The contraceptive patch Ortho-Evra exposes women to dangerous levels of the hormone estrogen, posing a possible two-fold increase in the risk of blood clots, and should be removed from the market within six months, Public Citizen told the Food and Drug Administration (FDA) in a petition.

Ongoing litigation has recently released unpublished studies that confirm the increased estrogen content of the patch, the organization said.

Evidence compiled by Public Citizens Health Research Group reveals that, compared to standard oral contraceptives, Ortho-Evra exposes women to:

• More estrogen and a greater range of estrogen levels;

• A possible two-fold increase in the risk of blood clots;

• Increased painful side effects such as breast discomfort, severe menstrual pain, nausea and vomiting;

• An increased likelihood of discontinued contraceptive use; and

• No improvement in contraceptive outcomes.

Because the patch is still superior to no contraception at all, withdrawal of any contraceptive from the market carries the risk that some users will not immediately replace their contraception with a method that is as effective as the banned product.

Public Citizen is requesting a six-month transition period in which Ortho-Evra will be available for refill prescriptions to allow women time to meet with their healthcare provider and seek a safer, alternative contraceptive method.

Seven days

Ortho-Evra patches are designed to be worn on the skin for seven consecutive days before removal. Three consecutive patches are worn followed by a patch-free week.

When Johnson & Johnson received FDA approval in November 2001 for marketing the patch, the company claimed that its product would have two key advantages over existing oral contraceptives:

1) A constant delivery of hormones instead of the ups and downs associated with pill use, and

2) improvements in compliance compared to the daily dosing regimen of oral contraceptives.

However, evidence soon emerged that these theoretical benefits are outweighed by side effects from receiving high and variable levels of hormone exposure.

A post-market study was the basis for a 2005 label change explaining that overall exposure to estrogen from the Ortho-Evra patch was 55 to 60 percent higher from the patch than a standard, 35 microgram (mcg) estrogen oral contraceptive.

Comparison studies have also shown that the amount of absorbed estrogen varied 1.2 to 3.5 times as much for women who used the patch than women who used oral contraceptives.

Had Ortho-Evra been designed as a pill, it is unlikely to have been approved because of its increased estrogen content, said Dr. Sidney Wolfe, director of the Health Research Group at Public Citizen.

In 1988, the FDA requested the withdrawal of all oral contraceptives with estrogen levels greater than 50 mcg because of the risk of blood clots and lack of additional contraceptive efficacy. The Ortho-Evra patch contains estrogen equivalent on average to a 56 mcg pill.

Label changed

The Ortho-Evra label was changed again in 2006 and 2008 to include findings from studies that revealed an up to two-fold increase in the risk of blood clots in women using the patch compared to standard oral contraceptives.

Further, side effects (such as breast discomfort, painful periods, nausea and vomiting) and discontinuation (stopping the contraceptive entirely) due to side effects were more common among women who used the patch compared to those who used pills.

Finally, Johnson & Johnson advertises that women who use the patch are more likely to use it correctly than women who use pills. Yet there are no measurable differences in pregnancy outcomes. In other words, the patch does not provide any additional benefit that would outweigh the risks of high estrogen, Public Citizen said.

Although demand for the patch has dropped dramatically in the past several years, from more than 9.9 million filled prescriptions in 2004 to 2.7 million filled prescriptions in 2007 (a decline of 73 percent), Ortho-Evra remains among the top 200 brand-name drugs by sales and prescriptions in the United States and is thus still a danger to large numbers of women in this country.

Women deserve a level of risk at least comparable to or less than the pill for their hormonal contraceptive, Wolfe said. The absence of any evidence of a unique benefit combined with the considerable safety problems of high-dose, variable estrogen exposure in Ortho-Evra tips the balance of risks and benefits against its availability as a contraceptive.