On Birth Control,“Plan B,” and…Batman
Dec09

On Birth Control,“Plan B,” and…Batman

The “morning-after” pill, used to prevent conception when other planning methods fail, became a political lightning rod this week. Reports by Pharmalot, NPR, Reuters, and many others relate how the Secretary of the U.S. Department of Health and Human Services blocked an FDA recommendation to provide over-the-counter access to this treatment to a wider range of patients (currently, women under the age of 17 must have a prescription to obtain Plan B). After the uproar generated by the announcement, I wondered what, exactly, was this contentious molecule, and what did it do? In the US, hospitals administer Plan B as two small pills, each with a 750 μg dose of the synthetic hormone levonorgestrel. First approved by the FDA in 1999, levonorgestrel prompted several companies, among them generic manufacturers Barr, Watson, and Teva, to jump in as suppliers in the ensuing decade. According to a 2011 Teva patent, Plan B is most effective when taken within 72 hours of when a person’s first-line contraceptive fails. The FDA estimates its success rate at 80-90%. Levonorgestrel binds to the same receptors as other sex hormones (think estradiol or progesterone), and prevents ovulation or impairs fertilization of egg cells. Some researchers believe that Plan B prohibits already-fertilized eggs from adhering to the endometrium (uterine inner wall), which might prevent further embryonic development leading to pregnancy. In fact, a large dose of 17-α-ethinylestradiol (EE) – the main ingredient in most birth control pills – can sometimes be used “off-label” to achieve the same effect. The uncertainty over whether Plan B actually terminates pregnancies brings it onto similar ground with mifepristone (RU-486) and diethylstilbestrol (DES). These two drugs, previously popular options for emergency contraception, have mixed public perception today; many associate RU-486 with abortion, and DES with endocrine disorders and tumor formation in offspring. Chemistry Note: It’s humbling to watch Mother Nature re-use the same chemical templates over and over, and that small changes in the overall steroid structure lead to huge biochemical consequences. Like Batman, with his never-ending supply of utility-belt gadgets, the steroid core structure can be tweaked in seemingly endless ways to produce biologically active molecules. I would have to devote (several) more posts to just how many modifications, but think about the effects simple oxidation (bile acids), ring expansion (cortistatins), or conjugation (sulfonated sterols) have on biological processes. The sex hormones have been puzzling synthetic chemists for nearly 100 years; in fact, two prominent chemists spent large portions of their careers perfecting the introduction of a single methyl group into the steroid core! Levonorgestrel claims “second-generation” hormone status; next-gen progestins, such as desogestrel, do away completely with C-3 oxygenation, and sport...

Read More
Green Chemistry Co-Founder Boxed In By Formaldehyde Politics
Oct16

Green Chemistry Co-Founder Boxed In By Formaldehyde Politics

Paul Anastas, co-founder of Green Chemistry, has hit a plywood wall. Not literally. But Anastas, President Barack Obama’s nominee to head EPA’s Office of Research & Development, is stuck in a political sticky wicket. And it’s not of his own making. Anastas directs the Yale Center for Green Chemistry & Green Engineering and is former director of ACS's Green Chemistry Institute. He was seen as a non-controversial shoo-in to lead EPA’s R&D effort. The Senate Environment & Public Works Committee easily approved his nomination in July and sent his name to the full Senate for a vote. Then an unnamed senator sent the Anastas nomination into limbo through an arcane procedural move called a “hold.” The Senate can’t vote on whether to confirm Anastas until the lawmaker lifts that hold. Inside the Beltway observers were scratching their heads over who had slapped a hold on Anastas and why. But the New Orleans Times Picayune followed the smell of formaldehyde offgassing from pressed board in FEMA-supplied trailers housing survivors of Hurricane Katrina. Reporter Jonathan Tilove confirmed that Sen. David Vitter (R-La.) had placed the hold on the nomination. Vitter’s move had nothing to do with Anastas’ record or qualifications, Tilove found. Instead, it has to do with Tilove calls the politics of formaldehyde. This has everything to do with EPA's new risk assessment of formaldehyde, a task that the agency has been busy on for many years and is nearly done with. Vitter wants the agency to send its assessment to the National Academy of Sciences for review before finalizing it. Such a move would delay, for two or three years, completion of the assessment. And the assessment would serve as the basis for a planned EPA regulation to limit the amount of formaldehyde that pressed wood products could offgas. Backing Vitter’s call for NAS review is the Formaldehyde Council, an industry group of formaldehyde producers and users. They include manufacturers of pressed wood products like plywood and particleboard, some of which are held together with a glue containing formaldehyde. In its web site, the council describes health risks of formaldehyde this way: “Formaldehyde like sunlight is necessary to life, it occurs naturally and we can not live without it. At higher exposures, it is an irritant. Too much sunlight, you get sunburned. Too much formaldehyde, your eyes water, your nose runs.” Meanwhile, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans. EPA’s 1991 risk assessment of formaldehyde, which the agency is currently revising, ranks formaldehyde as a probable human carcinogen. Among Vitter’s campaign contributors are the American Forest & Paper Association, according to the Federal...

Read More