How Clomid Works in Men

April 28th, 2010 § 885 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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§ 885 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?

    • maledoc says:

      It all depends on the patient. Each man is different, and I treat each one according to his specific needs.

      • Doug says:

        After reading the post on Clomid, my understanding that this drug is used for men with secondary hypogonadism since it affects the blockage of estrogen at the pituitary.

        Is this a correct interpretation?

        What affect, if any, does the drug have for those with primary hypogonadism?

        • maledoc says:

          Hi Doug, great question. My preference isn’t to label hypoandrogenism (low testosterone) as “primary” or “secondary” but rather to say whether the pituitary or the testes or both are involved, and then it makes it more clear how to diagnose and treat the condition. So if the pituitary is working but under the weather, then drugs like clomiphene or the aromatase inhibitors (read my posts and the comments section on those if you’re interested) can work. Similarly, if the testis is a little under the weather and the pituitary hasn’t responded as vigorously as it might, then these drugs can work as well. Hope this helps.

          • Doug says:

            I have Klinefelters Syndrome . I am using a compounded testosterone. Recently, my dosage was increased to 75mg per day and after 6 months my T level only increased 20ng/dl (481-501) but my total estrogen doubled from 110 to 221.

            Saying “working but under the weather” is a little misleading. My testis produce a minimal T output (>100ng/dl). I was thinking that the estrogen blocking drugs would produce more LH and I already have too much.

          • maledoc says:

            Hi Doug, I really feel for you. I’m really sorry, but I can’t address personal questions about your own health. Please read the FAQ.

  • mocha says:

    Hi Doctor,

    You mention in your article that in your experience, most men don’t feel anything as their testosterone rises.

    I guess I’m a bit confused about that- isn’t the whole point of taking clomid to address the symptoms of low testosterone? For example, if one were experiencing ED because they had low T, they would want to be able to achieve erections if the Doctor prescribed clomid to address their problem.

    Thanks for helping me understand!

    • maledoc says:

      That’s a great question, Mocha. Testosterone controls many body functions in men (and likely in women,) and different problems may arise if it is too low. A man might have problems with fertility but have no problems with energy or erections, for example.

  • Joanne says:

    Can this be used for low and abnormal sperm count?
    Thankyou

    • maledoc says:

      Hi Joanne, that’s a deceptively simple and really great question with a very complex answer. It’s answered in many different ways throughout this blog. I’d encourage you to read other posts about how sperm is made, etc., and especially the many comments, as there’s so much good information in what other people have asked and in answers to those questions.

  • Tim M says:

    Hi Doc,

    I have two questions actually.

    1. Is there a specific time of day you recommend your patients take clomid (e.g. morning evening, empty stomach, after eating etc).

    2. Is there a dose you generally start them on or a certain range you use to start with? I have ready mainly either 25mg or 50mg and wondering if with that dosage its effective at all.

    Thanks for a great post!

  • Rahul says:

    Hello Doctor,

    I have 3 questions.
    If a patient is on clomid & his testosterone levels are increasing.
    1. When does he stop using the drug ?
    2. What happens after he stops taking the drug ?
    3. How does the patient control the increasing estrogen levels ?

    • maledoc says:

      Hi Rahul, he sees a doctor to care for those things :) I also encourage you to read the other posts on this blog and especially the comments, as many questions are answered and there’s great information there.

  • Saulo says:

    Hello doctor,
    I was reading about some studies with clomiphene citrate. One performed with rats, reports the increase in weight of the pituitary gland (+ 80%), the liver and the adrenal glands, using relatively high doses compared to those used in humans (2mg / kg / day).
    What do you think about this, compared to lower doses used in humans? This weight gain cited in the study can be dangerous if it occur in humans?

    • maledoc says:

      Hi Saulo, see my post on dosing clomiphene here. I encourage you to read the other posts on this blog and especially the comments, as many questions are answered and there’s great information there.

  • Zehra says:

    Hi
    If someone was born with bilateral undescended testicles that were descended surgically when he had already developed beared and mustaches, and was diagnosed as NOA, had high FSH, high LH and very low T, do you think Clomid or Drugs like anastrozole and testolactone may be of some help in finding few sperms in ejaculate or in mTESE.

    regards

    • maledoc says:

      Hi Zehra, such a person with such a specific history would best be seen by a qualified doctor who could work with him and prescribe medications as they are needed. Please read the FAQ.

  • maledoc says:

    Hi everybody, I’m sorry, but if you’re asking personal questions about your own health or someone else’s, I can’t answer them. Please read the FAQ.

  • David says:

    thanks very much for the great information
    I understand that clomid primary used for ovulation induction
    but also can be used in men for the following:
    low libido
    low testosterone level
    low sperm count
    low energy
    muscles building*
    gynecomastia
    not sure about insulin resistant
    is there is any other indication or off label use of clomid ?
    at the level of GP /family physician can I prescribe the medication off label to my patient ?
    what the ratio of testosterone( free or total ) to estrogens in male according to their age, and what type of estrogens we measure in male ( oestrone , oestradiol , oestriol )?

    Thanks a lot
    David

    • maledoc says:

      Hi David, for the first set of questions, yes, if they’re caused by low testosterone. Libido, for example, is complex and involves more than just hormones. Sometimes the only way you can figure it out is to correct testosterone and see if the patient improves. Gynecomastia, no, that can be an effect of the medication, usually related to estradiol increasing, so it is something you’d want to look out for in a patient. If you are a qualified generalist, just like any medication, you can prescribe it (with an off-label discussion with your patient,) monitor effects, and involve a specialist as the need arises. A standard commercially available estradiol assay is all that is needed, and I generally use a threshold of 50 pg/mL rather than the ratio in my own practice over which I would modify therapy, such as change to an aromatase inhibitor. Take a look around the rest of the blog and especially the comments, as there’s good information in there. I even wrote a post just intended for physicians prescribing the medication. Follow me on Twitter as Craigni for more up to date information if you’re interested.

  • Gregory says:

    Does clomiphene cause hair loss in men

    • maledoc says:

      Hi Gregory, if a man has the right (or wrong, depending on your point of view) genes for it, testosterone converted to dihydrotestosterone at the hair follicle kicks out the hair. So increasing testosterone, which is what clomiphene is intended to do, may accelerate that process. The medicine per se does not “cause hair loss”, rather, it may hasten an existing process. Don’t forget to follow me on Twitter.

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