia (BPH).
For pregnancy termination, estradiol cypionate can be given as an intramuscular injection within 40 hours of mating to prevent implantation and terminate early pregnancy (Source). It is also sometimes used to suppress estrus in show dogs to prevent mating during competitions.
Estradiol cypionate is effective in managing abnormal estrus cycles in dogs, including persistent estrus and split heat. It helps regress follicular cysts and restore normal cycles. For vaginitis and prostatitis, estradiol can reduce inflammation and relieve symptoms.
In intact male dogs, estradiol cypionate may be used to treat benign prostatic hyperplasia (BPH). It causes prostatic involution and shrinkage by suppressing gonadotropins and testosterone production (Source).
Dosing and Administration
Estradiol cypionate is administered via intramuscular injection. The dose depends on the condition being treated and the animal species.
In dogs, the typical dose range for prevention of estrus is 0.01 to 0.1 mg per pound (0.02 to 0.2 mg/kg), given as a single injection. For treatment of prostatic hyperplasia in stud dogs, the dose is 0.25 to 0.5 mL injected once or twice.
In cats, the dose for prevention of estrus is 0.06 to 0.12 mL as a one-time injection. For treatment of anestrus in cats, the dose range is 0.25 to 0.5 mL injected once.
The injection is typically given within 40 hours after mating to prevent pregnancy. Precise dosing should be determined by a veterinarian based on the animal’s weight and health status (1).
Benefits and Efficacy
Estradiol cypionate has demonstrated benefits in treating several canine health conditions. According to research, it is an effective treatment for pyometra, a potentially fatal uterine infection, in dogs (https://pubmed.ncbi.nlm.nih.gov/28755579/). When administered along with prostaglandins, estradiol cypionate aided recovery in 100% of dogs with pyometra in one study. It helps prevent the reaccumulation of pus in the uterus.
Estradiol cypionate is also beneficial for treating hormone-responsive urinary incontinence in spayed female dogs (https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/estradiol-cypionate). The estradiol replaces missing hormones and helps strengthen the urethral sphincter to reduce uncontrolled urination. One study found over 80% of incontinent dogs had improved continence within one month of starting estradiol therapy.
Additionally, estradiol cypionate can help prevent estrus and pregnancy when administered shortly after mating. It interferes with ovulation, fertilization, and implantation of embryos (https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/estradiol-cypionate). This makes it an effective injectable contraceptive option for dogs.
Overall, research indicates estradiol cypionate has high efficacy in treating hormone-responsive conditions in spayed female dogs when dosed properly. Its benefits stem from replacing missing estradiol and exerting tissue-specific estrogenic effects.
Side Effects and Safety
Estradiol cypionate is generally well tolerated in dogs when used at appropriate therapeutic dosages. However, some potential side effects can occur:
At very high doses, estradiol can cause bone marrow suppression and an increased risk of bleeding disorders. Careful monitoring of blood cell counts is recommended, especially when initiating therapy (https://www.wedgewoodpharmacy.com/medications/estradiol-cypionate/).
Estradiol may increase the risk of developing pyometra (uterine infection) in intact female dogs. Therefore, estradiol cypionate is relatively contraindicated in dogs that have not been spayed (https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/estradiol-cypionate).
Long-term unopposed estrogen therapy has been associated with endometrial hyperplasia and a theoretical increased risk of endometrial cancer in dogs. However, the risk is low with the short-term use of estradiol cypionate for urinary incontinence or hormone replacement after spaying (https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/estradiol-cypionate).
Estradiol may cause elevated liver enzymes in some dogs. Periodic monitoring of liver function is recommended if therapy extends beyond 1 month (https://www.wedgewoodpharmacy.com/medications/estradiol-cypionate/).
Other potential side effects can include increased thirst/urination, restlessness, and mammary gland enlargement. Estradiol therapy should be discontinued if unacceptable side effects develop.
Alternatives
There are other drugs that can be used as alternatives to estradiol cypionate for reproductive suppression in dogs, including:
Proligestone (Delvosteron) – This progestin can be used for estrus suppression and contraception in dogs. It prevents ovulation and suppresses estrous behavior. Proligestone may cause side effects like weight gain and mammary development.[1]
Megestrol acetate – This progestin can suppress estrus in dogs by inhibiting gonadotropin release. However, it has been associated with side effects like weight gain, diabetes mellitus, and pyometra.[2]
Gonadotropin-releasing hormone (GnRH) agonists – Drugs like deslorelin can cause reversible infertility by suppressing pituitary function. They may be more expensive but avoid risks like pyometra.
Surgical sterilization – Spaying dogs is a permanent way to prevent estrus cycles and reproduction. It eliminates the need for repeated injections.
There are reasons veterinarians may recommend alternatives to estradiol cypionate, including avoiding potential side effects, permanent contraception, or patient factors. However, estradiol cypionate remains a widely used and effective option for estrus suppression in dogs.
Cost and Availability
Estradiol cypionate is available in injectable form from veterinary supply companies and pharmacies. The price can range from $50-150 for a 30mL vial containing 10mg/mL solution. Some key points on cost and availability:
Estradiol cypionate requires a prescription from a licensed veterinarian and cannot be purchased over-the-counter. Only veterinarians or pharmacies with a valid veterinary client patient relationship are permitted to dispense it. There may be additional state restrictions on the prescribing and dispensing of estradiol cypionate for animal use.
Because estradiol cypionate is not approved by the FDA for veterinary use, it is often custom compounded by specialty veterinary pharmacies. The specific formulation, concentration, and volume will be tailored to the individual animal and condition being treated. Compounding increases the cost compared to manufactured drug products.
For economic reasons, veterinary practices may compound estradiol cypionate on-site for their patients rather than outsourcing to a pharmacy. However, caution should be used with in-office compounding to ensure proper formulation, sterility, and record keeping.
When ordering estradiol cypionate, veterinarians should verify the pharmacy has a veterinary license and proper protocols in place. Illegal distribution or improper compounding can put animal health at risk.
Conclusion
Estradiol cypionate is a form of the female hormone estrogen that is often used in veterinary medicine to treat conditions in animals such as dogs and cats. The key takeaways from this article are:
- Estradiol cypionate has a similar chemical structure to natural estrogen but is longer acting.
- It works by binding to estrogen receptors and producing estrogen-like effects in the body.
- In veterinary medicine, it is primarily used in spayed female dogs to prevent issues like incontinence due to lack of estrogen.
- The dose is typically 0.1 mg/kg injected under the skin every 4-8 weeks.
- Benefits include preventing urinary incontinence, osteoporosis, and atrophy of reproductive tissues in spayed females.
- Potential side effects include bone marrow suppression, liver toxicity, and increased risk of mammary tumors if overdosed.
- Alternatives include natural estrogen creams, phenylpropanolamine, or hormone replacement implants.
- It requires a veterinary prescription and costs $15-30 per dose.
In summary, estradiol cypionate can be a useful hormone replacement option for spayed female dogs when administered properly under veterinary supervision. Owners should discuss the risks and benefits with their vet.