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The Use of Danazol for Ureteral Obstruction Caused by Endometriosis
OD22-5:347 /31/1251-0117$0.2.00/0 THE JOURNAL Gx' URa:...CGY
Copyright© 1981 by The 'Nilli;;.ms & Wilkins C0.
THE USE
DANAZOL FOR URETERAL OBSTRUCTION CAUSED BY ENDOMETRIOSIS B. GARDNER
AND
R H. WHITAKER
From the Department of Urology, Addenbrooke's Hospital, Cambridge, England
ABSTRACT
We report 2 successfully treated cases of unilateral obstruction owing to endometriosis. Treatment consisted of danazol alone in 1 case and surgical freeing of the obstructed ureter in the other. Danazol alone can reverse completely ureteral obstruction caused by endometriosis but if secondary fibrosis has occurred surgical treatment may be necessary. This is the first case reported of complete resolution of unilateral ureteral obstruction owing to endometriosis using danazol therapy alone. the right ureter at the pelvic brim (fig. 1, A). An IVP 10 years previously had been normal. The cause of the obstruction was considered to be endometriosis rather than the previous operation. Because of the previous postoperative complication a trial of conservative management with 200 mg. danazol daily was started. The pain improved 3 months later and an IVP revealed partial resolution of the right ureteral obstruction. In March 1976 the danazol was stopped because of side effects of weight gain and hot flushes. An IVP 18 months after the
The 2 broad approaches to the treatment of ureteral obstruction caused by endometriosis are conservative, using danazol or an estrogen/progestogen combination, and surgical. Herein we report 2 cases to illustrate the successful use of both approaches. CASE REPORTS
Case 1. Mrs. S., a 36-year-old nurse, had right iliac fossa pain in 1972. In March 1975 laparoscopy revealed widespread endometriosis, which was confirmed by laparotomy. The endome-
FIG. 1. Case 1.- A, IVP shows partial obstruction of right ureter at pelvic brim. B, IVP 18 months after original operation reveals resolution of dilatation on right side. ~
triosis involved the ovaries and right broad ligament. The abnormal tissue was removed. Postoperatively, a deep vein thrombosis developed and was treated by anticoagulants. A hemoperitoneum occurred 2 weeks later owing to bleeding from the right ovary. A right salpingo-oophorectomy was performed and anticoagulation was discontinued. Postoperatively, the main complaint was pain on the right side. An excretory urogram (IVP) 2 months postoperatively demonstrated partial obstruction of Accepted for publication April 25, 1980. 117
original operation indicated that the right ureteral obstruction had resolved fully and the right pelviocaliceal system had improved markedly (fig. 1, B). Case 2. Mrs. C., a 22-year-old teacher, had recurrent left iliac fossa pain and dyspareunia in 1976. At laparoscopy in March 1977 endometriosis, mainly on the left side, was diagnosed and treated with 200 mg. danazol daily. The symptoms improved greatly and the danazol was stopped after 6 months. In January 1978 left loin pain developed. An IVP and subsequent ascending ureterogram revealed a short obstruction of the left ureter 4 cm. above the bladder (fig. 2, A). In March
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GARDNER AND WHITAKER
Fm. 2. Case 2. A, IVP shows obstruction of left ureter by-endometriosis. B, IVP after operative relief of obstruction
1978 the left ureter was freed from the dense fibrous tissue causing the obstruction. Histologically, there was evidence of endometriosis in the fibrous tissue. Danazol was recommenced 1 month postoperatively since the pelvic pain had recurred. An IVP in June revealed that the left ureter was no longer obstructed (fig. 2, B). · DISCUSSION
Danazol is a synthetic 2,3 isoxazol derivative of 17 ethynyl testosterone. It reduces the plasma level of gonadotropins, especially follicle-stimulating hormone1 and, to a lesser extent, luteinizing hormone,2 thereby suppressing ovarian function as well as uterine and ectopic endometrium. Theoretically, it should be beneficial in the treatment of endometriosis and this has been demonstrated clinically,3 histologically and laparoscopically.4 The other conservative measures that may be used in the treatment of endometriosis are progestogens alone or estrogen/progestogen combinations. These will suppress ovarian function but are less satisfactory because they initially stimulate the ectopic endometrial tissue. Thus, while there have been reported cases of ureteral obstruction owing to endometriosis being reversed by estrogen/progestogen combinations, there also have been reports of these drugs being either of no benefit or initially causing an increase in the degree of obstruction. 5• 6 Endometrial stimulation would be more likely to increase the degree of ureteral obstruction caused by intrinsic rather than by extrinsic ureteral endometriosis and it is not always possible to distinguish these 2 forms from one another by radiological studies alone. 7 Therefore, it is preferable to use an agent, such as danazol, which does not initially stimulate the endometrium. The major side effects of danazol are weight gain, water retention, acne and temporary infertility. These side effects are minor, do not occur frequently and are easily treatable. In most of the reported cases of ureteral obstruction caused by endometriosis the major, and usually the only, form of treatment described is surgical and some authors have stated that an operation is the treatment of choice. 8 The decision as to
whether conservative or surgical treatment should be used in any individual case depends on several factors, such as whether the diagnosis is known, the state of the unaffected kidney, overall renal function, the extensiveness of the endometriosis, the acceptability or otherwise of the side effects of the drug, the likelihood of patient compliance with a prolonged course of the drug and those factors relating to the suitability of a patient for an operation. However, undoubtedly there are patients suffering from ureteral obstruction owing to endometriosis for whom danazol alone is the initial treatment of choice.
Mr. R. E. Robinson and Mr. M. V. Bright allowed us to report on their patients. REFERENCES
1. Wood, G. P., Wu, C.-H., Flickinger, G. L. and Mikhail, G.: Hormonal changes associated with danazol therapy. Obst. Gynec., 45: 302, 1975. 2. Sherins, R. J., Gandy, H. M., Thorslund, T. W. and Paulson, C. A.: Pituitary and testicular function studies. 1. Experience with a new gonadal inhibitor, 17a-pregn-4-en-20-yno-(2,3-d)isoxasol-17ol (danazol). J. Clin. Endocr. Metab., 32: 522, 1971. 3. Greenblatt, R. B., Dmowski, W. P., Mahesh, V. B. and Scholer, H. F. L.: Clinical studies with an antigonadotrophin-danazol. Fertil. Steril., 22: 102, 1971. 4. Dmowski, W. P. and Cohen, M. R.: Treatment of endometriosis with an antigonadotrophin, danazol. A laparoscopic and histologic evaluation. Obst. Gynec., 46: 147, 1975. 5. Lavelle, K. J., Melman, A. W. and Cleary, R. E.: Ureteral obstruction owing to endometriosis: reversal with synthetic progestin. J. Urol., 116: 665, 1976. 6. Brooks, R. T., Jr., Fraser, W. E. and Lucas, W. E.: Endometriosis involving the urinary tract: a report of 2 cases with ureteral obstruction. J. Urol., 102: 184, 1969. 7. Pollock, H. M. and Wills, J. S.: Radiographic features of ureteral endometriosis. Amer. J. Roentgen., 131: 627, 1978. 8. Abdel-Shahid, R. B., Beresford, J.M. and Curry, R.H.: Endometriosis of the ureter with vascular involvement. Obst. Gynec., 43: 113, 1974.
Copyright© 1981 by The 'Nilli;;.ms & Wilkins C0.
THE USE
DANAZOL FOR URETERAL OBSTRUCTION CAUSED BY ENDOMETRIOSIS B. GARDNER
AND
R H. WHITAKER
From the Department of Urology, Addenbrooke's Hospital, Cambridge, England
ABSTRACT
We report 2 successfully treated cases of unilateral obstruction owing to endometriosis. Treatment consisted of danazol alone in 1 case and surgical freeing of the obstructed ureter in the other. Danazol alone can reverse completely ureteral obstruction caused by endometriosis but if secondary fibrosis has occurred surgical treatment may be necessary. This is the first case reported of complete resolution of unilateral ureteral obstruction owing to endometriosis using danazol therapy alone. the right ureter at the pelvic brim (fig. 1, A). An IVP 10 years previously had been normal. The cause of the obstruction was considered to be endometriosis rather than the previous operation. Because of the previous postoperative complication a trial of conservative management with 200 mg. danazol daily was started. The pain improved 3 months later and an IVP revealed partial resolution of the right ureteral obstruction. In March 1976 the danazol was stopped because of side effects of weight gain and hot flushes. An IVP 18 months after the
The 2 broad approaches to the treatment of ureteral obstruction caused by endometriosis are conservative, using danazol or an estrogen/progestogen combination, and surgical. Herein we report 2 cases to illustrate the successful use of both approaches. CASE REPORTS
Case 1. Mrs. S., a 36-year-old nurse, had right iliac fossa pain in 1972. In March 1975 laparoscopy revealed widespread endometriosis, which was confirmed by laparotomy. The endome-
FIG. 1. Case 1.- A, IVP shows partial obstruction of right ureter at pelvic brim. B, IVP 18 months after original operation reveals resolution of dilatation on right side. ~
triosis involved the ovaries and right broad ligament. The abnormal tissue was removed. Postoperatively, a deep vein thrombosis developed and was treated by anticoagulants. A hemoperitoneum occurred 2 weeks later owing to bleeding from the right ovary. A right salpingo-oophorectomy was performed and anticoagulation was discontinued. Postoperatively, the main complaint was pain on the right side. An excretory urogram (IVP) 2 months postoperatively demonstrated partial obstruction of Accepted for publication April 25, 1980. 117
original operation indicated that the right ureteral obstruction had resolved fully and the right pelviocaliceal system had improved markedly (fig. 1, B). Case 2. Mrs. C., a 22-year-old teacher, had recurrent left iliac fossa pain and dyspareunia in 1976. At laparoscopy in March 1977 endometriosis, mainly on the left side, was diagnosed and treated with 200 mg. danazol daily. The symptoms improved greatly and the danazol was stopped after 6 months. In January 1978 left loin pain developed. An IVP and subsequent ascending ureterogram revealed a short obstruction of the left ureter 4 cm. above the bladder (fig. 2, A). In March
118
GARDNER AND WHITAKER
Fm. 2. Case 2. A, IVP shows obstruction of left ureter by-endometriosis. B, IVP after operative relief of obstruction
1978 the left ureter was freed from the dense fibrous tissue causing the obstruction. Histologically, there was evidence of endometriosis in the fibrous tissue. Danazol was recommenced 1 month postoperatively since the pelvic pain had recurred. An IVP in June revealed that the left ureter was no longer obstructed (fig. 2, B). · DISCUSSION
Danazol is a synthetic 2,3 isoxazol derivative of 17 ethynyl testosterone. It reduces the plasma level of gonadotropins, especially follicle-stimulating hormone1 and, to a lesser extent, luteinizing hormone,2 thereby suppressing ovarian function as well as uterine and ectopic endometrium. Theoretically, it should be beneficial in the treatment of endometriosis and this has been demonstrated clinically,3 histologically and laparoscopically.4 The other conservative measures that may be used in the treatment of endometriosis are progestogens alone or estrogen/progestogen combinations. These will suppress ovarian function but are less satisfactory because they initially stimulate the ectopic endometrial tissue. Thus, while there have been reported cases of ureteral obstruction owing to endometriosis being reversed by estrogen/progestogen combinations, there also have been reports of these drugs being either of no benefit or initially causing an increase in the degree of obstruction. 5• 6 Endometrial stimulation would be more likely to increase the degree of ureteral obstruction caused by intrinsic rather than by extrinsic ureteral endometriosis and it is not always possible to distinguish these 2 forms from one another by radiological studies alone. 7 Therefore, it is preferable to use an agent, such as danazol, which does not initially stimulate the endometrium. The major side effects of danazol are weight gain, water retention, acne and temporary infertility. These side effects are minor, do not occur frequently and are easily treatable. In most of the reported cases of ureteral obstruction caused by endometriosis the major, and usually the only, form of treatment described is surgical and some authors have stated that an operation is the treatment of choice. 8 The decision as to
whether conservative or surgical treatment should be used in any individual case depends on several factors, such as whether the diagnosis is known, the state of the unaffected kidney, overall renal function, the extensiveness of the endometriosis, the acceptability or otherwise of the side effects of the drug, the likelihood of patient compliance with a prolonged course of the drug and those factors relating to the suitability of a patient for an operation. However, undoubtedly there are patients suffering from ureteral obstruction owing to endometriosis for whom danazol alone is the initial treatment of choice.
Mr. R. E. Robinson and Mr. M. V. Bright allowed us to report on their patients. REFERENCES
1. Wood, G. P., Wu, C.-H., Flickinger, G. L. and Mikhail, G.: Hormonal changes associated with danazol therapy. Obst. Gynec., 45: 302, 1975. 2. Sherins, R. J., Gandy, H. M., Thorslund, T. W. and Paulson, C. A.: Pituitary and testicular function studies. 1. Experience with a new gonadal inhibitor, 17a-pregn-4-en-20-yno-(2,3-d)isoxasol-17ol (danazol). J. Clin. Endocr. Metab., 32: 522, 1971. 3. Greenblatt, R. B., Dmowski, W. P., Mahesh, V. B. and Scholer, H. F. L.: Clinical studies with an antigonadotrophin-danazol. Fertil. Steril., 22: 102, 1971. 4. Dmowski, W. P. and Cohen, M. R.: Treatment of endometriosis with an antigonadotrophin, danazol. A laparoscopic and histologic evaluation. Obst. Gynec., 46: 147, 1975. 5. Lavelle, K. J., Melman, A. W. and Cleary, R. E.: Ureteral obstruction owing to endometriosis: reversal with synthetic progestin. J. Urol., 116: 665, 1976. 6. Brooks, R. T., Jr., Fraser, W. E. and Lucas, W. E.: Endometriosis involving the urinary tract: a report of 2 cases with ureteral obstruction. J. Urol., 102: 184, 1969. 7. Pollock, H. M. and Wills, J. S.: Radiographic features of ureteral endometriosis. Amer. J. Roentgen., 131: 627, 1978. 8. Abdel-Shahid, R. B., Beresford, J.M. and Curry, R.H.: Endometriosis of the ureter with vascular involvement. Obst. Gynec., 43: 113, 1974.