Posts Tagged ‘hypogonadism’

Low Testosterone And Depression: there is a relationship

September 27, 2015

Testosterone is more important that sex drive\libido, erections, and energy levels. A new study has documented low testosterone and testosterone that is the lower limits of normal may be associated with depression.

The study from the George Washington School of Medicine and Health Sciences in Washington, DC. included 200 adult men, who were referred for borderline total testosterone levels between 200 and 350 ng/dL. Doctors typically treat men for hypogonadism or low T if they have symptoms of low testosterone and their testosterone levels are below 300 ng/dL.

The results show that more than half (56%) of the men had depression or depressive symptoms, which is significantly higher than rates seen in general populations. A recent survey of US adults found that 6% of those who are overweight or obese were depressed. One-quarter of the men used antidepressants.

Also worth noting, the men had high rates of overweight or obesity and physical inactivity. Common symptoms were erectile dysfunction, decreased libido, fewer morning erections, low energy, and sleep disturbances.

The study authors concluded that clinicians should consider screening for depression/depressive symptoms and overweight and unhealthy lifestyle risk factors in men referred potential hypogonadism.”

Testosterone replacement therapy can improve the signs and symptoms of low testosterone in these men who have documented low testosterone levels.

The researchers published their results online on July 1, 2015 in the Journal of Sexual Medicine.

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Low T (Testosterone) May Mean No Baby

February 19, 2015

I am often seeing men with symptoms of low testosterone levels who are still planning to have children. These men need to know that the standard treatment of hormone replacement may not apply to those men who are still interested in having children. This blog will discuss the management of men with low T and who wish to continue to have children.

Testosterone replacement therapy (TRT) can bring your testosterone levels back to normal and restore your sex drive.
But if you want to have children, there’s one downside to TRT you should know about. It gives you back your sex life, but it might also reduce your ability to father children as long as you’re on it.
Testosterone replacement therapy has a profound impact on a man’s reproductive potential.

Approximately 90% of men can drop their sperm counts to zero while on testosterone. By increasing testosterone, you’re not going to increase fertility.

Testosterone, the hormone produced in the testicles, plays an important role in making sperm. Your brain makes special hormones, called gonadotropin-releasing hormones (GnRH). These hormones signal the testes to make more testosterone, vital for a healthy sperm count. When you’re getting testosterone replacement therapy, testosterone is added into the bloodstream by patches, gels, or other treatment methods such as pellets placed under the skin. Your brain interprets this rise in testosterone levels as a sign that you now have enough testosterone. So it stops sending signals to the testes to make more testosterone. But when your testes don’t make more testosterone, your sperm production goes down.
Therefore, a low sperm count makes it harder to conceive a child. My advice is that if you have any kind of reproductive goal, you should not be using TRT.

If you have low testosterone, one way to improve sperm count is with gonadotropin injections. This stimulates the production of sperm. It may be considered as a way to increase a man’s fertility when your partner are having trouble conceiving a child.
It’s standard practice to check a man’s sperm count when a couple has difficulty getting pregnant. If your sperm count is low, the next step is to measure your testosterone. If it’s below normal, we can then inject the signal to produce more testosterone by giving a gonadotropin.

You should also make sure to follow a lifestyle of regular exercise and a healthy diet if you want to father a child. Overweight and obese men tend to have lower testosterone levels because excess belly fat converts testosterone to estrogen, another hormone that can impact sperm production. Shedding those extra pounds will likely have a positive effect on your fertility. Losing weight can definitely increase testosterone.

Bottom Line: If you have symptoms of low testosterone levels or if you have an abnormal sperm count, hormone replacement with testosterone is not the treatment of choice. You should consider gonadotropin injections as a solution.

Testosterone and the Prostate Gland-It’s Not Gasoline On a Fire

November 3, 2014

For the past two years I have made the decision of treating prostate cancer patients who are documented to be hypogonadal with testosterone replacement therapy. Many of my colleagues have asked me about this decision and I would like to provide you with the evidence that this treatment of hypogonadal men who have been treated for localized prostate cancer with either radical prostatectomy or radiation therapy is safe.

In the late 1980s Dr. Abraham Morgentaler, a urologist in Boston, Massachusetts, began researching the relationship between testosterone and prostate cancer.  Since the early 1940s testosterone had been believed to be a key contributor to the development of prostate cancer, and once cancer was established, testosterone was believed to be its fuel.  As a result, generations of medical students around the world were taught that providing additional testosterone to a man with prostate cancer was “like pouring gasoline on a fire.” On the flip side, it was similarly believed that low levels of testosterone protected a man from ever having prostate cancer.

As one of the first physicians in the modern era to offer testosterone therapy to otherwise healthy men with sexual problems, Dr. Morgentaler was concerned that this treatment, while effective, might precipitate rapid growth of undetected, “occult” prostate cancers in his patients.  In order to avoid causing more harm than good, Dr. Morgentaler took the bold step of performing prostate biopsies in these men to exclude the possibility that these men harbored an undetected prostate cancer, even though they had none of the standard indications for a biopsy, such as elevated PSA or a nodule.  Although it had been assumed these men were at extremely low risk for prostate cancer because of their low testosterone levels, Dr. Morgentaler and his colleagues found exactly the opposite. One in seven of these “normal” men that underwent biopsy was found to have cancer, a rate similar to that seen in men known to be at increased risk.

Dr. Morgentaler presented his findings at the annual meeting of the American Urological Association in 1995.  At the end of the presentation an influential chairman of a major urology department came to the microphone and loudly described this work as “garbage.” “Everyone knows high testosterone causes prostate cancer and low testosterone is protective,” he proclaimed in a booming voice.  The research was published the following year in the prestigious Journal of the American Medical Association.

As the testosterone and prostate cancer link became less persuasive, Dr. Morgentaler began to offer testosterone to men with pre-cancerous abnormalities on prostate biopsy, and reported no increased rate of subsequent cancer. Yet at his own hospital, the Beth Israel Deaconess Medical Center, a senior endocrinologist complained to the administration that this research was “dangerous”.

However, Dr. Morgentaler prevailed and went on to publish clinical research on the safety of testosterone in men with actual prostate cancer, some treated with radiation or surgery, and even in selected men with untreated prostate cancer.

Dr. Morgentaler’s results were difficult to accept initially because a longstanding treatment for advanced prostate cancer has been androgen deprivation, a surgical or medical treatment designed to permanently reduce testosterone levels as much as possible. Numerous studies in these men had shown improvement in prostate cancer with this treatment, so it seemed logical that raising testosterone would cause prostate cancer progression.

Dr. Morgentaler’s elegant solution to this apparent paradox was the saturation model, based on studies in humans, animals, and in prostate cancer cell lines in the laboratory. It turned out that prostate tissue does indeed require testosterone for optimal growth, but that it can only use a limited amount of testosterone (or its metabolite, dihydrotestosterone) before it reaches a maximum. In biological terms, this is called saturation.  Once saturation is achieved, additional testosterone has little or no capability to stimulate further growth. And saturation occurs at very low levels of testosterone, approximately 20ng\dl. This explained why testosterone treatments did not appear to harm men with existing or treated prostate cancer, namely because the cancers already had seen all the testosterone they could use.

The Evidence

A number of physicians have treated patients with testosterone despite the fact that they’d been treated for prostate cancer in the past. The first to publish their experience with doing this were Drs. Joel Kaufman and James Graydon, whose article appeared in the Journal of Urology in 2004.

In this article, Drs. Kaufman and Graydon described their experience in treating seven men with T therapy some time after these men had undergone radical prostatectomy as treatment for prostate cancer, with the longest follow-up being 12 years. None of the men had developed a recurrence of his cancer. Soon afterward, there was another paper by a group from Case Western Reserve University School of Medicine describing a similar experience in 10 men with an average follow-up of approximately 19 months. Then another group from Baylor College of Medicine reported the same results in 21 men.

In all these reports, not a single man out of the 38 treated with testosterone developed a cancer recurrence. It is important to emphasize that all these reports included only men who were considered good candidates because they were at low risk of recurrence anyway. And in some cases, the duration of time the men received T therapy was relatively short. But it was reassuring that none of the 38 men who had suffered from prostate cancer in the past and who were treated for years with testosterone had developed a recurrence of prostate cancer.

This reassuring experience was bolstered by the published experience of Dr. Michael Sarosdy, who reported the results of T therapy in a group of 31 men who had received prostate cancer treatment in the form of radioactive seeds, called brachytherapy. This less-invasive form of treatment does not remove the prostate, so theoretically there is the possibility that a spot of residual cancer might still be present. With an average of five years of follow-up in these men, none of the 31 men had evidence of cancer recurrence.

My Approach

Men who have low-grade prostate cancer, i.e., Gleason score of <6, and low stage disease, T1 or T2, and have a nadir of their PSA following curative treatment with either surgery or radiation for 9-12 months, and have symptoms of hypogonadism and documented low testosterone levels, are candidates for hormone replacement therapy. I provide them with educational materials similar to what is in this newsletter and request that they return every month to monitor their PSA levels. Any increase in PSA levels for two successive months results in cessation of their hormone replacement therapy. Of the several dozen patients that meet this criteria and have received testosterone replacement therapy, none have had a rise in their PSA or evidence of recurrence of their prostate cancer.

Bottom Line: Today, most urologists throughout the world, myself included, are comfortable using testosterone in men without the fear of causing prostate cancer, and in the US a majority will now offer testosterone treatment to some men previously treated for prostate cancer.  This revolutionary change in medical beliefs and practice resulted directly from the work of Dr. Morgentaler, who became a David against Goliath and was relentless in his pursuit of scientific truth and making it possible for some men who have prostate cancer with documented hypogoandism to receive hormone replacement therapy.

Testosterone and Its Impact On the Heart-Here’s the Good News

October 22, 2014

I am frequently queried by my patients about the safety of using testosterone and the risk of developing heart disease or a stroke. I would like to give you the evidence from the medical literature, and then help you make an informed decision if testosterone replacement is right for you.

Men have more than twice the risk of dying from coronary disease than women. It has been assumed that testosterone is deleterious to the male cardiovascular system and contributes to the risk of heart disease. In fact, there is little evidence that testosterone produced in body by the testicles is an adverse risk factor but the role of testosterone status and replacement therapy on male health is controversial.

High doses of anabolic steroids often used by body builders and athletes are undoubtedly associated with cardiac disease but these are doses much higher than what the body normally produces. Testosterone levels within the normal range do not appear to be harmful. Indeed, low rather than high testosterone levels in men are associated with several cardiovascular risk factors including an atherosclerosis or hardening of the arteries, insulin resistance, and obesity.

Let me give you information first from animal studies where the scientists can control the variables. Studies in male animals have shown that castration or induced hypogonadism increases atherosclerosis and testosterone replacement prevents this. In addition, testosterone has beneficial effects in men with cardiac disease. Testosterone is a potent coronary artery vasodilator. Testosterone therapy reduces total cholesterol, fat mass, waist circumference and pro-inflammatory cytokines associated with atherosclerosis, diabetes and the metabolic syndrome. Testosterone also improves functional capacity of the heart and insulin resistance in men with heart failure.

In an ageing male population low serumotal testosterone is common and has a prevalence of 30% in men over the age of 60 years. Testosterone deficiency may cause undesirable effects such as loss of bone and lean body mass, increased adiposity, low energy and impaired physical and sexual function. Until recently, these effects were viewed as the natural physiology of aging; however, four recent major studies have found low testosterone to be associated with increased all-cause mortality after controlling for baseline morbidity and age.

The effect of testosterone on mortality has demonstrated an increased risk of death due to cardiovascular diseases in men with low testosterone. One report found that mortality due to any cause and cardiovascular mortality was increased with a reduction in serum testosterone. Low testosterone status is therefore associated with mortality and vascular mortality, yet no study has specifically examined patients with established cardiovascular disease. This is important because men with manifest coronary artery disease are at a higher risk of cardiovascular mortality and represent a patient population prone to testosterone deficiency. In addition, those men with angina, chronic heart failure or diabetes may derive particular symptomatic benefit from androgen replacement therapy.

This study had two aims: first to assess the impact of testosterone status on life expectancy in men with pre-existing coronary disease, and second to identify the prevalence of biochemical testosterone deficiency in men with coronary disease. Our hypothesis was that low serum testosterone would be associated with an adverse survival.

One excellent study that was peer reviewed showed that the prevalence of testosterone deficiency is common in men with coronary disease and is present in 25% of the men. The data have confirmed that low T is related to all-cause and vascular mortality in a coronary disease population. Therefore, the study also concluded that borderline low levels of T may also have an adverse impact on survival.

This study is entirely consistent with previous studies of low testosterone as a cause of decreased life expectancy.

What is the pathophysiology of low testosterone status and the apparent increased mortality of atherosclerotic disease? Animal data show that testosterone deficiency accelerates atheroma or atherosclerosis and replacement with testosterone prevents this. Human studies have shown an increased progression of atheroma in men with lower testosterone. These data therefore suggest that testosterone deficiency is associated with progressive atherosclerosis and replacement, in animals at least, prevents this progression of the heart disease.

We have demonstrated that testosterone deficiency is associated with premature death in male patients with vascular disease; many of these patients died and will continue to die from cardiovascular disease. There is scientific evidence and several documented trials showing benefit in terms of risk factor modification and symptoms. If androgen deficiency is part of the underlying pathophysiology of atherosclerotic disease in men, then the serum testosterone level could be viewed as a modifiable risk factor as men can increase the T level by testosterone replacement therapy. Physiological testosterone replacement is an inexpensive and well-tolerated therapy but does require careful monitoring.

Bottom Line: Testosterone deficiency is common in middle aged and older men. Low testosterone levels appear to cause men to be at an increased risk of cardiovascular disease and even increased risk of death. Hormone replacement therapy for men who are symptomatic may be protective of heart disease but these men require close follow up consisting of a PSA test, a digital rectal exam, and a blood count to check that there is not an increased production of red blood cells.

Testosterone Replacement Therapy (TRT) After Prostate Cancer Diagnosis

March 7, 2014

For nearly 50 years the medical profession has had the opinion that men with prostate cancer or at risk for prostate cancer should avoid testosterone as it was like adding gasoline to a fire. Well, that assumption has been reversed and there are certain men with prostate cancer who have symptoms of low testosterone, such as lethargy, falling asleep after meals, loss of muscle mass, and decreased libido, and who have documented low blood testosterone levels.
Testosterone replacement therapy (TRT) might be suitable for men with hypogonadism who also have a history of prostate cancer, but more research is needed, according to a group of Canadian and American scientists.

Typically, TRT is not considered for this population because exogenous testosterone is believed to stimulate the growth of prostate cancer cells. However, recent research has suggested that TRT might be safe for these men. Still, these studies have been small and the safety of TRT is still questioned.
This study took another look at this issue. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, the researchers examined the prostate cancer-specific outcomes, disease-specific survival, and overall survival information for 149,354 men with prostate cancer. The men’s median age was 73 years. Less than one percent of the men (1,181) underwent TRT after their cancer diagnosis.

Testosterone was administered via injections or subcutaneous pellets. Men on TRT underwent a median of 8 years of follow up; for men who did not take testosterone, the follow-up median was 6 years. TRT was more common among men who had had radical prostatectomy and those who had well-differentiated tumors. TRT was less common among men on watchful waiting or active surveillance protocols.

Overall and cancer-specific mortality rates were higher among men who were not on TRT. Also, TRT was not associated with higher rates of salvage androgen deprivation therapy.
The researchers noted the following:
• TRT did not appear to raise the rates of overall or cancer-specific mortality. In fact, the men taking testosterone had fewer mortality events than those who were not on TRT. The researchers were not certain why this occurred and noted the need for more follow-up.
• The percentage of men using TRT was low and declined over time. In 1992, 1.24% of the men underwent TRT after prostate cancer diagnosis. By 2006, that rate fell to 0.40%. In contrast, the researchers pointed out that the prevalence of hypogonadism, for which TRT is often prescribed, is much higher, ranging from 2.1% to 25%, depending on the parameters used.
• Income and educational status were factors in TRT use. “Seemingly, educated young men of means are more likely to either seek out, be offered, or accept TRT than other men,” wrote the study authors.
They added, “As the effects of hypogonadism intensify with age, and as our understanding of hypogonadism and testosterone deficiency expands, improved access to testosterone replacement will be important for older, low-socioeconomic (SES) men with prostate cancer, should further studies corroborate TRT safety.”
In light of these results, the researchers concluded that TRT could be safe for men after prostate cancer diagnosis. However, they stressed the need for prospective studies to confirm their findings.

The study was published online in January in the Journal of Sexual Medicine.

Bottom Line: There are times when it is necessary to challenge old ideas and assumptions. This certainly applies to testosterone replacement therapy and men with prostate cancer. If a man has a stable PSA after treatment for localized prostate cancer, has symptoms of low testosterone, and a documented decrease in the blood testosterone levels, then hormone replacement therapy may be helpful.

Resources
The Journal of Sexual Medicine
Kaplan, Alan L., MD
“Testosterone Replacement Therapy Following the Diagnosis of Prostate Cancer: Outcomes and Utilization Trends”
(Full-text. First published online: January 21, 2014)
http://onlinelibrary.wiley.com/doi/10.1111/jsm.12429/full