Nondaily hormonal contraceptives: Establishing a fit between product characteristics and patient preferences

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Applied Evidence

Nondaily hormonal contraceptives: Establishing a fit between product characteristics and patient preferences

J Fam Pract. 2004 November;53(11):904-913

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References

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23. Hubacher D, Goco N, Gonzalez B, Taylor D. Factors affecting continuation rates of DMPA. Contraception 1999;60:345-351.

24. Backman T, Huhtala S, Luoto R, Tuominen J, Rauramo I, Koskenvuo M. Advance information improves user satisfaction with the levonorgestrel intrauterine system. Obstet Gynecol 2002;99:608-613.

25. den Tonkelaar I, Oddens BJ. Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use. Contraception 1999;59:357-362.

26. Danli S, Qingxiang S, Guowei S. A multicentered clinical trial of the long-acting injectable contraceptive Depo Provera in Chinese women. Contraception 2000;62:15-18.

27. Moore LL, Valuck R, McDougall C, Fink W. A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives. Contraception 1995;52:215-219.

28. Espey E, Steinhart J, Ogburn T, Qualls C. Depo-provera associated with weight gain in Navajo women. Contraception 2000;62:55-58.

29. Risser WL, Gefter LR, Barratt MS, Risser JM. Weight change in adolescents who used hormonal contraception. J Adolesc Health 1999;24:433-436.

30. Taneepanichskul S, Reinprayoon D, Khaosadad P. Comparative study of weight change between long-term DMPA and IUD acceptors. Contraception 1998;58:149-151.

31. Pelkman CL, Chow M, Heinbach RA, Rolls BJ. Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women. Am J Clin Nutr 2001;73:19-26.

32. Dieben TO, Roumen FJ, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 2002;100:585-593.

33. Dubuisson JB, Mugnier E. Acceptability of the levonorgestrel-releasing intrauterine system after discontinuation of previous contraception: results of a French clinical study in women aged 35 to 45 years. Contraception 2002;66:121-128.

34. Ronnerdag M, Odlind V. Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use. Acta Obstet Gynecol Scand 1999;78:716-721.

35. Gupta N, O’Brien R, Jacobsen LJ, et al. Mood changes in adolescents using depot-medroxyprogesterone acetate for contraception: a prospective study. J Pediatr Adolesc Gynecol 2001;14:71-6.

36. Westhoff C, Truman C, Kalmuss D, et al. Depressive symptoms and Depo-Provera. Contraception 1998;57:237-240.

37. Civic D, Scholes D, Ichikawa L, et al. Depressive symptoms in users and non-users of depot medroxyproges-terone acetate. Contraception 2000;61:385-390.

38. Smallwood GH, Meador ML, Lenihan JP, Shangold GA, Fisher AC, Creasy GW. Efficacy and safety of a transder-mal contraceptive system. Obstet Gynecol 2001;98:799-805.

39. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1996;347:1713-1727.

40. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB. Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies. JAMA 1995;273:799-804.

41. The Who Collaborative Study of Neoplasia and Steroid Contraceptives. Endometrial cancer and combined oral contraceptives. Int J Epidemiol 1988;17:263-269.

42. Ness RB, Grisso JA, Klapper J, et al. Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and Reproductions. Am J Epidemiol 2000;152:233-241.

43. Stanford JL, Thomas DB. Depot-medroxyprogesterone acetate (DMPA) and risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Int J Cancer 1991;49:191-195.

44. Parazzini F, La Vecchia C, Negri E, Maggi R. Oral contraceptive use and invasive cervical cancer. Int J Epidemiol 1990;19:259-263.

45. Kjaer SK, Engholm G, Dahl C, Bock JE, Lynge E, Jensen OM. Case-control study of risk factors for cervical squamous cell neoplasia in Denmark. Role of oral contraceptive use. Cancer Causes Control 1993;4:513-519.

46. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Depot-medroxyprogesterone acetate and risk of invasive squamous cell cervical cancer.The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Contraception 1992;45:299-312.

47. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995;346:1575-1582.

48. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1997;349:1202-1209.

49. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1996;348:505-510.

50. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Contraception 1998;57:315-324.

51. Prior JC, Kirkland SA, Joseph L, et al. Oral contraceptive use and bone mineral density in premenopausal women: cross-sectional, population-based data from the Canadian Multicentre Osteoporosis Study. CMAJ 2001;165:1023-1029.

52. Banks E, Berrington A, Casabonne D. Overview of the relationship between use of progestogen-only contraceptives and bone mineral density. BJOG 2001;108:1214-21.

53. Tang OS, Tang G, Yip PS, Li B. Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study. Contraception 2000;62:161-164.

54. Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM, Cundy T, Reid IR. The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women. Clin Endocrinol (Oxf) 1998;49:615-618.

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57. Sivin I, el Mahgoub S, McCarthy T, et al. Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T 380Ag intrauterine devices: a five-year randomized study. Contraception 1990;42:361-378.

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Women can also be advised that neither DMPA-IM nor combined oral contraceptives appear to significantly increase their risk of gynecologic cancers ( Table 2 ). In fact, as previously discussed, these contraceptives decrease the risk of endometrial cancer,^8,41 an effect that is particularly strong for DMPA-IM (an 80% reduction in risk for ever-users, which appeared to last for at least 8 years following cessation of use).⁸ Combined oral contraceptives are also associated with an approximately 50% reduction in risk of ovarian cancer.⁴² While there is no evidence that DMPA-IM reduces the risk of ovarian cancers, it does not appear to be associated with a significant increase in risk (RR=1.07; 95% CI, 0.6–1.8).⁴³

Because of confounding factors such as smoking, risk factors for sexually transmitted disease, and screening detection bias, it has been difficult to firmly establish the relationship between contraceptive use and cervical cancer. However, several studies suggest the use of combined oral contraceptives, particularly for longer durations, slightly increases the risk of invasive cervical cancer.^44,45 In contrast, the risk of invasive cervical cancer does not appear to increase in users of DMPA-IM, and no consistent pattern of risk with either duration of use or other time-related factors has been observed.⁴⁶

Cardiovascular risks

DMPA-IM. Only DMPA-IM and combined oral contraceptives have been the subject of large-scale epidemiological investigations to assess the risk of cardiovascular disease, also summarized in Table 2 . Increased risk for venous thromboembolism (VTE) is related to the dose of estrogen in combined oral contraceptives. While currently available low-dose combined oral contraceptives (<50 μg estrogen) confer less risk than the higher-dose preparations of the past, they still confer a 3- to 4-fold higher risk of VTE than that experienced by nonusers.⁴⁷ The risk of VTE conferred by DMPA-IM is less than half that of combined oral contraceptives.

Users of low-dose combined oral contraceptives are also at increased risk of acute myocardial infarction compared with nonusers, though this risk reflects the frequent coexistence of other cardiovascular risk factors.⁴⁸ In fact, acute myocardial infarction is very rare among younger women (<35 years) who use combined oral contraceptives but who do not smoke, with an estimated attributable risk of approximately 3 per million woman-years. However, this attributable risk rises steeply to nearly 400 per million woman-years in older women (≥35 years) who smoke.⁴⁸

Risk of stroke is slightly increased among users of low-dose combined oral contraceptives, again primarily among women aged ≥35 years. Overall, the excess attributable risk estimate is approximately 2 per 100,000 woman-years, which decreases to 1 per 200,000 woman-years in women <35 years who use low-dose combined oral contraceptives.⁴⁹

In light of these risks, combined oral contraceptives are contraindicated for smokers ≥35 years, women with an increased risk or history of thromboembolism, and women with cerebrovascular or coronary artery disease.

Epidemiologic data from the WHO found no association between DMPA-IM use and an increased risk of any type of stroke or myocardial infarction (MI) ( Table 2 ).⁵⁰ Although there was a slight increase in the risk of VTE compared with nonusers, this was not considered statistically significant (odds ratio [OR]=2.19; 95% CI, 0.66–7.26).⁵⁰ In addition, compared with nonusers, DMPA-IM users did not exhibit increased combined cardiovascular disease risk (eg, stroke, VTE, myocardial infarction) (OR=1.02; 95% CI, 0.68–1.54).⁵⁰

L-IUS, NE-patch, and EE-ring. Long-term epidemiologic data for these products are unavailable due to the relatively short postmarket experience, which precludes assumptions of long-term cardiovascular safety. Likewise, no evidence is available regarding whether the safety profile for transdermal or vaginal administration differs from oral administration. Therefore, it is not known whether NE-patch or EE-ring confer different risks for venous thromboembolism than combined oral contraceptives. Warnings about thromboembolic disorders are similarly listed in the package inserts of these options.^6,7

Norelgestromin has been reported to have minimal androgenic activity, suggesting a possible lower risk of myocardial infarction than reported for more androgenically active progestin formulation.⁶ In contrast, etonogestrel, the biologically active metabolite of desogestrel, has been associated with a higher risk of venous thromboembolism than some second-generation combined oral contraceptives.⁷ For women with these risk factors, progestin-only methods, such as DMPA-IM or L-IUS, should be considered.

Bone mineral density

Historically, data have shown that oral contraceptives most often effect bone mineral density (BMD) positively in premenopausal women; retrospective studies of menopausal cohorts have shown positive effects from oral contraceptive use on BMD.⁵¹ However, a recent study of 524 pre-menopausal women found that women who used oral contraceptives, compared with those that did not, had significantly lower BMD values (adjusted differences of 2.4% at the femoral neck to 4.3% at the trochanter).⁵¹