Advertisement

Gastrointestinal disease and oral contraception

  • Jürgen P. Hanker
    Correspondence
    Reprint requests: Jürgen P. Hanker, MD, Zentrum für Frauenheilkunde, Albert-Schweitzer-Strasse 33, D-4400 Munster, West Germany.
    Affiliations
    Zentrum für Frauenheilkunde of the Westfälische Wilhelms-Universität, Münster, West Germany
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Oral contraceptive steroids play a major role in modern family planning. With the present tendency to decrease the doses of both estrogens and progestogens, any factor that reduces the bioavailabilty of the lower-dose preparations may have an impact on contraceptive protection. Although ethinyl estradiol, the most commonly used oral estrogen, is liable to an enterohepatic circulation as unchanged drug, the commonly used progestogens are not. At present, no convincing evidence exists in the human subject that disruption of the enterohepatic circulation by antibiotics or antacids does reduce contraceptive efficacy of the pill. Oral contraceptive steroids are mainly absorbed from the small bowel, and contraceptive efficacy depends on its absorptive capacity. Enhanced passage of gastrointestinal contents or impaired absorption may thus contribute to contraceptive failures in patients who have chronic inflammatory disease, diarrhea, ileostomy, or jejunoileal bypass.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Population Reports. Oral contraceptives. Baltimore: John Hopkins University 1982; Series 6: 191.

        • Back DJ
        • Breckenridge AM
        • Crawford FE
        • et al.
        An investigation of the pharmacokinetics of ethynylestradiol in women using radioimmunoassay.
        Contraception. 1979; 20: 263-273
        • de la Pena A
        • Chenault CB
        • Goldzieher J
        Radioimmunoassay of unconjugated plasma ethynylestradiol in women given a single dose of ethinylestradiol or mestranol.
        Steroids. 1975; 25: 773-780
        • Düsterberg R
        • Hümpel M
        • Wendt H
        Plasma levels of active ingredients after single and repeated administration of a new oral contraceptive containing 2 mg of cyproterone acetate and 50 µg of ethinylestradiol (Diane) to five young women.
        Acta Obstet Gynecol Scand (Suppl). 1979; 88: 27-31
        • Goldzieher JW
        • Dozier TS
        • de la Pena A
        • et al.
        Plasma levels and pharmacokinetics of ethinylestrogens in various populations.
        Contraception. 1980; 21: 1-16
        • Nilsson S
        • Nygren KG
        • Johansson EDB
        Ethinyl estradiol in human milk and plasma after oral administration.
        Contraception. 1978; 17: 131-139
        • Pasqualini JR
        • Castallet R
        • Portois MC
        • Hill JL
        • Kincl FA
        Plasma concentrations of ethinyl estradiol and norethindrone after oral administration to women.
        J Reprod Fertil. 1977; 49: 189-193
        • Speck U
        • Wendt H
        • Schulze PE
        • Jentsch D
        Bioavailability and pharmacokinetics of cyproterone acetate-14C and ethinylestradiol-3H after oral administration as a coated tablet.
        Contraception. 1976; 14: 151-163
        • Warren RJ
        • Fotherby K
        Plasma levels of ethinylestradiol after administration of ethinylestradiol or mestranol to human subjects.
        J Endocrinol. 1973; 59: 369-370
        • Orme ML'E
        • Back DJ
        • Breckenridge AM
        Clinical pharmacokinetics of oral contraceptive steroids.
        Clin Pharmacokinet. 1983; 8: 95-136
        • Back DJ
        • Bates M
        • Burke MW
        • et al.
        Plasma Xa inhibitory activities and plasma concentrations of norgestrel and ethinyloestradiol in women on oral contraceptive steroids.
        Br J Clin Pharmacol. 1979; 8: 505-506
        • Hümpel M
        • Nieuweboer B
        • Wendt H
        • Speck U
        Investigations of pharmacokinetics of ethinyloestradiol to specific consideration of a possible first-pass effect in women.
        Contraception. 1979; 19: 421-432
        • Back DJ
        • Bates M
        • Breckenridge AM
        • et al.
        Drug metabolism by gastrointestinal mucosa-clinical aspects.
        in: Prescott Nimmo Drug absorption. ADIS Press, Sydney, Australia1980: 80-87
        • Back DJ
        • Breckenridge AM MacIver M
        The gut wall metabolism of ethinyloestradiol and its contribution to the pre-systemic metabolism of ethinyloestradiol in humans.
        Br J Clin Pharmacol. 1982; 13: 325-330
        • Bolt HM
        • Bolt WH
        Pharmacokinetics of mestranol in man in relation to its oestrogenic activity.
        Eur J Clin Pharmacol. 1974; 7: 295-305
        • Bolt HM
        • Bolt M
        • Kappus H
        Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinylestradiol in man.
        Acta Endocrinol. 1977; 85: 189-197
        • Bolt HM
        • Kappus H
        • Dasbohrer R
        Metabolism of 17α-ethinylestradiol by human liver microsomes in vitro: aromatic hydroxylation and irreversible protein binding of metabolites.
        J Clin Endocrinol Metab. 1974; 39: 1072-1080
        • Williams JG
        • Longcope E
        • Williams KIH
        Metabolism of [4-3H] and [4-14C] ethinylestradiol-3 methyl ether (mestranol) by women.
        Steroids. 1975; 25: 343-354
        • Helton ED
        • Williams MC
        • Goldzieher JW
        Human urinary and liver conjugates of 17α-ethinyloestradiol.
        Steroids. 1976; 27: 851-867
        • Fotherby K
        Metabolism of synthetic steroids by animals and man.
        in: Briggs Diczfalusy Pharmacological models in contraceptive development. WHO, Stockholm, Sweden1974: 119-148
        • Cargill DI
        • Steinetz BG
        • Gosnell E
        • et al.
        Fate of ingested radio labelled ethinylestradiol and its 3-cyclopentyl ether in patients with bile fistulas.
        J Clin Endocrinol Metab. 1969; 29: 1051-1061
        • Järvenpää P
        • Kosunen T
        • Fotsis T
        • Adlercreutz H
        In vitro metabolism of estrogens by isolated intestinal microorganisms and by human faecal microflore.
        J Steroid Biochem. 1980; 13: 345-349
        • Back DJ
        • Breckenridge AM
        • Crawford FE
        • et al.
        The effects of rifampicin on the pharmacokinetics of ethinylestradiol in women.
        Contraception. 1980; 21: 135-143
        • Bacon JF
        • Shenfield GM
        Pregnancy attribute to interaction between tetracycline and oral contraceptives.
        Br Med J. 1980; 1: 293
        • Dossetor J
        Drug interactions with oral contraceptives.
        Br Med J. 1975; 4: 467-468
        • von Hempel E
        • Böhm W
        • Carol W
        • Klinger W
        Medikamentöse Enzyminduktion and hormonale Kontrazeption.
        Zentralbl Gynäkol. 1973; 95: 1451-1457
        • Adlecreutz H
        • Pulkkinen MO
        • Hämäläinen EK
        • Korpela JT
        Studies on the role of intestinal bacteria in metabolism of synthetic and natural steroid hormones.
        J Steroid Biochem. 1984; 20: 217-229
        • Back DJ
        • Breckenridge AM
        • MacIver M
        • et al.
        The effects of ampicillin on oral contraceptive steroids in women.
        Br J Clin Pharmacol. 1982; 14: 43-48
        • Friedman CI
        • Huneke AL
        • Kim MH
        • Powell J
        The effect of ampicillin on oral contraceptive effectiveness.
        Obstet Gynecol. 1980; 55: 33-37
        • Joshi JV
        • Joshi UM
        • Sankhali GM
        • et al.
        A study of interaction of low dose combination oral contraceptive with ampicillin and metronidazole.
        Contraception. 1980; 22: 643-652
        • Leigh DA
        • Reeves DS
        • Simmons K
        • Thomas AL
        • Wilkinson PJ
        Talampicillin: a new derivative of ampicillin.
        Br Med J. 1976; 2: 1378-1380
        • Hurwitz A
        Antacid therapy and drug kinetics.
        Clin Pharmacokinet. 1977; 2: 269
        • Khalil SAH
        • Iwunagwu M
        The in vitro uptake of some oral contraceptive steroids by magnesium trisilicate.
        J Pharm Pharmacol (suppl). 1976; 28: 47
        • Joshi JV
        • Sankolli GM
        • Shah RS
        • Joshi UM
        Antacid does not reduce the bioavailability of oral contraceptive steroids in women.
        Int J Clin Pharmacol Ther Toxicol. 1986; 24: 192-195
        • Goldzieher JW
        • de la Pena A
        • Chenault CB
        • Wouterz TB
        Comparative studies of ethinylestrogens used in oral contraceptives. II. Anti-ovulatory potency.
        Am J Obstet Gynecol. 1975; 122: 619-6124
        • Benoni C
        • Nilsson A
        Smoking habits in patients with inflammatory bowel disease.
        Scand J Gastroenterol. 1984; 19: 824-830
        • Bures J
        • Fixa B
        • Komarkova O
        • Fingerland A
        Nonsmoking: a feature of ulcerative colitis.
        Br Med J. 1982; 285: 440
        • Harries AD
        • Baird A
        • Rhodes J
        Non-smoking: a feature of ulcerative colitis.
        Br Med J. 1982; 284: 706
        • Jick H
        • Walker AM
        Cigarette smoking and ulcerative colitis.
        N Engl J Med. 1983; 308: 261-263
        • Logan FRA
        • Edmond M
        • Somerville KW
        • Langman MJS
        Smoking and ulcerative colitis.
        Br Med J. 1984; 288: 751-753
        • Somerville KW
        • Logan RFA
        • Edmond M
        • Langman MJS
        Smoking and Crohn's disease.
        Br Med J. 1984; 289: 954-956
      2. Ramcharan S The Walnut Creek Contraceptive Drug Study: a prospective study of the side effects of oral contraceptives. Vol III. US Government Printing Office, Washington, D.C.1981
        • Rhodes JM
        • Cockel R
        • Allan RN
        • et al.
        Colonic Crohn's disease and use of oral contraception.
        Br Med J. 1984; 288: 595-596
      3. Royal College of General Practitioners: Oral contraceptives and health. London, England: Pitman Medical, 1974.

        • Vessey M
        • Jewell D
        • Smith A
        • Yeates D
        • McPherson K
        Chronic inflammatory bowel disease, cigarette smoking, and use of oral contraceptives: findings in a large cohort study of women of childbearing age.
        Br Med J. 1986; 292: 1101-1103
        • Lesko SM
        • Kaufman DW
        • Rosenberg L
        • et al.
        Evidence for an increased risk of Crohn's disease in oral contraceptive users.
        Gastroenterology. 1985; 89: 1046-1049
        • Kirsner JB
        • Shorter RG
        Recent developments in “nonspecific” inflammatory bowel disease (part two).
        N Engl J Med. 1982; 306: 837-848
        • Cotton PB
        • Lea Thomas M
        Ischaemic colitis and the contraceptive pill.
        Br Med J. 1971; 3: 27-28
        • Kilpatrick ZM
        • Silverman JF
        • Betancourt E
        • Farman J
        • Lawson JP
        Vascular occlusion of the colon and oral contraceptives.
        N Engl J Med. 1968; 278: 438-440
      4. Anonymous: Small bowel ischemia and the contraceptive pill. Br Med J 1978; 1: 4.

        • Hurwitz RL
        • Martin AJ
        • Grossman BE
        • Waddell WR
        Oral contraceptives and gastrointestinal disorders.
        Ann Surg. 1970; 172: 892-896
        • Ritschard TH
        • Filippini L
        Entzündliche Darmerkrankungen and hormonelle Antikonzeption.
        Schweiz med Wschr. 1986; 116: 594-597
        • Grimmer SFM
        • Back DJ
        • Orme ML'E
        • Cowie A
        • Gilmore I
        • Tjia J
        The bioavailability of ethinyloestradiol and levonorgestrel in patients with an ileostomy.
        Contraception. 1986; 33: 51-59
        • Nilsson LO
        • Victor A
        • Kral JG
        • Johansson EDB
        • Kock NG
        Absorption of an oral contraceptive gestagen in ulcerative colitis before and after proctocolectomy and construction of a continent ileostomy.
        Contraception. 1985; 31: 195-204
        • Philipson BM
        • Brandberg A
        • Jagenburg R
        • Kock NG
        • Lager I
        • Ahren C
        Mucosal morphology, bacteriology, and absorption in intraabdominal ileostomy reservoir.
        Scand J Gastroenterol. 1975; 10: 145-153
        • Kay RM
        • Cohen Z
        • Siu KP
        • Petrunka CN
        • Strasberg SM
        Ileal excretion and bacterial modification of bile acids and cholesterol in patients with continent ileostomy.
        Gut. 1979; 21: 128-132
        • Victor A
        • Odlind V
        • Kral JG
        Oral contraceptive absorption and sex hormone binding globulins in obese women: effects of jejunoileal bypass.
        Gastroenterol Clin North Am. 1987; 16: 483-491