February 7th, 2010
Cellular metabolites: woven together like a rug
Call me a nerd, but I have to admit that I am pretty excited about metabolomic technology. Uh, what? Metabolomics is the study of the chemical fingerprints that cells leave behind. It does not look at genes, DNA, RNA or proteins, but is a peek into the products or metabolites that result from all this genetic orchestration. It is a “physiological snapshot” of a living cell.
This past week, we published a study that applies metabolomics to male infertility. If you have been reading this column, you are well aware of my interest in helping sterile men become fathers. Over the last decade, it has become clear that many men with azoospermia (no ejaculated sperm) may have small pockets of sperm in the testicle. The question is how to safely find that sperm without causing undo harm to the testicle. Current methods for evaluating whether sperm are present include somewhat invasive techniques such as testicular biopsy and microdissection and less invasive ones such as FNA Sperm Mapping that I invented 13 years ago. However, as I always say, there is always room for improvement.
Wouldn’t it be nice to find the “pockets” of sperm in the testis through a simple scan and avoid a biopsy? Maybe even a scan that involves no radiation exposure, like an MRI? Well, that is precisely what we have developed in this study.
We showed that magnetic resonance (MR) spectroscopy can measure metabolic activity in the testis. And given that most metabolic activity in the testis is concentrated on building sperm (remember, normally men produce 1200 sperm/heartbeat!), metabolic measurements in the testis generally reflect sperm production. The study showed that the metabolomic scanning is as accurate as a more invasive testis biopsy in reading several abnormal patterns of sperm production typically associated with infertility. It also showed that testes that contain sperm carry a distinct chemical “signature” that can be distinguished by MR Spectroscopy.
How does it work? Essentially, the scan looks for chemicals in the testis that are the building blocks for sperm production. The theory is if you see a pile of bricks in the yard, then there is a good chance that a house is being built. In the study, phosphocholine was observed as one of the building-block chemicals in the testis. The more there is, the more likely sperm are being made.
Not only that, MR Spectroscopy can evaluate for sperm in as many as 100-200 areas within the testis, significantly increasing the ability to sample for sperm well beyond any of the more invasive techniques commonly used today.
Are we ready to replace a testis biopsy with an MRI scan? Not yet, but give me some time to tweak the system a bit and perform clinical trials comparing it to current approaches. My motivation runs deep, as I know that men would rather have their picture taken than have a surgical procedure to understand whether they can be fathers.
Tags: Assisted Reproduction, azoospermia, babies, fertility preservation, fertility restoration, FNA mapping, male infertility, men's health, reproduction, sexual health, sperm, sperm count, testicle
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January 31st, 2010
Do you agree with the Ancients on the good of the hood?
To circumcise or not. A loaded subject to be sure. The practice of male circumcision is ancient, likely far older than the biblical account of Abraham in Genesis. The Jewish faith, but not that of the Greeks or Romans, routinely recommended circumcision of newborn males. In the past century, it became “medicalized” as a preventative procedure only to be debunked in the last decade. Well, it may be now a procedure on the rise once again.
Circumcision is the removal of some or all of the foreskin or prepuce from the penis. The august American Academy of Pediatrics continues to recommend that circumcision is medically unnecessary, that it lacks any proven benefit, and that it should not be performed routinely in neonates. Maybe that is why the incidence of neonatal circumcision in the U.S. has continued to decline, from 80% in the 1960’s to 60% in 1996, to 55% of boys in 2001.
Why should circumcision be avoided? Issues of neonatal pain, behavioral changes and the potential for loss of sexual sensitivity from removal of the prepuce are age-old arguments for its discontinuation. However, a military study showing that there is a higher rate of urinary tract infections (UTIs) in non-circumcised boys and the fact that penile cancer tends to occur almost exclusively in uncircumcised men has kept the procedure alive and well.
In a somewhat radical departure from earlier recommendations, public health officials are now arguing that circumcision of men is a key weapon in the fight against human immunodeficiency virus (HIV) in Africa. Three recent, large, controlled studies have shown that circumcision reduces infection rates by 50 to 60% among heterosexual African. These studies stem from 3 different parts of the continent: South Africa, Uganda, and Kenya. In fact, two of the three clinical trials were stopped early because of overwhelmingly positive results. Experts now estimate that more than 3 million lives could be saved in sub-Saharan Africa alone if the procedure becomes widely used. And there is more recent data showing that the incidence of Herpes virus and HPV (Human Papilloma Virus) may also be reduced in circumcised men.
How circumcision prevents HIV transmission is not completely understood, but it is believed that the foreskin acts as a reservoir for HIV-containing secretions, increasing the contact time between the virus and target cells in the foreskin.
The problem with HIV and circumcision is that it is much more than a simple “behavior-based” intervention and this may ultimately be its biggest obstacle to wide acceptance. Changing social mores and behavior is one thing, but the “cold, hard steel” aspect of this public health initiative may not survive in the long run. If you don’t live in Africa, a clean penis and a clean life may be all that’s needed to replace the knife.
Tags: cancer, circumcision, erections, HIV, men's health, reproduction, sex drive, sexual health, sexually transmitted disease
Posted in men's health | 1 Comment »
January 24th, 2010
Is faster better? Not always.
What is the most common sexual health problem affecting men? That’s easy, it’s erectile dysfunction, right? Nope. Try premature ejaculation. Hands down more common than erection issues, affecting 25-40% of men in the U.S.
Variably called early ejaculation, or early or rapid climax, it is defined as male ejaculation earlier than the subject or his partner desires. It used to be defined as ejaculation within 2 minutes of sexual intercourse, until it was realized that 75% of men ejaculate within 2 minutes in over half of their sexual encounters. What the definition really implies is that is some element of poor control over ejaculation that is stressful and may result in interpersonal difficulty.
Is this a medical disorder? In some cases, yes. Think of ejaculation as a reflex, like sneezing. There is a point of no return and this is what comes too soon in men with early ejaculation. The problem has two forms: lifelong and recent. The former is believed to result from low levels of the neurotransmitter serotonin (5HT) that normally modulates the ejaculation reflex. The recent form does not have as clear a biological basis, but may occur from psychological stress or from the need to overcome an erection problem.
The good news is that there are treatments available, and more treatments being reviewed by the FDA. Currently, the most effective treatments are pills called SSRIs, which elevate 5-HT levels and include anti-depressants such as Prozac, Zoloft, Celexa, and Lexapro. A newer form of SSRI drug, called Priligy, is now available in nine countries but has still not been FDA approved in the states. Also, a metered-dose aerosol spray has been developed to increase time to ejaculation by numbing the skin on the penis and decreasing sensation. Maybe this will help. Unfortunately, with all drug treatments for this condition, when the drugs are stopped, the issue generally returns.
What I find interesting is that companies are vigorously trying to drum up sympathy and attention for premature ejaculation as a widespread medical disorder, when in many cases it may be only an occasional annoyance that does not need constant treatment. Treatment might be perfect for a few men with debilitating disease, but it appears that they are trying to create and market a whole new category of disease. Good idea: create a “huge unmet need,” an epidemic that is perfect for a blockbuster, quality of life drug. Well what about a pill for shyness, or talking too fast? Where does it end? The larger issue here might be the “medicalization” of our daily lives in which there is a healthy and wide variation of normal.
Do I believe that some men have debilitating early ejaculation? You bet, and I see them every day. Do I think that a pill will treat this issue? Sure, for many, but only while you take it. Will blockbuster pills be the cure-all for early ejaculation? No way. The cure will come with more holistic treatment, by empowering men through behavioral changes that teach them to control and “own” the problem. Works superbly for my patients, pill or no pill.
Tags: erections, libido, men's health, premature ejaculation, reproduction, sex drive, sexual health, testosterone
Posted in men's health, sexual health | 3 Comments »
January 17th, 2010
Throwing a wrench in the machinery of sperm production...
I have to admit, the testis “mapping” procedure that I developed some years ago has truly been a workhorse technique for my male infertility practice. And for the practices of other male reproductive specialists around the world as well. Creating fertility from sterility. I bring it up again because it is gathering more attention in the press as this week we recently published another paper that highlights its utility—this time in cancer survivors.
In a related study from 2002, we published that the majority of men who had been exposed to chemotherapy for cancerous or non-cancerous disease and who were “sterile” afterwards have sperm in the testis that can be safely used for fatherhood with assisted reproduction. Fine needle aspiration (FNA) mapping was employed in this study and its potential to help cancer survivors to conceive was convincingly demonstrated. The recent paper expands that group of men to include those who received not only chemotherapy and radiation therapy but also a relatively extreme treatment for certain cancers termed bone marrow transplantation.
Let’s back up a minute for a biology lesson. How does chemotherapy affect a man’s fertility? Well, the basis of its effectiveness in curing cancer is that chemotherapy preferentially kills rapidly dividing cells more than slowly dividing cells. In general, cancer cells divide more rapidly than do normal body cells. The term for this difference in cell susceptibility is “therapeutic index”. Unfortunately, sperm are also produced very rapidly (about 1200 sperm are made every heartbeat) and therefore sperm precursor cells are also very sensitive to the effects of chemotherapy. Think of sperm production as a rapidly turning set of gears and chemotherapy as a wrench being thrown into them. Ka-chunk! Machine comes to a loud and crashing halt. Sperm production is over, or tremendously slowed down. The same action is true for radiation therapy treatment.
Now, imagine not just one small wrench being thrown into the gears, but a huge wrench (or many wrenches) being suddenly thrown into the machine of sperm production. The result? More damage to the sperm-making machinery and a much higher chance of sterility. This is the essential difference between the patients from the 2002 paper on mapping and the most recent one. The cancer survivors in this week’s paper got blasted with the heaviest doses of chemotherapy imaginable, and topped off with a dollop of radiation therapy just to be sure. Hard to believe, but they also had usable pockets of sperm in their testicles. And normal babies as a result.
So, with techniques like FNA sperm mapping, there continues to be hope and good news about fertility after the storm of cancer treatment has passed.
Tags: Assisted Reproduction, azoospermia, babies, cancer, fertility preservation, fertility restoration, FNA mapping, IVF, male infertility, men's health, reproduction, sexual health, sperm, sperm count, TESE, testicle
Posted in male infertility, men's health, sexual health | 2 Comments »
January 10th, 2010
Bacchus is no longer a role model...
What you weigh affects how your sperm play. And your fertility. Overweight men tend to have lower semen volumes, less sperm and more oddly shaped sperm. The same is also true for men who are too thin. So, along with the many other health hazards associated with obesity, add poor semen quality to the list.
Obesity in both sexes is known to be associated with heart disease, diabetes, hypertension, and metabolic syndrome among other nasty conditions that can shorten your life. Typically, obesity is measured with BMI or body mass index, which looks at weight in relation to height. Not a perfect measure, but reasonably accurate. Using this tool, the ideal BMI for men (and women) is considered to be 20-25. A Danish study of 1600 men showed that overweight men with a BMI > 25 had a 22% lower sperm concentration compared with healthy weight men. Interestingly, a BMI of <20 was also associated with poor semen quality. For optimal sperm production, then, it helps to be not too fat and not too thin.
But what about fertility? Is it also affected by obesity? Yup. Another recent study showed that for every 20-pound increase in a man’s weight, there is a 10% increase in the chance of infertility. And this remained true when other factors that might influence the results were accounted for, including obesity status of the women, the man’s age, cigarette smoking, alcohol intake, and solvent and pesticide exposure. In addition, obesity was associated with infertility in both older and younger men.
So what is it about weight that influences men’s sperm production and fertility? One theory is that sex hormone metabolism is altered by changes in weight. Sex hormones are the “fuel” for the engine (testis) to make sperm. Obesity increases fat stores and fat converts male hormones (testosterone) into female hormones (estrogens). Too much estrogen in men is bad for sperm production. Another theory posits that normal 2-degree difference in testis temperature relative to the body is lost with obesity, as excessive fat provides too much insulation and results in overheating. On the other hand, when a man is too thin, he may take on a “catabolic” metabolic state. With a body in “starvation mode,” fertility is not the first thing on its mind and sperm production and fertility suffer.
So, is the epidemic of obesity the reason why sperm counts have been falling in Western countries over the last 50 years? Maybe. But this problem is unique in that it is utterly and entirely preventable. Eat well and in moderation, sleep well and treat your body like a temple. You used to it for your own health; now do it for the health of your future family.
Tags: alternative medicine, babies, birth rates, libido, male infertility, men's health, reproduction, sex drive, sexual health, sperm, sperm count, testicle, testosterone, women's health
Posted in male infertility, men's health, sexual health | 2 Comments »
January 2nd, 2010
Heirlooms for the species.
As a living, breathing being on this good earth, we tend to take things for granted. The ability to have offspring can be one of them. That is, until the day that a serious medical condition like cancer rears it ugly head and puts childbearing at risk. In addition to the sterilizing effect of cancer treatments, the mad rush to treat the disease often marginalizes efforts to preserve fertility. Fire all the canons and check for collateral damage later.
Fertility preservation seeks to protect men, adolescents and children from a common, serious and impactful side effect of cancer treatment: infertility. The goal of fertility restoration is to empower patients who are cured and potentially infertile to bear children. These related fields have burgeoned recently because medical care is now shifting from curing cancer to improving the quality of life among survivors. And without a doubt, for many, fertility is a key quality of life issue at some point. Thankfully, exciting new methods of restoring fertility have already been developed and even newer technologies are under study.
Classic techniques for fertility preservation in men include gonadal shielding and sperm banking. Gonadal shielding uses lead-based devices to protect the testicles from being struck directly by sterilizing radiation treatment. Sperm banking is the process of freezing healthy sperm before cancer treatment begins for later use to conceive. But there is more. For patients who are too young to bank sperm, for those who have precious little time to bank sperm, or for those who have no ejaculated sperm to bank, testis sperm retrieval by biopsy (TESE) or needle aspiration (TESA) for banking is now possible before cancer treatment. In fact, in some cases of testis cancer, it is possible to remove only the cancerous nodule instead of the whole testis, or to freeze sperm from the testicle after it is surgically removed. These are now routine ways to preserve fertility in men.
Fertility restoration for men has also seen real advances lately. Sperm “mapping” is an innovation that I developed for men who survive cancer treatment but have no sperm in the ejaculate. It non-invasively and non-surgically deciphers whether there are small numbers of mature sperm in the testis, too few to get into the ejaculate, but usable nonetheless. In men who sustain nerve injury from cancer surgery and who are unable to ejaculate, a special medical instrument can produce an ejaculate for fertility purposes in a process termed electroejaculation. Techniques such as these are valuable tools to help men deemed “sterile” after cancer treatment to become fathers.
One of the most exciting areas of fertility restoration involves stem cell technology. Yes, the “promise” that we have all heard about stem cells curing disease will likely find its way into the fertility field as well. In pre-pubertal boys with cancer, ejaculated sperm is not present. Despite this, it may be possible to freeze the early stem cells from the testicles of boys before sterilizing treatment. After thawing, these “adult” stem cells may later be used to create sperm after further growth in a Petri dish or after transplantation back into the same individual. Also on the horizon is our ability to take skin cells from a sterile man, convert them into an embryonic-like stem cells and then “drive” these cells to become mature sperm in a dish–a true “artificial testicle.” So, with the belief that hope can cure misery, the world of science has taken fertility research from science fiction to reality. Not convinced? Stay tuned!
Tags: Assisted Reproduction, babies, cancer, conception, fertility preservation, fertility restoration, FNA mapping, IVF-ICSI, male infertility, men's health, reproduction, sexual health, sperm, stem cells, TESA, TESE, testicle, testis cancer
Posted in male infertility, men's health, testis cancer | 4 Comments »
December 12th, 2009
A woman whose independence lasted longer than most countries.
Excuse my diversion from men’s health, but a very important woman in my life has just passed away. My last grandmother (known as Oma) lived a fiercely independent life for over 99 years, longer than most countries.
She brought our family to America from what is now Czechoslovakia in 1950, after 1000 years of farming the land and a generation of recent persecution. She brought a husband, a son (my father) and her daughter, each with a single suitcase, to Connecticut to start life anew. And we have prospered here since. A typical immigrant story.
She lived in her own home for 56 years, preparing every meal from scratch, and died there. A simple humble, life and a simple humble death. If you got to her house too late in the morning after a winter storm, you would find her clearing the snow from her driveway well into her 90’s. I only knew her as a gray-haired grandmother, but she was a constant and a compass to the entire family: our north, our south, our east, and our west. Rooted, decisive and opinionated, she was usually right, but never wrong.
She was a woman of the land, a gardener and a grower. In the words or Rilke, she knew the sound that small flowers make when they open in the morning.
The Germans play a card game call Setback, like Bridge. If you played on her team, you usually won. It was something about those million fine wrinkles that gave her the perfect poker face.
She leaves to 6 grandchildren and 8 great-grandchildren on both coasts a spirited legacy of wisdom, willfulness and fortitude that will survive for generations.
Tags: women's health
Posted in men's health | 2 Comments »
November 25th, 2009
Tickle the ivories and delight the senses.
I spent an evening this past weekend listening to the mighty Berlin Philharmonic Orchestra, conducted by Sir Simon Rattle. Listening to their performance of Wagner, Schoenberg and Brahms left me utterly breathless. A magnificent musical experience. Why? Because every single musician thinks and responds incredibly quickly and appears to give their all to a whole that is far greater than the sum of the parts. The mastery of these technically demanding movements was superb and it was clear that this orchestra, led by a conductor filled with supreme passion, could turn on a dime at any moment.
Can a surgeon perform surgery like a world-class symphony performs music? Absolutely. While a resident in general surgery, I remember watching a pediatric heart surgeon name William Norwood at the Children’s Hospital of Philadelphia perform his own Norwood Procedure on children with malformed hearts. Dr. Norwood’s hypoplastic heart surgery on infants at the brink of death was exhilarating to behold. Appearing intense and focused, with no wasted movements of his ambidextrous hands, he could repair an aorta or pulmonary artery in a minute with either hand, throwing absolutely perfect sutures as rapidly as a sewing machine. All the while working on hearts the size of shrunken plums and veins slimmer than angel-hair pasta. A technical virtuoso. All while listening to Albinoni’s Adagio in G Minor.
Aside from sheer talent, what makes William Norwood and Sir Simon Rattle the giants that they are, is a vision of perfection and the ability to inspire the best from others. Helping others achieve more than they could otherwise is a key element of leadership, especially in the setting of complex team performances like heart surgery or Schoenberg movements.
Inspired by these maestros, I too strive for perfection in my corner of the medical world, that of reproductive microsurgery. I view vasectomy reversal surgery as a craft best done by artisans. The chance to lead a roomful of others, throw 300 knots all with equal precision into an organ the size of spaghetti, gauge biology like a painter eyeing a still life, and help to create new life as a result. There is art in all that we do. Have you found your canvas?
Tags: babies, men's health, no scalpel vasectomy, sperm, sperm count, vasectomy reversal
Posted in Uncategorized | 4 Comments »
November 15th, 2009
Making the world a better place with modern technology.
In this forum, I’ve already talked about how erections occur and also about pills used to treat erectile dysfunction in men. But what if they don’t help? What comes after the pill?
There are about 30 million men in the U.S. affected by erectile dysfunction. For 20% or more of men, common prescription therapies – Viagra, Levitra or Cialis – are not effective. For these men, we have many things “up our sleeves” to help. Before reviewing this cornucopia of cures, I really need to emphasize again the idea that erectile dysfunction may be a message that your body is not perfectly healthy. Think of it as a loud noise coming from under the hood of the car. It may run fine if you keep going, but you never know. Similarly, medical conditions such as high blood pressure, heart disease, high cholesterol, diabetes and low testosterone are important “loud sounds” that are associated with erectile dysfunction; they should be treated first and foremost. Often, by treating these illnesses, not only will erections improve, but you might live better and longer too.
Ok, so your cholesterol is fine. How then can erections be improved? Well the answer may be to “go local.” Local therapies attempt to improve erections by going to the source to treat the problem: the penis itself. Help the big guy out without involving the rest of the body. Penile salves, creams and urethral pills are available in many forms and are often compounded by pharmacies. One of these is a pill (MUSE) that is inserted just inside the urethra (the urine tube within the penis) and is absorbed by the penis to stimulate an erection. A little unconventional, but very effective in some men.
Although more difficult to imagine, local therapy can also involve injecting the side of the penis with highly active erectogenic agents such as papaverine, phentolamine and prostaglandins. Not the most palatable way to get an erection, but highly effective for the vast majority of men who fail to respond to pills. A more inviting alternative is based on recent developments in transdermal technology and involves delivering the same three medications in a clear gel into the urethra (TriMix Gel). Rub it in for a minute or two and you are up and running.
Available for 30 years now, penile vacuum pumps will also work in the majority of men. By creating 6 atmospheres of negative suction pressure around the penis, these mechanical devices draw blood directly into the penis. Once filled, a rubber ring is placed around the base of the penis to keep the blood in and away you go. But please don’t keep the ring on too long (more than 45 minutes) as bad things could happen…
In the most resistant cases, surgical implants may be needed to resurrect the erection. Reliable and realistic, implants are the most invasive kind of local therapy and are effective in virtually all men. They can be rigid but bendable, inflatable, antibiotic coated and can have other neat widgets and gadgets. But they do require surgery, which distinguishes them from other treatments. They are also irreversible in the sense that they permanently alter penile anatomy, rendering ineffective most other treatments discussed here. So, let it be known that “vee have vays” of getting those erections back in case the pill doesn’t work.
Tags: erections, libido, men's health, reproduction, sex drive, sexual health, testosterone, Viagra
Posted in sexual health | 1 Comment »
November 8th, 2009
Miles and Microsurgery: it doesn't get any better.
For as long we have pounded drums and plucked strings, listening to music has affected people’s sense of well-being, lifting and consoling their spirits, inducing calm and tranquility, or the trance of dance. I have listened to the sounds of classical jazz during microsurgery operations throughout my professional career as a surgeon. Coltrane, Miles, Evans, Djavan, Caetano Veloso and all the greats sweetly waft in the operating suite and overcome the din of devices within the room. Does music in the operating room lead to less wasted and more fluid surgical motion, and therefore faster procedures and better patient outcomes? Who knows. But as the background makes the painting, the music may make the maestro.
A recent study suggests that listening to music in surgery may also benefit patients. Maybe this is why oral surgeons and dentists offer earphones and video glasses to their patients. Anything is better than listening to the whine of the drill during a root canal. The effect of music on cortical, limbic or higher brain centers has previously been studied in patients undergoing brain surgery. These centers control feeling, thoughts and memory. In this recent research, a neurosurgeon studied the effect of different kinds of music on deeper portions of the brain, located in the thalamus. This region is responsible for sensation, motor function, consciousness, sleep and alertness. This study of music and Parkinson’s patients is quite different from what Oliver Sacks describes in his book Musicophilia, in which music therapy is used to increase the mobility and responsiveness of Parkinson’s patients.
According to this new study in awake patients undergoing surgery for Parkinson disease, music slowed the neuronal firings deep within the brain. As a consequence, patients became physically more relaxed, calm and even slept during their surgery. And pure melodic music appeared to be the most soothing to most patients.
So music in the operating room may make more sense than we think. In addition to helping the surgeon with his surgery, it may reduce patient anxiety. This in turn, could shorten operative times, reduce the need for anesthetic medication, and lead to quicker patient recovery and shorter hospital stays. In a word, more music, less pills.
Tags: complementary medicine, evolution, men's health, sexual health, sleep
Posted in men's health, sexual health | 4 Comments »
