The AFA Blog

The Story of Testosterone

by Craig Niederberger, M.D., F.A.C.S.

When you think of what makes up the inside of the testes, think spaghetti. Imagine a bunch of spaghetti noodles squished together. Inside of the noodles are the developing sperm cells. Between the noodles are cells called “Leydig cells” whose job it is to make the male hormone testosterone. They start with cholesterol, and churn out testosterone.

Not only is testosterone critical to the factory inside the spaghetti that makes sperm, it is important for many parts of the male body to work well. Adequate testosterone is needed for bone and muscle strength, and men with low testosterone may experience low sex drive, problems with mental focus and depression.

The relationship between testosterone and how the penis works is less clear. Men with low testosterone can get erections, but of course sex drive can be a problem. And if a man’s testosterone is low, correcting it may improve the performance of drugs like Viagra, Levitra and Cialis.

Total testosterone doesn’t tell you the whole story. Testosterone circulates in the blood in two forms. Testosterone that is either free or loosely bound to blood protein is called “bioavailable”, and as the name implies, is available for the cells to work. Testosterone that is bound to sex hormone binding globulin (“SHBG”, but also called androgen binding protein,) is blocked from acting in cells. Although many labs offer to measure free testosterone, often the most reliable way to measure bioavailable testosterone is to have the blood tested for albumin, sex hormone binding globulin and testosterone, and then to use a calculator for bioavailable testosterone. One is available on the International Society for the Study of the Aging Male’s web site, and another for iPhones and iPod touches can be found in the iTunes store. A man may have adequate total testosterone, but still suffer from the ravages of low testosterone levels if his bioavailable testosterone is low.

Testosterone levels rise and fall during the day, with a peak in the early morning, and the lowest point in the late afternoon. That’s why many a man’s sex drive is highest in the morning, and it’s time for a nap in the afternoon.

Testosterone is converted to dihydrotestosterone, which makes the hair fall out of your hair follicles if your family tree has male pattern baldness. Dihydrotestosterone also enlarges the prostate. Drugs like finasteride (Propecia and Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone.

All men have a little estrogen, the female hormone. An enzyme called “aromatase” converts testosterone to estrogen. If the estrogen level is too high, it may interfere with the working of testosterone.

One last important point about the making of testosterone: levels in the testis are twenty times greater than in the blood. So if a man is given testosterone, his blood levels may increase, but the pituitary tells the testis, “hey, there’s enough testosterone around, so stop making it.” As a result, testosterone levels in the testis fall, sperm stop being made, and the testes shrink. That’s why many body builders who take testosterone and other similar chemicals experience shrinking testes. Testosterone can be great for men with low levels later in life, but for men who want to have children, it can really work against sperm production.

 

Leading experts bring infertility prevention awareness to University of Colorado

DENVER, Feb. 21, 2011 /PRNewswire/ -- The American Fertility Association (The AFA), a national family-building non-profit organization, is heading to college campuses around the country to educate young men and women about infertility - a disease affecting one out of 6 couples in the U.S. The 2011 College Tour Series kicks off on March 4th at the University of Colorado in Boulder with a presentation entitled "Why Mother Nature Wants You To Get Laid Right Now". Students will learn about preventing infertility by avoiding certain environmental toxins, STI (Sexually Transmitted Infection) prevention, and about the realities of the biological clock. Brenda Strong, The AFA's national spokesperson, board member, and Desperate Housewives actress, will be on hand to talk about the benefits of yoga to help alleviate stress, which can affect fertility. She will also lead a yoga demonstration for the students. Though The AFA's goal is to prevent infertility whenever possible, sometimes infertility can't be avoided. Dr. Mark Bush, a reproductive endocrinologist with Conceptions Reproductive Associates in Denver, will speak at the event so students are aware of savvy treatment options.  Executive Director Ken Mosesian and Program Director Corey Whelan will discuss infertility prevention for men and women, environmental toxin avoidance, and STI (sexually transmitted infection) avoidance.

Later that night, The AFA will honor Dr. Mark Bush with the Joyce M. Vargyas, MD, Visionary Award at the Illuminations Denver cocktail party. Dr. Bush has extensive experience in all aspects of reproductive endocrinology, infertility, and assisted reproductive technologies. He has published numerous scientific and clinical papers in the field of women's health. Recently, Dr. Bush has taken a serious interest in elective single embryo transfer in order to avoid multiple births. The AFA strongly supports the use of single embryo transfer when possible for the safety of the patient and the child.

This year's Illuminations Denver will focus on The AFA's work, empowering young men and women to take control of their fertility. Illuminations Denver will be held at Palazzo Verdi at Fiddler's Green, and special guests will include Brenda Strong, Dr. Kevin Fitzgerald from Comedy Central and Animal Planet and pianist Joseph Eisele with the prestigious Young Musicians Foundation of Colorado. The event is designed to raise much-needed funds to support the educational outreach work of The American Fertility Association.

The media is welcome, and encouraged, to attend both events. The AFA would like to thank all of our sponsors who are helping to make both of these events a huge success, including our Platinum Event Sponsors, Ferring Pharmaceuticals and Conceptions Reproductive Associates, and our Gold Event Sponsor EMD Serono. Special thanks to Disney / ABC Television Group for their support as the Charter Sponsor of our 2011 College Tour. If you're interested in sponsoring Illuminations Denver or purchasing tickets, please contact Corey Whelan at 718-853-1411.

Press Contact: Merry Armentrout Director of Communications, The AFA 205-470-9406 [email protected]

The American Fertility Association, a 501(c)(3) national non-profit organization, is a resource for infertility prevention, reproductive health and family-building. AFA services and materials are provided free of charge and without reservation. These services include an extensive online library, resource directory, hosted message boards, daily fertility news and a toll-free support line. http://www.theafa.org or 888.917.3777

This press release was issued through eReleases(R). For more information, visit eReleases Press Release Distribution at http://www.ereleases.com.

SOURCE American Fertility Association

Read more: Preventing Infertility and the Future of Fertility Treatments - The Denver Post http://www.denverpost.com/coloradocorporatestatements/ci_17442679#ixzz1EdBw9Rec
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Antioxidants and Reproductive Health

By Harry Fisch, MD

Everybody knows that we need oxygen to live. In the body, oxygen is vital for many of the chemical reactions that keep us alive and healthy. But these reactions also produce "free radicals" – highly unstable molecules that can damage cells. Free radicals are produced when the body breaks down foods for use or storage. They are also produced when the body is exposed to tobacco smoke, radiation and environmental contaminants.
 
The body protects itself from free radicals by producing antioxidants – molecules that neutralize or destroy free radicals. We also get antioxidants from food. Antioxidants are abundant in vegetables and fruits and are also found in grain cereals, teas, legumes and nuts. Examples of antioxidants include anthocyanins, beta-carotene, flavonoids, lipoic acid, lutein, lycopene, selenium, and vitamins C and E.
 
In lab experiments, antioxidant molecules clearly block the damage that can be caused by free radicals. It is not as clear whether consuming antioxidants – in food or supplement form – actually benefits health. Many studies have now been conducted and the evidence is mixed. Interestingly, however, it may be that one area in which antioxidants play a key role is in supporting sexual health and fertility.  
 
A recent article in the respected Cochrane Database of Systematic Reviews found that among couples undergoing fertility treatments, men taking antioxidants were over fourfold more likely than men not taking supplements to get their partner pregnant and see a successful live birth.
 
"When trying to conceive as part of an assisted reproductive program, it may be advisable to encourage the male partner to take an oral antioxidant supplement to improve his partner's chance of conceiving," the authors concluded.
 
Further studies are needed to confirm these results, but the findings are certainly encouraging. They also make sense from a physiological perspective. Semen contains vitamins E and C and other antioxidants to scavenge free radicals, which can break down sperm membranes and damage sperm DNA. It may be that oxidative stress damage to sperm contributes significantly to male subfertility. Antioxidants are a key ingredient in a supplement I’ve developed called the Sexual Health Formula.

The clinical trials that were reviewed in the Cochrane paper used a wide range of antioxidant supplements, predominantly vitamin E, vitamin C, carotenoids, ubiquinol, folate and zinc. No one antioxidant seemed to be better than another.   
 
As with any type of supplement, you shouldn’t use antioxidants as a replacement for a healthful diet and lifestyle. Fresh fruits and vegetables contain a wealth of important nutrients in addition to antioxidants, and your overall sexual health is supported by many things such as getting enough exercise, sleep, and avoiding obviously unhealthy habits such as smoking.

It’s also a good idea to let your doctor know if you decide to take an antioxidant supplement and to avoid mega-doses, which might be harmful. The bottom line, though, is that antioxidants are very beneficial and they may be particularly helpful in maintaining sexual health and fertility.

 

Just dance.

by Corey Whelan

There are some weeks when my days begin like bubbling cauldrons.  Too much work (a good thing, seriously).  Too little time.  A book to illustrate.  A teenager to placate.  A life to live.  That makes me one of the lucky ones, btw.

One day last week I popped on my headphones and turned on my computer and found, well, nirvana.  The AFA's dear friends and allies at Associacao Portuguesa de Fertilidade, had posted a Michael Buble video on their Facebook wall with the simple affirmation "Music Break".  Ok, that I can do! Because music, and movement, shifts reality in only positive ways.  But of course, you already know that.

My dear sisters.  For those of you who are currently TTC and gritting your teeth.  For those of you who are pregnant after TTC and freaked out.  For those of you who are finally mommies and haven't brushed your hair in three days.  Breathe, girlfriends. 

Oh, and by the way?  For you brave and amazing men who just "don't know what she wants, how the hell can I be there for her anymore?" I have a simple directive for all of you.

Just dance.

Hey people.  It's Monday morning.  What could be more important than this?

Just dance.

 

 

Your infertility arsenal for 2011

by Corey Whelan

A new year, a new you. 

Easier said than felt, particularly for women who have spent the last year (or longer) trying to get pregnant, without success.

Let's face it, we often experience Infertility as a powerful enemy.. And one of this most hated enemy's weapons is it's ability to diminish the feeling of control that we so covet, even require, in our own lives. 

While it's true that you may not be able to eradicate infertility at will from your own life, you can absolutely opt to disable this element of the experience and to achieve more balance, and control, than you currently may be experiencing.  And you have the right to do that.  Believe it or not, you have an arsenal at your finger tips.  You simply need to call it up, and now is a good time to practice doing that.  While every woman's arsenal will vary somewhat, there are a few handy dandy items you should always tote around in yours.

Laugh. Ever hear the expression "fake it till you make it"?  There's nothing wrong with having fun, and joy in your life. It's not fattening and it won't stop you from getting pregnant.  Funny movies and television shows are more than just a diversion. They are often a life saver.  Pick your pleasure, and pick it often.

Talk. It's no secret that infertility puts a strain on the hardiest of relationships. You may be feeling this in your romantic life, your family life and your friendships.  But always remember, you are loved, even if you may not be feeling an avalanche of the kind of support you need coming at you from friends and family right now.  Something that might help is this.  Enlist the shoulder of the person that you feel is best armed to support you through this piece of your life, and request of him or her an oasis of time, just for you, on a daily basis to simply talk.  This is your opportunity to dump, to scream, to cry, to blurt out everything you are feeling without judgement or even that person's opinions or comments (unless you request them).  If you need to enlist more than one person, that's ok.  And if no one comes to mind but this sounds like something you could use, well, that's what therapists are for.

Choose.  Not everyone will be able to hang in there with you through this time.  It doesn't mean they don't care about you or you about them.  But you have the right to choose who you spend time with and who you don't.  If you can't handle that annual family get together or party, then don't go.  Baby showers?  Up to you.  And, if you get a nagging feeling that a friend is not able, or willing to support you through this right now, gently put a hiatus on the friendship. You're in control, remember?  Exercise that control.

Move.  Movement displaces anxiety.  Take a walk, take a run, take a yoga class, but take your body to a transformative place by giving it time to breathe, and heal, through movement.  Your body, despite it's current trying to conceive and not getting there state, is still an instrument of joy, and pleasure.  Let it be that for you.

Touch. You have the right to enjoy your sex life.  Baby making sex is not the only kind of sex there is, remember?  Find creative ways to get back in touch with that, and then, find some more.

Thank. Think about what you have in your life to be grateful for and give thanks for that.  You are still you, and there is more to you than this experience.  Try giving thanks for what you currently have.  If this feels too difficult for you right now, let it go for a day, or two. Consider it a goal for tomorrow.  But hold onto this one, it's a goal worth acheiving. 

Remember. Yesterday is gone, and tomorrow is a new day.  Your life will not always feel like this.  Remember to be kind to yourself and to hold on to all of the tomorrows, and all of the dreams, that are still ahead of you.

Happy New Year to all of the women who so want to be mommies but who are not there yet. I hope that 2011 will be your year.     

Reprinted with permission from examiner.com

Photo: 123RF

Timing Sex

by Craig Niederberger, M.D., F.A.C.S.

If you’re trying to get pregnant, something useful to know is how often to have sex.  Sperm counts peak at two to three days after ejaculation, meaning, after you have sex (or masturbate,) the swimmers will be most abundant two to three days later.  Sperm live for about 48 hours in the female reproductive tract, so the optimum timing is sex every other day.

However, don’t freak out if you have an especially romantic weekend with a little extra frequent activity, or get caught up and miss a few days.  Stressing out about sex is counter productive, as stress itself can result in poorer sperm quality.

I’m often asked when during the month (or cycle) a couple should try to conceive.  Studies show that conception usually happens up to six days before, and ending on, ovulation.  The big problem is that most tests for ovulation show the event after it happens.  So a good plan is start having sex every other day after menstruation ends, and keep going until the next menstruation.

So, soldier on.  Have sex every other day.  Doctor's orders.

Craig Niederberger, M.D., F.A.C.S. is a highly published author and editor, and head of the Department of Urology, University of Illinois at Chicago. His blog, Male Health, and other writings will be syndicated on this page for The American Fertility Association's readership 

Cervical Stenosis from an Abnormal PAP Smear

by Fred Licciardi, M.D.

Today we are going to talk more about blockage of the cervical canal: Cervical Stenosis. We will concentrate on the most common causes of cervical stenosis; scaring that results from the treatment of an abnormal pap smear.

Treatment of an abnormal pap can cause scarring of the lower part of the cervix, the external os. This type of scar is a problem for two reasons. First, it reduces the number of mucus producing cells, sometimes lowering natural fertility. Second, it may make fertility procedures, such as insemination or embryo transfer, more difficult.

Most cases of cervical stenosis occur as a result of improper healing from a surgical procedure. It may not be that the procedure was done improperly; it’s just that the healing did not cooperate

It is cells in the area of the external os that are tested during a pap smear. When these cells look abnormal, we need to remove them before they progress to cervical cancer. We treat the abnormal cells by either by destroying them or removing them: both processes can cause scarring. Examples of destroying the tissue include cauterization (basically burning away with electricity or a laser) and cryo.

Cautery just basically fries the cells away, some abnormal and some normal tissue. Cryo literally freezes off some of the tissue of the external os, removing abnormally growing cells and some normal tissue. Cryo and cautery are not popular because they do not give you any tissue to send to the lab.

Rather than destroying cervical tissue, there are other procedures that remove a small piece. Examples of tissue removal include a cone biopsy or a LEEP (Loop Electrosurgical Excision Procedure). The cone procedure and LEEP are basically the same thing, however if necessary the LEEP can be a little more precise and remove a smaller amount of normal tissue. The LEEP and the cone biopsy cut away pieces of tissue that can be further evaluated under the microscope.

A cone involves and old fashioned scalpel, and takes away a larger piece in the shape of a cone (pictures to follow). The LEEP uses a thin wire loop that scoops out a little piece. However, sometimes using a LEEP the doctor needs to take a larger area as if a cone were being performed. Today, most procedures are LEEP procedures because the biopsy can be directed; in other words, only a small area can be removed if necessary. In addition, the LEEP can be performed in the office as opposed to the hospital. Finally, there is a lower chance of bleeding with a LEEP.

No matter which of these procedures is performed, a small percentage of people can have post-op scarring that leads to cervical stenosis. The more tissue removed or destroyed, the greater the chance of a scar.

Why do some people scar an others not? Some people are just more prone to it. Scaring is the normal way we heal. For some women, the scarring is more robust and progresses enough to cover over the cervical canal. Certainly, if any of these procedures are followed by infection, scarring will be more likely.

Let’s go through the pictures.

Here is our uterine drawing showing the uterus and cervix.












The next picture is a drawing of what your doctor sees when she puts in the speculum. It’s the cervix, actually the very bottom of the cervix.








Let’s say your pap comes back abnormal. This usually means that there are some cells around the external os that are abnormal. Depending on the severity of the pap, these cells may need to be removed. Using some special techniques, you doctor would look very carefully at your cervix under magnification to try to determine the extent and location of the abnormality.
This picture is an example of abnormal cells in a very small area.







Here, the doctor does not need to remove much tissue, and this is not likely to lead to scarring. The doctor will probably use the LEEP procedure, but only a small amount of cervix needs to be removed. This picture shows a cervix with a small abnormality and a small LEEP.












This picture shows a case where there is a larger amount abnormal cells and they take up a larger area on the cervix.









In this case, the abnormal cells are all around the external os. Here, the doctor needs to take away much more tissue.






You can see that the shape of the removed tissue is in the shape of a cone, thus the term cone biopsy. A larger LEEP will also make a cone shaped biopsy. While the odds of scaring remain low, if it does happen, it is more likely to come from taking more tissue. The next picture shows a post-LEEP scar.











The good news is that in most cases, scarring at the external os is the easiest to deal with. Unlike scar tissue that forms higher up in the cervix, scarring at the external os can be seen with a speculum and the scar is usually shallow. The scar is usually on the thin side and can be easily opened, usually in the office.

After opening, the scar may have a tendency to return, but re-opening is not that difficult. In the case of fertility treatments such as insemination and embryo transfer, the scar can be opened just prior to these procedures without much difficulty. Unfortunately some women can have more serious scarring after these procedures that is not so easy to deal with. Additionally, some women need to have multiple biopsies, and this will increase the scar risk.

Varicose Veins in the Scrotum: What's the Deal?

by Craig Niederberger, M.D., F.A.C.S.

The testes must be kept cool for the proper production of sperm.  One way the human body achieves this is to house them outside the body.  Another is to have a network of veins surrounding the artery pumping blood into the testis: the veins take the heat away in a “counter-current” heat exchange similar to a radiator.  (The human body is an amazing piece of engineering.)

Arteries don’t need to worry about moving blood; there’s a huge amount of pressure coming from the heart to help with that.  But once the blood goes through the capillaries and into the veins, getting back to the heart isn’t easy.  Veins have little valves to help hold the blood while it pulses its way back.  If those little valves start to separate, the vein expands, causing the condition known as a “varicose vein.”  Varicose veins can happen in many places in the body, often visibly in the skin of the legs, but, believe it or not, also in the scrotum.  And if varicose veins develop in the scrotum, they can disturb the counter-current heat exchange.  The testes then get hot, posing a problem for developing sperm cells.

Varicose veins in the scrotum are called a “varicocele,” and there are three kinds.  A grade I varicocele can’t be felt or seen without equipment like ultrasound.  Almost all experts now consider grade I varicoceles to be unimportant.  Varicoceles that can be felt (grade II) or visible by the naked eye (grade III) are the ones that may cause problems with sperm production.

Some men have such high sperm production that their varicoceles don’t significantly alter their chance of making women pregnant.  But many men’s testes are affected by grade II or III varicoceles.

What can be done about a varicocele that may be throwing a wrench into the sperm factory?  A urologist can tie or clip the veins in a procedure called “varicocelectomy,” or an interventional radiologist can inject material into the veins to block the flow of blood.

Craig Niederberger, M.D., F.A.C.S. is a highly published author and editor, and head of the Department of Urology, University of Illinois at Chicago. His blog, Male Health, and other writings will be syndicated on this page for The American Fertility Association's readership 

Painkillers in pregnancy and male babies

by Maria Portella  

In the written press as well as on the  internet these last couple of weeks, particularly in Europe, articles have started to appear, stating that common painkillers could be linked to male reproductive disorders.  It was reported that scientists had found a link between the use of mild painkillers in pregnancy and the risk of giving birth to a son with undescended testicals with the possible consequences of having both poor sperm quality, as well as the potential for the emergence of testicular germ cell cancer in later life.

The study was done by researchers from the University of Copenhagen as well as other academic and medical institutions in Denmark, Finland and France.

The study featured both an analysis of pregnant women’s medication use and also data on animal research studies which analyzed testes development in rats; one potential outcome of the study indicated that the timing and duration of the mild painkiller use during pregnancy was linked to the risk of undescended testes in male babies. The research also suggests that ibuprofen, aspirin, and other nonsteroidal anti-inflammatory painkillers act as hormonal "endocrine disruptors" thus interfereingwith normal male sexual development.  The greatest window of risk appears to be in the second trimester of pregnancy in humans.

To anyone reading the headlines these articles might be worrying at first blush.  For example, it seems to suggest that even paracetemol (acetaminophen) may increase the risk in male babies (to a lesser degree).  

In addition, there are many women presently being prescribed low dose aspirin during pregnancy to address cases of miscarriage risk or blood-clotting disorders (it is important to note that low dose aspirin is only a quarter of the regular, standard dose). Women in this situation may feel in a conundrum about what to do when managing the relative risks of both taking, and not taking, this medication.  First up the advice to anyone pregnant that has taken such painkillers and is concerned about these findings is clear:  consult with your doctor.  

The British NHS Choices website states: "It is preliminary but important evidence, although at the moment, it is unlikely to change the current recommendations to pregnant women. These are to: avoid medications in general and to use paracetamol rather than ibuprofen or aspirin if painkillers are needed. However, advice should always be sought from a GP or midwife before taking medication."  And if your doctor has recommended that you take medication, such as low dose aspirin, consult with him or her as to what to do, if anything.

 Some believe that there are shortcomings to the research, for example, small sample sizes and the number of analyses involved reducing the certainty of its finding.  The direct causal link has not firmly been proven.  Nor does it examine the case of women who have been taking low dose aspirin (quarter the standard dose).  Also, there are many other studies which show the benefits and upsides of taking the low dose for miscarriage risk/blood clotting issues on doctor's recommendation.  Therefore the reports do need to be read with caution.  What is clear is that this is an important area which needs more urgent research.  While the rates of undescended testes seen in the study were still relatively low, it seems, as unfortunately happens with reporting in the press, the risk factors quoted can vary from article to article and some of the headlines can be alarmist, suggesting a 'global sperm decline'. 

The NHS Choices website concludes: "Overall, this study does not prove a link between use of painkillers in pregnancy and this reproductive disorder in boys but it does suggest an important avenue for more research."  Let's hope this research and investigation happens swiftly. As always, it is better to be informed than ignorant, however, information such as this may put a lot of pressure on the reader to think critically as a result - which is easier said than done if it affects you personally. 

No matter how level-headed you are normally, to anyone who has suffered or is suffering from primary or secondary infertility, reading such an article could prove to be quite unsettling.  Whatever your situation, it is essential to consult with your doctor if you are or have been taking mild painkillers and are worried in order to address any concerns you may have.

 Maria Portella is originally from the U.K. and now resides in the West Indies.  Her special interest is promoting better education about fertility amongst working women.  She reached out to The American Fertility Association because she wished to share her story.

Photo: Courtesy M. Portella

Doctor's Corner: Clomiphene Rx

by Craig Niederberger, M.D., F.A.C.S.

Every 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.