Link To All Ferret Health Care Articles

Why Do I Need To Spay Or Neuter My Ferret – Are There Alternatives?

Ron Hines DVM PhD

You can spay or neuter your dog and cat, or just supervise their activities to prevent unwanted offspring. But when your pet is a ferret, that issue and your options are much more complicated. That is because the reproductive hormone cycle of ferrets is unique among our common pets.

Heat (estrus) cycles in all animals are associated with raging hormones. Follicle Stimulating Hormone (FSH), produced by your ferret’s pituitary gland, stimulates its ovarian follicles (the future eggs) to mature as well as stimulating the ovaries to produce estrogen. This added estrogen stimulates the reproductive tract to prepare for ovulation and fertilization. Luteinizing hormone (LH), also produced by the ferret’s pituitary gland, is the actual trigger for ovulation.

Ferrets  retained their wild tendency to be seasonal breeders – much more than dogs and cats. An area of the ferret’s brains just above their pituitary gland (their SCN) keeps track of the season of the year by noting changes in the length of the day. When that area of the ferret’s brain senses that spring (longer days) is approaching, it releases pulses of its own messenger hormone, GnRH . GnRH hormone instructs your ferret’s pituitary gland to increase its production of FSH and LH.

That is why the breeding season of ferrets in the norther hemisphere is from about mid-February to September (~June 21 is our longest day). Breeding season reverses in the southern hemisphere. Their longest day is ~21st of December.

As I mentioned, both male (hobs) and female ferrets (jills), respond sexually to day length. The testicles of intact male ferrets begin to swell soon after our winter solstice. The high testosterone level of intact male ferrets during breeding season often makes adult males more aggressive, more likely to bite and more likely to mark their territory at that time. Within their reproductive season, intact female ferrets that are old enough to come into heat (about 6-8 months old) do so. Males generally come into heat the first time when they are a month or two older. A few females beginning to cycle in the summer as early as 5 month of age.

What Is The Estrus Health Challenge That Is Unique To Female Ferrets?

The unique thing about ferrets (and all members of the weasel family) is that they are induced ovulators. That is, once their reproductive cycle begins they require the physical act of mating to stimulate their LH hormone surge which releases their mature ovarian eggs into their uterine horns. (ref)  If a female ferret in heat (=estrus) is not bred, it cannot ovulate and remains “trapped” in heat. I mentioned that heat (estrus) is a time of very high estrogen levels; and persistently high estrogen is a very unhealthy situation.

Preparing the ferret’s reproductive tract for pregnancy is not the only effect that estrogen has. Estrogen decreases the production of erythropoietin, a kidney hormone your ferret needs to produce new red blood cells (RBCs) in its bone marrow. Over time this abnormally high estrogen level (hyperestrogenism) also suppresses the pet’s bone marrow inhibiting it from producing RBCs and other essential blood cells (thrombocytes/=blood platelets, and neutrophils). Over time, the deficiency of these blood cells is fatal to female ferrets if they remain in heat but are not bred. (ref)  Even mating a female ferret to a vasectomized male ferret allows the female to ovulate and escape from these destructively high estrogen levels. (ref) Vasectomy surgery is not a common procedure in North America. The only veterinarian I know of who routinely performs them is Dr. Scholz at Balsburg Animal Wellness in Pennsylvania. I am sure that there are others. Let me know and I will list them. If your veterinarian want to learn the procedure he/she can read how the surgery is performed here.

How Will I know If My Ferret Is In Heat Or Even Trapped In The High-estrogen Portion Of its Heat Cycle?

Swelling of your female ferret’s vulva revealing its pink color is the most obvious sign you will see that your ferret is in heat. Individual ferrets vary in their degree of vaginal swelling (tumescence). Vaginal secretions are more obvious in some jills than others.

If you have an un-neutered male ferret in the household, it will likely attempt to mate with the female. Breeding ability in male ferrets is also seasonal. Mating tends to be a very violent activity (“in rut”) in ferrets. When post-mating ovulation occurs, it is generally 30 to 40 hours later (post-coitus). After that the (ferret’s estrogen level gradually returns to normal. Should you intact female ferret not be bred, those estrogen levels often remain dangerously high. One Czech veterinarian, experienced in ferret medicine, suggests that about half of the unbred ferrets that are in this situation develop potentially fatal anemia while the other half do not. (ref) I do not know if that percentage has been confirmed by others.

In the female ferrets that do eventually develop anemia, pallor, increased respiratory rate and effort (hyperpnea / dyspnea), exercise intolerance, and even bleeding due to a lack of thrombocytes often occurs.

I mentioned that abnormally high estrogen levels affect the ability of your ferret’s bone marrow to produce red blood cells and the thrombocytes so important to the blood clotting process. But prolonged high estrogen levels also decrease the ferret’s ability to produce white blood cells (WBCs) That situation is called pancytopenia. Pancytopenia opens the door to all sorts of infections.

In male ferrets (hobs), the increased FSH level associated with sexual maturity causes their testicles to swell and stimulates the production of fertile sperm; while LH increases the production of testosterone. Whether an intact or vasectomized male ferret breeds or does not breed does not appear to have any effect on its health.

Is Estrogen Anemia A Common Problem In Pet Ferrets Today?

No. High estrogen-associated anemia is much rarer than it once was. That is because the majority of ferrets sold in North America were neutered and spayed before they were sold. It is also because most ferret owners (and veterinarians) are now aware that it is very unwise not to breed an intact female (or, alternatively, not to offer an intact female ferret a fertile or vasectomized male ferret’s companionship).

I suppose that occasionally, a remnant of one or both ovaries might be missed during surgery. I am told that that is not that unusual in Europe. The staff of the large commercial ferret breeding operations I know in the US rarely make that error. I have never encountered an ovarian remnant in a ferret. But I have encountered them in dogs and cats.

Today it is considerably more common for a ferret’s vagina to swell due to the presence of adrenal gland tumors. Those adrenal gland tumors form due to over-stimulation of the pet’s adrenal glands. That stimulation is due to excessive release of ACTH by the spayed or neutered ferret’s pituitary gland. That situation causes the ferret’s vulva to swell because the adrenal glands also have the capacity to releases large amounts of estrogen (excessive estradiol=hyperestrogenism) and DHEA. (refIn that situation, many ferrets also become moderately anemic – but rarely as anemic as they due when their ovaries are the source of the estrogen.

If This Problem Is Occurring In My Non-spayed Female Ferret How Will My Veterinarian Confirm It?

Your veterinarian will request a detailed history and description of your home situation to rule out toxins, medications or nutritional deficiencies as the source of the anemia. Ruling out an underlying lymphoma of the bone marrow – another possible cause of anemia – can be more difficult. That requires a bone marrow biopsy.

Early in high-estrogen disease, white blood cell and thrombocyte counts (WBC) can actually be increased. But with time, the estrogen destroys the ability of the ferrets bone marrow to replace those cells. Those pets have very low white blood cell counts along with profound anemia. The gum pallor, rapid respiration and general weakness (lethargy) are all due to anemia. Having noted that, you veterinarian will probably run a PCV, Hct and/or an erythrocyte count to confirm that. Those anemias are what veterinarians refer to as “non-regenerative” anemias. Non-regenerative anemias are confirmed when blood tests also confirm a low reticulocyte count.

When the examination is over, your veterinarian might also mention that he/she detected a heart murmur. Heart murmurs are common whenever anemia is severe. With time, it is often the lack of thrombocytes that causes the most damage. Low thrombocyte counts allow small superficial hemorrhages to occur (petechia). Some ferrets hemorrhage into their intestines producing bloody stools (melena). Eventually deeper more massive hemorrhages often occur leading to the ferret’s demise. Many anemic ferrets loose hair.  Lack of white blood cells open the door to secondary bacterial infections (septicemia).

If My Ferret Becomes Stuck In Its Heat Cycle What Treatment Options Do I Have?

Estrogen-induced aplastic anemia in ferrets is a very hard disease for me to successfully treat. My successes have all been in ferrets in which the problem was discovered early when the pet’s PCV level was 25% or greater. Those successes occurred when I gave the ferrets injections of human chorionic gonadotropin (HCG) . I accompanied that with clitoral/cervical stimulation with a glass rod, but I do not know if that was of any value. If the ferret is physically up to it and an intact or vasectomized male is available, breeding is an option. Successes should be accompanied by reduced vulvar swelling and an increase in the number of blood reticulocytes.

Anemic, immunosupressed ferrets are at high risk during surgery. But in desperation, many vets would opt to to spay these anemic ferrets. I have done so. Surgical hemorrhage was always a problem. I  never had any of those ferrets survive – even when the surgery went smoothly. I suppose if I had given more ferrets ferret blood transfusions prior to their surgery I might have had better outcomes. But ferret blood is not easy to obtain or administer to these fading ferrets.

To some of them, I administered a blood substitute marketed for Jehovah’s Witnesses, FlusolDA20®. Those ferrets did well when I maintained them in an oxygen tent. But they did not survive when I removed them from the high-oxygen environment. Other veterinarians have tried other blood substitutes (oxyglobin etc.) . Others have attempted to administer GnRH. They are rarely successful. As with me, their degree of success is highly dependent on a relatively mild anemia at the time of administration. In nature, your ferret’s ovaries receive GnRH in short pulses that trigger ovulation, never in quantities delivered by an ordinary injection.

Are There Healthier Alternatives To Spaying, Breeding Or Sham-breeding My Female Ferret And Why Might I Consider Them?

Yes.

Many veterinarians believe that neutered and spayed ferrets are more at risk of developing adrenal gland tumors as they become older adults. The pet’s pituitary gland is in charge of monitoring sex hormone levels in the blood of both male and female ferrets and instructing the testicles or ovaries to produce more of those sex steroids when blood levels are low. The theory is that since neutered pets all have low estrogen or testosterone (depending on their sex) the pet’s pituitary gland continually releases GnRH hormone in an attempt to get the (missing) gonads to increase their sex hormone production. Your ferret’s pituitary gland is unaware of your pet’s prior spay/neuter surgery. The theory continues that in the face of this continuous GnRH hormone over-stimulation, tumors eventually develop in your ferret’s adrenal glands because those glands are also affected by GnRH. (rptref)

Many veterinarians believe that a better alternative would be a long acting medication that shuts off GnRH – that is, interrupts the hormone cascade at a higher level. GnRH agonists and antagonist medications have the ability to do that without the need to spay or neuter. They have been used successfully in human and zoo-animal medicine for 4 decades. (ref

One of them is approved for ferrets. It is an implantable pellet containing deslorelin. But it is only approved in the United States as a treatment for ferret adrenal gland tumors, not as an alternative to spaying your female ferret. Deslorelin, belongs to a class of compounds called GnRH modulators. There are two kinds of modulators, agonists and antagonists.  Deslorelin is one of the agonist types. Agonists bind tightly to sensors present on the surface of your ferret’s pituitary cells that are responsible for producing GnRH – the master hormone of fertility. After causing a short burst of GnRH, LH, FSH and estrogen hormone activity, the levels of all those hormones drop precipitously – effectively shutting down the ovaries and testicles for long periods. Some describe that as a “chemical castration”. When medications like deslorelin implants loose their effectiveness they must be re-administered or ovaries and testicles return to their normal function. Deslorelin is currently manufactured under the trade name, Suprelorin® by the Virbac pharmaceutical company. It is not labeled as an alternative to spay or neutering. Because I treated the most ferrets prior to the availability of deslorelin, I have more experience using two sister GnRH agonists. One is called luprolide (Lupron®), the other goserelin (Zoladex®)

In 2012, Suprelorin® 9.4mg implants were approved in Europe as an alternative to castration of male ferrets. (ref1, ref2, ref3) It was approved for that use in the same year by the FDA @4.7mg every 12 months. (ref)

The Company, Virbac, suggests that the effect of these implant lasts up to 4 years in male ferrets (these implants are not always successful in improving the behaviors that some ferret owners find  objectionable in male ferrets and 4 years of activity/implant is a bit of a stretch). (ref

Others suggest that when implanted in female ferrets, these implants protect female ferrets from experiencing heat cycles for 1-2 years. (ref

A 2014 study found that a 4.7mg deslorelin implant prevented heat cycles in female ferrets for 301 to over 1339 days (mean 1012±38 days). The authors suggested replacing the implant in female ferrets every year – although they thought that replacement every two years would suffice for most female ferrets. (ref) 2009 and 2012 studies reached similar conclusions. (ref1, rptref2)    

The UK SPCA also suggests deslorelin as perhaps a safer way to keep ferrets from coming into heat. They suggest that the 4.7mg deslorelin implant be given yearly while the 9.4mg implant should prevent heat cycles for two years. (ref)  The University of London’s RVC also considers these implants to be a safe alternative to spaying female ferrets. (refThe effect of these implants on male and female cats is quite similar. (ref

Other veterinarians even suggest these implants might protect already-spayed ferrets from developing adrenal gland tumors later in life. (ref

I mentioned earlier that these agonist medications produce a short-lived burst of sex hormone in both males and females. That surge in females is long enough for a female ferret to become pregnant when housed with a fertile male. (ref) I do not know of a case where that initial hormone burst ever lasted long enough to cause aplastic anemia. If you do, please let me know and I will add your comments here.

I know that in the UK and Europe, it is common to give intact female ferrets a “jill jab” of anti-progesterone drugs such as proligestone (Covinan®, Delvosteron®) in early spring or at the first sign of estrus. I am hesitant about doing that because the administration of progestogens to dogs and cats predisposes them to reproductive tract disorders, lethargy and weight gain and perhaps diabetes.

There are other compounds under study that effectively neuter or spay ferrets chemically. One I am familiar with is Müllerian inhibiting substance. However, to the best of my knowledge it has only been utilized experimentally. (ref1, ref2)  Although folks currently giving it to ferrets in university setting thought it would produce effects similar to deslorelin but without the initial estrogen or testosterone surge. (ref) Some of that ferret research was funded through the Michelson Prize.

Any drug powerful enough to suppress reproduction has the potential to producer unwanted side effects. Deslorelin is no exception. In humans, similar drugs have been associated with low-estrogen osteoporosis and vaginal atrophy. However drugs like deslorelin have the option to be discontinued should serious side effects occur. Your vet can easily removed implants, but surgical spay or neuter is irrevocable. I suggest you not consider implants in female ferrets unless you make the commitment to check for the early signs of estrus frequently.