Clinical Review

Sizing up a new generation of OCs

OBG Manag. 2002 August;14(8):34-44

References

1. Schleussner E, Brueckner J, Brautigan J, Michels W. Influence of two low-dose oral contraceptives on pulsatile gonadotropin secretion. Gynecol Endocrinol. 2001;15:259-264.

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4. Poindexter A. The emerging use of the 20-microg contraceptive. Fertil Steril. 2001;75(3):457-465.

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6. The reduction in risk of ovarian cancer associated with oral contraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med. 1987;316:650-655.

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

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A 40% reduction in the risk of ovarian malignancy has been reported with OC therapy, as has a decrease in borderline epithelial ovarian cancer. Most data concern preparations containing 30 μg or more of EE₂.⁵ The effect appears to accrue within several cycles of OCs and last 10 to 15 years after the pills are discontinued.⁶ In a study involving 282 women taking OCs containing 35 μg or less of EE₂, Royar and colleagues noted a 52% reduction in ovarian cancer risk in women who had ever used OCs.⁷

A 50% reduction in the risk of endometrial adenocarcinoma also has been reported with OC therapy.⁸ This risk reduction appears to persist for up to 15 years after discontinuation of OCs. Other noncontraceptive benefits are included in TABLE 2.

Ultra-low-dose pills also have been associated with a lower incidence of dysmenorrhea. However, no randomized clinical trials (RCTs) have shown this benefit to be greater than placebo. Data are limited regarding their effects on cancers, as well as benign gynecologic conditions such as fibrocystic breast disease, ovarian cysts, chlamydial and gonococcal infections, and pelvic inflammatory disease (PID).

A common misconception is that OC therapy will inhibit height if initiated during adolescence. However, once menarche occurs, endogenous estrogen production stimulates epiphyseal closure. It is this—and not OCs per se—that determines height.

During perimenopause, low-dose OCs have a number of benefits, such as the reduced risk of ovarian and endometrial cancer mentioned earlier, a lower incidence of acute PID, and maintenance of bone mineral density (BMD). Even the 20-μg pill has been shown to prevent bone turnover.⁴ In a metaanalysis of 13 studies, 9 showed OCs to have a positive effect on BMD, and none noted a decrease in BMD.¹⁰ This information is important because 20 million individuals are affected by osteoporosis and 1 million annually experience BMD-related fractures. Consequently, barring contraindications, OCs are a reasonable option for perimenopausal women.

In menopausal patients, OCs have been shown to help maintain BMD by preventing the acceleration of resorption that accompanies aging.⁹

TABLE 2

Noncontraceptive benefits of OC therapy

MENSTRUAL IMPROVEMENTS
Regularity
Improvement in dysmenorrhea
Reduced flow
Restoration of regular menses in oligoanovulatory women
REDUCED INCIDENCE OF BENIGN CONDITIONS
Fibrocystic breast disease
Pelvic inflammatory disease
Ectopic pregnancy
Rheumatoid arthritis
REDUCED INCIDENCE OF GYNECOLOGIC MALIGNANCIES
Ovarian malignancy
Epithelial ovarian cancer
Endometrial adenocarcinoma
INCREASED BONE MINERAL DENSITY

Adverse effects

Thromboembolic disease and cancer often are mentioned as 2 of the gravest potential effects of OC use. Low-dose OCs (those containing less than 35 μg EE₂) are associated with a lower risk of thromboembolism than higher-dose formulations.¹¹ Thus, the incidence of thromboembolic phenomena appears to be related to the dose of estrogen. However, ultra-low-dose OCs do not appear to be associated with any significant difference in the incidence of venous thromboembolism (VTE). Additional research is needed.

Stroke. Epidemiologic studies regarding smoking and OC use in women over 35 have questioned whether the risk of arterial events is greater with formulations containing more than 50 μg EE₂. The evidence is conflicting regarding those containing less than 50 μg EE₂, with one large study finding a slightly increased risk of stroke with low-dose pills (an increase of approximately 2 per 100,000)^12,13 and another finding a slight increase in the risk of thromboembolic stroke.¹⁴ Two similar trials found no increased risk of ischemic or hemorrhagic stroke among women taking a low-dose OC, although there was a possible association between hemorrhagic stroke and the use of OCs containing norgestrel.^15,16 A meta-analysis concluded that a healthy nonsmoker’s risk of stroke would increase with low-dose OC use from 4.4 to 8.5 per 100,000.¹⁷ That is, among this population, it would take 24,000 women on OCs to cause 1 additional ischemic stroke per year.

Cancer. The overall incidence of breast cancer does not appear to rise with OC therapy. Although several studies suggest an increased risk with recent or current OC use, detection bias likely accounts for these findings.¹⁸ Women who had taken OCs and then discontinued them for 10 years or more had no increased risk of breast cancer, although a small but significant increase in the relative risk (RR, 1.24) associated with current OC use has been reported.¹⁹ The increased risk was found primarily in women with localized breast disease. Interestingly, the incidence of metastatic disease was lower in current OC users, possibly a reflection of earlier diagnosis.¹⁹

A possible link between OCs and cervical cancer continues to be debated. Factors such as smoking, early age at first sexual encounter, and multiple sexual partners may predispose an individual on OCs to cervical cancer.⁸ I prescribe OCs to women with these risk factors only after obtaining informed consent.