Drospirenone-Related Venous Thromboembolism Risk: “The Rest of the Story” *

Discussion

Unplanned pregnancy remains a major public health issue in the United States and worldwide. Nearly 50% of pregnancies are estimated to be unplanned. ¹ Therefore, recent trends in contraceptive technologies have focused on acceptability and compliance dependence of various methods, as well as their safety.

The safety of DSP versus LNG in terms of venous thromboembolism (VTE) risk was recently reviewed looking at the risk of all users and new users. ² The odds ratio for VTE adjusted for age, duration of use, and year are 2.4 (95% CI 1.7–3.4) and 2.7 (95% CI 1.7–4.1) in DSP and LNG users respectively. However, the absolute risk is 12.5/100,000 woman years and 30.8/100,000 woman years, still much lower than the VTE risk associated with normal pregnancy 10/10,000 and the postpartum period 50/10,000. Further, the maternal mortality rate from any cause in the United States is 1.8/10,000 live births. ³ Nonetheless, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) reviewed and recommended that providers discuss the potentially increased risk of VTE with patients when prescribing OCs containing drosperinone. ⁴

While emphasizing that the absolute risk of VTE is low, the package insert found in drospirenone- containing OCs summarizes the findings of a study result reporting up to a threefold risk of VTE with DSP versus LNG. ^3,5 The package insert specifically advises women to talk to their health care provider about their individual risk. ⁵

When discussing risk and benefit of DSP containing OCs, it is important to evaluate individual risk in the context of potential benefit derived from DSP. DSP is an anti-androgenic progestin with efficacy in the treatment of physical and emotional premenstrual symptoms. When administered as a 24/4 regimen it achieves greater ovarian suppression than conventional 21/7 regimens containing DSP or other long-acting progestins. ⁶ It has been shown to be effective in the treatment of premenstrual mood disorder and acne. ⁷

Given that this patient misses pills, she is at risk for unplanned pregnancy. She asks about and certainly could consider a less compliance-dependent contraceptive method. These include the contraceptive ring or a long-acting reversible contraceptive (LARC) such as contraceptive injection or implant or intrauterine contraception. The decision depends on a number of factors including her reproductive plans, whether the patient wishes to experience regular withdrawal bleeds, and whether she is comfortable with oligomenorrhea, amenorrhea, or irregular bleeding because these are common symptoms associated with LARC. It is important to emphasize that the presence or absence of bleeding is not related to the efficacy of the LARC.

Once reassured that there is no significant underlying reason for irregular bleeding and that their contraception is still efficacious, many women can tolerate bleeding patterns other than monthly scheduled bleeding. Those who prefer less frequent bleeding may achieve this with an extended cycle or continuous combined contraceptive methods. If amenorrhea is acceptable and/or preferred, a contraceptive injection or the levonorgestrel intrauterine system could be offered. The latter along with the copper intrauterine device and the contraceptive implant provide highly efficacious contraception for months or years without the need for daily or even monthly dosing. When given a choice of contraceptive methods without cost as a consideration, (though these methods are cost effective as well), the Contraceptive Choice project reported two thirds of women chose intrauterine contraception or implant. ⁸

In this patient, the next best step is to screen for sexually transmitted infections, including chlamydia, gonorrhea, trichomonas, and Ureaplasma as these may cause irregular and postcoital bleeding. ⁹ It is unlikely that postcoital bleeding would be due to cervical dysplasia alone. However, this is yet another opportunity for discussion and if appropriate initiation of the human papilloma virus vaccine, which is recommended for males and females 9–26 years old. ¹⁰ Additionally her intermittent and irregular bleeding may be related to missed pills. If it is not related to a sexually transmitted disease and is limited to late-cycle breakthrough bleeding, a triphasic formulation may also be helpful.

Another counseling point worthy of discussion would be to review the availability, efficacy, and safety of emergency contraception especially in the setting of inconsistent contraceptive use. ¹¹

The correct answer is B: Obtain cultures for sexually transmitted infections

Answer A is incorrect because an endocervical polyp was not visualized.

Answers C and E, which proceed to treatment prior to excluding infection in a young sexually active woman having unprotected intercourse, would not be the appropriate next step.

Answer D is incorrect because an abnormal cervical cytology generally precedes colposcopy. We have no information about a current cervical cytology, therefore it would be appropriate to perform this now.

Answer B takes the next logical step in ruling out an infectious etiology for the bleeding. Chlamydia, gonorrhea, Ureaplasma, and trichomonas may all be associated with irregular bleeding and postcoital bleeding. After this step, counseling and consideration of either the same OC, an alternative OC, or alternative contraception is appropriate.