Researcher promotes awareness of accidental hormone exposure in pets

VIN tallies more than 100 case reports since 2003

Published: June 08, 2011
By Edie Lau

Cynthia Stuenkel, MD, an endocrinology researcher and past president of the North American Menopause Society, is actively spreading the word that pets may develop health problems from inadvertent contact with hormone creams, gels and sprays used by their owners. Photo courtesy of the North American Menopause Society.

Just over a year ago, Cynthia Stuenkel, MD, a prominent endocrinologist in San Diego, Calif., knew nothing of the possibility that topical hormone therapies popular with menopausal women could cause health problems in patients’ dogs and cats.

Today, Stuenkel is a tireless messenger on the topic.

On Saturday, Stuenkel brought the matter to the annual conference of the Endocrine Society in Boston, where she gave a “poster” style research presentation, complete with photographs of a spaniel whose accidental exposure to topical estrogen caused conspicuous swelling of the genitals and nipples.

“People were pretty incredulous,” Stuenkel reported.

Surprise and disbelief are common reactions Stuenkel has elicited in recent months as she raises the topic among physicians in venues around the country. During a recent talk to internists, Stuenkel recalled, “People in the audience were audibly gasping.”

Amid amazement comes acceptance. At a continuing-education presentation in Denver in February, she said a resident in obstetrics and gynecology came up afterward to say she suspected her own mother’s dogs were similarly exposed. “I think she was having an ‘aha’ moment,” Stuenkel said.

Stuenkel’s own “aha moment” came in May 2010 when the Veterinary Information Network (VIN) News Service began investigating the issue and contacted the North American Menopause Society for comment. Stuenkel is past president of the society and a professor at the University of California, San Diego. VIN is an online community, resource and membership organization for veterinarians. The news service is its media arm.

The phenomenon of secondary hormone exposures in pets had been brought to the attention of the VIN News Service by a veterinarian in Bradenton, Fla. The veterinarian, Dr. Terry Clekis, realized what was happening after he’d operated on a 1-year-old spayed pug, looking in vain for ovarian remnants that might explain the dog’s signs of heat. It turned out the excess estrogen in the pug’s system was coming not from her own body but from licking and cuddling with her owner, who used a custom-compounded hormone cream on the wrists. Once the owner became aware and stopped exposing her pet, the problem resolved.

VIN staff veterinarians and news reporters subsequently found numerous cases mentioned on VIN’s online message boards, most from the past 18 months but one dating as far back as 2003. One practitioner said in an interview she had seen her first case 20 years ago in Texas.

At last count, the VIN News Service tallied more than 100 suspected cases, including reports received through telephone interviews and e-mail with practitioners and pet owners who read VIN News Service articles on the subject. Thirteen reports were logged this year alone.

Most of the cases involve small spayed female dogs or puppies, but large breeds, males and dogs of all ages are susceptible as well. Clinical signs common to both sexes are swollen nipples and mammary glands. Females typically exhibit grossly enlarged vulvas. Males may have unusually small penises and/or prostate infections. Patients sometimes present with hair loss and skin discoloration.

Cats also have been affected, generally showing behavioral changes as if in heat.

Depending on the period of exposure, clinical signs may take months to resolve. Veterinarians caution that lengthy exposures in dogs could heighten their risk of mammary cancer or lead to bone marrow suppression resulting in chronic anemia, although no such cases have been documented.

Dr. James Esh of Chico, Calif., was one of the earliest clinicians to recognize what was going on. He reported on a VIN message board in November 2005 that he was treating two dogs he suspected were absorbing estradiol from the hands of their owners, who were using the cream in hormone replacement therapy.

One dog was a 5-year-old spayed fox terrier with persistent vulvar enlargement. The other was a 12-year-old spayed miniature schnauzer with marked generalized mammary development.

At his veterinary practice in Bradenton, Fla., Dr. Terry Clekis has seen at least three dogs that were inadvertently exposed to their owners’ cutaneous hormone therapies. Clekis, pictured with a puppy that was not among those affected, alerted the Veterinary Information Network (VIN) News Service to the phenomenon. Photo by Laura Tracy-Clekis.

“Has anyone encountered this before?” Esh asked. “If not, it seems like something to get in the literature. If the dogs are affected, what about grandkids, husbands, etc.?”

The subject is underreported in the scientific literature. To date, it appears that only one case has been published in a journal — that of an intact 4-month-old bichon frise, whose experience was reported in “Theriogenology Question of the Month,” published July 15, 2008, in the Journal of the American Veterinary Medical Association.

In that case, the dog’s owner was asked repeatedly by the specialist to whom she had been referred whether the dog was exposed to an outside source of estrogen. It wasn’t until the third or fourth visit that the owner wondered aloud whether the estrogen cream she put on her arms, and which the dog liked to lick, was behind the dog’s swollen vulva and bloody discharge.

On the human side, several published reports exist of children and adults alike exhibiting symptoms of excess estrogen due to secondary exposure to cutaneous estrogen products. A paper in the April 4, 2000, edition of the journal Pediatrics, for example, describes three unrelated cases of boys, ages 28 months, 33 months and 8 years, who developed gynecomastia, or breast development, as a result of indirect exposure to high concentrations of estrogen contained in compounded topical creams used by their mothers. (The authors note that women who give birth at “advanced” ages may use hormone replacement therapy to relieve perimenopausal symptoms before their children reach puberty.)

The problem isn’t limited to women’s hormone use. The U.S. Food and Drug Administration (FDA) in May 2009 reported eight cases of children being accidentally exposed to testosterone gels used by men. The children, ages 9 months to 5 years, presented signs including enlargement of the penis or clitoris, development of pubic hair, advanced bone age, increased libido and aggressive behavior. The cases prompted the FDA to require manufacturers of two testosterone gel products to include boxed warnings on the product labels.

(In one unusual case relayed by a veterinarian to the VIN News Service, a 1-year-old male papillon in Arizona was exposed to topical estrogen and testosterone used by his female and male owners, respectively. The dog had chronic inflammation of the prepuce, incontinence, enlarged nipples, hair loss, prostatic cysts and abnormal internal structures in his reproductive organs.)

In July 2010, the FDA posted a safety announcement about unintended exposure of children and pets to Evamist, a spray-on estrogen applied to the inside of the forearm between the elbow and wrist. The agency said it had received reports of eight such cases in children since Evamist was approved for sale in July 2007. The children, boys and girls ranging in age from 3 to 5 years, had breast development.

On the veterinary side, the FDA told the VIN News Service in August 2010 in response to a Freedom of Information Act request that it had received four reports of unintended topical hormone exposure in dogs. Three were spayed females exposed to Evamist; the fourth was a neutered male exposed to compounded estradiol and progesterone.

Word of the phenomenon reached a health writer at the New York Times, who blogged about the subject in October.

Despite coverage in the popular press and government pronouncements on the topic, awareness remains limited. Stuenkel said those who reviewed her poster presentation last weekend at the Endocrine Society conference clearly were unfamiliar with the problem, which suggests they had not heard about the FDA notice on Evamist.

“Some of them shook their heads and went, ‘I’ve never heard of anything like that,’ ” Stuenkel said.

Stuenkel, who prepared her poster in collaboration with VIN, said she intends to continue raising the subject. Although the Endocrine Society meeting was attended by more than 9,000 people, only a subset would have seen her presentation, which was grouped with researchers’ more unusual offerings. “A guy next to me had treated a woman with cysts of tapeworm in the brain,” Stuenkel recounted.

As oddball as the pet hormone exposure phenomenon may appear, Stuenkel takes it seriously. “I am convinced this is a medical issue and I want to participate in bridging the gap between human professionals and veterinary professionals so we can increase awareness and reduce the occurrence,” she said.

In addition to addressing physicians on the subject, Stuenkel said she would be willing to speak with veterinary groups, with the aim of familiarizing veterinarians with the names and types of hormone products in use so that clinicians may feel more at ease in discussing the issue with their clients. More than one practitioner has admitted feeling reluctant to pry into clients’ personal health matters.

Not all are reticent, of course. Esh, the veterinarian in Chico, Calif., suggested that any question is appropriate when trying to solve a medical mystery. “I ask people about methamphetamine (use) when dogs come in kind of wired and toxic,” he said. “I just tell people, ‘This is confidential, it doesn’t leave this room and we need to figure this out.’ ”

VIN, meanwhile, has begun a telephone survey to veterinarians with suspected cases, with the goal of establishing a standardized base of information and developing data submissible to scientific journals.

An earlier attempt by VIN to survey practitioners electronically received a tepid response, possibly because many lack detailed laboratory analyses on cases. Clekis, the veterinarian in Florida, for example, described a style of diagnostics that is both practical and low-cost:

“I don’t think we’ve ever gotten blood levels,” said Clekis. “It’s like, ‘You’re using estrogen cream? Stop it.’ And then (the problem) goes away.”

Clekis, who has treated at least three probable cases since 2009, said when he raised the topic at a meeting of his local society of veterinarians in Manatee County, he discovered that “everyone has one or two cases.”

Referring to the number tallied by VIN so far, Clekis said, “Your 100 is just the tip of the iceberg.”

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