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.
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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How does nolvadex compare to clomid for the same treatment? Could it be used instead of the clomid? Any benefits to using clomid over nolva?
cheers
Doctors have studied tamoxifen (the generic name of Nolvadex) for the same uses as clomiphene, but there are more studies in the medical literature for using clomiphene in men. To my knowledge, there aren’t any well-controlled head-to-head studies of tamoxifen versus clomiphene for use in increasing testosterone in men.
What duration of time have you had male patients on clomid? Is it possible that the hypothalmus/pituitary will eventually become insensitive to it?
That’s a great question. Unfortunately, as clomiphene is generic, drug companies don’t have an incentive to fund the longitudinal trials that would be required to answer it. In my practice, I’ve observed a variability of response with some men’s testosterone levels declining with time, but I can’t say that when that happens, it isn’t due to the testis itself changing over time.
Hello,
My name is Chris and I am 31 years old. I work as an RN pulling 12 hour shifts 7p-7a. My wife and I have one child and she was a long time coming. In the past year I have had certain S/S there were well disturbing to me. Low sex drive , erectile dysfunction, mood swings, hot flashes, diaphoresis….etc. I asked a couple of Docs I work with and they told me to have a few tests run specifically testosterone. My testosterone was around 240. They placed me on Testared 30 mg. I definitely feel better. But am concerned about fertility. My wife’s gynecologist has recommended going to and see a urologist and possibly stopping testosterone and start clomid. What is you advice?? Thank you for your time.
Respectfully,
Chris
Hi Chris, I unfortunately can’t answer specific questions about your own health. See the FAQ at http://www.maledoc.com/blog/faq/. I definitely recommend seeing a urologist who is familiar with treating male endocrine issues.
Thank you sir.
Is it contraindicated to take testosterone and Clomid together or at least can you taper off of testosterone when clomid is started. Would taking the testosterone hinder the the action of the clomid. I’m guessing it would or at least slow down/mess up the negative feedback process. Also once a person is on Clomid must they stay on it forever or can it help reboot the body’s natural process of testosterone production.
Thanks,
Chris
Hi Chris, this seems more like a personal question than a general one. I recommend that you see an expert in your area. “Find a Doc” on the SSMR site (http://www.ssmr.org/doctors/locate.aspx) can help you.
Generally, how long does a patient with secondary hypogonadism have to be on Clomid? Is it a life-long therapy, or can the patient be tapered off?
And what are the potential side effects from elevated testosterone levels?
It’s variable, and depends on the specific case. I’m not sure what you mean by “elevated testosterone levels”.
A few questions about Clomid:
1. Is there any long-term risk from using Clomid in men? I’ve read some studies which have treated men with it for 4 months and more with no side effects. However, I’ve also read about bodybuilders who use it to restart their testosterone after using steroids; they believe it causes side effects and they cease use after a month or so. What is the safety of the drug?
2. Have you heard of the drug Androxal? It is an isomer of Clomid which is being developed to treat male secondary hypogonadism. Supposedly, in men with 250 ng/dL, a 25 mg dose of Androxal increased T levels by around 260 ng/dL. It’s in phase 2 trials right now.
Thanks.
Hi David, the answer to the safety question is similar to that of the question that Jason posed January 13th: unfortunately, as clomiphene is generic, drug companies don’t have an incentive to fund the longitudinal trials that would be required to answer it. We don’t know the long-term risks, and it’s important for a doctor and patient to discuss what we do and don’t know about any treatment, and what the potential risks and benefits of therapy are prior to making a decision about medication.
Enclomiphene (Androxal) is the trans-isomer of clomiphene. There’s interest in seeing whether certain isomeric forms of some medications are more active, and as for enclomiphene, the jury’s out until the results of clinical trials are in. The good news is that at least we’ll get the kind of data that the FDA requires of new drugs.
I keep reading about this drug Androxal, and it seems that the company that makes it, Repros, is in periodic financial difficulty. So getting the drug through the pipeline is going to be a while.
So, since there’s no money in selling generic Clomid for men, the pharmaceutical companies won’t do anything about this serious problem. Gotta love the market. The way I see it, since most cases of male hypogonadism are secondary, wouldn’t you find a way to treat this, by enhancing the body’s testosterone production rather than shut it down completely. This is especially important for men who want to father children.
I am a doc who uses clomid to treat male hypogonadism. Does it make sense to use Arimidex in men who fail to respond or respond suboptimaly?
You would expect from the pharmacology of these drugs that if an antiestrogen like clomiphene didn’t result in increase in downstream testosterone, an aromatase inhibitor like anastrozole wouldn’t either as both effectively prevent estradiol action on the pituitary. However, I have had patients who responded to anastrozole who didn’t to clomiphene, especially if estradiol was elevated.
The concept was brought up in a conversation w/ one of Dr Lipschultz’s fellows. I guess that the idea was to raise serum T levels w/ the clomid and then minimize its conversion to estradiols w/ the Arimidex.
If you’re referring to concurrent treatment with both medications, to my knowledge the number of structured investigations that have been reported is limited.
Is it possible for both partners to take Clomid when trying to conceive?
If the woman has ovulatory problems that are treated with clomiphene, and the man has low testosterone, it’s not infrequent that both are taking the medication at the same time. While the effects of clomiphene on the pituitary are similar in men and women, the target organs are obviously different, testes for the man and ovaries for the woman.
My husband and i have had one child but it took 4 years his sperm levels are very low what can he take to get pregnant its been 7 years since my son was born and still nothing he also has sugar diabetes.
Please help i am really wanting to get pregnant again
I’m sorry to hear of your difficulties, Lee-Anne, but I can’t answer personal questions about your own health. Please read the FAQ.
Can my husband take stamnigro and clomid to increase his sperm count will it help?
Lee-anne, I really can’t answer personal questions about your husband’s health. Please read the FAQ.
I took pills for 3 years called methan for budy building it’s something lik anabol – after 2 years of stopping the drug i found out that my sperm count is between 1 and 2 millons – can clomide do any effect after all this period?
I’m sorry, but I can’t answer personal questions about your health. Please read the FAQ.
Hi
I have low testosterone level. My doc has prescibed both clomiphene and arimidex.
1 tablet of 1mg arimidex daily and 1 tablet of 50mg of clomiphene every other day.
Isn’t this overdose ???
I’m sorry, but I can’t answer personal questions about your own health. Please read the FAQ.
Generally, how long does does it take for clomiphene to begin to raise testosterone levels? Does it act fairly quickly (days) or take a couple of weeks?
Based on what I’ve observed in laboratory assays at one week, testosterone should increase to its new level by that time. I usually assess testosterone at two weeks to insure that enough time has passed.
A question was asked earlier about whether it contraindicated to take testosterone and Clomid together. It seems that Clomid would work in conjunction, not counter, to testosterone repleacement therapy. Have you prescribed both concurrently?
The use of the two together has not been investigated and reported in the typical manner, and I would be hesitant to draw conclusions based on studies of each individually. I would imagine that the greatest hurdle to concurrent use would be titrating each for an individual patient, but that’s a speculation.
Have there been any studies, where no sperm was present in the semen, to find sperm after taking clomid or clomiphene?
Yes. In fact, our study suggests that about two-thirds of men with no sperm in their ejaculate will have sperm appear with clomiphene treatment.
Will Clomiphene increase sperm count in males who have had a vasectomy?
Typically men who have had a vasectomy have good sperm production. If everything’s normal, clomiphene treatment wouldn’t help. If, after vasectomy reversal, a hormonal problem is discovered, then clomiphene may help.
Based on your knowledge, what in your opinion would be the most effective regimen for best results and the least side effects with clomid. Dosage times per day/ month followed by how long on? Followed by how long off? On again?? I guess concerning best results, raise in testosterone, sperm count, and motility. Concerning the least side effects I speak of a desensitization, reliance on clomid and other “more hard to deal with side effects”. Also is there a high success rate in pregnancies from the use of clomid?
I have a whole post for doctors on how I use clomiphene in the Doctor’s Corner.
My Hubby recently had a semen analysis done. His results were 20.1 mil count, 24% motility and 2% morphology analysis…meaning total motile 7.7 mil. Would you recommend clomid as a good treatment to increase his sperm count?
I’m sorry, but I can’t answer personal questions about your Hubby’s health. Please read the FAQ.
Can you tell me if astheno teratozoospermia is directly linked to alcohol intake, or cigarrette use?
That is a really great question. Teratozoospermia, probably not. Read my post about sperm shape to get an idea of the difficulties we face correlating sperm shape to anything at all. As for medications, alcohol and cigarettes, I was just today asked by a patient about medications and thought, what a great idea for a post on Maledoc! So, stay tuned…
Hi,sir my semen analysis shows 10million sperms/ml and 1% motility.my doctor suggested me clomid for three months…is it safe for me to take clomid for three months???
I’m sorry Tanveer, but I can’t answer personal questions about your own health. Please read the FAQ.
Can Clomid raise LH levels above the normal range?
Hi MisterScott, as I explained in the post, clomiphene works by increasing LH:
“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.”
Increasing LH levels “above the normal range” implies a certain definition for a normal range. Most labs use a statistical sampling of men, and derive 12 IU/L as the upper limit of normal. Here, “normal” doesn’t necessarily mean the absence of disease; it’s just the range of most men’s LH. So certainly clomiphene may increase LH above the normal range, if normal is defined in this way.
Not being able to get a script for clomid for men is just not true. If it was I wouldn’t have a script like I do now.
Hi Jeff, “off label” doesn’t mean a doctor can’t prescribe a medication. It means that the doctor is prescribing a medication for a condition which is not listed in the package insert, which the FDA regulates. Patients should understand that the medication is being prescribed for an “off label” use. By writing this post, I’m letting people know about that.
Good evening and congratulations for the website. I have two questions:
1) Is there any difference in effectiveness between using 25 mg of Clomid (half a pill) every day versus 50 mg every other day?
2) have you ever tested low-level terapies, for example 25 mg every other day?
Thank you
Charlie
Thanks, Charlie! I explain to doctors how I prescribe clomiphene in Doctor’s Corner: Clomiphene Rx.
Can clomid reverse gyno?
Hi Jay, I’m not sure what you mean by “gyno”?
Would it make sense to prescribe Fontesta and Clomid after a patient’s testosterone declined drastically while Testim was used?
Hi Nellie, this really feels like a patient-specific question. Please read the FAQ.
If I am understanding the above post correctly, you seem to say that artificial testosterone introduction leads to a decrease in body’s own production of testosterone because the body “thinks” that enough is being produced. That’s why you would recommend Clomid for patients?
Yes, you are right, that was a loaded question. My husband has been seeing a urologist and … well, you can gather the results. My OBGYN sent us to him. We have an appointment with a fertility specialist, but would she be able to assist in male reproductive issues?
Thank you so much!
I’m sorry, Nellie, but I can’t answer specific questions about anyone’s health in this blog. Please read the FAQ.
After starting Clomid, how long does it take to effect the sperm count, or testosterone levels?
Pituitary response is quick, within a matter of days. Sperm production lags, for the reasons described in this post.
Hi
I have been reading about the effects of Clomiphene on raising Serum T levels.
A common theme seems to be that although Clomid can raise the levels in a clinical sense, the associated benefits such as improved cognitive function, energy levels and sex drive as well as reduced body fat and increased lean body mass are not as pronounced as when testosterone levels are raised by the application of bio-identical testosterone.
Based on your experience of treating patients with low testosterone with clomiphene citrate, what are your thoughts on this?
Thanks
Colin
Colin, that’s a great question. In order to answer it, you’d need to do a study that was blinded to the source of testosterone, (which would be difficult, as oral forms of testosterone are not available in the U.S.,) and matched bioavailable testosterone and estradiol levels in the subjects to whatever outcomes were measured. No one has done that yet (to my knowledge,) and as a result saying one is better is pure speculation. In my opinion, it doesn’t make sense that applying testosterone should be more effective, if–and this is crucial–the levels of bioavailable testosterone and estradiol rendered are the same. My experience reflects this belief, but then again, to prove it would require that study.
Thanks.
Just to clarify then, in your experience do you find that men experience the same or similar physical and psycological changes when their testosterone levels are raised from low/low-normal to normal, regardless of the method used to raise the level?
Also, what are your thoughts on combining drugs such as arimidex with clomid to counteract the rise in oestrogen levels? The reason I ask is that anecdotal evidence seems to suggest that the use of Clomid in men may cause them to feel more emotional and this could be related to a rise in oestrogen.
Finally! In your experience, how would you rate the actual change in general well-being felt by the patient after their levels have risen from low/low-normal to normal/high-normal? Would you say the changes are generally great or small, or somewhere in between (be specific :P) ?
Thanks again
Colin
Hi Colin, for the first question: yes. For the second: the increase in estradiol is variable. I mainly use the testosterone to estradiol ratio, which should be greater than ten to one, to consider anastrozole as a treatment option. As anastrozole alone is effective in increasing testosterone, I do not generally prescribe it with clomiphene. For the third question: the feeling of well-being is highly variable among patients. Many factors change it beyond hormonal ones. Sorry I can’t be specific 🙂
Thanks so much for the feedback!
Fell out of bed feeling down. This has brightneed my day!
thanks for your informative website.can you please tell me if clomid can be used in a case of low sperm count of 5million which all dies after two hours?
thanks
I’m sorry, Rose, but I can’t answer personal questions about a specific man’s health. Please read the FAQ.
Is there a site like this for women?
Hi Michelle, check out our Google knol. It has a lot of information about female reproductive care there. Blogs can be found by Googling “fertility blog”. Take a look at the results, and let me know what the good ones are!
Hi maledoc,
I have spent hours reading forums and have had trouble finding out if any of this treatment is permanent. I see that may questions do not get answered but I will attempt to be as general as possible because where I am located the GP’s that are available to me have little or no understanding of “clomid therapy”
Hypothetically,
If someone were to increase their testosterone synthetically and then come to a sudden stop, they may find they have trouble producing testosterone again naturally for a number of months to follow as the body try’s to kick the glands into gear. Its my understanding this can lead to low sex drive / low motivation. I am aware by just my reading that in theory, clomid would likely increase the testosterone. The question becomes whether or not one could argue that this product has potential to kick testosterone into gear and restore the glands normal function, or if the clomids only purpose to achieve temporary restoration, and upon ceasing treatment production will go right back to where it was prior to taking the medication. I understand completely that you can only speculate, I would appreciate that greatly as I have no other source of information. I am in no way asking if you think that I, or anyone I know, should be medicated with ‘clomid’ – Just trying to get a better understanding of the drug. Thanks in advance!
Hi Mark, I’ve prescribed clomiphene for a number of men who needed to stop testosterone therapy, typically because they wanted sperm to return to the ejaculate. Sometimes the men don’t respond to clomiphene and need to be treated with HCG, which looks like LH to the body, to stimulate testis production of sperm. Whether men need to have clomiphene or HCG long term depends on their own body chemistry and how long they were taking testosterone.
When you prescribe a clomiphene treatment to those men who need to stop testosterone therapy how long do you have them wait (after stopping testosterone therapy) before starting the clompihene? Do you still see the testosterone level rise within 1-2 weeks as you typically see?
Again, this is really a patient related question that I can’t answer. I urge you to see a physician who specializes in male reproductive medicine. I’ve described how to find a good one in the FAQ.
Would use of clomid increase sperm count and motility in men?
That’s a million dollar question, Erwin. Because clomiphene has been around for a while, we’ll not get good double blind placebo-controlled studies performed by the manufacturer to answer it. Investigators have conducted a number of studies, but few are double blind placebo-controlled, and they seem to be split on the effect on sperm. Another problem is that past studies did not say whether the men had low testosterone levels before taking clomiphene. It makes sense to me, biologically speaking, that clomiphene should increase count and motility especially if the testosterone starts out low, but I’d love to see a good study to prove it.
Hi maledoc
Question on symptoms of low testosterone in the men you have treated (not clomid specific so apologies if it is not relevant to this forum)…
Do you find that a symptom of low testosterone is that the men experience thinning or lost hair. Do you find that raising the levels causes hair to thicken or grow back where it had gone. I am talking about hair on top of the head!
Thanks
Colin
Hi Colin, if a man has the right genetics, hair follicles on the head kick out hairs when they see good testosterone levels. Some say that’s why baldness is a sign of virility 🙂
Thanks again!
What would be the right dosing when taking clomid for men? (Starting dose)
Hi Erwin, if you look up a few comments, you’ll find that I answered that I have a whole post for doctors on how I use clomiphene in the Doctor’s Corner.
Is it better to take clomid in the morning or evening time, or it doesn’t matter what time of the day you take it? Thanks for answering all of my queries.
I explain the half-life of clomiphene in that post, Erwin.
hi maledoc, will it be possible for clomid to restore testicular function completely and size? im asking if this applies in a person who has taken anabolic steriods like deca or test?
how long and what is the correct dosage?
thanks!
Hi Sharif, this really feels like a personal question. Please read the FAQ
Thanks a lot maledoc !!
Maledoc
My ever increasing knowledge of the effects of clomiphene citrate on treating low testosterone has raised another question which I hope you can answer:
Some of the reports I have read suggest that the effects of Clomid might initially work for a short period (a matter of weeks) and then subside. Have you found this to be the case in your experience with some of your patients? If so, are there any reasons why this may happen and anything that can be done to avoid it?
Thanks again
Colin
Hi Colin, it’s been my experience that tachyphylaxis is very uncommon with clomiphene.
OK thanks.
Hello Maledoc,
Does taking Clomid for men lead to increased risk of twins, triplets, etc.? If so, then how long would you recommend stopping usage before that risk decreases?
Thank you!
Hi Bill, it doesn’t make biological sense to me, and I’m not aware of any evidence that it would. Twins (and triplets, etc.) are either the result of more than one egg being released and fertilized or genetics. I can’t see how a man taking clomiphene would alter either.
Thank you for the response, your blog is very helpful.
can clomiphine treatment be used to treat opoid induced hygogonadism ? whats your opinion and experiance on this issue. thanks
That’s an excellent question. Opioid induced hypoandrogenism can be very difficult to treat, and clomiphene may be a part of the solution depending on the nature of the specific case. The best strategy is to wean from opioid use if at all possible.
thanks. i appreciate your response.