Newer forms of progesterone in combination hormonal contraceptives carry higher venous thromboembolic (VTE) risk than older forms, a population-based study affirmed.
Women on the pill with the older, levonorgestrel version were at three times the risk of VTE as those not on any hormonal contraception, said Ojvind Lidegaard, MD, of Rigshospitalet at the University of Copenhagen, Denmark, and colleagues.
But oral contraceptives containing desogestrel, gestodene, drospirenone, or cyproterone boosted the risk six to seven times over that of non-users, the group reported online in BMJ.
The number needed to treat with levonorgestrel instead of the other progesterone forms to prevent one VTE in one year was about 2,000.
These findings from national registry data in Denmark from 2001 through 2009 — after the launch of the newest synthetic progesterone, drospirenone, in that country — largely matched results of their earlier analysis from 1995 through 2005.
Other studies over the decades also have found almost universally elevated VTE risk with hormonal contraception, with the estrogen and progestogen (synthetic progesterone) components both appearing to play a role.
But the absolute risks remain small, at about 10 in 10,000, for current users of even the newer pills, noted Philip C. Hannaford, MD, of the University of Aberdeen, Scotland, in an accompanying editorial.
The risks appear real and may lead many clinicians to prescribe a combined oral contraceptive with levonorgestrel whenever possible, he wrote.
“It is crucial, however, not to exaggerate the risk — oral contraceptives are remarkably safe and may confer important long term benefits in relation to cancer and mortality,” Hannaford cautioned.
The updated analysis included more than 1.2 million non-pregnant 15- to 49-year-old women in Denmark without a history of thrombotic disease. Data came from national vital status, inpatient, cause of death, and pharmacy registries.
From 2001 to 2009, 4,307 first-ever VTEs occurred in this cohort. Most were deep vein thrombosis only (63.6%) or pulmonary embolism with or without deep vein thrombosis (26.2%).
Compared with women not taking hormonal contraception, confirmed venous thromboembolism was elevated for users of oral contraceptives containing 30 to 40 ?g ethinylestradiol plus the following:
- Levonorgestrel, with a relative risk of 2.9 (95% confidence interval 2.2 to 3.8)
- Desogestrel, with a relative risk of 6.6 (95% CI 5.6 to 7.8)
- Gestodene, with a relative risk of 6.2 (95% CI 5.6 to 7.0)
- Drospirenone, with a relative risk of 6.4 (95% CI 5.4 to 7.5)
With levonorgestrel-containing pills as the comparator, rate ratios of confirmed venous thromboembolism adjusted for length of use were:
- 2.2 with desogestrel (95% CI 1.7 to 3.0)
- 2.1 with gestodene (95% CI 1.6 to 2.8)
- 2.1 with drospirenone (95% CI 1.6 to 2.8)
Progestogen-only pills (low-dose norethisterone or desogestrel alone) or hormone-releasing intrauterine devices didn’t have any impact on VTE risk compared with non-users.
Lower estrogen doses were associated with modestly lower VTE risk for oral contraceptives with norethisterone, levonorgestrel, desogestrel, or gestodene but not with drospirenone, the investigators reported.
Phasic combined oral contraceptives with levonorgestrel slightly, but not significantly, increased VTE risk compared with levonorgestrel plus 30-?g of ethinylestradiol (relative risk 2.28 versus 2.19), which the researchers suggested “could be due to the slightly higher total dose of estrogen in the former group.”
The results appeared stable through the study period.
The researchers noted that their results wouldn’t have been affected by recall bias or “left censoring,” but lack of data on body mass index and family disposition may have contributed to some residual confounding.
The analysis was funded by Bayer Schering Pharma, which gave the funds to Rigshospitalet.
Lidegaard reported having financial links with Bayer Pharma Denmark and Novo Nordisk, and planning to serve as an expert witness for plaintiffs in a U.S. legal case.
Hannaford reported that his academic department has received payments from Schering Plough and Wyeth Pharmaceutical for his lectures and advisory board work.
Article source: http://www.medpagetoday.com/Cardiology/VenousThrombosis/29272