|Gonadotropins and Steroid Hormones|
Panel Discussion II
Endometriosis, Aspects and Proceedings of a Symposium
DR. BLAKE H. WATSON, MODERATOR: The following question has been directed to Dr. Clyman: You mentioned fimbriaplasties that were done transvaginally. What is the incidence in these cases of cuff cellulitis or tuboovarian abscess'? And secondly, do you use prophylactic antibiotics with this procedure'?
DR. CLYMAN: I do use prophylactic antibiotics, and since doing so I have had no instances of infection at all. Three infections have occurred where wedge resection of the ovaries was done without antibiotics. One case was in a diabetic, and I would not again attempt this procedure in a diabetic patient. I am very pleased with the results, with both tuboplasties and fimbriaplasties.
MODERATOR WATSON: Do you use pre-operative antibiotics? DR. CLYMAN: Yes, I do.
MODERATOR WATSON: And what do you use postoperatively'?
DR. CLYMAN: I use both pre- and postoperative antibiotics. One can employ any combination preferred, although I use ampicillin with streptomycin, or procaine penicillin with streptomycin; or gentamicin can he used. Any of the broad-spectrum agents can be used-ampicillin usually covers most of the "bugs." It won't cover them all, but it will take care of most of them.
QUESTION: Over the last several years, we have had 1 1 cases of endometrial adenocarcinoma, the youngest patient being 27 years old. Surgery and radiation were done in these patients. During this same period of time, we had 16 cases of endometrial atypical hyperplasia. Specimens from several of these patients show endometriosis to a greater or lesser degree, although no malignancy was found in the area of endometriosis. My question is: how often do you see malignancy in the ectopic endometrium? It would appear to be rather rare.
DR. KISTNER: I would like to respond to this question. The incidence of adenocarcinoma arising in endometriosis is extremely rare. In 1953 Hertig and l reported 14 cases of primary adenocarcinoma of the ovary arising in endometriosis. The reason for its rarity is that although many carcinomas of the ovaries may arise in endometriosis, by the time the pathologist sees the specimen, there is no vestige of the previously existing endometriosis remaining.
In all of the cases that we reported, and these were all adenoacanthomas, we had to show, according to Sampson's criteria, transition from endometriotis tissue into carcinoma. Personally, I believe many adenocarcinomas of the ovary do indeed arise in areas of endometriosis.
QUESTION: How concerned would the panel be if danazol were given to a woman in early pregnancy, as far as masculinization of the female fetus is concerned?
DR. GREENBLATT: I wouldn't be concerned at all. Danazol has been inadvertently given to women in early pregnancy in a few instances without any untoward effect.
DR. BLACKMORE: May I comment on this point? In regard to pregnancy, many of the patients who were treated for endometriosis had a secondary diagnosis of infertility. Although we do not yet have the results of all of the long-term follow-up which is currently underway, you may be interested to know that at this point 67 women who wished to conceive after treatment with danazol have become pregnant within six months after discontinuation of the drug. They delivered normal infants with no abnormalities or problems.
QUESTION: I would like to hear the panelists' personal thoughts on the relationship between endometriosis and infertility?
DR. KISTNER: That is too broad a question to adequately answer in a panel discussion. I.C. Rubin stated that if the incidence of infertility in the general population is 12-15%, the incidence of infertility in a couple in which the woman has endometriosis of moderate degree is at least two to three times that figure. 1 think approximately 25-30% of patients with moderately extensive endometriosis will be infertile because of that disease. Certainly, however, there are patients with endometriosis who become pregnant easily, so that it is not an "all or none" situation.
I would like to pose a question. Dr. Greenblatt, could you comment on the relative insufficiency of the endometrium immediately following danazol therapy, and whether or not you have instructed patients not to try to become pregnant during the first two to three months, on the possibility that the abortion rate might be higher due to endometrial insufficiency?
DR. GREENBLATT: I think what we are seeing with danazol therapy is that danazol puts some mechanisms to rest but allows the patient to rebound very rapidly. We have no clear explanation for it, but we have not advised our patients to abstain from intercourse just because they have been on danazol therapy.
DR. KISTNER: So the endometrium returns to normal?
DR. GREENBLATT: Yes, it does.
QUESTION: Since the object of this symposium was to discuss medical versus surgical treatment for endometriosis, and since apparently danazol may make some other forms of hormonal therapy obsolete, I wonder if the panel would care to discuss the possibility for a reduction in the need for surgery with danazol or other agents?
DR. KISTNER: It may be that danazol will do everything that the estrogenprogestogens do, or that androgens or estrogens were supposed to do. But I think that the surgical approach to infertility caused by endometriosis will remain exactly the same. The decision as to whether or not surgery is elected should be made on the basis of endoscopic examination and by the determination of the extent of the disease and the tubo-ovarian abnormality.
I have never been convinced that any type of hormonal treatment, and particularly pseudopregnancy, can make an infertile woman fertile if she has an anatomical deformity. And I don't think it will change the incidence of surgery one iota.
DR. COHEN: I would certainly agree with Dr. Kismet on this point. I don't think that danazol will make the scalpel obsolete in endometriosis.
MODERATOR WATSON: Dr. Greenblatt, would you care to comment?
DR. GREENBLATT: Personally, I feel the time will come when the patient with mild endometriosis, when surgery alone is not considered the treatment of choice, will be given a trial of danazol before rushing to the surgical table. And if she can conceive following a three- or four-month waiting period after a three- or six-month trial of danazol, we may be able to avoid a lot of unnecessary surgery.
I think surgery will in many cases still be necessary, but I also feel that in selected patients a trial of danazol is appropriate before surgery, and that we will be gratified to find that in many of these patients, surgery will not have to be performed.
DR. CLYMAN: I think age is a factor here as well. If, as Dr. Cohen stated, the patient is over 30 and doesn't want to waste any time, and you feel surgery is indicated, I don't think t would at all delay in proceeding with surgery. In the younger woman, where you have more time and there is an infertility problem rather than a problem of pelvic pain, I think a more conservative approach is worth trying.
QUESTION: You mentioned in treatment with danazol that for those patients who receive from 200 to 800 mg, the course of therapy can take five to seven months, or in exceptional cases, up to nine months. Is this to be expected, or does it indicate recurrence of the disease?
DR. GREENBLATT: One course can be for three months, another for six months and yet a third for nine months, depending on the severity of the disease. It is important to emphasize that nothing, not even danazol, can cure endometriosis, except complete surgery-oophorectomy. Danazol treatment is a temporizing measure, by which we hope to have a patient conceive, lessen her pain, and maintain her functions and organs intact for as long a period as possible.
DR. BLACKMORE: On the data that were presented I mentioned that 75% of the patients received the 800 mg dose, which is the dosage level for which we have the most information and the one which is presently recommended. From a review of the symptomatology it would appear that in most cases patients were completely or almost completely free of symptoms at three months. It would have been ideal if we could have set up a study to do a laparoscopy before treatment, at three months and at six months. We have had difficulties, however, in having patients return for a second laparoscopy when they are symptom-free and have no problems; therefore, we have been unable to obtain data at times other than at the end of treatment. I am sure that we would have seen marked regression of endometrial implants in many of them if we had been able to do a three-month laparoscopic examination.
MODERATOR WATSON: I would like to thank all of the panel members for
their enlightening comments.
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