Turning Lemons into Lemonade

Gynecology can be a bit of a schizophrenic field. I don’t know of any other area of medicine where the desired clinical outcome can be so completely opposite. I’m speaking of course, about pregnancy. We’re either trying to prevent it, or trying to make it happen, not infrequently in the same patient, just at different times in her life.

One upside to this schizophrenic medicine is that if a treatment worsens one of the outcomes, it may then be good for the other. Take, for example, the Cox-2 inhibitors (Vioxx, Celebrex, Bextra).

COX-2 and the Ovary

Cox-2 is shorthand for cyclo-oxygenase 2, an enzyme that catalyzes the production of prostaglandins from their precursor phospholipids. Prostaglandins are produced in cells all over the body, where they do things like cause smooth muscle to contract, or stimulate pain receptors. They are why you may have menstrual cramps, among other things.

Cox-2 in the prostglandin production pathway

But prostaglandins are not just bad guys – they are thought to have an important role in the physiologic process of ovulation. The ovary has it’s own stores of prostaglandin precursors and cox-2. As ovulation time nears, cox-2 activity in the follicle increases, converting the precursors to prostaglandins. The prostaglandins act to break down the follicle wall and contract the smooth muscle cells in the wall of the ovary, leading to extrusion of the egg. Pretty neat, huh?

Just how important is the Cox-2 enzyme to ovulation? Well, let’s just say that knock-out mice lacking the enzyme are completely infertile. I’d call that important, wouldn’t you?

Cox-2 Inhibitors (The Lemon Part)

Now, as I said before, drugs that interfere with Cox-2 are called Co-x 2 inhibitors. You know them as Bextra, Celebrex and the now defunct Vioxx. You may even have taken them for treatment of menstrual cramps. (For which they are an effective treatment.)

But now that you know what Cox-2 does, you won’t be surprised to find out that taking them can interfere with ovulation. (That’s the lemon part.) In fact, the adverse effect on ovulation is strong enough that it is recommended that women avoid using the Cox-2 inhibitors if they are trying to get pregnant.

A Different Angle (The Lemonade Part)

But, let’s think about it another way, as did the authors of a very interesting study published last month in Human Reproduction.

The investigators took women who were just about to ovulate, and randomized them to receive either the emergency contraceptive pill (ECP) or the ECP + a Cox-2 inhibitor. (Remember that the primary mechanism of action of the ECP is to inhibit ovulation.)

As the graph shows, the addition of the cox 2 inhibitor increased the number of cycles where ovulation was inhibited. This effect was strongest the farther away from ovulation the meds were given, so that the larger the follicle,and the closer to ovulation, the lower the odds were that the treatment would prevent the follicle from rupturing. That’s probably because cox-2 activity is kind of like a runaway train – if you get it early, you can put on the brakes, but if you wait too long, well, let’s just say you’d better step out of the way…

Conclusion? Cox-2 inhibitors are a bad thing if you are trying to get pregnant. But if pregnancy is something you’re trying to avoid right now, they may prove to be quite useful medications.

See? Lemonade.

Make your own Lemonade

The key to great lemonade is to dissolve the sugar by making a syrup. Add some fresh mint to your glass for a special taste.

1 cup of sugar
1 cup of water
Juice of 4-6 lemons (about 1cup)

Pour water into a small sauce pan. Add sugar, and heat, stirring frequently, until the sugar is dissolved completely. Cool a bit. Add the juice and the sugar water to a pitcher. Add around 4 cups of cold water, more or less to the desired strength. Refrigerate 30 to 40 minutes.

Serve with ice and sliced lemons. Serves 6.
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References: Massai MR et al. Human Reproduction 2006; 22: 434-439. / Sirois J et al. Human Reproduction Update 2004 10(5):373-385. (Photos used with permission from Photostock.com. Pathway used with permission from Wickipedia.