Clinical Review

OCs, breakthrough bleeding, and patients’ need to know

OBG Manag. 2007 April;19(4):49-63

Patricia A. Lohr, MD

Managing expectations is as important as adjusting formulations

PDF Download

IN THIS ARTICLE

Four causes of bleeding
Type of progestin affects bleeding
How patients contribute to the problem

References

1. Pratt WF, Bachrach CA. What do women use when they stop using the pill? Fam Plann Perspect. 1987;19:257-266.

2. Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: A prospective evaluation of frequency and reasons. Am J Obstet Gynecol. 1998;179:577-582.

3. Thorneycroft IH. Cycle control with oral contraceptives: A review of the literature. Am J Obstet Gynecol. 1999;180:S280-S287.

4. Speroff L, Darney PD. A Clinical Guide for Contraception. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001.

5. Rosenberg MJ, Waugh MS, Burnhill MS. Compliance, counseling, and satisfaction with oral contraceptives: A prospective evaluation. Fam Plann Perspect. 1998;30:89-92-104.

6. Belsey EM, Machin D, d’Arcangues C. The analysis of vaginal bleeding patterns induced by fertility regulating methods. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1986;34:253-260.

7. ESHRE Capri Workshop Group. Ovarian and endometrial function during hormonal contraception. Hum Reprod. 2001;16:1527-1535.

8. Kaunitz AM. Oral contraceptive estrogen dose considerations. Contraception. 1998;58(Suppl):15S-21S.

9. Preston SN. A report of a collaborative dose-response clinical study using decreasing doses of combination oral contraceptives. Contraception. 1972;6:17-35.

10. Akerlund M, Rode A, Westergaard J. Comparative profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150 mcg desogestrel and either 30 mcg or 20 mcg ethinyl oestradiol. Br J Obstet Gynaecol. 1993;100:832-838.

11. Gallo MF, Nanda K, Grimes DA, Schulz KF. Twenty micrograms vs >20 microg estrogen oral contraceptives for contraception: a systematic review of randomized controlled trials. Contraception. 2005;71:162-169.

12. Endrikat J, Hite R, Bannemerschult R, Gerlinger C, Schmidt W. Multicenter, comparative study of cycle control, efficacy and tolerability of two low-dose oral contraceptives containing 20 μg ethinyl estradiol/100 μg levonorgestrel and 20 μg ethinyl estradiol/50 μg noresthisterone. Contraception. 2001;64:3-10.

13. Hickey M, Fraser I, Dwarte D, Graham S. Endometrial vasculature in Norplant users: preliminary results from a hysteroscopic study. Hum Reprod. 1996;11(Suppl 2):35-44.

14. Smith SK. Steroids and endometrial breakthrough bleeding: future directions for research. Hum Reprod. 2000;15(Suppl 3):197-202.

15. Song JY, Markham R, Russell P, Wong T, Young L, Fraser IS. The effect of high-dose medium- and long-term progestogen exposure on endometrial vessels. Hum Reprod. 1995;10:797-800.

16. Hickey M, Dwarte D, Fraser IS. Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding. Hum Reprod. 2000;15:1509-1514.

17. Rodriguez-Manzaneque JC, Graubert M, Iruela-Arispe ML. Endothelial cell dysfunction following prolonged activation of progesterone receptor. Hum Reprod. 2000;15(Suppl 3):39-47.

18. Lockwood CJ, Runic R, Wan L, Krikun G, Demopolous R, Schatz F. The role of tissue factor in regulating endometrial haemostsis: Implications for progestin-only contraception. Hum Reprod. 2000;15(Suppl 3):144-151.

19. Clark DA, Wang S, Rogers P, Vince G, Affandi B. Endometrial lymphoid cells in abnormal uterine bleeding due to levonorgestrel (Norplant). Hum Reprod. 1996;11:1438-1444.

20. Hatcher RA, Trussell J, Stewart FH. Contraceptive Technology. 18th ed. New York: Ardent Media; 2004.

21. Saleh WA, Burkman RT, Zacur HA, Kimball AW, Kwieterovich P, Bell W. A randomized trial of three oral contraceptives: comparison of bleeding patterns by contraceptive types and steroid levels. Am J Obstet Gynecol. 1993;168:1740-1747.

22. Lawson JS, Yuliano SE, Pasquale SA, Osterman JJ. Optimum dosing of an oral contraceptive. A report from the study of seven combinations of norgestimate and ethinyl estradiol. Am J Obstet Gynecol. 1979;134:315-320.

23. Stenchever MA, Ling FW. Comprehensive Gynecology. 4th ed. St Louis, Mo: Mosby; 2001.

24. Maitra N, Kulier R, Bloemenkamp KW, Helmerhorst FM, Gulmezoglu AM. Progestogens in combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2004;(3):CD004861.-

25. Corson SL. Efficacy and clinical profile of a new oral contraceptive containing norgestimate. US clinical trials. Acta Obstet Gynecol Scand Suppl. 1990;152:25-31.

26. Anderson FD, Hait H. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception. 2003;68:89-96.

27. Miller L, Hughes JP. Continuous combined oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial. Obstet Gynecol. 2003;101:653-661.

28. Upton GV. The phasic approach to oral contraception: the triphasic concept and its clinical application. Int J Fertil Steril. 1983;28:121-140.

29. Mishell DR, Jr. Oral contraception: past, present, and future perspectives. Int J Fertil Steril. 1991;37(Suppl):s7-s18.

30. Van Vliet H, Grimes D, Helmerhorst F, Schulz K. Biphasic versus triphasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006;3:CD003283.-

31. Van Vliet H, Grimes D, Helmerhorst F, Schulz K. Biphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006;3:CD002032.-

32. Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: Risk indicators for poor pill taking and discontinuation. Contraception. 1995;51:283-288.

33. Potter L, Oakley D, de Leon-Wong E, Canamar R. Measuring compliance among oral contraceptive users. Fam Plann Perspect. 1996;28:154-158.

34. Stubblefield PG. Menstrual impact of contraception. Am J Obstet Gynecol. 1994;170:513-1522.

35. Talwar PP, Dingfelder JR, Ravenholt RT. Increased risk of breakthrough bleeding when one oral-contraceptive tablet is missed. N Engl J Med. 1977;296:1236-1237.

36. Wallach M, Grimes DA. Modern Oral Contraception: Updates from the Contraceptive Report. Totowa, NJ: Emron; 2000.

37. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John’s Wort with oral contraceptives: effects on the pharmacokinectics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005;71:402-408.

38. Baron JA, Greenberg ER. Cigarette smoking and estrogen related disease in women. In: Smoking and Reproductive Health, ed. Rosenberg MJ. Boston: PSG; .1987:149–160.

39. Jusko WJ. Influence of cigarette smoking on drug metabolism in man. Drug Metab Rev. 1979;9:221-236.

40. Basu J, Mikhail MS, Palan PR, Thysen B, Bloch E, Romney SL. Endogenous estradiol and progesterone concentrations in smokers on oral contraceptives. Gynecol Obstet Invest. 1992;33:224-227.

41. Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit FFPRHC Guidance (October 2003): First prescription of combined oral contraception. J Fam Plann Reprod Health Care. 2003;29:209-222.

42. Sparrow MJ. Pregnancies in reliable pill takers. NZ Med J. 1989;102:575-577.

43. Kanarkowski R, Tornatore KM, D’Ambrosio R, Gardner MJ, Jusko WJ. Pharmacokinetics of single and multiple doses of ethinyl estradiol and levonorgestrel in relation to smoking. Clin Pharmacol Ther. 1988;43:23-31.

44. Rosenberg MJ, Waugh MS, Stevens CM. Smoking and cycle control among oral contraceptive users. Am J Obstet Gynecol. 1996;174:628-632.

45. Vessey MP, Villard-Makintosh L, Jacobs HS. Anti-estrogenic effect of cigarette smoking. N Engl J Med. 1987;317:769-770.

46. Darney PD. OC practice guidelines: minimizing side effects. Int J Fertil Womens Med. 1997;42(suppl 1):158-169.

47. Krettek JE, Arkin SI, Chaisilwattana P, Monif GR. Chlamydia trachomatis in patients who used oral contraceptives and had intermenstrual spotting. Obstet Gynecol. 1993;81:728-731.

48. Gaudet LM, Kives S, Hahn PM, Reid RL. What women believe about oral contraceptives and the effect of counseling. Contraception. 2004;69:31-36.

49. Belsey EM. The association between vaginal bleeding patterns and reasons for discontinuation of contraceptive use. Contraception. 1988;38:207-225.

50. Jung-Hoffman C, Kuhl H. Intra- and interindividual variations in contraceptive steroid levels during 12 treatment cycles: no relation to irregular bleedings. Contraception. 1990;(42):423-438.

51. Rosenberg MJ, Waugh MS, Long S. Unintended pregnancies and use, misuse and discontinuation of oral contraceptives. J Reprod Med. 1995;40:355-360.

Fast Track

Low-level estrogen in combination with a progestin is excellent for contraception but may not sustain endometrial integrity in some women

Regardless of the type of progestin or amount of estrogen, breakthrough bleeding generally decreases with successive cycles

Though a patient may experience more breakthrough bleeding on an extended-cycle regimen, the number of planned and unplanned bleeding days may still decrease

Skipping pills, smoking, and taking certain medications and herbal supplements are common causes of breakthrough bleeding

Tell the patient that bleeding is common, and usually declines after 3 or 4 months

An OC user who still has bleeding after 3 or 4 cycles should have other causes ruled out with a pregnancy test, Pap smear, endometrial biopsy, or other test

Recommendations for practice

Lack of adherence is a common cause of breakthrough bleeding. Focus counseling on ensuring that patients understand and can follow pill-taking instructions before switching pills or contraceptive method
If breakthrough bleeding extends beyond 4 cycles and a woman wishes to continue using an oral contraceptive, consider switching to a pill with a higher ethinyl estradiol:progestin ratio, either by increasing the estradiol dose or by decreasing the relative progestin dose
Breakthrough bleeding may be due to progestin type; switching from an estrane to a gonane may reduce it
Women who have breakthrough bleeding after having well-controlled menstrual cycles on an oral contraceptive should be assessed for causes not related to their birth control pills, such as pregnancy, cervicitis, smoking, or interactions with medications.

In 1982, more than 20% of women surveyed in a nationally representative sample had discontinued oral contraceptives (OCs) on their own or at the recommendation of their physician due to bleeding or spotting.¹ Sadly, the percentage today has not decreased much.

Understandable concern, embarrassment, and annoyance lead these women to abandon OCs.^1,2 What they often don’t know, though, is that breakthrough bleeding generally is greatest in the first 3 to 4 months after starting OCs,³ and it steadily declines and stabilizes by the end of the fourth cycle.⁴ Timely counsel could enable many of these women to cope with the bleeding and stick with an effective contraceptive method. Additional incentives are noncontraceptive benefits of OCs: improved menstrual regularity and decreased menstrual blood loss, dysmenorrhea, and risk of ovarian and endometrial cancer.

Women who discontinue OCs on their own switch to less effective methods of birth control or use no method.^1,2 Consequences may be unexpected pregnancies and an increased abortion rate.⁵ With patients who are using an OC, it would be appropriate to ask periodically whether they are satisfied with OC use.

In this review, we discuss the mechanisms and management of breakthrough bleeding in women taking OCs, and provide tips for counseling that may help decrease the risk of discontinuation due to menstrual abnormalities in the initial months of use.

Breakthrough bleeding in this review refers to either unplanned spotting or bleeding, regardless of requirement for protection—unless defined otherwise by a specific study under discussion.

How is irregular bleeding defined?

For the purpose of performing studies, unplanned bleeding is classified by the World Health Organization into 2 categories:

breakthrough bleeding, which requires sanitary protection, and
spotting, which does not require sanitary protection.⁶ Despite this formal classification, trials have varied in their terminology and method of recording menstrual irregularities, making comparisons between studies difficult. In addition, there is wide variation among women in tolerance to bleeding abnormalities, perceptions of heavy vs light bleeding, as well as the need for protection.³

Nevertheless, menstrual abnormalities are consistently cited as a common reason for discontinuing OCs. A prospective US study of 1,657 women performed in the 1990s reported that 37% of OC users had stopped taking OCs by 6 months after starting a new prescription because of side effects.² Irregular bleeding was the most common cause, cited by 12% of women, followed by nausea, weight gain, and mood changes, which ranged from 5% to 7%.

Four causes of bleeding

Breakthrough bleeding may be due to any the following variables:

physiologic effects of OCs on the endometrium,
OC-related parameters, including dose, formulation, and regimen,
patient behavior (including compliance, using concomitant medications, and smoking),
benign or malignant pathology.

OCs and the endometrium: Estrogen-progestin balance significant

Progestin and estrogen in combination OCs have profound effects on the endometrium that, although not contributing to contraception, do lead to a predictable pattern of bleeding or such problems as breakthrough bleeding or lack of withdrawal bleed.

Normally, estrogen causes the endometrium to proliferate. Progesterone stabilizes the growing uterine lining. Since the introduction of OCs in 1960, the trend in formulation has been to use the least amount of hormone necessary to inhibit ovulation. Given that the progestin is primarily responsible for the contraceptive efficacy of OCs, the risk of pregnancy is not altered with decreases in the estrogen component. However, significantly lowering the estrogen in OCs may account for breakthrough bleeding. Unplanned bleeding, though, is not dependent solely on the estrogen component, as variations in the progestin can contribute to breakthrough bleeding.⁷