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Mammary Hyperplasia

Dr. Cris Bird

Savannah Super Cat
Sorry, I originally posted this as a "reply" to Per's introduction. I was reading replies and didn't see a way to start a new thread. Now that I see the "new thread" option was on the first page, I am re-posting properly.
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Hello Per, I have a question for you. It's pertaining to a Chausie queen, not a Savannah, but the two breeds often have similar issues. This was a young queen that developed a surprising amount of mammary development during a false pregnancy. The mammary glands became swollen and sore. The condition persisted long after the false pregnancy was over. When she became pregnant later, the mammary glands became swollen very early in the pregnancy. By the time the kittens were born, the glands were painful and engorged. I had to hand-feed the kittens until they were weaning age, as it was nearly impossible for them to nurse. I saw the same kind of exaggerated and prolonged mammary swelling several other times. I finally realized it was mammary hyperplasia. My generalist vet had not dealt with that before, but it didn't matter. By then I had decided to spay the queen because it was obvious that it was neither kind nor practical to keep breeding her. By the time I realized what I was dealing with, I had been breeding the queen for 2 years. She didn't suffer anything but some discomfort from the swelling. However, I remember reading somewhere that mammary hyperplasia can lead to mammary ulcers and infections. In the future, if I see mammary hyperplasia in, for example, female relatives of the queen, should they be spayed immediately? In other words, just how risky is the condition? Thanks.
 

Per Lausund

Moderator
Staff member
Hi, Cris, you really came up with a tough one, there!

Mammary hyperplasia is luckily not a common condition in felines, and although it's described as a "benign" condition it can be pretty dramatic. It can be a true hyperplasia with cell growth or lobular increase, but mammary edema should also be considered. It certainly is a condition that should make you contact your vet!

It is generally caused by progestins either produced by the cat herself, they should normally lead to mammary development, or by injected or orally given progestins (usually used to prevent a cats sexual cycle from continuing by mimicking pregnancy). A pseudo-pregnancy could give the same effects by increasing progestin production. Sometimes something doesn't quite work in the regulation of development, and you can get hyperplasia. It is at least uncomfortable, sometimes painful and will always increase the risk of local infection, either in the skin or in the mammary glands themselves. So, it needs to be treated.

In non-breeders the traditional treatment for all sexually related diseases, i e spaying, usually works. Mind you, spaying may be technically complicated by the mammary masses. In breeders you want to conserve the sexual functions, so spaying is a no-no. And having said that, I personally would not advocate immediate spaying just because of mammary dysplasia. However,mif it leads to a non-functional udder and leaves you hand-feeding I would advise you to choose another cat for breeding (as you described).

So, what to do? One of the problems associated with the condition is edema, and that can be alleviated with gentle massage and varmth (warm towels). This will reduce the risk of skin infection, it will comfort the animal and reduce swelling somewhat. Reduction of edema is very important, as this alone may lead to a non-functional udder: just ask the large-animal vets, they see this often in cattle! Your vet may suggest a diuretic as well. In non-breeding females mammary hyperplasia is yet another reason not to use synthetic progestins (aside from a possibly increased cancer risk and the chances of pyo: I would routinely spay around puberty. In breeding females I would suggest thet you, in cooperation with your vet use conservative treatment, anything that reduces edema, ans since this is a progestin dependent condition it is possible that an anti-progestin like http://www.drugs.com/international/aglepristone.html could help. Warning: this is off-lable use, and needsa vet to be responsible for and follow up on treatment, and it would be experimental. However, it has been used to successfully treat pyos in cats (also off-label), and cats seem to tolerate it well.

How risky is the condition? Varies with how serious it is, all cats will experience some degree of mammary edema when they start cycling and become sexually mature, hyperplasia is when it goes too far. If the condition is established chronically, like you experienced, spaying and possibly surgical removal of the mammaries would be indicated, but this is rarely seen. Luckily! A little hyperplasia and edema is to be expected and accepted, but don't be afraid to involve your vet, and if you don't get help find another one!

In non-breeders: avoid using progestins. In breeders: DON'T use them!
 

Per Lausund

Moderator
Staff member
Just a reminder: dysplasia may be confused with, or conceal, a mammary infection/mastitis. If your cat appears depressed or is running a temperature when you see mammary dysplasia, seek help at once. Mammary infections can be horrible, and treatment needs to begin early!


Just wanted to add a (possibly) helpful link, the Merck veterinary manual. It gives some helpful hints sometimes, but is not a substitute for your vet!
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/112005.htm

and also

http://www.vetmed.ucdavis.edu/vmth/small_animal/reproduction/pdfs/ceFeline_Mammary_Hyperplasia-1.pdf
 

Dr. Cris Bird

Savannah Super Cat
Thank you, Per, for a thorough, interesting, and very helpful reply. I appreciate it. Yes, my vet was not happy about having to spay my queen. The swelling of her mammary glands made the surgery difficult, but he knew it had to be done. It took several *months* for my cat's mammary glands to return to normal, but at last they did. She's a much happier cat now.
 

Per Lausund

Moderator
Staff member
just a small cutout from the British Small Animal Vet Asscn forulation book:
http://www.bsava.com/LinkClick.aspx?fileticket=hWXp1smd2tw=&tabid=292&mid=3787

Aglepristone (Alizin) POM-V Formulations: Injectable: 30 mg/ml solution.
Action: Progesterone receptor blockage leads to reduced progesterone support for pregnancy.
Use: Termination of pregnancy in bitches up to 45 days and in queens up to 35 days after mating. In bitches confirmed as pregnant, a partial abortion may occur in up to 5%; owners should be warned. A clinical examination (uterine palpation) is always recommended
10 days after treatment and at least 30 days after mating in order to confirm termination. After induced abortion an early return to oestrus is frequently observed (the oestrus-to-oestrus interval may be shortened by 1-3 months). Can also be used for the treatment of pyometra in dogs, although recurrence is fairly common. Bitches will usually be able to carry subsequent pregnancies successfully. May also be used to induce parturition and to treat progesterone-induced acromegaly in dogs. In cats can be used to treat progesterone- induced fibroadenomatous mammary hyperplasia.

the last sentence seems relevant to this thread. I've also used it to treat pyometra in breeders, it often works wonders (off label! so not formally recommended).
per
 

Dr. Cris Bird

Savannah Super Cat
Thanks, Per, that's interesting. Now, of course, I have more questions. :)

With regard to pyometra, I know that Lutealyse (prostaglandin treatment) induces gentle uterine contractions and thereby has a lancing effect on the uterus. I have used Lutealyse (under supervision of a reproductive veterinary specialist) to treat open pyometra several times, and it has always been successful. (That may be because in every case the pyometra was diagnosed very early in development.)

But how does blocking progesterone receptors treat pyometra? Pyometra is not maintained by progesterone the way pregnancy is -- or not in the same manner (no placentas in pyometra). I am interested in the mechanism because that would give me a better idea what the pros and cons of aglepristone might be compared to Lutealyse.

Next question -- when do you think aglepristone would be helpful in a case of mammary hyperplasia? The queen would probably still be unusually sensitive to progesterone after treatment, and the mammary hyperplasia would eventually return unless she was spayed, right? So, I am thinking aglepristone would mainly speed the queen's recovery from mammary hyperplasia. That would make her comfortable more quickly -- but she would still be likely to get mammary hyperplasia again if she continued to be used for breeding, right?

Thanks!
 

Per Lausund

Moderator
Staff member
Blocking progesterone receptors gives the same effect as stopping prog production, which is what you effectively do with luteolyse (PG F2alpa if I remember correctly). However, the prostaglandins induce contractions directly as well, and can be very tough, and they have effects in other systems as well. A specific progesterone receptor blocker works well in the uterus because the progesterone is the problem: it maintains a relaxed uterine environment allowing things that expand the uterus to grow. foetus, pyo, it´s the same for the uterus, only a pyo does not give signals to corp luteus to stop progesterone production and open up and react to contractile signals. So the blocker stops the progesterone effects, and allows the uterus t revert to normal, a contracted muscle. In pregnancy this would expel the foetus, which is why the foetus is the one who initiates pregnancy termination. A pyo is dependant on an active corpus luteum, which is why it usually starts right after oestrus or mating. The blocker stops the effect on the uterus, and a hormonal feedback mechanism makes the corpus luteum regress. In the meantime the uterus opens and contracts ... and expels what´s there. Progesterone blockers also initiate abortion.
That was the simple explanation. The same with mammaries: they react to progesterone by increasing mass (hyperplasia), blocking the receptors stops this.
p
 

Dr. Cris Bird

Savannah Super Cat
Thanks, Per.You put me on the right track, and that was a good start.

My first degree was in mammalian physiology, but the last university course I took in reproductive physiology was about 35 years ago. I decided after reading your explanation that I needed a refresher. LOL. So, I went back and looked at a basic textbook explanation of progesterone's effects. That still wasn't helping me get the full picture. Regulation of pregnancy and parturition is complex. I felt I needed to know more *exactly* what aglepristone does. Iin research we are used to not having the full picture and keeping at it until we do. I kept digging. I found the following journal article:
http://www.reproduction-online.org/content/140/4/623.full

Now I understand. The subjects of the study were cows, but it's likely that the same processes occur in cats. Apparently, aglepristone blocks progesterone receptors in the ovaries, but it does not seem to have much effect on placentas or developing fetuses. That explains why aglepristone does not always produce a clean abortion.

The authors say that aglepristone causes the cervix to open and some uterine contractions to occur. However, the contractions are not as strong as during normal delivery. Moreover, the fetal membranes and placentas remain intact and strongly attached. Also, the birth canal did not fully expand. Apparently, signals from the fetuses are needed to induce placentas, fetal membranes, and the birth canal to loosen up and "let go."

My guess is that aglepristone would work better for terminating early pregnancies and for curing uncomplicated pyometra. It probably would not be enough by itself in late pregnancy or when it is a complicated case of pyometra.

But that is also true for lutealyse. I think it's useful to know that aglepristone opens the cervix effectively.

Now -- I still have my question about mammary hyperplasia. Let me put it this way. If you had a queen with mammary hyperplasia, would you keep breeding her even if you had to treat her with aglepristone twice a year to keep her in good condition?

Or, would you only use aglepristone once to clear up mammary hyperplasia and then spay the queen at the earliest opportunity?

It is the practical side of this that I would like to understand now.

Thank you!
 

Per Lausund

Moderator
Staff member
:)
I´d certainly not want to breed a queen with persistent mammary hyperplasia, both for welfare and genetic reasons (you cannot assume there is no genetic basis for a condition like that), and the same goes for recurrent pyo: I would be more likely to allow a pyo repeat, though, as it does easily happen in cats and is usually open and uncomplicated and doesn´t make the queen very uncomfortable if treated early. Aglepristone would never be a drug I used often on a cat.

There are differences in anatomy, physiology and cycle in ruminants and carnivores that have a bearing on the effects of progestin receptor blockers and other drugs. In dogs and felines aglepristone works very well in inducing abortions, and I believe you see total expulsion in >90% of treated animals, which is good.

The signalling from the uterus is quite elegant, with blood vessels passing close to the ovaries on the return from the uterus to allow hormones to register.

It´s complicated but obviously works quite well!
regards
per
 
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