May blew by, and I didn’t manage a single new post.  The annual meeting of the American Urological Association and a big burst of research activity in my bioengineering lab did keep me busy, but really, there’s no good excuse, and it’s time to blog again.

One very active area of this blog is How Clomid Works in Men, with over a hundred comments to date.  I’m grateful to Robert for inspiring this post.  His question is, are there medications that decrease estrogen?

To review how the pituitary controls the making of testosterone in the testis, testosterone is converted to the female hormone estrogen, and rising levels of estrogen tell the pituitary to make less luteinizing hormone (“LH”).  The role of LH in a man is to stimulate the testis to make testosterone, and as the pituitary sees more testosterone in the blood through the lens of estrogen, it tells the testis to make less testosterone by reducing LH.  I likened this negative feedback system to a thermostat and a heater: as the room becomes hotter, the thermostat turns down the heater.  Clomiphene binds tightly to the pituitary, (and hypothalamus for you biological sticklers), and tricks the pituitary into thinking less estrogen is bouncing around in the bloodstream.  The pituitary labors to make more LH as a result, and the testis makes more testosterone.  The drug tamoxifen works in a similar way.

But Robert’s question hinted at another way to trick the pituitary: there is a way to decrease estrogen directly so that the pituitary sees less of it and makes more LH.

The enzyme aromatase turns testosterone into estrogen.  Drugs like anastrozole and testolactone block aromatase, causing estrogen to decrease in the blood.  The pituitary makes more LH as a result, and the testis produces more testosterone.  If a man has low testosterone and high estrogen, these drugs can simultaneously increase testosterone and decrease estrogen. In a study published in the Journal of Urology in 2002, doctors Raman and Schlegel report evidence that anastrozole seems to work a little better than testolactone, at least in terms of increasing sperm production.  In that study, the doctors also suggest that these drugs are best used if the ratio of testosterone is less than ten to one.

As I wrote in my post on How Clomid Works in Men, all of these drugs are off-label for use in the male, meaning that the Food and Drug Administration didn’t approve their use in men.  That doesn’t mean that they can’t be used.  It means that doctors need to tell patients what we know about these drugs, allowing for an informed decision on their use.  It also means that many of the questions we have about these drugs don’t have answers.  A good question about aromatase inhibitors in men is whether estrogen plays an important role in some health concerns in men, and if it is decreased for a long period of time, can other health problems occur?  We don’t know.  My current practice for prescribing aromatase inhibitors is mostly to limit their use to male fertility, and to stop the medication as soon as possible.

So there you have the two basic ways that pills can trick the pituitary into telling the testis to make more testosterone.  Thanks, Robert!