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On Birth Control,“Plan B,” and…Batman

The “morning-after” pill, used to prevent conception when other planning methods fail, became a political lightning rodlevonorgestrel 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.

DESThe 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.

Desogestrel

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 a new alkene at C-11. These new atomic decorations lead to improved side-effect profiles and lower the overall EE dose in combined pill formulations.

Update (6:05PM, Dec 9, 2011) – Changed “mg” to “μg”  (Thanks, Ed!) 

3 Comments

  • Dec 9th 201112:12
    by Ed

    Two 750 mg doses of a steroid hormone seems way too high. Maybe 750 ug?

  • Dec 9th 201112:12
    by Chemjobber

    The structure of DES is so interesting in that (I hate to admit it) it looks just a little like BPA. That said, DES is pretty darn planar and BPA really isn’t…

  • Dec 9th 201119:12
    by See Arr Oh

    @Ed – Good catch, the FDA prescribing information does indeed say 1.5 mg of active sterol. I’ll change it post-haste!

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