Hello, my name is***** and I have over 20 years of experience as a veterinarian.
I am very sorry to hear about Rawr's swollen leg, dilated pupils, hissing, and howling all of which point toward severe pain.
I do not believe this is related to your progesterone cream.
Is this a rear leg or front leg?
The most common cause of his symptoms would be a blood clot thrown from his heart blocking the blood flow to his leg (if this is in his rear leg it is called a saddle thrombus). Are his pads on that foot colder to the touch or blue in color compared to his other feet?
These cats usually have heart disease that alters normal blood movement through the heart which allows clots to form in the heart. If he has a heart murmur, abnormal heart rhythm or a very fast heart rate I would be suspicious of heart disease and a blood clot causing his symptoms.
In most cases with these patients on blood work we will see high levels of CPK (creatinine phosphokinase) due to muscle tissue breakdown when the blood clot cuts off blood flow to muscles in the rear legs. Unfortunately prognosis for these kitties is very guarded due to severe underlying heart disease.
Trauma or a severe allergic reaction to an insect bite or sting are other possible causes. Does he go outside unsupervised?
Some sort of myositis or neuritis, an autoimmune type reaction that can sometimes be associated with a vaccine, such as Rabies is possible. Was he given a vaccine recently? In those cases steroids would be helpful to quiet the over-active immune response as well as decreasing painful inflammation.
At this point I highly recommend that he see a veterinarian. I know it might be difficult to pick him up because he is in pain. I recommend throwing a blanket or towel over him, scooping him up into a carrier or heavy box.
He needs to be seen on an emergency basis however.
Please let me know if you have any further questions.