Doctor’s Corner

Ever so often, I get asked questions from doctors, and I figure that here is a reasonable place to put how I answer the frequently asked ones.  As with everything I write, it’s my opinion, and doctors opinions vary.

One question I get asked a lot is how to prescribe clomiphene for a male.  Here’s how I do it.

First, clomiphene works by stimulating the pituitary.  If the pituitary’s already in overdrive, clomiphene won’t help.  So if a man’s LH is high, like 25 IU/L, I don’t prescribe clomiphene.

The next decision to make is what the target for therapy will be.  If it’s augmenting a low testosterone level, then I’ll use the bioavailable testosterone calculation described in a previous post.  As a reasonable threshold for total testosterone is 300 ng/dL and the portion of bioavailable testosterone ranges between 52% and 70%,¹ I use the range between 156 ng/dL to 210 ng/dL as a lower limit of what is likely an adequate bioavailable testosterone level for a man.  If the target for clomiphene therapy is stimulating the testis to make sperm, I use a higher threshold.  If possible we try for twice as much, about 400 ng/dL for bioavailable and 600 ng/dl for total testosterone.  It’s not always possible to achieve those levels.

I start with 25 mg clomiphene a day.  As the pills come in 50 mg, and the half-life is relatively long, patients can take a pill every other day.  Some prefer talking half a 50 mg pill daily.  After two weeks, I have the patient get tests for testosterone, LH, albumin, SHBG (sex hormone binding globulin) and estradiol.  In some instances, the estradiol will increase, but as long as the ratio of total testosterone to estradiol is greater than ten-to-one, that shouldn’t be a problem.  If the estradiol increases substantially, other therapy, like an aromatase inhibitor, is preferred.  If the testosterone is still low, then we’ll increase the clomiphene by 25 mg every other day or daily, and repeat the tests.  I’ll increase the clomiphene to a maximum of 100 mg daily.

I believe that clomiphene works better if a man’s testosterone is low.  That’s a good indication that there is a problem that may be corrected.  If the testosterone is reasonable at the start, 400 ng/dL or more, then pushing it higher may not be as effective.  But that’s my opinion, and as of present, scientific studies don’t definitively prove it right or wrong.

It’s important to note that clomiphene is “off-label” for use in the male.  I explain this in a previous post.

¹S. Bhasin. Chapter 18: Testicular disorders.  In: Kronenberg H. M., Melmed S., Polonsky K. S., and Reed Larsen P., eds. Williams Textbook of Endocrinology 11th ed. Philadelphia, W.B. Saunders Company, 2008; 647.