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New Treatments for Endometriosis 

Adenomyosis is endometriosis in the endometrium, specifically in the musculature, and if it is found below the basement membrane. Endometriosis has been found in an estimated ten percent of the general population. This was found a long time ago when we did tubal ligations on endometreosis.

The mean age of diagnosis is approximately 25 to 29 years. There have been several studies demonstrating a familial trend of endometriosis. One of these studies looked at women with endometriosis and looked at the sisters of their husbands to see what the prevalence of endometriosis was in the family that she was married to.

There are many theories as to the pathogenesis of endometriosis, but to just briefly review, one of the leading ones is that the uterine endometrium is transplanted to ectopic locations. This occurs by retrograde menstruation out through the fallopian tubes. This is supported by laparoscopy, where patients have been seen to have retrograde menstruation and also supported by the fact that the number one place for endometriosis to occur is the ovary and the second is the cul-de-sac. So it is the most dependent portion of the pelvis. Of course, there is the metaplastic transformation of cells lining the pelvic peritoneum and this is how endometriosis can possibly be found throughout all cells, not just in the pelvis, but it has been reported in the lung, the umbilicus and several other places.

The number one place for endometriosis to be is in the ovary, followed by the cul-de-sac and less likely on the fallopian tubes. The gold standard for diagnosis still remains laparoscopy. However, studies have tried to propose CA-125 as a possibility; however, that is not very sensitive and not very specific. As you know, CA-125 is elevated by a number of other disease processes, including cancer, patients with pelvic inflammatory disease.

Endometriosis a lot of times has a pleomorphic appearance and can be difficult to see unless it that clear blackish-bluish appearance that we all know. Martin did a study looking at biopsying all kinds of different types of what he thought might be endometriotic implants and found that in the blackish lesions, ninety-four percent of them were endometriosis and the white lesions were eighty percent.

The pathophysiology should be broken down into two different distinct entities. Patients either complain of pain or infertility with endometriosis. The treatment for these two different things differs. The pathophysiology for pain is that it is thought that the deeper penetration of implants actually causes the pain. This is supported by the fact that suppression of implants by medical therapy relieves the pain. As far as infertility is concerned, when the patient has moderate or severe endometriosis they have anatomic distortion of the pelvis and it becomes difficult for that fimbriated portion of the fallopian tube to pick up an egg as it is ovulated, because of the severe pelvic adhesions. However, minimal or mild endometriosis has always played an unclear role in infertility. It is thought that perhaps there are peritoneal macrophages, the role of prostaglandins, autoimmunity, etcetera. So it is not quite clear when there is a minimal or mild endometriosis.

We will talk about treatment and divide it between medical and surgical treatment. There are four classes of drugs currently recognized for the treatment of endometriosis. They include danazol, progestins, oral contraceptives and GnRH agonists. Surgical treatment can be divided into conservative surgical management, radical or definitive surgery and then other therapies.

Danazol is a derivative of testosterone. It has androgenic side effects and works by suppressing FSH and LH so that the patient eventually becomes amenorrheic. Unfortunately, there are side effects to this medication. The dose is 200 mg three to four times a day in order to achieve amenorrhea. It offers good symptomatic relief and regression of lesions. Unfortunately, since it is like testosterone, it can cause acne, oily skin, weight gain and hirsutism. Prolonged use will also cause an adverse effect on the lipids. Danazol reduces pain significantly better than placebo. For

The next drug is high-dose progestin, which you can give orally, intramuscularly, etcetera. It also causes decidualization of the endometriotic implants and can cause amenorrhea, although some patients do complain of breath through bleeding or prolonged anovulation. With regards to pain,

Oral contraceptives cause a pseudo-pregnancy and should be given continuously without that seven-day placebo interval for the withdrawal bleeding and it causes atrophy of the endometrial implants. It offers good symptomatic relief and there are relatively few side effects with oral contraceptives. However, there is the least amount of data with oral contraceptives and endometriosis. In fact, there are only two studies that have been done looking specifically at endometriosis and oral contraception. One was done in 1979 and was a randomized control study, not placebo, because one arm had danazol and the other arm had oral contraceptives. These patients were laparoscoped before and after treatment. They found that danazol was more effective than oral contraceptives at relieving pain and laparoscopic assessment showed better results with danazol. However, this was only a study of twenty-five patients, but it was a randomized study.