Massive intestinal infarction in young women: complication of use of oral contraceptives? KEE S. KoH, MB, BS (HoNs); RUDY G. DANZINGER, MD, B SC (MED), FRCS[C], FACS
Massive intestinal infarction due to occlusion of the celiac, superior mesenteric and inferior mesenteric arteries occurred in two young women, one of whom subsequently died. Both were smokers. They had ingested oral contraceptives for 5 and 8 years, respectively, but this therapy could not be proven to be a causative factor in their ischemic bowel disease; although such an association is uncommon, it should be considered in young women with abdominal pain. Des infarctus massifs de l'intestin dus a locclusion des art.res coeliaques et m6senteriques superieures et inferieures sont survenus chez deux jeunes femmes; une d'entre elles devait decoder par Ia suite. Toutes deux faisaient usage de tabac. Elles avaient utilise des contraceptifs oraux pendant 5 et 8 ans, respectivement; toutefois, Ia preuve n'a pu .tre faite que cette therapie ait pu contribuer a leur maladie ischemique de l'intestin. Bien qu'une telle association soit peu frequente, elle devrait .tre prise en consideration chez les jeunes femmes souffrant de douleur abdominale. Oral contraceptives are used mainly by young women in excellent health. It now seems certain that the use of oral contraceptives carries a definite, though small, increased risk of thromboembolism, hypertension, thrombotic stroke and reversible cholestatic jaundice.1 We report two cases in which occlusion of the celiac, superior mesenteric and inferior mesenteric arteries was associated with long-term use of oral contraceptives.
Case reports Case 1
A 37-year-old woman, gravida IX, para 4, abortus 5, was admitted to hospital for investigation of vague epigastric pain that had begun 8 months before. The pain was associated with nausea, vomiting and regurgitation of acid after meals. She also From the department of surgery, University of Manitoba and St. Boniface General Hospital, winnipeg Presented in part to the Manitoba chapter of the American College of Surgeons, Nov. 29, 1975, Winnipeg Reprint requests to: Dr. R.G. Danzinger, Department of surgery, St. Boniface General Hospital, 409 Tache Ave., Winnipeg, Man. R2H 2A6
had nonbloody diarrhea alternating with constipation, and a weight loss of about 14 kg. The patient had been taking Ovral (ethinyl estradiol, 0.05 mg, and norgestrel, 0.25 mg) for 5 years, had smoked 30 cigarettes daily for 20 years, had had intermittent claudication of the left leg for 2 years (determined only by close questioning after she recovered from the intestinal infarction) and had undergone vagotomy and pyloroplasty. Blood group was A, Rh positive. Mild generalized abdominal tenderness and hyperactive bowel sounds were detected. Blood pressure was 114/80 mm Hg and all peripheral pulses were palpable and normal. Results of gastroscopy, oral cholecystography and barium examinations of the whole intestine were interpreted as normal. The following serum values were determined on admission: glucose, 118 mg/dl; cholesterol, 177 mg/dl; triglycerides, 130 mg/dl; and cortisol, 10.0 mg/dl. Serum protein electrophoresis revealed a normal pattern. Two weeks after the patient's admission an acute abdomen developed with signs of peritonitis. Laparotomy revealed peritonitis with gangrene of almost the entire small bowel plus the sigmoid colon. All but the duodenum and the distal 10 cm of the terminal ileum was resected, then an end-to-end duodenoileal anastomosis was made. The sigmoid colon was excised, the rectum was oversewn and a descending colostomy was fashioned. Histopathologic examination of specimens removed at operation showed "nonthrombotic infarction" of the entire small bowel and the sigmoid colon. In the early postoperative period an arterial occlusion developed in the patient's right leg. A right femoral embolectomy was attempted but no thrombus or embolus was found. Subsequently a belowknee amputation was carried out. Histopathologic examination revealed gangrene of the foot and occlusion of all major arteries by laminated blood clot with minimal underlying arteriosclerotic changes. A cecal fistula developed and persisted despite three attempts at closure. Six months later it became apparent that the right side of the transverse colon was nonfunctioning; this segment was removed, then a side-to-end cecal-transverse colostomy was created. Total parenteral nutrition was begun following the laparotomy. Within 4 months the patient began to show gradual improvement with a positive nitrogen balance. Arrangements were begun 9 months postoperatively for a home care program with intravenous alimentation. In mid-July 1975 she became febrile. Oropharyngeal moniliasis was discovered and treated with topical nystatin and systemic amphotericin B. However, her con-
dition deteriorated and she died almost 1 year after admission. The immediate cause of death was Candida albicans septicemia. Autopsy revealed thrombosis of the celiac, superior mesenteric, inferior mesenteric and common iliac arteries, and premature atherosclerotic changes in the common iliac arteries. Case 2 A 29-year-old woman, gravida 11, para 2, was admitted to hospital with severe lower abdominal pain, particularly in the right lower quadrant. For 3 months she had been having crampy epigastric pain and vomiting approximately 15 minutes after meals. The pain radiated to her back and had been increasing in severity. Radiography following a barium meal and oral cholecystography revealed no abnormality and serum amylase value had been normal. One week prior to admission she had begun to have crampy lower abdominal pain associated with nonbloody diarrhea. She had lost almost 6 kg in weight. She had been taking Ortho-Novum 2 (mestranol, 0.1 mg, and norethindrone, 2 mg) almost continually for 8 years except for 1 year during which time she had had her second spontaneous vaginal delivery at term; this child had weighed only 1.36 kg at birth. She had smoked 20 cigarettes daily for 13 years. Physical examination revealed pelvic peritonitis. Blood pressure was 150/90 mm Hg. Blood group was B, Rh positive. The diagnosis was perforated acute appendicitis. At laparotomy a gangrenous loop of ileum was found to be perforated. After resection of 122 cm of ileum an end-toend anastomosis was performed. The vessels of the submucosa of the resected gangrenous bowel and those of the attached mesentery contained fibrinous thrombi; there was no evidence of vas culitis. Postoperatively a midstream abdominal aortogram showed complete occlusion of the celiac, superior mesenteric and inferior mesenteric arteries (Fig. 1). Total parenteral nutrition, intravenous antibiotic therapy and administration of heparin, 1200 U/h, were begun. Serum cholesterol value was 171 mg/dl, serum triglyceride value was 25 mg/dl and serum protein electrophoresis showed a normal pattern. Six weeks after operation barium studies of the upper and lower gastrointestinal tract revealed a large lesser-curve gastric ulcer and a fistula between the upper jejunum and the transverse colon. Subsequently the patient passed several intestinal casts. 60 to 90 cm long, per rectum. Twelve weeks after operation signs of peritonitis developed again. Laparotomy disclosed a high jejunocolic fistula (just distal to the ligament of Treitz), complete
CMA JOURNAI./MARCH 5, 1977/VOL. 116
513
Table I-Data on patients with reversible ischemic bowel disease
Patient and reference nos.
Age (yr) 29
Oral contraceptives used Duration of Components (mg) use (mo) Mestranol, 0.15 47 Norethynodrel, 9.85
32
Ethinyl estradiol, 0.05 Norethindrone acetate, 2.5
38
24
47
39
58
29
Mestranol, 0.1 Norethynodrel, 2.5 Mestranol, 0.1 Norethindrone, 2.0 Mestranol, 0.15 Norethynodrel, 9.85 Mestranol, 0.08 Norethindrone, 3.0
68
27
Mestranol, 0.1 Ethynodiol diacetate, 1.0 Mestranol, 0.15 Norethynodrel, 9.85
514 CMA JOURNAL/MARCH 5, 1977/VOL. 116
2 15 5
Clinical features Lower abdominal pain, vomiting, bloody diarrhea
Location of radiographic "thumbprint" after barium enema Cecum, ascending colon
Lower abdominal pain, bloody diarrhea
Cecum, ascending colon
Crampy lower abdominal pain, nausea, bloody diarrhea Crampy upper abdominal pain, loose stools (blood-streaked)
Colon
Crampy left lower quadrant pain, bloody diarrhea
Splenic flexure, descending colon (localized mucosal infarction)
Distal transverse colon
48 30
24 1
Crampy epigastric pain, vomiting, bloody diarrhea
Proximal colon
Table Il-Data on patients with irreversible ischemic bowel disease Oral contraceptives used Patient and reference nos. 18
Age (yr) 21
Duration of use (mo) 9
Components (mg) Mestranol, 0.15 Norethynodrel, 9.85
28
27
Mestranol, 0.15 Norethynodrel, 9.85
39
37
410
30
511
32
Mestranol, 0.15 Norethynodrel, 9.85 Mestranol, 0.075 Lynestrenol, 2.5 Mestranol, 0.1 Norethisterone acetate, 2.0
6"
38
712
38
812
Clinical features Right lower quadrant pain, nausea
Pathologic findings* and outcome SMV thrombosis; gangrenous jejunum, ileum, cecum and right colon; survived
1/3
Lower abdominal pain, vomiting
SMV thrombosis; gangrenous jejunum and ileum; survived
2
Generalized peritonitis
2
Right upper quadrant pain, shock Crampy epigastric pain, vomiting
SMV thrombosis; gangrenous small bowel; died Celiac artery thrombosis; died
18
SMV thrombosis; gangrenous ileum; survived
Ethinyl estradiol, 0.05 Norethisterone acetate, 3.0 Mestranol, 0.1 Norethynodrel, 2.5
36
45
Mestranol, 0.15 Lynestrenol, 5.0
11
Mid-abdominal pain, vomiting
9t
37
Ethinyl estradiol, 0.05 Norgestrel, 0.5
60
Epigastric pain, peritonitis
Celiac artery, SMA and IMA thrombosis; gangrene of entire small intestine; died
lot
29
Mestranol, 0.1 Norethindrone, 2.0
80
Crampy epigastric pain, vomiting, peritonitis
Celiac artery, SMA and IMA thrombosis; gangrene and ischemic atrophy from proximal jejunum to splenic flexure; survived
52
Crampy lower abdominal pain, bloody stools Left-sided abdominal pain, vomiting, diarrhea
SMA thrombosis; gangrenous small bowel; died SMA thrombosis; gangrene from duodenum to mid-transverse colon; died SMA thrombosis; gangrene from mid-jejunum to mid-ascending colon; survived
*SMV = superior mesenteric vein; SMA = superior mesenteric artery; IMA = inferior mesenteric artery. tThe patients in our cases 1 and 2.
and four cases of superior mesenteric vein thrombosis. Our two cases fall into the last category, the most severe gastrointestinal condition associated with the use of oral contraceptives. Conclusion There is no direct means to determine if use of oral contraceptives was a causative factor in the ischemic bowel disease of our two patients; the association may well have been fortuitous. Present evidence does not permit the unqualified conclusion that these medications are responsible for such disease since the number of reported cases is small and there have been no controlled studies. However, current understanding of the possible relation between oral contraceptive therapy and thromboembolic phenomena makes this association noteworthy. Therefore, it behooves clinicians to search for and recognize vascular insufficiency of the bowel as a cause of abdominal pain in young women so that it may be diagnosed at a potentially treatable stage. We suggest that today's oral contra-
ceptives not be prescribed for women with known vascular occlusive disease. The long-term use of anovulatory drugs should be discouraged, especially in women over 25 years of age, and their use should be discontinued immediately if symptoms suggestive of arterial occlusive disease occur. We thank Dr. Joseph Kagan for requesting consultation on the second patient, Miss Joan Matthewson for secretarial assistance, Mr. J. Harraveld for photographic assistance, and the personnel of the departments of nursing, pharmacy, home care and social service of St. Boniface General Hospital for their help in the long-term management of the two critically ill patients. The Scribner "artificial gut" catheter was obtained from Belding H. Scribner, Division of nephrology, Department of medicine, Mail stop RM-1 1, University of Washington, Seattle, WA 98195.
References 1. HEYMAN A, HURTIG HI: Clinical complications of oral contraceptives. DM 3, Aug 1975
3. JICK H, WESTERHOLM B, VESSEY MP, et al:
Venous thromboembolic disease and ABO blood type. A cooperative study. Lancg.t 1: 539, 1969
4. SARTWELL PE: Oral contraceptives and thromboembolism: a further report. Am J Epidemiol 94: 192, 1971 5. KILPATRICK ZM, SILVERMAN JF, BETANCOURT E, et at: Vascular occlusion of the colon
and oral contraceptives. Possible N Engi J Med 278: 438, 1968
6. BRINDLE MJ, HENDER5ON IN: Vascular oc-
clusion of the colon associated with oral contraception (C). Can Med Assoc J 100: 681, 1969
7. WARD GW, STEVENsEN JR: Colonic disorder and oral contraceptives (C). N Engi I Med 278: 910, 1968 8. HURWITZ RL, MART5N AJ, GROSSMAN BE,
et at: Oral contraceptives and gastrointestinal disorders. Ann Surg 172: 892, 1970
9. REED DL, CooN WW: Thromboembolism in patients receiving progestational drugs. N Engi I Med 269: 622, 1963 10. WELIN G, PERssoN T: Oral contraceptive and thrombosis of the coeliac artery (C). Lancet 2: 1348, 1968 11. LOWRY JB, OaR KG, WADE WG: Infarction of the small intestine associated with oral contraceptives. I Irish Med Assoc 62: 260, 1969 12. BRENNAN
2. IREY NS, MANION WC, TAYLOR HB: Vascular lesions in women taking oral contraceptives. Arch Pathol 89: 1. 1970
relation.
MF,
CLARKE
AM,
MACBETH
WAAG: Infarction of the midgut associated with oral contraceptives. Report of two cases. N Engi I Med 279: 1213, 1968
CMA JOURNAL/MARCH 5, 1977/VOL. 116 515
Massive intestinal infarction due to occlusion of the celiac, superior mesenteric and inferior mesenteric arteries occurred in two young women, one of whom subsequently died. Both were smokers. They had ingested oral contraceptives for 5 and 8 years, respectively, but this therapy could not be proven to be a causative factor in their ischemic bowel disease; although such an association is uncommon, it should be considered in young women with abdominal pain. Des infarctus massifs de l'intestin dus a locclusion des art.res coeliaques et m6senteriques superieures et inferieures sont survenus chez deux jeunes femmes; une d'entre elles devait decoder par Ia suite. Toutes deux faisaient usage de tabac. Elles avaient utilise des contraceptifs oraux pendant 5 et 8 ans, respectivement; toutefois, Ia preuve n'a pu .tre faite que cette therapie ait pu contribuer a leur maladie ischemique de l'intestin. Bien qu'une telle association soit peu frequente, elle devrait .tre prise en consideration chez les jeunes femmes souffrant de douleur abdominale. Oral contraceptives are used mainly by young women in excellent health. It now seems certain that the use of oral contraceptives carries a definite, though small, increased risk of thromboembolism, hypertension, thrombotic stroke and reversible cholestatic jaundice.1 We report two cases in which occlusion of the celiac, superior mesenteric and inferior mesenteric arteries was associated with long-term use of oral contraceptives.
Case reports Case 1
A 37-year-old woman, gravida IX, para 4, abortus 5, was admitted to hospital for investigation of vague epigastric pain that had begun 8 months before. The pain was associated with nausea, vomiting and regurgitation of acid after meals. She also From the department of surgery, University of Manitoba and St. Boniface General Hospital, winnipeg Presented in part to the Manitoba chapter of the American College of Surgeons, Nov. 29, 1975, Winnipeg Reprint requests to: Dr. R.G. Danzinger, Department of surgery, St. Boniface General Hospital, 409 Tache Ave., Winnipeg, Man. R2H 2A6
had nonbloody diarrhea alternating with constipation, and a weight loss of about 14 kg. The patient had been taking Ovral (ethinyl estradiol, 0.05 mg, and norgestrel, 0.25 mg) for 5 years, had smoked 30 cigarettes daily for 20 years, had had intermittent claudication of the left leg for 2 years (determined only by close questioning after she recovered from the intestinal infarction) and had undergone vagotomy and pyloroplasty. Blood group was A, Rh positive. Mild generalized abdominal tenderness and hyperactive bowel sounds were detected. Blood pressure was 114/80 mm Hg and all peripheral pulses were palpable and normal. Results of gastroscopy, oral cholecystography and barium examinations of the whole intestine were interpreted as normal. The following serum values were determined on admission: glucose, 118 mg/dl; cholesterol, 177 mg/dl; triglycerides, 130 mg/dl; and cortisol, 10.0 mg/dl. Serum protein electrophoresis revealed a normal pattern. Two weeks after the patient's admission an acute abdomen developed with signs of peritonitis. Laparotomy revealed peritonitis with gangrene of almost the entire small bowel plus the sigmoid colon. All but the duodenum and the distal 10 cm of the terminal ileum was resected, then an end-to-end duodenoileal anastomosis was made. The sigmoid colon was excised, the rectum was oversewn and a descending colostomy was fashioned. Histopathologic examination of specimens removed at operation showed "nonthrombotic infarction" of the entire small bowel and the sigmoid colon. In the early postoperative period an arterial occlusion developed in the patient's right leg. A right femoral embolectomy was attempted but no thrombus or embolus was found. Subsequently a belowknee amputation was carried out. Histopathologic examination revealed gangrene of the foot and occlusion of all major arteries by laminated blood clot with minimal underlying arteriosclerotic changes. A cecal fistula developed and persisted despite three attempts at closure. Six months later it became apparent that the right side of the transverse colon was nonfunctioning; this segment was removed, then a side-to-end cecal-transverse colostomy was created. Total parenteral nutrition was begun following the laparotomy. Within 4 months the patient began to show gradual improvement with a positive nitrogen balance. Arrangements were begun 9 months postoperatively for a home care program with intravenous alimentation. In mid-July 1975 she became febrile. Oropharyngeal moniliasis was discovered and treated with topical nystatin and systemic amphotericin B. However, her con-
dition deteriorated and she died almost 1 year after admission. The immediate cause of death was Candida albicans septicemia. Autopsy revealed thrombosis of the celiac, superior mesenteric, inferior mesenteric and common iliac arteries, and premature atherosclerotic changes in the common iliac arteries. Case 2 A 29-year-old woman, gravida 11, para 2, was admitted to hospital with severe lower abdominal pain, particularly in the right lower quadrant. For 3 months she had been having crampy epigastric pain and vomiting approximately 15 minutes after meals. The pain radiated to her back and had been increasing in severity. Radiography following a barium meal and oral cholecystography revealed no abnormality and serum amylase value had been normal. One week prior to admission she had begun to have crampy lower abdominal pain associated with nonbloody diarrhea. She had lost almost 6 kg in weight. She had been taking Ortho-Novum 2 (mestranol, 0.1 mg, and norethindrone, 2 mg) almost continually for 8 years except for 1 year during which time she had had her second spontaneous vaginal delivery at term; this child had weighed only 1.36 kg at birth. She had smoked 20 cigarettes daily for 13 years. Physical examination revealed pelvic peritonitis. Blood pressure was 150/90 mm Hg. Blood group was B, Rh positive. The diagnosis was perforated acute appendicitis. At laparotomy a gangrenous loop of ileum was found to be perforated. After resection of 122 cm of ileum an end-toend anastomosis was performed. The vessels of the submucosa of the resected gangrenous bowel and those of the attached mesentery contained fibrinous thrombi; there was no evidence of vas culitis. Postoperatively a midstream abdominal aortogram showed complete occlusion of the celiac, superior mesenteric and inferior mesenteric arteries (Fig. 1). Total parenteral nutrition, intravenous antibiotic therapy and administration of heparin, 1200 U/h, were begun. Serum cholesterol value was 171 mg/dl, serum triglyceride value was 25 mg/dl and serum protein electrophoresis showed a normal pattern. Six weeks after operation barium studies of the upper and lower gastrointestinal tract revealed a large lesser-curve gastric ulcer and a fistula between the upper jejunum and the transverse colon. Subsequently the patient passed several intestinal casts. 60 to 90 cm long, per rectum. Twelve weeks after operation signs of peritonitis developed again. Laparotomy disclosed a high jejunocolic fistula (just distal to the ligament of Treitz), complete
CMA JOURNAI./MARCH 5, 1977/VOL. 116
513
Table I-Data on patients with reversible ischemic bowel disease
Patient and reference nos.
Age (yr) 29
Oral contraceptives used Duration of Components (mg) use (mo) Mestranol, 0.15 47 Norethynodrel, 9.85
32
Ethinyl estradiol, 0.05 Norethindrone acetate, 2.5
38
24
47
39
58
29
Mestranol, 0.1 Norethynodrel, 2.5 Mestranol, 0.1 Norethindrone, 2.0 Mestranol, 0.15 Norethynodrel, 9.85 Mestranol, 0.08 Norethindrone, 3.0
68
27
Mestranol, 0.1 Ethynodiol diacetate, 1.0 Mestranol, 0.15 Norethynodrel, 9.85
514 CMA JOURNAL/MARCH 5, 1977/VOL. 116
2 15 5
Clinical features Lower abdominal pain, vomiting, bloody diarrhea
Location of radiographic "thumbprint" after barium enema Cecum, ascending colon
Lower abdominal pain, bloody diarrhea
Cecum, ascending colon
Crampy lower abdominal pain, nausea, bloody diarrhea Crampy upper abdominal pain, loose stools (blood-streaked)
Colon
Crampy left lower quadrant pain, bloody diarrhea
Splenic flexure, descending colon (localized mucosal infarction)
Distal transverse colon
48 30
24 1
Crampy epigastric pain, vomiting, bloody diarrhea
Proximal colon
Table Il-Data on patients with irreversible ischemic bowel disease Oral contraceptives used Patient and reference nos. 18
Age (yr) 21
Duration of use (mo) 9
Components (mg) Mestranol, 0.15 Norethynodrel, 9.85
28
27
Mestranol, 0.15 Norethynodrel, 9.85
39
37
410
30
511
32
Mestranol, 0.15 Norethynodrel, 9.85 Mestranol, 0.075 Lynestrenol, 2.5 Mestranol, 0.1 Norethisterone acetate, 2.0
6"
38
712
38
812
Clinical features Right lower quadrant pain, nausea
Pathologic findings* and outcome SMV thrombosis; gangrenous jejunum, ileum, cecum and right colon; survived
1/3
Lower abdominal pain, vomiting
SMV thrombosis; gangrenous jejunum and ileum; survived
2
Generalized peritonitis
2
Right upper quadrant pain, shock Crampy epigastric pain, vomiting
SMV thrombosis; gangrenous small bowel; died Celiac artery thrombosis; died
18
SMV thrombosis; gangrenous ileum; survived
Ethinyl estradiol, 0.05 Norethisterone acetate, 3.0 Mestranol, 0.1 Norethynodrel, 2.5
36
45
Mestranol, 0.15 Lynestrenol, 5.0
11
Mid-abdominal pain, vomiting
9t
37
Ethinyl estradiol, 0.05 Norgestrel, 0.5
60
Epigastric pain, peritonitis
Celiac artery, SMA and IMA thrombosis; gangrene of entire small intestine; died
lot
29
Mestranol, 0.1 Norethindrone, 2.0
80
Crampy epigastric pain, vomiting, peritonitis
Celiac artery, SMA and IMA thrombosis; gangrene and ischemic atrophy from proximal jejunum to splenic flexure; survived
52
Crampy lower abdominal pain, bloody stools Left-sided abdominal pain, vomiting, diarrhea
SMA thrombosis; gangrenous small bowel; died SMA thrombosis; gangrene from duodenum to mid-transverse colon; died SMA thrombosis; gangrene from mid-jejunum to mid-ascending colon; survived
*SMV = superior mesenteric vein; SMA = superior mesenteric artery; IMA = inferior mesenteric artery. tThe patients in our cases 1 and 2.
and four cases of superior mesenteric vein thrombosis. Our two cases fall into the last category, the most severe gastrointestinal condition associated with the use of oral contraceptives. Conclusion There is no direct means to determine if use of oral contraceptives was a causative factor in the ischemic bowel disease of our two patients; the association may well have been fortuitous. Present evidence does not permit the unqualified conclusion that these medications are responsible for such disease since the number of reported cases is small and there have been no controlled studies. However, current understanding of the possible relation between oral contraceptive therapy and thromboembolic phenomena makes this association noteworthy. Therefore, it behooves clinicians to search for and recognize vascular insufficiency of the bowel as a cause of abdominal pain in young women so that it may be diagnosed at a potentially treatable stage. We suggest that today's oral contra-
ceptives not be prescribed for women with known vascular occlusive disease. The long-term use of anovulatory drugs should be discouraged, especially in women over 25 years of age, and their use should be discontinued immediately if symptoms suggestive of arterial occlusive disease occur. We thank Dr. Joseph Kagan for requesting consultation on the second patient, Miss Joan Matthewson for secretarial assistance, Mr. J. Harraveld for photographic assistance, and the personnel of the departments of nursing, pharmacy, home care and social service of St. Boniface General Hospital for their help in the long-term management of the two critically ill patients. The Scribner "artificial gut" catheter was obtained from Belding H. Scribner, Division of nephrology, Department of medicine, Mail stop RM-1 1, University of Washington, Seattle, WA 98195.
References 1. HEYMAN A, HURTIG HI: Clinical complications of oral contraceptives. DM 3, Aug 1975
3. JICK H, WESTERHOLM B, VESSEY MP, et al:
Venous thromboembolic disease and ABO blood type. A cooperative study. Lancg.t 1: 539, 1969
4. SARTWELL PE: Oral contraceptives and thromboembolism: a further report. Am J Epidemiol 94: 192, 1971 5. KILPATRICK ZM, SILVERMAN JF, BETANCOURT E, et at: Vascular occlusion of the colon
and oral contraceptives. Possible N Engi J Med 278: 438, 1968
6. BRINDLE MJ, HENDER5ON IN: Vascular oc-
clusion of the colon associated with oral contraception (C). Can Med Assoc J 100: 681, 1969
7. WARD GW, STEVENsEN JR: Colonic disorder and oral contraceptives (C). N Engi I Med 278: 910, 1968 8. HURWITZ RL, MART5N AJ, GROSSMAN BE,
et at: Oral contraceptives and gastrointestinal disorders. Ann Surg 172: 892, 1970
9. REED DL, CooN WW: Thromboembolism in patients receiving progestational drugs. N Engi I Med 269: 622, 1963 10. WELIN G, PERssoN T: Oral contraceptive and thrombosis of the coeliac artery (C). Lancet 2: 1348, 1968 11. LOWRY JB, OaR KG, WADE WG: Infarction of the small intestine associated with oral contraceptives. I Irish Med Assoc 62: 260, 1969 12. BRENNAN
2. IREY NS, MANION WC, TAYLOR HB: Vascular lesions in women taking oral contraceptives. Arch Pathol 89: 1. 1970
relation.
MF,
CLARKE
AM,
MACBETH
WAAG: Infarction of the midgut associated with oral contraceptives. Report of two cases. N Engi I Med 279: 1213, 1968
CMA JOURNAL/MARCH 5, 1977/VOL. 116 515
