Endometriosis: Hormonal and Surgical Treatment

Robert W. Kistner, M.D.
Assistant Professor of Obstetrics and Gynecology, Harvard Medical School, Boston; Associate Chief of Staff, Boston Hospital for Women, Parkway Division, Boston

Endometriosis, Aspects and Proceedings of a Symposium
Saint John's Hospital and Health Center, Santa Monica, California
Editor: J.J. Marik

In 1956, the author began to threat patients with endometriosis by inducing pseudopregnancy with the administration of combinations of estrogens and newer synthetic progestins for 6 to 9 months. This concept of therapy was predicated on the fact that pregnancy usually brings about both objective and subjective improvements in patients with extensive pelvic endometriosis. Thus, a state similar to pregnancy would seem of particular value when the patient is infertile, does not desire pregnancy, or is unmarried. It was further suggested that the changes in endometriosis brought about by pregnancy were due to a combination of (1) anovulation and amenorrhea, (2) decidual transformation of functioning endometriotic tissue, and (3) decidual necrosis and absorption.

A morphologically similar decidual reaction can be brought about both in the endometrium and in areas of endometriosis by the prolonged administration of estrogens and progestogens. It is suggested that the decidual cells undergo a gradual process of necrosis that is followed by liquefaction and absorption. The decidual reaction produced in areas of endometriosis by newer agents in lower dosage is just as extensive as that noted in previous studies utilizing extremely large doses of Enovid.(R)

The optimal treatment for endometriosis is prolonged cessation of menstruation. If pregnancy can be obtained, this is recommended as primary therapy. If culdoscopy or laparoscopy reveals ovarian endometriosis without anatomical deformity of the ovary or tube, pseudopregnancy for 6 months, induced by norgestrel plus ethinyl estradiol (Ovral'R) or norethynodrel plus mestranol (Enovid-E''), is suggested. Endoscopy repeated at the end of 6 months usually reveals no evidence of endometriosis. If no other cause for infertility exists, pregnancy may be expected to occur in approximately 50% of these patients within one year of cessation of therapy.

Prolonged hormonal therapy is applicable in the following patients:

1 . Unmarried patients with maximal symptoms and minimal palpable findings. Extension of the disease may be prevented and subsequent fertility preserved.

2. Patients with recurrent disease after a previous conservative operation. Pregnancies have been noted subsequent to hormonal treatment in patients to whom hysterectomy has been suggested.

Short-term hormonal therapy is indicated in the following situations:

1. Prior to conservative surgery. Areas of endometriosis will enlarge and appear hemorrhagic, making identification and excision simpler and more complete. Six to eight weeks of therapy are adequate.

2. Subsequent to conservative therapy (in order to inhibit ovulation and prevent reactivation of remaining areas of endometriosis). Twelve to twentyfour weeks of therapy are adequate. Postoperative pseudopregnancy is utilized only when the disease is extensive and if all areas of endometriosis cannot be excised.

In patients who demonstrate unusual or excessive side effects to the es-
trogenic component of Ovral`"' or Enovid-E,'"' we have utilized Depo-Provera`"' (Upjohn) (depo-medroxy-progesterone acetate). However, this preparation should not be used if pregnancy is immediately desirable, since its long action may prevent ovulation for 6 to 12 months subsequent to cessation of therapy. This anovulatory situation may usually be corrected by the administration of clomiphcne alone or human chorionic gonadotropin.
The regimen we have used is as follows: 100 mg of Depo-Provera" every 2 weeks for four doses, then 200 mg monthly for 4 additional months. Breakthrough bleeding occurs frequently because of the antiestrogenic activity of Depo-Provera,'" but this may be alleviated by the administration of ethinyl estradiol, 0.02 mg daily, for 21 days of each month.

Analysis of our results during- the last 20 years indicates that a pregnancy rate of approximately 50% may be expected following pseudopregnancy alone in patients whose only abnormality, as determined by endoscopy, is surface ovarian endometriosis without endometriomas or tubo-ovarian adhesions (50.8% in 186 patients).

The pregnancy rate in our series subsequent to surgical treatment of ovarian endometriomas, with or without peritoneal endometriosis involving the bladder, uterus, cul-de-sac, or lateral pelvic wall, was 76% in 232 patients. It should he noted, however, that postoperative pseudopregnancy was used in these patients only if all areas of endometriosis could not be excised at the time of surgery. Furthermore, 96% of these patients were under 32 years of age and no other factors contributing to infertility were present.

The incidence of pregnancy following surgical therapy in 106 patients who were found to have ovarian and peritoneal endometriosis complicated by tubo-ovarian, utero-ovarian, or sigmoido-ovarian adhesions, however, was only 37%. Since 1966 we have administered dexamcthasone-promethazine pre-operatively, intraperitoneally, and postoperatively in all patients undergoing surgery for infertility. Postoperative pseudopregnancy was also utilized in this group of patients with adhesions only if all areas of endometriosis could not be excised. The pregnancy rate for those patients who received postoperative hormonal treatment was essentially the same as for those who did not. However, it is obvious that pseudopregnancy was invariably utilized in patients with more extensive disease.

Estrogen-progestogen pseudopregnancy is contraindicated under the following conditions:

1 . Unproved endometriosis or merely a suspicion of the disease by history, with minimal palpable findings.

2. Obscure diagnosis of pelvic lesions, particularly when ovarian enlargement is of such degree that a neoplastic growth cannot be excluded.

3. Uterine leiomyomas of such size that the stimulation of growth by estrogenic substances could initiate complications.

In contemplating surgical treatment of endometriosis, one should remember that functioning ovarian tissue is necessary for the continued activity of the disease. Therefore, successful treatment of endometriosis depends on a knowledge of when it is reasonably safe or desirable to maintain ovarian function and when it is necessary to destroy it. It is obvious that ovarian function should be preserved in treating the very early, and perhaps symptomless, lesions, and hysterectomy should be performed only when the ovaries are destroyed by endometriosis. Unfortunately, the majority of cases fall between these two extremes and may present problems in surgical judgment seldom encountered in any other pelvic disease.

As our knowledge of the life history of endometriosis has increased, there has been a definite tendency to become more conservative, particularly in the treatment of the infertile patient. In general, it is believed that one should err on the side of conservatism; this belief is based on the facts that endometriosis (l) usually progresses slowly over a period of years; (2) is not, and rarely becomes, malignant; and (3) regresses at the menopause.

Early implantations on the surface of the peritoneum should be excised. Extensive electrocoagulation is not recommended because of the possibility of subsequent adhesions to the small intestine or the adnexal structures. Small endometrial cysts on the ovary may be excised or a major portion of one or both ovaries may be resected. Small endometrial implants on the intestines should be excised. To aid in the prevention of recurrence, conservative operations should be accompanied by correction of uterine displacements, relief of cervical obstruction, and removal of any other concomitant pelvic pathologic changes. Endometriosis coexisting with uterine myomas, ovarian cysts, or other pelvic abnormalities may be insignificant; on the other hand, the extent or location of these may make conservative surgery hazardous. Decisions cannot always be made prior to laparotomy, and the patient should be so informed.

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