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.
Subscribe by RSS
Ok now i see in what has been stated that this drug helps with reproductive problems and just all around low testosterone. If you do not have these problems but take this drug for the testosterone boosting effects what might happen? Also extended usage of this medication would cause what to happen in men?
That’s a really general question, Leo. Read the other posts on this blog and the comments, I write quite a bit about clomiphene beyond this one post.
What is your take in using clomid and sustanon in mass enhaancing for body building?
Hi Titus, please read the FAQ.
ive got klinefelter syndrome , would clomid help for my testosterone levels? i exercise daily but still have body fat in the places woman gain weight , love handles, stomach , legs , pecs. do you think clomid would be worth trying?
sorry i only see now you cant answer personal questions!
1.are there any human/rat studies that show LH / Testosterone/ E2 return to pre treatment baseline levels after cessation or is there a change?
Hi Toerm, that’s in the FAQ. Please read it.
Thx, The Pharmakinetics of exogenous estrogens in different organs is intriguing. Is there any thing in the literature or your clinical observation showing clomid reduces igf-1 in males?
Is it common practice to even to check for such events?
IGF has been investigated to a very limited extent in male reproduction, and the outcomes and interpretations are as yet not entirely known or consistent. Consequently, the clinical importance and utility of IGF in male reproduction is currently unknown.
I understand that the pituitary regulates LH release based on how much estrogen it can see. So my question is does estrogen alone cause a negative feed back or does testosterone also. Like when men take steroids does thier own system shut down because of aromitisation of testosterone or can the pituitary sense to much testosterone also?
The majority of the negative feedback is by estradiol, not testosterone. That’s why aromatase inhibitors (see my other posts) work well. LH increases, and in response testosterone, by decreasing estradiol.
So if a man is taking testosterone will an aromitase inhibitor help keep his own testosterone production going?
Not sure exactly what you mean, Jon, but yes, an aromatase inhibitor stimulates LH production, which stimulates testosterone production in the testis. I write a bit about it in other posts, please read more than just this one!
I believe Jon is asking; will either suppression of estrogen formation (from taking an AI) or suppression of estrogen action at the hypothalamus (through the use of Clomid), be enough to keep LH production in the presence of high androgen levels.
i.e. will Clomid work at stimulating LH when someone is taking anabolc steroids. I believe the answer to this is no. very high androgen levels will prevent GnRH from the hypothalamus.
If that’s the case, I hope that he read the FAQ 🙂
Im a 40yr old male. Used nandrolone for 4-6 wks. Followed by FAKE testosterone.
Had test and free test checked as part of yrly physical. Levels came back 4-6x lower than low range. Doctor never saw it. I informed him what I did.
His answer was to inject me in office with test cyp.
Shouldn’t I have got normal production jumpstarted or at least tried before putting more synthetics in body?
Pls help
I’m sorry, Anthony, but I can’t answer personal questions about your own health. Please read the FAQ.
Thanks for the great info. I was recently diagnosed with low testosterone and my MD put me on Clomid. I’m not a good pill taker (a bad patient if you will) and really did my internet research on the subject. I did run into insurance issues and then was quoted prices which were astronomical in range. I advise patients to shop around. The lowest price I found was $45 for 30-pills. The far end of the range was $375 for the same amount.
If I been takin steroids an stop I want to have a child with my fiancé should I take clomid to help make my sperm fertile
I’m sorry, Torben, but I can’t answer personal questions about your own health. Please read the FAQ.
Dear maledoc,
can you please explain how would clomid improve sperm count? Would a man with a very low sperm count (less than 5 million)) expect much by taking clomid?
Another question is should a man have concerns while taking clomid that the benefit is less than the side effects?
Really good questions. Please read through the comments on this post and my other posts, as I’ve answered them more than once. If a man’s testosterone is low, often his sperm production is as well as testosterone is critical to sperm production. Hence, for that man, increasing testosterone in the testis may increase sperm production. But it is highly individual, and different men respond differently, which leads into your second question. As the benefit is different for different men, and the side effects are different for different men, then each man must be treated individually by his doctor, and make decisions accordingly.
When a man stops taking Clomid, how many days would it be before T level, LH, FSH return to pre Clomid treatment level.
The half life–the amount of time it takes until half of a drug is left in the body–of clomiphene is long, about a week. So about 6% will be left after a month, and only about a third of a percent after two months.
Dear maledoc,
what consider to be high Estradoil after 7 months of clomid?
Is 59 too high?
Thank you
Hi Isaac, that’s so specific a question that it seems to be related to one person’s health. I can’t answer patient questions on this site. Please read the FAQ.
It seems to me that diabetics using metformin should be particularly interested in clomid. I’ve heard that recent research suggests that the Metformin causes a drop in testosterone and an increase in estrogen. I’ve heard that women sometimes use both drugs in combination to treat PCOS, so if must not be too unsafe. Is there any indication that the same combination in men might offset the testosterone lowering effects of the metformin? Or are the mechanisms such that effects might worsen?
Great question, Ben. Much has been studied about potential interactions between the insulin pathway and the testosterone pathway, but it’s still unclear how they would interact, if at all, in a man with low testosterone and diabetes. As diabetes is so important to treat, it makes sense to me to get the blood sugar under control, and address low testosterone if it is present.
Hi, can you give me a ballpark success rate for male low sperm count once they start taking clomid? My husband was just put on the stuff for low testosterone and a sperm count below 3 million. Just want to know what are the statistics that it works and results in a successful vaginal pregnancy.
I’m sorry, Nana, but I really can’t answer personal questions about your husband’s health. Please read the FAQ.
Hi,
Is high estradoil common after long term use of clomid?
Thak you
Hi Isaac, read my other posts and the comments: I write a lot about estradiol.
hi were trying to fall pregnet and im on steroids im not abusing it im taking 1 mill a week and wanna know if that cann afect me and ive done a sperm check and it all came good would it help me if i take clomid cause my wife just recently went on it would that afect me or help me cause we have been trying for a year?
I’m sorry, Ahmad, but I can’t answer personal questions about your own health. Please read the FAQ.
hi,
do you believe it would be reasonable to supplement bioidintical testosterone replacement therapy with clomid, in young men, whos treatment may continue for 12 months or longer.. particularly if fairly substantial amounts of testosterone are administered? (relative to maximum average range for age group..for talks sake 5-15% over)
Or is this intensity of therapy likely to not risk a patients current natural T production even further?
Hi Alex, not sure what you mean by, “bioidintical testosterone replacement therapy”.
Hi, would Clomid have the side effect of increasing body hair and other such things attributed to testosterone levels?
Effects of testosterone, such as male pattern baldness in men genetically predisposed to it, would occur no matter how testosterone is increased, including with clomiphene.
Hi, if being on topical testosterone replacement shuts down the production of sperm. Would it be good for your doctor to prescribe clomid on a 20 day on/5 off schedule to try and maintain sperm production for men who want to have children later in life?
Men don’t cycle like women do, so clomiphene is prescribed differently in men and women. In men, it’s prescribed continuously.
Would clomid be prescribed along with testosterone replacement to maintian sperm count? Doesnt testosterone replacement shut production nature production of sperm?
Hi Joe, that’s one of the questions that I answer most frequently. Please read the other comments on this post, the other posts on this blog, and the FAQ.
Hi doctor, you mentioned that you had two patients develope gynecamastia while taking clomid. Is that caused by the clomid directly or is that a side effect of it raising estrogen levels? In other words did those patients have elevated estrogen that caused the gynecamastia?
Great question. We haven’t always measured estradiol, and the first patient I don’t know what the levels were. The second patient had elevated estradiol. I currently measure estradiol in patients taking the medication, and warn them if its elevated of this possible side effect. If it’s too elevated, we’ll usually try a different medical strategy.
Thanks doctor. What is considered to be too high of an estrogen level for men?
It really varies on the man, his clinical picture and other laboratory assays.
Hi Doctor,
I’ 32 years old, been married for 2 years but no children.
My semen analysis shows:
Total volume: 2ml
PH: 7.5
Sperm count: 15 billion/ml
normal Sperm morphology: 6%
Sperm motility: 26%
Hormone test: LH & Prolactin+ testosterone are within normal level.
FSH: 12.50 mIU/ml ( normal 2.5 – 5 mIU/ml)
Varix: 2.1mm
Can I use chlomiphene 50g daily in 2~3 months to increase my fertility?
Thank you
I’m sorry, lehonghnvn, but I can’t answer personal questions about your own health. Please read the FAQ.
Hi Doctor,
Thanks for your reply.
Clomid works by increasing FSH then boost testis produce sperm.So, my concern is that what side effect to my sperm quality if I take clomid while my FSH is already 2 times higher than normal redline level. Thank you
First, I can’t answer personal questions about your own sperm quality. Read the FAQ. It’s bad medicine, and I won’t practice it. Second, clomiphene does not work by increasing FSH. I’ve written a lot about clomiphene citrate. Please read this blog, its posts and all the comments.
how long men can take clomiphene?
Please read through the other posts on this blog, and the comments. I’ve answered that a few times.
I read carefully, the blog said, men can take the clomiphene either for fertility or low testosterone levels. But my question was “how long men can take clomiphene for fertility or low testosterone levels.?
Please read the comments of the posts as well: I know there are a lot of them, but they contain good information. As I’ve written in this post, clomiphene is off-label for use in the male, meaning that studies on long term use would not be funded by the manufacturer, and so we don’t have that information yet. Many physicians use it long term, though, with informed patients. This blog is intended to help inform men.
Doc,
Can you comment on the efficacy of Eurycoma Longifolia in increasing testosterone in men
Thanks
There seems to be some limited data suggesting that effect in animals, for example, here. But often early data doesn’t pan out, so I don’t have a strong opinion at this point.
Can taking clomid help to increase semen volume or only sperm production?
In theory, if a man has low testosterone for many years, the accessory sex glands like the seminal vesicles and prostate might be relatively small, and restoring testosterone may make them larger and deliver more volume. However, that’s just a theory, and only one possibility. I’d encourage any man with such concerns to see a doctor who can measure his testosterone, semen volume, and fully evaluate him.
Do you think taking clomid to raise testosterone is more likely to raise estrogen than prescription testosterone? In other words is it accurate to say that you will experience the same level of increaed estrogen regardless of how the testosterone is raised?
As I’ve written a few times here, the response to treatments that increase testosterone in increasing estradiol is really individual. If one kind of treatment isn’t quite right, another can be tried. A man contemplating therapy to increase his testosterone who is concerned about his estradiol should be under the care of a doctor with experience in hormonal treatments.
Hi Doctor, thanks for this blog. It’s great. You said:
“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.”
that’s a really interesting comment, and a bit of a cliffhanger… Can you explain for the reasons why some men “feel” a difference on Clomid and some don’t? most men that go on Clomid *want* to feel those things – increased libido, energy, etc, so it’s sort of startling when you casually say “most men don’t feel anything.” When you say most “don’t,” does that mean the changes/improvements are much more subtle, and perhaps play out over a longer period of time?
thanks for further vetting this.
Hi T, it’s a really good question, and gets to the meat of a basic problem that we all have in medicine. We understand certain biological mechanisms that are common to everyone, but individuals are so complex that responses to what we prescribe are highly varied, especially when it comes to what people feel. I can imagine all sorts of reasons why a man might or might not feel differently on a medication, but most, if not all, are speculative.
Thanks Doctor. Yes, that seems to be the heart of the matter. Very relative, and variant according to person.
I think, for those that fall into that “most” camp – those that don’t necessarily feel that total energy/well being/libido – should at least (i think, anyway), take comfort in knowing that ideally, some of the other sinister symptoms of low T, such as bone density issues, are being addressed and stymied via the raising of T through Clomid and other methods. The nasty little things you can’t feel – at least on the surface/right away. The more long term issues.
Where and do I purchase this drug clomid for men ?
In the United States, a physician prescribes it.
I have used clomiphene citrate because i have low mobile sperm count.
Using clomiphene, i feel, i have lower libido. My sex drive dropped and i don’t know how to bring it back. I have used 50mg clomiphene citrate (25 day, 5 days break for 3 months).
Please help.
I read that clomiphene citrate increase testorteron, but same time increases estrogen. When you stop clomiphene citrate, increase estrogene disentitize Leydig cells, to you feel low sex drive.
Any idea about this? Please let me know.
I’m sorry, Serdar, but I can’t answer personal questions about your own health. Please read the FAQ.
Is it possible for clomid to cause side effects like causing testicles to hurt the way ovulating can be painful to a woman? And if so does this side effect go away with use or is it something to be concerned about? I am trying to find out all side effects. Thanks in advance.
I listed the side effects I’ve seen in this blog. That’s not one that I’ve seen, but anythings possible. A man experiencing side effects of any medication should discuss them with his doctor.
Is it a well known side effect that after using clomiphene citrate, men have low sex drive? What kind of solutions are there to get rid of this side affect?
Rarely, men report a paradoxical decrease in libido after clomiphene, but it is by no means common. Typically, libido increases if it changes on therapy.
“Is it a well known side effect that after using clomiphene citrate, men have low sex drive? What kind of solutions are there to get rid of this side affect?”
i hope the good Doctor weighs in on this, but i don’t believe that this is a side effect that happens often. I mean, if Clomid raises T levels, why would it have an adverse effect on libido? and if it does, isn’t that completely defeating the purpose of taking it in the first place? I’d imagine doctors wouldn’t prescribe it.
I used Clomid for years to boost a low sperm count. It raised it somewhat but on the down-side I developed larger breasts. I heard this was a possible side effect but I’ve been off the drug for years and my breast size has not gotten smaller.
Doc,
Often times you mentioned that you have already answered a certain questions. I can see that there are some 500+ comments, but I can see maybe a fraction of them.
Could you make all of them visible so that we dont repeat the questions ?
Many thanks and you are doing an awesome job
Arnold
Hi Arnold, that’s a great question. When I wrote this post, I had no idea that it would be so commented on. I’m hesitant to turn off commenting, because great questions still appear here, but it has become very long. My suggestion is to use the search feature of your browser: when I’ve looked at this with browsers, it doesn’t paginate, so all of the questions and answers should appear in one place, suitable for search within a browser. If anyone has a good suggestion for a WordPress plugin for searching comments, please let me know. And please read my other posts, too–I write about endocrine therapy in men in more than one place!
I take 50mg of clomiphene citrate every other day and my testosterone level rose to 917 ng / dl. I was subjected to a varicocele surgery two months ago and have always had low levels of testosterone. She rose a little but not the amount I wanted, so I started taking Clomid. The problem is that the level of estradiol also increased and, for me, greatly increased: now it is 96.8 pg / ml, when the normal should be up to 30pg/ml.
.
This is an expected result due to increased testosterone or something is wrong?
I’m sorry, Eduardo, but I can’t answer personal questions about your own health. Please read the FAQ.
Does cholmiphine have side effects for males
Hi Robert, welcome to this blog! Please read the rest of the comments and other posts and their comments, and you’ll find the answer to your question, and much, much more 🙂
Would it be expected when using clomid 25mg/day to stimulate testosterone for the estriodol to decrease or increase over the baseline reading? If the estriodol increases from the normal range to elevated, what is the significance of this increase and what is the physiologic mechanism of the increase?
With clomiphene, as testosterone increases, so does estradiol, but the effect is highly variable depending on the activity of an individual man’s aromatase. The significance is variable and individual as well.
When the aromatase appears to be overactivated and producing an excess of estriodiol in relation to the testosterone produced from the clomid, have you used arimidex either alone or in combonation with clomid to achieve an improvement in the testosterone/estriodiol ratio over the baseline measure?
Hi William, I’ve answered this question a lot in various forms. Read through the FAQ, my other posts, and the comments on this and other related posts. I try to avoid mixing drugs if possible.
what would be ideal relationship between testosterone and estrogen in men? The calculation must be done in the same unit of measure? Generally T is measured in ng / dl and estrogen in pg / ml. So it should be converted to one another the same unit of measure?
Investigators have proposed a ratio of testosterone in ng/dL to estradiol in pg/mL of ten to one as a threshold, but that isn’t a hard and fast rule. Therapeutic decisions of a doctor treating a man are individualized to that particular man.
is there any way to measure the level of aromatase activity?
Aromatase activity per se is not typically measured in the clinical setting. Estradiol concentration is what is useful, and that’s what’s measured.
Please i want to find out if my husband can use clomiphene citrate since he was diagnosed of having low sperm count (2ml) which was considered too low and that sperm mortility is low too. How long can he take it and is clomid and clomiphene citrate work the same? Please i need to know these questions
I’m sorry, Precious, but I can’t answer personal questions about your husband’s health. Please read the FAQ.
just anecdotal evidence: just got my blood work results – after just 5 weeks on clomiphene citrate – my total T went from 194 ng/dl (wow, so low) to 630 ng/dl! and my estrodial is in a good range.
i’d say i’m a success case, and that i’ve “passed” the C challenge. Not sure what my long term plan will be in terms of staying on it or tapering off – i’ll leave that up to my urologist – but i don’t want to lose these gains. I think i plan to stay on for a couple of months, and see what happens next.
zero side effects.
Hi doc, how do you figure what dosage of clomid is right for someone? Let’s say a small dose raises levels to a low normal range but the individual has the potential the be in a higher range,how do you know what level is right for someone?
Hi Jake, check out my Doctor’s Corner: Clomiphene Rx post.
Is it common for men who take clomid to have a fluctuation of testicle size and hardness on different days?
Men typically don’t report that. I’d recommend that any man having that unusual effect see his doctor.
Is it better to take clomid in the morning or at night?
Clomiphene has a long half-life, up to a week, so it doesn’t matter what time of day that one takes it.
Doctor,
Does clomid in men has side effects like weight gain?
Hi May, I’m pretty sure that I’ve answered this before, so please read through the comments on this post and my other posts related to clomiphene and their comments. You’ll find useful information there. Some men report an increase in weight, and it could be related to either increased appetite or muscle mass.
I have used Testosterone plus deca durabolin for atleast 4 months . One testosterone depot 250mg and deca 50mg . I lately felt that my sexual drive is going down. I could not get an erection . Now I have started taking clomid I feel better but erection is not tthat hard …what do you suggest I am 60 years old and spend one and a half hours in the gym doing running , weight lifting etc . Please guide me what to do….I will be grateful
Hi Jawed, I can’t and don’t treat patients on this blog. Please read the FAQ.
“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.”
I’m a little confused. Why prescribe clomid to boost testosterone if it does not usually help with the symptoms of low test? Or have I misunderstood?
Would you say that clomid is equally effective for treating symptoms of low test when compared to straight testosterone therapy if it brings a patient to the same numerical levels? Or is there something else going on here?
Also, in your FAQ you mention that you do not recommend concurrent use of clomid and testosterone because there is no way to tell if it is working. But you do not say if it is unsafe (the stated question) or if it would have any effect in preserving fertility for a TRT patient.
Interesting blog. Thanks for the posts.
Men who have issues with fertility and low testosterone often don’t have other symptoms.
Hello Doc,
Have you heard of any studies linking the use of clomiphene to the occurrence or re-occurrence of testicular cancer? And will it’s use effect tumor makers like Beta-HCG or Alphafeto (s/p?) protein?
Best Wishes
I’ve not seen a well conducted study establishing a link between clomiphene and testis cancer. Keep in mind that there are different forms of testis cancer. The bHCG test may cross react with an increasing internal LH due to clomiphene, but that would be expected to be a highly individualized response.
Hello…I have cfs and been using small dose of clomid for 8 months /few miligrams per week. Is clomid safe? I have had no side effects just remarked imporvements.
Hi Hrvolje, scan through the comments on this post, and you’ll discover that I can’t answer personal questions about your own health. Please read the FAQ.
Yes i understand. Just wanted to know is it generally safe to use it..as some people said it has lot of side effects.. Thank you
I understand that different men react in different ways to HRT and this has been discussed before. But I am still confused about one thing.
Why is it that you could have two different men with the same testosterone levels but one man has higher estrogen levels than the other?
I know that you have answered a similar question before but possible explanations or theories on why some men have higher estrogen conversion than others have not been discussed. In other words do you guys have any explanation as to why this may be?
It’s a really good question. The answer is that the enzyme that converts testosterone to estradiol, aromatase, is different in different men. Geneticists call variations in genes that make the same protein “polymorphisms,” and these variations can cause subtle differences in the structure and function of the protein, in this case, aromatase. When you think about it, the reason that we’re all different from each other is in our polymorphisms.
1-Based on your practice or literature what are the recommended ranges of total and free testosterone before recommending Clomid?
2-What is the expeted range/percent in boosting total and free testosterone? Is it 20%, 50%,..etc?
3-What is the maximum length of clomid studies? I am interested in knowing if the side effects were studied only using short term or long term studies.
Thanks,
Mike
1. I use 300 ng/dL for total and 155 ng/dL for bioavailable as thresholds, adjusted for an individual man’s symptoms, physical examination, and other laboratory results. 2. It’s different for every man. 3. The vast majority of studies track side effects as a secondary outcome measure, not a primary one.
Does clomid work when both total and free testosterone are low? what is the main function of clomid when both total and free testosterone are low? When giving clomid to boost testosterone, does the patient need to take clomid forever?
Hi Rick, I’ve answered the “forever” question a few times: read through the other blog posts and comments, and you’ll find it there. As for clomiphene increasing free and total testosterone, typically it results in both.