How Clomid Works in Men

April 28th, 2010 § 864 comments

With the suspension of Cincinnati Reds pitcher Edinson Volquez for performance enhancing drug use and a swirl of rumors that the agent involved was clomiphene (also known as Clomid,) I thought it timely to write about how clomiphene works and how it’s used. From what I read on the internets, there is an enormous amount of misinformation floating around out there.

To understand how clomiphene works, you need to know how the pituitary controls the making of testosterone in the testis. Testosterone is made by Leydig cells in the testis, which I explained in my last post. The pituitary releases a hormone called luteinizing hormone (“LH”) that stimulates the Leydig cells to make testosterone. Testosterone is converted to the female hormone estrogen, (which I also explained in my last post,) and estrogen tells the pituitary to stop making more LH. This kind of negative feedback system is common when it comes to how hormones work. It’s just like a thermostat and heater. As the room gets warmer, the thermostat sends less electricity to the heater. When the room gets colder, the thermostat sends more electricity to the heater.

LH testosterone.png

Clomiphene works by blocking estrogen at the pituitary. The pituitary sees less estrogen, and makes more LH. More LH means that the Leydig cells in the testis make more testosterone.

As I explained in my last post, giving testosterone to a man does just the opposite. The pituitary thinks that the testis is making plenty of testosterone, and LH falls. As a result, the testis stops making testosterone, and the usually high levels of testosterone in the testis fall to the lower level in the blood.

So clomiphene is a way to increase testosterone in the blood and the testis at the same time. It preserves testis size and function while increasing blood testosterone.

Unfortunately, clomiphene is not FDA approved for use in the male. Like most of the medications that we use to treat male fertility, the pharmaceutical company that originally sought approval by the FDA did it for women. Clomiphene is now generic, and it’s unlikely that anyone will pony up the hundreds of millions of dollars necessary to get it approved for the male. That’s the bad news. The good news is that it means that this medication is fairly inexpensive, cheaper than most forms of prescription testosterone. Can a doctor prescribe clomiphene for a man? Yes. It’s “off label”, meaning that it’s not FDA approved for use in men.

As a medication, clomiphene is usually well tolerated by men. In my experience, most patients don’t feel anything as their testosterone rises. Those that do feel an increase in energy, sex drive, and muscle mass, especially if they work out. Very rarely I’ve had patients report that they feel too aggressive, or too angry. Very very rarely (twice in the last 20 years) I’ve had patients report visual changes. That’s worrisome, as the pituitary is near the optic nerve in the brain, and visual changes suggests that the pituitary may be changing in size. Because the skull is a closed space, it’s alarming if anything in the brain changes in size. In the last twenty years, I’ve also had two patients who had breast enlargement (called “gynecomastia”) while using clomiphene. Needless to say, for any of these problematic side effects, the clomiphene is discontinued.

So that’s the story with clomiphene. It can be used in the male, either for fertility or low testosterone levels. It’s an off label prescription drug. It works, and is usually well tolerated by men who take it.

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§ 864 Responses to How Clomid Works in Men"

  • Dr Mo says:

    Hi Dr Niederberger,
    Thanks for this great blog.

    I would like to throw some questions if you don’t mind and I will be pleased to have your opinion.

    “In my experience, most patients don’t feel anything as their testosterone rises. Those that do feel an increase in energy, sex drive, and muscle mass, especially if they work out” Do you mean that if the chief complaint is low Testosterone related absent libido won’t improve in most patients on clomiphene?

    Do young (below 30) patients with high total Testosterone and LOW FREE Testosterone improve with Clomiphene (low to absent libido as a chief complaint )?

    Why in your opinion do they have this imbalance or discrepancy between total and free testosterone? I mean what causes this sudden and acute drop (usually they describe it as over night or a switch that suddenly turned off) in the FREE portion of Testosterone? even if the reason is high SHBG, why does it happen that rapid and sharp?

    • maledoc says:

      Hi Dr Mo, tests for free testosterone vary in quality. We use total testosterone, sex hormone binding globulin, and albumin to calculate the bioavailable testosterone. You can find a calculator at http://www.issam.ch/freetesto.htm. The reason that bioavailable testosterone may be low is if sex hormone binding globulin is increased. Many factors determine sex hormone binding globulin levels, and it is an area of active research.

  • jon b says:

    Hi Dr Niederberger,

    Do you typically require an MRI before prescribing Clomid? Is there any concerns with taking it prior to having an MRI?

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