The Veterinary Information Network (VIN) plans to survey tens of thousands of veterinarians around the world to gauge how widespread and significant are accidental exposures of pets to their owners’ topical hormone preparations.
The problem has been described intermittently in online discussion boards of VIN and elsewhere for years, but the phenomenon has received scant mention in the medical literature.
In the past three years, the U.S. Food and Drug Administration has garnered reports of at least eight children and four dogs inadvertently exposed to topical female hormone products. In July, the agency issued a safety announcement about the potential for accidental exposures in children and pets to Evamist, a spray-on estrogen treatment for hot flashes.
An investigation by the VIN News Service published in June found that a number of cases of accidental exposures in pets involve the use of hormone replacement therapies prepared by compounding pharmacies, as well. One of the canine exposures reported to the FDA was to a compounded product containing estradiol and progesterone. Yet the agency has not issued a caution about compounded hormone preparations.
However, David Miller, CEO and executive vice president of the International Academy of Compounding Pharmacists (IACP), said he would be willing to help alert pharmacists to the need to warn consumers of the risk of topical medication transfer.
“It is fantastic that this issue is being raised not only in the veterinary community but to patients in general,” Miller said. “We so often take for granted prescription medications and over-the-counter medications. We don’t realize we’re dealing with pretty potent and potentially dangerous substances.”
Dr. Paul Pion, president and co-founder of VIN, an online professional community, said the survey will be distributed to the nearly 28,000 practitioner members of VIN, the majority of whom are small-animal veterinarians.
Pion said that while the survey will not document with scientific precision the prevalence of accidental exposures in pets, it may give a first estimate of the problem. “It’s just the next step to try to figure out what we’ve stumbled upon,” he said.
Observers anticipate that as Baby Boomers age and turn to hormone therapies to combat the effects of aging, the potential for secondary exposures will rise.
“I think it’s going to become a bigger and bigger problem,” predicted Dr. Joni Freshman, a veterinary internal medicine specialist in Colorado and consultant to VIN and the laboratory of VCA Antech. Freshman saw her first case in a male German shepherd mix in Texas nearly 20 years ago. Now she comes across suspect cases two or three times a month in her role as a consultant.
Veterinary cases usually involve dogs that have been exposed to hormone creams, gels, lotions or sprays used by their owners, either by coming in contact with or by licking the owner’s treated skin. Although the owners generally are menopausal women, topical hormone therapies are used by men as well, and the same risk presumably applies.
Female dogs exposed to female hormone products typically present with swollen vulvas, nipples and/or mammary glands. Male dogs exposed to female hormones also may exhibit swollen mammary tissues as well as abnormally small or underdeveloped penises and/or testes and prostate problems. Exposed dogs of either gender may lose fur, as well.
Overexposure to estrogen may be toxic to dogs and cats, potentially causing bone marrow suppression leading to chronic anemia, and raising the risk of mammary cancer.
The phenomenon of accidental secondary exposures in pets was brought to the attention of the VIN News Service this spring by a clinician in Florida who had seen three such cases within a year. In the most compelling of those cases, Dr. Terry Clekis, owner of Braden River Animal Hospital in Florida, operated on a pug he had previously spayed, thinking he’d left behind remnants of ovarian tissue. It wasn’t until after the surgery that he realized the pug’s signs of apparent heat were caused by exposure to her owner’s compounded hormone replacement cream.
In its investigation, VIN News Service documented 22 cases of probable cutaneous hormone product exposure in dogs. Most, but not all, were puppies and small breeds.
After the story was posted on the Internet, several pet owners wrote to say that their dogs similarly were affected.
Among them was Carole Curtis, whose e-mail message from Australia suggests the problem is international in scope. Curtis, of Gold Coast, Queensland, wrote that about five months after she began using a compounded estrogen cream, her 10-year-old Shih Tzu-Chihuahua mix, Poppie, developed discoloration on the skin of her stomach, inner thighs and vulva. Then Poppie went bald on her underside, and her vulva began to swell.
Curtis said the dog was examined by two different veterinarians and underwent several blood tests that showed her liver, kidney and thyroid functions were normal, and that she was not diabetic. Her hormone levels were not measured. The symptoms had persisted for nearly a year when Curtis came across the VIN News article about accidental hormone exposures.
Like other loving dog owners, Curtis said she cuddled Poppie frequently without a notion that the dog might be affected by contact with the cream.
“It is such a nice moisturiser, I have used it on my face and neck and hands,” she wrote. “I am always smooching Poppie and carrying her around and kissing her as she is only 2.5 kilo (5.5 pounds) in weight.”
Once she recognized the possible link between Poppie’s symptoms and exposure to the cream, Curtis acted immediately. “I have now changed all my bed linen, washed all my clothes that Poppie may have come in contact with and will be using my cream on my tummy and applying it with gloves,” she wrote. “... I hope I have discontinued the use of cream in areas accessible to Poppie in time for her to fully recover.”
In what may be the only published scientific paper on the subject, Rebecca Schwarze and Dr. Walter Threlfall, a veterinary reproduction expert at The Ohio State University, described a single case of secondary hormone exposure involving an intact 4-month-old bichon frise. The case study appeared in the Journal of the American Veterinary Medical Association, Vol. 233, No. 2, July 15, 2008, under the title “Theriogenology Question of the Month.”
The case illustrates how blind pet owners may be to the possibility that their medications and behavior may be the source of a pet’s ills. This owner, five days after purchasing the pup, noticed that the pet repeatedly licked her vulva and had a bloody discharge. The vulva was swollen, as well.
Threlfall said in an interview that he asked upfront whether the dog was exposed to an outside source of estrogen. The owner said no. The veterinarian began a series of diagnostic tests, thinking perhaps the pup had follicular cysts. It wasn’t until the third or fourth visit that the owner asked, “Could it be the estrogen cream that I put on my arms? She likes to lick it.”
As a comparative theriogenologist, Threlfall said he has seen a variety of species with hyperestrinism. He routinely asks whether the animal may have had exogenous estrogen exposure, such as through an injected or implanted medication or something it ate (red clover, for example, contains isoflavones that mimic estrogen in the body).
“It’s tough to diagnose when people knowingly or not knowingly give you the wrong answer,” he said.
At the same time, the subject of a client’s own health history and habits is so delicate that Threlfall said he would hesitate to inquire aggressively, even after that experience. “I think that is getting a little personal,” he said. “I have to stay in my area. You have to walk a thin line. If the same (situation) came out today, I wouldn’t specifically pinpoint it. I probably would be a little more diligent in beating around the bush.”
Even pet owners who are medical professionals can be unaware. A primary-care physician whose dog developed nipple enlargement was oblivious to the cause until she heard about secondary-exposure risk via the North American Menopause Society (NAMS), which was alerted by the VIN News Service investigation.
The physician used the spray-on topical estrogen Evamist. Dr. Cynthia Stuenkel, president of NAMS, said the physician was stunned to make the connection between her hormone therapy and her pet’s condition. “Oh my god,” she realized, “I’m petting my dog and my dog is licking me.”
At the University of Tennessee College of Veterinary Medicine, Dr. Jack Oliver, a professor in the Department of Comparative Medicine, runs a clinical endocrinology diagnostic laboratory. He sees some 50 cases a week of dogs with hyperestrinism.
Most of those animals have adrenal gland disorders such as Cushing’s disease. With experience, Oliver has come to recognize distinctions between those dogs and the animals whose problem is likely exposure to exogenous sex hormones: Whereas the typical adrenal case will have an estradiol level of 85 pg/ml in the blood, dogs with outside exposures have much higher readings — well over 100 pg/ml, and usually on the order of 150 pg/ml or greater. Oliver said he has seen levels as high as 250 pg/ml.
In addition, the dogs often have an associated increase in levels of progesterone and 17-hydroxyprogesterone, which Oliver surmises is due to topical hormone products having both an estradiol and progesterone component.
Oliver said he began noticing cases of exogenous hormone exposure in dogs five to six years ago. The frequency has since increased. “In the last two or three years, we’ve seen ... maybe one or two a month,” he said.
Another of Oliver's observations is that hormone levels are confoundingly slow to abate after exposure ends. “The biological half-life of steroids is about an hour. You’d think they’d go away fairly quickly,” Oliver said. But in cases he’s seen for follow-up analysis, the levels remained high even after a few months. “In one dog, it took almost nine months for the clinical signs like nipple enlargement and swollen vulva to go away,” he said.
Oliver went on: “I always suggest the potential for hormone exposure when I see cases with high estradiol levels and especially in young dogs with new owners. But we’re just one lab. More veterinarians need to become aware of this potential toxicity with estradiol.”
"Atypical Cushing's"/Congenital adrenal hyperplasia-like syndrome/ Hyperestrinism
Re: Congenital adrenal hyperplasia-like syndrome/ Hyperestrinism/ "Atypical Cushing's
