Newer Birth Control Pills Again Tied to Blood Clots

NEW YORK (Reuters Health) - A study out Monday adds to evidence that a newer type of birth control pill may carry a higher risk of blood clots than older versions.

The study, of 330,000 Israeli women, found that those who used birth control pills with the hormone drospirenone -- found in brand-names like Yaz and Yasmin -- were more likely than other Pill users to develop blood clots called venous thromboembolisms.

Overall, there were just over six cases of venous blood clots per 10,000 Pill users each year in the study. But the risk was 43 percent to 65 percent higher with drospirenone-containing pills, compared with older, so-called second- and third-generation pills.

That increased risk would translate to about eight to 10 clots per 10,000 women per year.

Venous thromboembolisms most commonly form in the leg veins, but can travel to the lungs, where they cause a pulmonary embolism.

It has long been known that women on the Pill have a small, although higher-than-average risk of blood clots. But recent studies have suggested the risk may be relatively higher with pills containing drospirenone -- which include Yaz, Yasmin, Beyaz and Safyral, along with their generic equivalents.

It's important to remember that all oral contraceptives are associated with a risk of blood clots, said Dr. Susan Solymoss of McGill University in Montreal, who wrote an editorial published with the study in the Canadian Medical Association Journal.

She suggested that women who are considering their birth control options have an open discussion with their doctor on the risks and benefits of various contraceptives.

One key thing to consider, Solymoss said, is whether you have other risk factors for blood clots, like obesity or high blood pressure. It may make sense to avoid the Pill formulation with the highest clot risk.

Dr. Naomi Gronich, who led the new study, agreed.

Age is another factor, according to Gronich, of the Technion-Israel Institute of Technology in Haifa. In this study, she told Reuters Health in an email, blood clot risk gradually increased after the age of 25. (Women who are older than 35 and smoke -- another clot risk factor -- are already advised to avoid birth control pills in general.)

For any woman, avoiding birth control pills altogether is an option. However, Solymoss said, other contraceptives may not be as effective at preventing pregnancy. And pregnancy is a bigger risk for blood clots, she pointed out.

For every 10,000 women who become pregnant in a year, about 20 will develop venous blood clots. That compares with the rate of six women per 10,000 among Pill users overall and three in 10,000 women who are not on the pill.

Earlier, industry-funded studies of Yasmin, Yaz and related pills had indicated no elevated risk versus other Pill formulations. But several studies since 2009 have linked the newer contraceptives to relatively higher blood clot risks.

Just last week, the U.S. Food and Drug Administration (FDA) released the latest update of its own investigation of the question.

Based on records for more than 800,000 U.S. women who used the Pill between 2001 and 2007, the agency found that the risk of blood clots was higher among those on drospirenone-containing pills.

The FDA said the risk translated into about 10 cases of blood clots for every 10,000 women using the newer pills in a year -- compared with six per 10,000 among women using older Pill versions.

The agency is set to discuss the issue at a meeting on December 8.

Bayer HealthCare, which makes Yaz, Yasmin, Beyaz and Safyral, said it was still reviewing the new study from Israel and could not comment on it.

But in an email to Reuters Health, Bayer pointed to its own post-marketing studies that have failed to turn up a heightened clot risk with drospirenone contraceptives versus older ones.

Drospirenone is a progestin, a synthetic version of the hormone progesterone.

The different generations of the Pill vary in which progestin they use. Second-generation pills contain the progestins levonorgestrel or norgestrel. Because they can cause side effects like acne and body-hair growth, the third-generation of progestins were developed in the 1980s to lower the odds of those problems.

But some studies later found that third-generation pills carried a higher blood clot risk than their predecessors -- suggesting that risk is influenced by the progestins in the formulation.

Yasmin arrived on the scene a decade ago. Its progestin, drospirenone, was different from older ones, which are derived from testosterone. And the Yaz products have been promoted as causing less weight gain and swelling than older-generation pills.

For women seeking birth control, Yaz and Beyaz can also be used to manage moderate acne or so-called premenstrual dysphoric disorder -- a severe form of PMS that causes physical symptoms and serious mood swings before a woman's period.

After its approval in 2006, Yaz quickly became the top-selling birth control pill in the U.S. -- though its sales have dropped off in the past couple years (partly because of generic competitors). Worldwide, Yaz and its sister pills had sales of about $1.07 billion in the first nine months of this year according to company financial statements.

For women who have already been using Yaz or related pills without a problem, there may be little reason to switch, according to both Solymoss and Gronich.

In this study, Gronich pointed out, blood clot risk was greatest in the first few months of use.

A woman already on drospirenone for four months probably shouldn't be more worried than if she (were on) another second- or third-generation contraceptive, Gronich said.

SOURCE: bit.ly/qB3Mku CMAJ, online November 7, 2011.