Doctor’s Corner: Clomiphene Rx

July 6th, 2010 § 83 comments

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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.

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§ 83 Responses to Doctor’s Corner: Clomiphene Rx"

  • justin says:

    starting clomid for hypothalamus hypogonadism. What is the longest you have ever prescribed clomid? I am starting it now, since my system didn’t restart

    • maledoc says:

      Hi Justin, I can’t answer specific questions about a patient’s care on this blog. I take it that a doctor prescribed the medication? That would be a great question to ask him or her.

  • JC says:

    I have a total testosterone of 235 with an LH of 4.1 so I would probably be a good candidate for this. Unfortunately nobody will prescribe it to me because it’s off label and all they will offer me is straight TRT which I refuse to do for obvious reasons. I really feel terrible and I would like to try this. What is the best way to find a doctor who will prescribe it? I was thinking of trying it on my own but without access to labs it could be dangerous. Not sure what to do.

  • maledoc says:

    Hi JC, you would benefit from seeing a doctor with experience in male reproductive endocrinology. Usually doctors will refer patients to other subspecialty care physicians for patients who need that kind of care. If you live in the United States, the American Urological Association (http://www.auanet.org/) can direct you to a Urologist in your area, and if that doctor can’t treat you, her or she can direct you to someone who can.

  • AK says:

    Doctor, Does maintaining clomiphene’s “stimulation” of the pituitary require continuous treatment, or is this something that men can take for a finite period – after which the pituitary would “remain” stimulated? In other words, is clomiphene in men prescribed for weeks, months, or life?

    • maledoc says:

      Great question, AK. If the underlying problem is finite, (the pituitary has suffered some ill from which it is recovering,) then clomiphene treatment can be short term. If not, then it would need to be continuous. Often times, that can only be determined by trying to discontinue the medication once it has been prescribed. The target of therapy also needs to be taken into account: if the testosterone is in borderline range and clomiphene is prescribed in an attempt to stimulate the making of sperm, then it can be discontinued after the baby (or babies) has (have) come.

      • AK says:

        Thanks for the reply. The reason I asked is because I had heard that clomiphene is not used in men for more than a 90-day therapeutic period – even in cases of chronic central hypogonadism, and, that even during the therapeutic period, it’s recommended that patients not take the pills for several days of each month to give estrogen receptors a chance to be re-stimulated a little. The thinking, apparently, is that estrogen is needed for bone structure in men and that many under-active pituitary glands – even those that have been under-active for decades can be “jolted” back into permanent normal functioning after the therapeutic period is over. It sounded very unrealistic when I heard it which is why I was anxious to hear your expert opinion. To me, it sounds like “kicking an old TV set to get better reception” Have you ever heard of this? Does it have any merit? And, if not, is there any literature about the safety of continuous long-term use of clomiphene in men?

        • maledoc says:

          There are a number of opinions based on biology, but I don’t believe my clinical experience supports that particular one. Unfortunately, there is not long-term safety data available on the use of clomiphene.

  • AK says:

    Thanks again. I’ve been continuing my research. I know that message boards filled with people’s personal experiences with medications are usually hard to judge anything from, however i’ve been seeing a common complaint online among many that have “tried” clomiphene for hypogonadism stating that their already low libidos went even lower on the medication. It sounds hard to believe given how the medication works, but it’s a complaint repeated by many – not just a random few. Is it possible that this is an “early” effect and that these patients are not giving the medication a chance to work? How long should it be expected to take for beneficial effects like normalized libido, energy, and memory to be felt from clomiphene?

  • David Morris says:

    In your practice or in studies are there any known “common” side efects or reactions to clomid in men? Another question: knowing there are no long-term studies, is there evidence that you know of re. adverse effects to the pituitary, and its consequences?

    • maledoc says:

      Hi David, I answer most of this in my post, How Clomid Works in Men. Head on over there, and then let me know if you have any questions.

      I really need to figure out a way to make this blog easier to navigate. I thought the word cloud might be helpful, but it’s not as useful as I originally thought. If any of you are WordPress gurus, please let me know the kinds of UI navigation systems that work well…

  • Scott says:

    Question
    Do you think it would be safe to take androgel and clomid at 50 mg a day to keep LH up at the same time long term as long as LH stayed in the normal range?
    If not why not?

  • Joe says:

    If Androgel is take for an extended period of time doesn’t the production of FSH decrease? Doesn’t FSH cause sperm production? How would a person in their 30s take TRT and still be able to have children later in life?

    • maledoc says:

      Hi Joe, it depends on the guy. Many men who take testosterone (e.g. Androgel) have high FSH as an indicator of their deteriorating sperm factory. FSH is involved in sperm production, yes, but it’s not the only factor. Such a person in their 30s who might need testosterone treatment and who is interested in fertility should really see a qualified health professional who can help him do both. That person might find the FAQ helpful in identifying a good doctor.

  • Don says:

    From the work of Dr. Katz et. al. it appears long term data to support the use of clomiphene for secondary hypogonadism is becoming available.

    I don’t understand at this point it is considered off label use for this condition. How long should it take for the large insurance companies and the FDA to agree a treatment is considered conventional.

    Thank-you for your blog Maledoc.

  • Don says:

    I guess the blog filters web link. So google ‘Katz clomiphene modernmedicine.com” and the article should come up.

  • Greg says:

    Wondered what your thoughts were about the phase 2 trials with androxal (a related drug to clomid )? Is this something you will consider for your patients long term if/when it receives FDA approval?
    Thanks.

  • Dr. Harris says:

    “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. ”

    And what is the ratio of TT to estradiol is <10 but the response of clomid to TT level is good? What implications can elevated estradiol have for males?

    Thanks

    Dr. H

    • maledoc says:

      My clinical observation has been that above 50 pg/mL, estradiol is associated with effects in the male such as gynecomastia and heightened emotions. I typically target estradiol in therapy to be less than that level.

  • Dr. Harris says:

    Thanks for your quick reply. And if estradiol is above 50 pg/ml, is there anything to suppress this (e.g. aromatase inhibitor)?

  • Dr. Harris says:

    Thanks. I did read that, but can you use anastrazole and clomid in combination?

  • Dr. Harris says:

    Why do men on clomid gain weight? Do you think weight gain is to to water retention or something else?

    • maledoc says:

      Not everyone gains weight while taking clomiphene, but many men do, and for different reasons. Increasing muscle mass increases weight, and some men say that they’re hungrier and eat more.

  • harris says:

    Thanks. In your 20-year experience of using clomid in men, have you had any cases with liver tumors or any other cancers? Any other serious effects in long-term users based on your experience?

    • maledoc says:

      No, but without a well done, long-term study, I can’t be sure that there aren’t problems with long-term use. That’s why I counsel men that these studies haven’t been done, and let them make up their own minds. Someday, we’ll hopefully have long-term data.

  • Kim D. says:

    Dr NIederberger,
    Few questions here, I have searched all your blogs and have not seen the information elsewhere so I hope I’m not reasking anything.
    First, How would you expect to see sperm counts rise in accordance with tx? As the Testosterone level increases would you expect to see sperm counts doing the same or would you not expect to see changes in the sperm count until the total level is around/maintained in 600ng/dl range?
    Second, I recently heard a doctor stating that if the pitutary is fx than there is no reason why testosterone would cause a decrease in sperm production and that it is still able to be taken even while trying to conceive. Is there any truth to this, everything I have heard and researched seems to suggest that if a ouple is trying to conceive that testosterone should be avoided (that is the impression I get from your blog and knol post and other information).
    Third have you seen much success with sperm return after 5+ years of TRT? Are there any parameters you use for a cut off to say that in certain situations one would most likely not see a return or increase in sperm?
    Thank you for any information you can provide! Your blgs and other resources I have come across are wonderful!!!

    • maledoc says:

      The relationship between testosterone and sperm is different for each man, and depends on the underlying problem with testosterone production. I would encourage any man who is concerned about his testosterone and sperm to see a doctor for individualized treatment.

  • harris says:

    can clomid cause urge to urinate several times at night even though the bladder is not full?

    • maledoc says:

      That’s not a typical side effect of the medication. Any man experiencing the urge to urinate several times at night would be best served by a visit to a urologist.

  • Peter says:

    When using clomid for TRT, would you say in your experience that it is also effective for treating low T symptoms? I have heard conflicting reports concerning its helpfulness for symptom relief despite universal agreement that is raises T levels.

  • Dr S says:

    What is your take on exemestane used in place of clomid? Exemestane has shown no side effects when compared to clomid, in fact Exemestane mainatins IGF-1 levels in men and no effect on lipids.

    This isnt something i have prescribed, however i have been researching it ever since my patient brought it up in converstaion.

    I’ve seen warnings of Damage to sperm production from Exemestane use, But again studies seem to only be based on doses of 200times normal human administered doses.

    • Dr S says:

      as an adjuct to my previous post, rumour has it- but i cant find the evidence that exemestane is currently being used in fertility treament in men.

    • maledoc says:

      Hi Dr. S, exemestane is an aromatase inhibitor unlike clomiphene. The aromatase inhibitor with which I have the most experience is anastrozole, and I’ve written about it a bit on other posts on this blog.

  • Dr S says:

    letrozole also has studies indicating damage to sperm production if used.
    see study. http://repository.ias.ac.in/21560/1/307.pdf

    i dont reccomend letrozole based on this study alone

    so going back to your blog, clomid or tamoxifen would be best for testosterone increases.

    clomid has shown itself to decrease in the LH response to LH-releasing hormone after a period of 6 weeks, tamoxifen does not for the same effect.

    is there a reason for your preference of clomid over tamoxifen apart from previous studies?

    • maledoc says:

      I’ve answered this a few times in other posts and comments, so you’ll want to peruse those. Mainly due to the majority of studies being performed with clomiphene.

      • Dr S says:

        yes i know you use clomid based on more studies being available for clomid- i have perused your bloods and replies-but the studies shown on the newer generation tamoxifem show that tamoxifen doesnt desensitise the body to LH, Clomid does- also tamoxifen requires 20 mg vs clomids 150mg for the same resultant testosterone increase ~150%

        Thought it would be of interest to you as a Dr specialising in mens health- i like to share my experiences with fellow Drs.

  • Dr S says:

    http://www.ncbi.nlm.nih.gov/pubmed/8174730
    this is the study showing the clomids effect on LH response to LHRH- sorry i neglected to attach this in my previous post

  • Dan says:

    Does taking Androgel seriously increase the risk of prostate cancer? I’ve heard it is fine to take if you don’t have any cancer, but if you do it is like “throwing gasoline on a fire”. I’ve also read that most any male over 60, if their prostate were dissected, would find some cancer cells. Would taking Androgel then cause those few cancer cells, that might just remain very very slow growing and never cause any harm, to suddenly begin multiplying with the addition of Androgel, and lead to an ‘active’ cancer?

    • maledoc says:

      Dan, you ask a very important question to which we still don’t completely know the answer. If a man has prostate cancer that responds to testosterone, it is called “androgen dependent” and giving testosterone may encourage it to grow. That’s why it’s so important for a man taking Androgel or any testosterone supplement to be monitored under the care of a doctor.

  • Austin says:

    I saw a comment on your “How Clomid Works in Men” entry that directed a user here for information on typical dosages and periods on/off.

    I see where you like to start with dosages of 25mg and can either go up from there or stop the use of Clomid and prescribe an aromatase inhibitor.

    However, I can’t find where you show typical periods of use. I know that long-term effects are uncertain and that you let the patient know this and have them make up their mind on how long to take Clomid, but in a typical scenario how often does a patient take Clomid and can they expect the benefits from Clomid to disappear when use is discontinued?

    • maledoc says:

      Hi Austin, there really isn’t a typical scenario for duration of use. All patients have different needs and goals, and it’s tailored to the individual. It usually requires an involved discussion in person.

  • Hank says:

    Hi Dr Niederberger,

    I wondered what your thoughts/experiences are of using pregnenolone instead of, or in addition to, clomiphene in order to raise testosterone levels? Have you found either solution to be effective?

    Thanks,
    Hank

    • maledoc says:

      Hi Hank, I haven’t used pregnenolone in the male. As far as I can tell, there are very few studies on its use in the male either in animals or humans, so I don’t know whether it would inhibit pituitary hormones or provide more building blocks for testosterone (or both or neither.)

  • Dan says:

    Does the effect of clomiphene vary according to the time of day of when it is taken?
    Thank you for an excellent resource.

  • Trevor Smith says:

    Doc, really enjoyed your blogs they are very informative. I was on clomid for 1 month and my low testosterone, fsh, lh more than doubled. I had 1 month off and after another blood trst fsh and lh decreased almost to what they were however the test reduced but not as low as it was previously. Folks clomid works..and it doesnt screw up your fertility unlike trt. When i was on trt for 3 years it took 9 months for my test to rise but even then it only rose to what it was before.

  • mark says:

    HCG produces the same effect as Clomid: It blocks estrogen at the pituitary, thus preserving the pituitary’s secrection of LH. Do you prefer Clomid over HCG? Any reasons why? Is it possible or necessary to alternate Clomid and HCG? Thanks, this blog is great!!!

    • maledoc says:

      Thanks, Mark! Clomid works on the pituitary, where hCG takes over the pituitary. As hCG is more difficult for guys, (it has to be injected,) and is much more expensive than clomiphene, it seems like the best first choice in most situations.

  • mark says:

    Why not prescribe Anastrozole and Clomid together? Seems like they could work in harmony with natural chemistry if estrodiol is too high. Clomid stimulates testosterone production, and Anastrozole prevents too much testosterone conversion to estrodiol.

    • maledoc says:

      Mainly because anastrozole does the trick alone. The reason that I recommend clomiphene first in men is that estrogen is necessary in men for things like bone density. But if the estradiol is too high, anastrozole will both increase testosterone and lower estradiol. Guys need to be monitored on anastrozole by their doctors to make sure that problems aren’t occurring because the estradiol is no longer there.

  • linda says:

    Are there any studies or information about clomid causing problems for people with mood disorders? I can’t find any information about this issue with Clomid although there is plenty of information out there about the problems with steroid meds such as testim or androgel. I think I have fairly thoroughly checked your site, so if it’s on here already would appreciate direction in how to find it.

  • Felipe Negron says:

    I am looking for a doctor in the Chicago land area that can treat me for Low T. Can you help?

  • Stan says:

    What, if any experience have you had with Nebido? I know that it supposedly is released over a period of 3 months or so. But the effects of it compared to other TRT? Also it is not available in the U.S.
    Thank you for your comments

    • maledoc says:

      Hi Stan, as a U.S. physician, I have no experience with Nebido. I’ve heard that the FDA is considering it and should make their decision shortly. (In the U.S. it will apparently be called Aveed.)

  • Tim peterson says:

    Why is clomid prescribed for 25 days on with 5 days off? Even with a 24 hr plus half life it would seem days 2-5 off would have a much lower T level is there another med prescribed for those 5 days or just a resting period…does the 5 days off affect fertility?

  • Venkat says:

    Kindly differentiate clomiphene citrate and clomifine..

    • maledoc says:

      Hi Venkat, I hadn’t heard of “clomifine” before, but it sounded like “clomiphene”, so I just looked it up on Wikipedia and found that it’s the international nonproprietary name for clomiphene. Thanks for teaching me something!

  • Venkat says:

    Sir before my query, as perper Tim PetersonPeterson…

    He was suppose to say that the dose was prescribed to take daily one upto 25days for a month and take 5days rest and start again to 1-25 for men only..

    But i learned that dose for 24days daily with 25mg and take rest for six days and initiate again as same.. And i also learned that these kind dosage may shortened the possibility than the dose taken as below..

    25mg of clomiphene for day after day/ day other day upto 3 to 6 months as per directed by the physicians.

    But here it was prescribed the tab named CCQ 25mg which additionally included UBIDECARENONE SALT WITH Clomiphene. But dosage was quite confused here they prescribed the dosage for 3months daily one tab FOR MEN.

    After i found that THE REGULAR USAGE OF THE CLOMIPHENE IN MEN MAY ALSO CAUSE LOWER THE SPERM QUALITY N QUANTITY FOR VERY FEW PEOPLE.

    DOCTER PLEASE GUIDE US IN GOOD MANNER.

    THANKS FOR THE APPRECIATION SIR.

    AND Vitamin E, WHAT KIND OF ROLE PLAYING IN infertility developing and if included with Ubidecarenone also……?

  • Venkat says:

    And finally need the dosage schedule.

    It should take with breakfast or with lunch or dinner.

    And what kind of medicine / health drinks not to be intake while this course of dosage. And in addition is there any health drink like Ensure, horlicks…etc to be taken or can be taken…?

    And finally when he should start the intercourse to take the possibilities to positive within the due course….?

    Please please don’t skip my two comments..

    Here it is not so easy to get the correct directions/info and even we have no hopr to get so..

    Is Ubidecarenone was mandat or that was also can help in sperm quality or only for heart left ventrical disorder..?

    Plz help us.

  • Venkat says:

    Sir atleast a few ans’s for my queries, m from india.

    • maledoc says:

      I’m sorry, but I would be doing you a disservice to practice medicine over the internet. Please read the FAQ. India is a special and wonderful place: I’ve been there a number of times. I am sorry that you are experiencing personal health difficulties, and I wish you the very best.

  • NP-BD says:

    “My clinical observation has been that above 50 pg/mL, estradiol is associated with effects in the male such as gynecomastia and heightened emotions. I typically target estradiol in therapy to be less than that level.”
    ===============================================
    But if a patient has more than 50 pg/mL along with gynecomastia and low testosterone before starting Clomid, then what will be the treatment method? Clomid & Aromatase Inhibitor together?

  • Chris says:

    Hi. I started a patient on clomiphene for sustained low testosterone. He did not want injected testosterone and I saw this as an option. I just did the two week follow up labs-testosterone did increase nicely but LH and FSH did as well. 12.2 and 15.7 respectively. Everything else normal. Any parameters, specifically with LH and FSH, that should be noted with the variance in these labs as far as maintaining patient on medication? Thank you

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