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.

 

Keeping Your Package Safe

By Harry Fisch, MD

As every guy knows, the penis and testicles are not very well protected from the vagaries of life. If the testicles didn’t have to be cooled to below body temperature for maximum efficiency, nature surely would have tucked them up inside the body somewhere safe and sound, the way a woman’s ovaries are. But, no … we have to deal with the fact that our crucibles for our genetic legacy are, literally, swinging in the wind and subject to injury from any number of sources.

Here are a few ways to help protect yourself:

• Wear a jock strap or hard cup during contact sports
• Buy a bicycle seat that has a groove or cut-out area down the center to reduce pressure on the nerves and arteries feeding the penis and scrotum
• Wear a seat belt (one lesser-known source of testicular injury is car accidents)

If you do have the unfortunate luck of sustaining a blow to your testicles, you should use some kind of scrotal support (i.e. jock strap) and apply ice packs to the groin as quickly as possible to reduce swelling; reapply every 3-4 hours afterwards for the first 12 hours or so. An anti-inflammatory pain medicine (i.e. ibuprofen) may be helpful. If swelling or tenderness are not reduced within 24 hours, or if you pass blood in your urine, see a doctor. If a blood vessel is leaking, it may need to be surgically repaired. Blood in the scrotum, or distended veins in the scrotum, can raise the temperature of the testicles and reduce, or stop, the production of sperm. This is definitely not a part of the body you want to take chances with!

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 

What causes problems with sperm, and how can they be treated?

 
by Harry Fisch, M.D.

Genetics
Perhaps surprisingly, much of male infertility is thought to be due to genetics. With the human DNA sequence completed by the Human Genome Project in April 2003, more conditions of male infertility caused by genetics will be discovered in coming years. Some known genetic causes of problems with male fertility include (among many others):

• Klinefelter syndrome: two sex X chromosomes in addition to the Y (XXY)
• Kallmann syndrome: pituitary production of LH and FSH is low or absent
• Kartagener syndrome, primary ciliary dyskinesia, immotile cilia syndrome: these are structural problems in the microscopic tubes in the sperm tail
• Congenital bilateral absence of the vas deferens (CBAVD): changes in the gene responsible for cystic fibrosis cause the vas deferens on both sides to be absent
• Androgen insensitivity syndrome: the receptor that binds to testosterone is altered
• 5-a-reductase deficiency: the enzyme that converts testosterone to the more active form dihydrotestosterone is altered
• Persistent Müllerian duct syndrome: female organs develop in the male embryo
• Changes in the deleted in azoospermia (DAZ) gene: alterations in a gene on the Y chromosome involved in making sperm

Azoospermia
Azoospermia refers to the condition where no sperm are found in the ejaculate. Azoospermia is different than anejaculation, where the man does not ejaculate. Azoospermia with a low ejaculate volume (typically less than one milliliter) may be caused by:

• Obstruction of the ejaculatory ducts emptying semen into the urethra. This may be treated by using surgery to open the ejaculatory ducts, or if surgery is not possible or unsuccessful, to extract sperm directly from the testis or epididymis for IVF.
• Retrograde ejaculation of sperm into the bladder. Rather than being propelled forward during ejaculation, sperm goes backwards into the bladder. This may be treated by medicines to strengthen the bladder neck, or retrieving sperm from the bladder for artificial insemination or IVF.
• Conditions like CBAVD which cause problems in development of the prostate and seminal vesicles. These may be treated by extracting sperm directly from the testis or epididymis for IVF.

Azoospermia with a normal semen volume may be caused by obstruction of the epididymis or vas deferens ("obstructive azoospermia", OA) or to problems with spermatogenesis ("non-obstructive azoospermia", NOA). A doctor can distinguish between obstructive and non-obstructive azoospermia with approximately 90% accuracy by measuring testis size and FSH. Biopsy of the testis is occasionally necessary to determine whether azoospermia is obstructive or non-obstructive.

A man may be born with obstructive azoospermia or he may have had a vasectomy, injury or infection as a cause later in life. The treatment of obstructive azoospermia is to correct the obstruction with microsurgery if possible. If surgical reconstruction is not possible or successful, sperm is extracted from the testis or epididymis. As it is immature, sperm extracted from the testis or epididymis must be used in IVF, typically with intracytoplasmic sperm injection (ICSI).

Like obstructive azoospermia, non-obstructive azoospermia may be present from childhood, or acquired later in life due to injury or infection. A man with non-obstructive azoospermia may be treated with medicine to stimulate spermatogenesis, requiring three months or more of treatment. If sperm is not found in the ejaculate after treatment, or if the couple prefers immediate treatment, sperm is extracted from the testis for IVF.

A surgeon may use many different ways of extracting sperm from the testis, including open surgery, microsurgery, using a needle to aspirate draw out sperm, and retrieving sperm from the testis or epididymis. All choices are possible with obstructive azoospermia, as large numbers of sperm are present in the testis. Non-obstructive azoospermia limits a surgeon's choices. In order to obtain enough sperm, a surgeon may use microsurgery, open surgery, or multiple needle punctures from the testis.[9]

Extracted sperm may be frozen for later use with IVF. Advantages of freezing sperm include that the couple may choose a date for the extraction procedure, the female partner may be present for the extraction, and the couple will know whether sperm was able to be extracted before IVF is done. There is no difference in the success of IVF with frozen sperm or sperm extracted on the day of IVF.

Hormones
Failure of the pituitary to release LH and FSH causes failure of the testis to produce testosterone and sperm. This condition is diagnosed by low testosterone accompanied by relatively low LH levels. The most extreme example of pituitary failure is Kallmann syndrome, which may be treated with HCG and recombinant FSH, often requiring lengthy treatment periods of a year or more. Milder forms of pituitary problems are common, and may be treated with clomiphene citrate if the pituitary is responsive.

Failure of the Leydig cells in the testis to make testosterone results in low levels of testosterone accompanied by very high levels of LH as the negative feedback of testosterone on the pituitary is decreased. Treatment is surgical extraction of sperm if possible, as the body is already providing its own hormonal stimulation.

Testosterone therapy is not used for male fertility. Although the blood levels of testosterone rise with external application of testosterone, negative feedback on the pituitary and the resulting fall in LH causes the very high levels of testosterone in the testis to fall. For this reason, scientists have studied external testosterone for male contraception.

High levels of the female hormone estradiol may impair male fertility; this condition can be treated with medications such as anastrozole (Arimidex). High levels of sex hormone binding globulin may also lower the amount of effective testosterone, referred to as “bioavailable” testosterone. If the total or bioavailable testosterone is too low, clomiphene citrate may be used to increase the production of testosterone in the testes.

Varicocele Because it is outside of the body, the testis is cooler than other organs, a condition that is important to sperm survival; conversely, heat is toxic to sperm production. The cords transporting blood to and from the testis are arranged in a radiator-like “counter current heat exchange.” A common cause of male fertility is varicose veins in the scrotum that heat the testis and disrupt sperm production. Varicose veins in the scrotum are called a varicocele. Until the 1990s, doctors argued whether varicoceles were important to male fertility, and if treating them helped. It was discovered that treating varicoceles that were neither felt nor visible to the naked eye was not helpful, but that varicoceles that could be felt or were visible damaged sperm production, and that male fertility improved with treatment. Treating a varicocele usually involves an outpatient surgical procedure called a “varicocelectomy,” which may be done with the surgeon using magnifying lenses or the operating microscope to preserve the tiny arteries carrying blood to the testis. A varicocele may also be treated by an experienced interventional radiologist.

Childhood conditions Sperm production in the pre-adolescent boy is inactive until he reaches puberty. If the testis does not descend in the scrotum, a condition called cryptorchidism, early sperm cells may be permanently damaged. Early treatment of cryptorchidism by surgery to bring the testis into the scrotum, called orchidopexy, is important to preserve a male's later fertility. Other childhood conditions that may affect future fertility include:

• Mumps orchitis: mumps involving the testis. Treatment is prevention of mumps, or if it occurs, treating as best as possible the episode of mumps.
• Testis torsion: the testis twists on itself. Treatment is surgical untwisting of the testis as soon as possible.
• Testis trauma: injury significant enough to disrupt the inside of the testis. If the outer sheath of the testis is ruptured, treatment is surgical repair.

The immune system
White blood cells in the semen release toxic chemicals that may affect sperm function. Antioxidants and anti-inflammatory medication may help prevent sperm damage by excessive white blood cells in the semen.

If the man's body is producing antibodies to his own sperm, “antisperm antibodies,” steroids may be used to desensitize the immune system. Intrauterine insemination with washed sperm may be used , but IVF with ICSI may be necessary to treat antisperm antibodies.

Problems with erections and ejaculation
Difficulty with erection of the penis becomes increasingly likely as a man ages. Many treatments are available to treat erectile dysfunction. Problems with ejaculation may be due to injury to the nerves controlling ejaculation, such as in spinal cord injury, or disease of the nerves by conditions like diabetes. Anejaculation (a condition where a man cannot ejaculate) may be treated by collection of sperm with vibratory stimulation of the penis or stimulation of the nerves using a procedure called electroejaculation, or by surgical extraction of sperm from the testis or epididymis and IVF.

Here are some surgery questions.

by Fred Licciardi, M.D.

If you have severe endometriosis and pain with a history of multiple laparoscopies, and you are at the end of your rope, is a hysterectomy the answer? This is too complicated for me to give any hard advice here. The options are to get another opinion from a doctor is an established endometriosis laparoscopy doctor, who can maybe improve your pain without a hystersctomy. Maybe even someone who is not in your area. On the other hand, there are some women who say the hysterectomy was the best decision they ever made, and some who are neutral and some who are not happy with the results.

Is a laparoscopy through 3 incisions better than a laparoscopy where the doctor only used 2 incisions? Impossible to say. Some surgeons are really crafty using only 2, some need 4. Sometimes a doctor who usually uses 2, will need to use 3-4 in the really tough cases. But redoing a laparoscopy just because only 2 incisions were used does not make sense.

What if there is a hydro on hsg and at laparoscopy the tube does not fill with dye? Should the doctor assume the tube developed proximal occlusion and just leave it? I think not. For some reason, sometime tubes just to not fill with dye at the laparoscopy. Even normal tubes sometimes do not fill, but a post op hsg shows normal tubes. So if they are hydros at hsg, but closed at laparoscopy, your doctor should consider removal.

Is it normal to have a myomectomy and have some fibroids left behind at surgery? This does happen, but I do not leave any behind. I could see rare cases of fibroids left behind for a couple of reasons. Fibroids on the cervix are more dangerous to remove because the cervix is where the uterine arteries bring blood to the uterus, so around the cervix there is more blood flow and more chance for heavy bleeding during the operation. Also, if there are very thick intestinal adhesions attached to a fibroid, separating the intestine from the fibroid may cause excessive bleeding or damage to the intestines. That being said, leaving fibroids behind should be reserved for the most extreme cases. I have not left a fibroid in 15 years. The doctors I work with do not leave in fibroids. However I am aware of doctors who routinely leave in some of the smaller or difficult to reach fibroids, and I do not know if this is the best thing. A myomectomy is not minor surgery. In many cases, smaller fibroids get bigger. So if your problems are bad enough that you need the myomectomy, getting them all is the best thing. It is also true that the doctor may do a great job getting them all out, and sure enough, 3 months later a scan shows another fibroid. This is harder to explain, but probably there was a very small one that could not be seen, and it that grew after the initial surgery.