A review of post-marketing safety and surveillance data for oral contraceptives containing norgestimate and ethinyl estradiol

Recent publications have suggested a twofold increased risk of venous thromboembolic (VTE) disease with desogestrel-and gestodene-containing oral contraceptives (OCs) compared with those containing other progestins. These studies did not contain enough patients using norgestimate-containing OCs to make any statistically valid assessment. To address this issue, an analysis was performed of the number of spontaneous reports of deep vein thrombosis, pulmonary emboli strokes, and myocardial infarctions reported for norgestimate-containing OCs worldwide during the period 1986-1995. A unique opportunity was afforded by the fact that in North America (U.S., Canada), norgestimate-containing OCs were introduced at almost the same time as desogestrel-containing OCs. Additionally, the products were characterized in a similar manner (i.e., combination OCs containing progestins with low intrinsic androgenicity). The formulations were introduced by the same sales force to the same physician audience. Thus, the comparative data generated from this geographic area are not subject to prescribing bias or healthy-user effect. Although an absolute ratio of events cannot be determined, the data provide useful information about the relative rates of events for norgestimate-and desogestrel-containing products. In North America, with more than 47 million cycles of norgestimate-containing OCs distributed, 13 cardiovascular events were reported during the period. Forty-three cardiovascular events were reported for desogestrel-containing OCs with 36 million cycles distributed. These data have been reported to the European Union's Committee for Proprietary Medicinal Products and to the U.S. Food and Drug Administration. While the data do not demonstrate a causal relationship between desogestrel-containing OCs and an increased risk of venous thromboembolic disease vs. OCs containing other progestins, they do fully support the favorable cardiovascular safety profile of norgestimate-containing OCs.