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As published in the 'Horse Journal, Volume 7. Number 12, December 2000' Note: The important point about this article is that we, the manufacturers of Hormonise, had no input whatsoever in these trials and were only aware that they were being conducted in about October 2000. Steve Russell, Equine Health and Herbal All you can do is treat the symptoms to make the horse more comfortable, and an herbal approach shows great promise. The symptoms of Cushing's syndrome, a common ailment of older horses, are so classical most vets skip the diagnostic tests. And we don't blame them. Not only are these tests expensive ($80-$100+), but they often return with negative or equivocal results. There's no known cure for Cushing's, so veterinarians focus on treating these symptoms. Prescription drugs do show results and aren't a bad choice, but we've also found an herbal supplement that shows incredible promise. What's Cushing's Cushing's syndrome is a collection of clinical signs and symptoms that are the result of hormonal imbalances. These are caused by either overactivity of the pituitary gland or a tumor in the gland itself. The hallmark of Cushing's is an abnormally long, thick, curly or coarse hair coat that does not shed in the spring, although there are other obvious symptoms (see box below). Poor immunity, both to infections and internal parasites, often develops, related both to the poor overall condition and the hormonal factors. In advanced cases and/or with large tumors, blindness may occur due to pressure on the optic nerve. The horse may also tilt his head. Sometimes you can decrease or stop Cushing's treatment in the early summer. Summer's longer day lengths probably result in less stimulation of the melanotrope cells, which produce the problematic POMC hormone. Symptoms return in the fall, which is a common time for laminitis to appear.
Pituitary Hormones The pituitary gland, located in the brain, is the hormone control center. It has been assumed that the pituitary tumor produced high levels of ACTH (adrenocoritcotropic hormone), which stimulated high cortisol production. High blood cortisol induces a diabetes-like state. However, not all Cushing's horses have abnormal cortisol levels. POMCs (proopiomelancortins) are high in some horse pituitary tumors. POMCs may then be converted to ACTH or directly cause the production of cortisol, although at lower levels than ACTH. Another possibility is that the hormone prolactin is causing the insulin resistance in Cushing's horses. Prolactin has this effect in other species. High prolactin levels would also explain the enlarged mammary glands, loss of cycling in mares and even abnormal hair coats. With these hormones in mind, we decided to try an herbal product, Hormonise, which is made from a plant called the Vitex Agnus Castus (chasteberry). It has been used in Europe to control a variety of human reproductive problems, including PMS, menopause and polycystic ovaries. The common denominator in these syndromes is a high level of prolactin, a pituitary hormone that is known to be elevated in many cases of pituitary tumor in humans. Our initial experience with Hormonise involved a three-year-old who had a history of "mare" behaviour problems. She was downright nasty. She was also cycling every 14 days. We didn't want to use regumate or substances that had a calming/tranquillising effect, so we tried Hormonise. Her response was excellent (more on Virex/Hormonise and mares in an upcoming issue). When Dr. Eleanor, our technical editor, realised a high prolactin level is associated with both these mare-ish problems and pituitary tumors in some people, she suggested that even if only some of the horses with Cushing's disease had tumors of the type that secrate large amounts of prolactin, Hormonise might be helpful. We decided to find out. A study in the 1993 Hormonal Metabolism journal showed Vitex is capable of blocking the release of prolactin from pituitary cells. Despite this documented effect on pituitary prolactin levels, we couldn't find references to using Vitex in prolactin-secreting tumors, so we knew we were in largely uncharted territory. Our trial involved 10 horses.
First Three Geldings We initially gave Vitex to a horse and two ponies (all geldings) with classical Cushing's symptoms. Emerald Valley Botanicals*, the manufacturer of Hormonise, recommended we use the larger end of the recommended dosage scale and give it daily, rather than in three-weeks-on/one-week-off cycles. The response was rapid and dramatic. Within two to three weeks, shedding was occurring rapidly. One pony was white and would leave huge piles of hair ('giant nests') around the field. The old hair has been coarse, dry, thick and curly, but the new growth was normal, sleek and has a high shine. All three geldings shed out completely for the first time in years, most with an early large loss of hair, followed by continued slower shedding or a few bursts of shedding until the abnormal hair was lost. The other obvious change was increased energy levels. A chronically foundered pony was also getting around much better, even trotting, although no one would call him "sound." It was difficult to tell if the increased activity level was related to his newfound energy or to improvement in the lamnitis. One pony failed to receive his Vitex for a three-week period, due to communication problems with the caretakers. Interestingly, his energy level dropped again and the abnormal coat began growing back rapidly. Resuming the Vitex led to a rapid shed and a higher energy. *Hormonise is manufactured by the Animal Health Co Ltd. in the UK. Emerald Valley Botanicals are the sole USA Distributors.
Welsh Cross Gelding Our next field test was a 17-year-old Welsh cross pony gelding. At 12, he started problems with laminitis and weight gain. The initial laminitis was believed to be due to a vaccine reaction (a four-way vaccine was administered). The laminitis was handled by limiting his diet and grass time. In 1998, his caretakers noticed he did not shed out as well as in prior year and requested body clipping. By June 1999, his coat was obviously abnormal and he did little shedding. Abnormal fat deposits (looking like cellulite) were noticed across his rump. Energy levels were sagging as well. He was described as being depressed and bad-tempered. Blood work in November 1999 confirmed Cushing's. His blood glucose was 278, insulin 192.5, both extremely abnormal (remember that different labs have different "normal" ranges in the tests they run). He was started on Cyproheptadine (see page 6) and responded with a small amount of shedding. He was on a maintenance dose at the time we began working with him in February 2000. He started on Hormonise and discontinued cyproheptadine in mid February. Three weeks later, reports were that he was shedding like mad (mostly on the left for some reason), his feet were remaining cooler and his energy levels had sky-rocketed. Previous referred to as "Dan, Dan, the Old White Man," his movements were described as elderly and slow. After the Vitex for three weeks, he was squealing, kicking, rearing and playing with the other horses-something he had not done for the previous three years. More objectively, after four weeks, his insulin had dropped to 119 and his glucose was down to 148. No further laboratory work was done. He continued to do well until supplements were stopped, at which point symptoms returned within three weeks. Morgan Mare For notes on this horse, see photo box ("Tiffany") on this page. Morgan Gelding A 23-year-old Morgan gelding (no lab work available) had been slowing down steadily for several years, attributed to old age. This year it was noted he had an abnormally thick and curly coat that did not shed out. He was started on the Vitex and within 10 days began to shed heavily, growing in a normal, slick coat, which is also coming in this winter. Energy levels and general interests in life have improved significantly.
Tennessee Walker Gelding A 20-year-old Tennessee Walker gelding had been diagnosed with Cushing's five or six years previously on the basis of abnormal hair coat, increased thirst and increased urination. He was initially treated with cyproheptadine and had been switched to pergolide three years prior to starting the Hormonise. Blood glucose before the Vitex, on pergolide, was running in the 300 to 366 range (normal 60-125). Insulin just prior to Vitex was 30.47, with upper limit of normal being 30. These tests indicated the horse was entering the final stages of the disease-a true diabetes (insulin insufficiency) rather than just insulin intensitivity. He was on the supplement for one month, during which time there was no change in his condition. The horse then came down with a serious lung infection and the owner preferred to switch him back to pergolide. We don't believe the switch to Vitex had anything to do with the lung infection, and the attending vet concurred. Infections and weakened immunity are common complications of long-term Cushing's disease. This horse did have a somewhat lowered lymphocyte count in his blood at the start of theHormonise, which is typical for immunocompromised horses that have Cushing's syndrome. Nevertheless, under the circumstances, the owner's wishes/concerns were honoured, and the horse was withdrawn from the field trial. Thoroughbred Gelding A 16-year-old Thoroughbred gelding had been showing early signs of Cushing's for three years. He had also been showing increased water consumption and urination over the past year. Blood chemistry and dexamethasone suppression test in 1999 were normal. In June 2000, blood chemistry showed his glucose was normal at 97 but insulin was 41.4-low for a Cushing's horse (indicating it was early in the disease) but about twice the upper limit of normal. He was started on Hormonise and shed out completely within three weeks. No other changes were noted. Repeat blood work after 2 1/2 months on the Vitex showed glucose the same at 97, insulin 49.6. His winter coat also started growing in early and thickly. 13 year old mare One of our most challenging horses was a 13-year-old mare who had symptoms suggestive of Cushing's dating back five years. When first purchased at eight, she had unusual mouth ulcers and a tendency for skin infections. She was extremely aggressive about her food. She had been noticed to leak fluid from her udder, which was extremely sensitive. In 1999, she began excessive urination and thirst, urinating even when being worked. Over the winter 1999-2000, her coat came in exceptionally long and thick and did not shed out completely. She stopped cycling. The owner insisted an insulin test be run and it was abnormal at 180. She was started on cyproheptadine and started to shed out within a week but the increased thirst and urination continued unchanged. After three weeks on cyproheptadine the insulin was down to 131. Shedding continued when the mare went on the Hormonise, and she was completely shed out in three to four weeks. She seemed to vacillate in how well controlled the thirst/urination was, having good days and bad. The same was true for energy levels. On days she did not drink excessively, urine was normal colour and amount. Within two months, she began cycling again and was showing strong estrus every 18 days but was extremely touchy and irritable. We eventually learned this mare was consuming huge amounts of salt, in excess of six ounces in an eight hour period when it was measured. Limiting the mare's salt to what she needed resolved the increased thirst and urination to a large extent. After six weeks on the Hormonise, her insulin level had dropped markedly to 57. Urination and energy levels continued to gradually improve for this mare. However, her estrus behaviour was also intensifying and by the end of the summer she was beginning to grow a thicker coat. As of mid-October, her coat was thick and curly (she is half a mustang) but not long. A repeat insulin showed it was up to 96, but she accidentally had been receiving a large amount of glucosamine, which has a profound effect on insulin sensitivity and could have contributed. As of this writing, the glucosamine has been stopped but no follow up obtained on her insulin. Another possible complicating factor might be that she had resumed cycling. Estrogen has a strong stimulatory effect on prolactin levels and might be counteracting the Vitex to some extent, or at least promoting fluctuations in prolactin levels. This could at least partially explain her higher insulin and the thicker hair coat. More studies are planned, and additional therapy may be needed.
Palomino Gelding A 20 year old palomino gelding was diagnosed with Cushing's five years before he entered our trial, with a history of laminitis dating back eight years. Diagnosis was confirmed via elevated ACTH level of 59.2 (normal is three to 39). He had the typical long, curly coat that did not shed out, increased thirst, voracious appetite, obesity with a cresty neck, poor heat tolerance and a long-standing laminitis. He was never completely sound. He had been on cyproheptadine for three years with little change. Glucose prior to starting the Vitex and while on cyproheptadine, was normal at 84. After about three weeks on Vitex, He started to shed out in large amounts and the new hair was softer. He was also laying down less than before the Hormonise and taking a much shorter time to come to feeding, with some evidence of brighter attitude and more interest in his surroundings. He did well throughout the summer. However, in late August, he began to grow in a winter coat that was again long and curly. He also had an exacerbation of his laminitis at this time, although it was noted that ground conditions were much harder than normal.
Bottom line All 10 horses in this field trial showed improved, rapid shedding of abnormal coat as a response to Vitex. Improved energy levels, lifting of "depression" and improvement in laminitic pain were noted in all horses that had these symptoms. A drop in blood insulin levels was documented in two horses, one of which had a marked improvement over that seen with cyproheptadine treatment. Improvements were maintained over the summer. By late August, all horses were beginning to grow longer/winter coats. In two of these, which were also the most advanced cases based on history and blood work, the coat resembled a Cushing's coat while in the others it was a normal winter coat. It appears that horses with advanced Cushing's changes, especially when they involve glucose metabolism, tended to have a less dramatic response to the Vitex. While much more work needs to be done, we believe these observations indicate Hormonise may be an effective supportive agent and a viable alternative to current prescription medications. The differences in early winter coats suggest the hormonal output of pituitary tumors or pituitary hyperplasia in horses may be of more than one type, as described for humans. Although Hormonise is available without prescription, we don't recommend you use this supplement without involving your veterinarian. Hormonise is manufactured in the United Kingdom by Animal Health Company and distributed in the United States by Emerald Valley Botanicals 888/638-8262. It is not inexpensive. Effective dosage was found to be 10 cc/200 pounds of body weight. Cost is $44.95 per litre, which is about $2.25 per day for a 1,000 pound horse to treat Cushing's. by Elanor Kellon VMD
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