Since both methods provide constant low blood levels of EE, it was hoped that this might reduce risk for thrombosis. The FDA took the unusual step of issuing a “black box warning” for the EE/norelgestromin patch after several thrombosis cases were reported, and a small study of pharmacodynamics was interpreted as showing higher mean EE blood levels for the patch than with the oral route of administration. A small crossover study found increased activated protein C (APC) resistance when women were changed from a 30 μg EE/150 μg desogestrel pill to either the patch or the EE/etonogestrel ring. This was interpreted as prothrombotic (215). In another study, women on a variety of OCs had baseline measurement of APC resistance, and protein S. The patients were then switched either to the patch or to the ring. Those moving to the patch had changes in laboratory parameters that could be interpreted as prothrombotic, while those moved to the ring showed an improvement in the same studies, theoretically reducing the risk of clotting (216).
Three databased epidemiologic studies looked at thrombosis in patch users compared to oral contraception. The first found no difference, but two subsequent studies did find risk. One study found an overall doubling of the risk of deep vein thrombosis when patch users were compared to users of an OC containing 30 μg EE/150 μg levonorgestrel, but the risk estimate was of borderline statistical significance and disappeared when the analysis was restricted to women aged 39 or less (217). After publication of this study the FDA issued a new document for consumers suggesting that women concerned about thrombosis and considering the patch discuss the issue with their physicians (218).
No similar FDA warnings were issued about the ring. There are two case reports in the world literature of venous thrombosis with the ring. Both were women in their 30s who sustained cerebral venous thrombosis (219,220). The authors of the fist report note that several other thrombosis cases in women using the ring were reported to Health Canada (220). It is best to assume that the ring has the same risk for thrombosis as the other combination hormonal contraceptives and to counsel women about risk in the same way.
DMPA, a suspension of microcrystals of a synthetic progestin, was approved for contraception in 1992. A single 150-mg intramuscular dose will suppress ovulation in most women for 14 weeks or longer (221). The regimen of 150 mg every 3 months is highly effective, producing pregnancy rates of about 0.3 per 100 women per year. Probably because of the high blood levels of the progestin, efficacy appears not to be reduced by administration of other drugs and is not dependent on the patient’s weight. Women treated with DMPA experience disruption
Figure 10.8 Bleeding pattern and duration of use of depomedroxyprogesterone acetate (DMPA): percentage of women who have bleeding, spotting, or amenorrhea while taking
DMPA 150 mg every 3 months. (From Schwallie PC, Assenzo JR. Contraceptive use-efficacy study utilizing medroxyprogesterone acetate administered as an intramuscular injection once every 90 days. Fertil Steril 1973;24:331–339, with permission.) of the menstrual cycle and have initial spotting and bleeding at irregular intervals. Eventually, total amenorrhea develops in most women who take DMPA; with continued administration, amenorrhea develops in 50% of women by 1 year and in 80% by 3 years (Fig. 10.8).