Do You Have Hypogpnadism (low T)?

Overview - What is Hypogonadism?

Hypogonadism is a condition associated with low serum testosterone levels and symptoms such as fatigue, decreased libido, weakness, and weight gain. It is known to occur with aging, as most men have declining testosterone levels beginning in their 30’s. 

Low testosterone levels have been associated with decreased muscle mass and strength, osteoporosis, depression, decreased cognition, ED, and metabolic syndrome. Testosterone replacement therapy (TRT) has been shown to increase lean body mass, improve bone mineral density, increase cognitive performance, and improve sexual function.

Diagnosis and Treatment

Currently, there is no single consensus statement regarding diagnosis and management of hypogonadism. 

In general, the diagnosis requires a low serum testosterone level coupled with at least one clinical symptom of low testosterone. Absolute ranges of normal testosterone levels are difficult to establish. Therefore, treatment is generally geared toward improvement of clinical symptoms rather than an absolute serum testosterone level.

Historically, the concern for TRT was its effect on the prostate. Despite evidence that the prostate does enlarge slightly on TRT, no studies have shown any significant worsening of urinary symptoms while on therapy. 

Studies have also demonstrated no significant change in PSA while on therapy. An increasing PSA while on TRT may indicate underlying malignancy and warrants evaluation. 

There has been no increased risk of prostate cancer demonstrated with TRT. Additionally, studies have demonstrated no increased risk of recurrence in men on TRT after undergoing treatment for prostate cancer. Small studies of men with active prostate cancer have shown no progression of disease on TRT.

There are many options for TRT, each of which has its benefits and disadvantages. The decision about which one is right for you will depend on your personal preferences and a discussion with your physician. 

 In some cases, different insurance companies may cover one option and not another, which may also be taken into consideration. If the desired effects are not achieved with your initial choice, a different option can be tried to see if it is a better fit for you. A summary of the most commonly used TRT options is provided below.

Topical Gels: Advantages include more constant levels with daily dosing, high patient satisfaction, and avoidance of needles. Disadvantages include increased cost compared to injectables, the potential for transference of the gel to others (e.g., spouses and young children) through contact with your skin or clothes, messiness of gel application, and potential skin irritation. 

Injectables: Advantages include efficacy and patient satisfaction, weekly to biweekly dosing, and low cost. Disadvantages include increased fluctuation (peaks and valleys) in testosterone levels compared to daily dosing options and the requirement for needles and self-injection.

Implantable: The advantages of this therapy include convenience and decreased frequent of dosing. As this requires a short office procedure, there are risks including bleeding, infection, and pellet extrusion in less than 1% of cases.

Monitoring

Regardless of the type of testosterone replacement therapy chosen, you will need to be monitored at regular intervals (usually every 3-6 months); both to confirm good control of your symptoms and to ensure that there are no potentially dangerous side effects. The follow-up regimen usually consists of the following:

• Physical examination, including digital rectal exam to rule out prostate nodules (yearly).
• Routine blood work for testosterone levels and other hormones (every 3-6 months)
• Routine blood work for lipids, hemoglobin and hematocrit, and PSA (prostate-specific antigen) (every 6 months).

Testosterone Therapy and Human Growth Hormone

As discussions around performance enhancing drug scandals, doping and potential multi-game suspensions continue to plague Major League Baseball and some of its top talent; Health Talk recently talked with U of M experts about how human growth hormone (HGH) and testosterone actually affect performance.

We sought out University of Minnesota College of Pharmacy pharmacology and drugs of abuse expert David Ferguson, Ph.D., and Bradley S. Miller, M.D., Ph.D., a pediatric endocrinologist with the University of Minnesota Medical School who has studied growth and development associated with HGH.


Can HGH and testosterone be considered performance-enhancing drugs?

Definitely. Testosterone is listed in the textbooks for performance enhancement and HGH, while newer to the game, is also listed. Football, baseball, the Olympics and many other sports list both as performance enhancers, although football still isn’t testing for HGH.

So both HGH and testosterone can enhance performance. Do they work in similar ways?

The two function differently. Testosterone is a steroidal hormone that causes fairly rapid increases in lean muscle mass and strength. It’s a small molecule that’s primarily responsible for growth, and it influences and enhances male characteristics such as muscle and bone mass, aggression, and facial hair among other things. Testosterone is very potent when taken orally as a pill, applied topically as a gel, or injected with a syringe. The consequences of abuse are well documented to produce long-term effects in users. HGH, on the other hand, is a protein. HGH activates a receptor that tells cells that cause growth to turn on. It’s a large protein, as opposed to a small molecule. Additional HGH is introduced to the body via an injection… not pills or gels.

HGH introduces a slower onset of strength than testosterone might. HGH tells the body to use calories to build muscle and bone. If you were deficient, you would store them as fat. Studies have shown you recover from injury associated with athletics more quickly.

How do we detect use?

Testosterone use is very well documented. There are really good tests out there to detect it’s abuse.

You can measure levels and ratios of growth hormones in the body to detect HGH. But you’d have to catch somebody the day they take HGH, because it has a pretty quick half-life. Levels come down pretty quickly once you stop taking it. Mayo Clinic researchers are currently looking into better ways to detect it.

Both HGH and testosterone are available with a prescription. What are their appropriate uses?

Testosterone can help restore libido in older men, which can help with erectile dysfunction. It is commonly used in replacement therapy to alleviate metabolic disorders or deficiencies in people young or old.

HGH, on the other hand, is responsible for growth. It has a lot of uses in pediatrics and in people with growth-related disorders. For example, it can help cancer patients—especially children—regain growth after chemotherapy.

What about long-term affects of unnecessary use or abuse?

We don’t have data on what’s going to happen to someone that uses HGH who shouldn’t be using it in five years. With patients who take HGH for legitimate reasons, when they stop taking it they tend to see a little bit of a relapse, because their body doesn’t produce it, but HGH production does recover and normal function comes back.

Andre the Giant and Jaws from the 007 movies are good examples of the physical changes that can occur from too much growth hormone. Both had a tumor producing growth hormone that made them unusually tall, resulting in an enlarged jaw and dental problems. Too much HGH can lead to pre-diabetes symptoms, but we don’t know if that stops after HGH use ends. One question out there is, as you get older and take HGH unnecessarily, can it increase your cancer risk? HGH doesn’t make cancer happen, but it might make someone predisposed to cancer experience an accelerated rate of development.

With testosterone abuse, the body stops producing the levels of testosterone it needs naturally. Shrunken testicles are the classic long-term effect of abuse, but there’s a whole list of negative effects: shrunken muscle mass leading to hanging flesh on the body, an inability to produce enough testosterone later on, enlarged heart, kidney and liver problems, increased male characteristics in females and increased female characteristics for men, et cetera. If you use something like testosterone off-and-on, it can put you at a greater risk for injury during the low point of that cycle.

What’s the bottom line?

HGH and testosterone use encourages artificial enhancement of the body’s natural capabilities. Artificial enhancement is cheating, and sooner or later, the abuse of these drugs will catch up to them in one way or another.

Testosterone Replacement Therapy

Hypogonadism, or Low Testosterone

Hypogonadism, also known as low testosterone or “low T,” can lead to symptoms of decreased energy and libido, difficulty building lean muscle mass, moodiness, difficulty concentrating, and even loss of bone density. Men who have some or all of these symptoms and demonstrate low testosterone on a blood draw are candi­dates for testosterone replacement therapy (TRT).

There are many options for TRT, each of which has its benefits and disadvantages. The decision about which one is right for you will depend on your personal preferences and a discussion with your doctor. In some cases, different insurance companies may cover one option and not another, which may also be taken into consideration. If the desired effects are not achieved with your initial choice, a different option can be tried to see if it is a better fit for you, your health, and your life­style.
Evaluation of Low Testosterone

Regardless of the type of testosterone replacement therapy chosen, you will need to first be evaluated by your doctor and then monitored at regular intervals (usually every 3-6 months) to confirm good control of your hypo­gonadal symptoms, check levels of testosterone and perform other related bloodwork, and to ensure that there are no potentially dangerous side effects.

The evaluation and follow-up regimen usually consists of the following:

• Physical examination every 6 months, including digital rectal exam assess for signs of prostate enlargement and prostate cancer.
• Bloodwork every 3-6 months for testosterone levels and other hormones.
• Bloodwork every 6 months for lipids, hemoglobin and hematocrit, and PSA (prostate-specific antigen).

Is Testosterone Therapy Safe?

Millions of American men use a prescription testosterone gel or injection to restore normal levels of the manly hormone. The ongoing pharmaceutical marketing blitz promises that treating "low T" this way can make men feel more alert, energetic, mentally sharp, and sexually functional. However, legitimate safety concerns linger. For example, some older men on testosterone could face higher cardiac risks.

"Because of the marketing, men have been flooded with information about the potential benefit of fixing low testosterone, but not with the potential costs," says Dr. Carl Pallais, an endocrinologist and assistant professor of medicine at Harvard Medical School. "Men should be much more mindful of the possible long-term complications."

Signs of low testosterone

MIND

• Depression
• Reduced self-confidence
• Difficulty concentrating
• Disturbed sleep

BODY

• Declining muscle and bone mass
• Increased body fat
• Fatigue
• Swollen or tender breasts
• Flushing or hot flashes

SEXUAL FUNCTION

• Lower sex drive
• Fewer spontaneous erections
• Difficulty sustaining erections

The low-T boom

A loophole in FDA regulations allows pharmaceutical marketers to urge men to talk to their doctors if they have certain "possible signs" of testosterone deficiency. "Virtually everybody asks about this now because the direct-to-consumer marketing is so aggressive," says Dr. Michael O'Leary, a urologist at Harvard-affiliated Brigham and Women's Hospital. "Tons of men who would never have asked me about it before started to do so when they saw ads that say 'Do you feel tired?'"

Just being tired isn't enough to get a testosterone prescription. "General fatigue and malaise is pretty far down my list," Dr. O'Leary says. "But if they have significant symptoms, they'll need to have a lab test. In most men the testosterone level is normal."

If a man's testosterone looks below the normal range, there is a good chance he could end up on hormone supplements—often indefinitely. "There is a bit of a testosterone trap," Dr. Pallais says. "Men get started on testosterone replacement and they feel better, but then it's hard to come off of it. On treatment, the body stops making testosterone. Men can often feel a big difference when they stop therapy because their body's testosterone production has not yet recovered."

This wouldn't matter so much if we were sure that long-term hormone therapy is safe, but some experts worry that low-T therapy is exposing men to small risks that could add up to harm over time.

What are the risks?

A relatively small number of men experience immediate side effects of testosterone supplementation, such as acne, disturbed breathing while sleeping, breast swelling or tenderness, or swelling in the ankles. Doctors also watch out for high red blood cell counts, which could increase the risk of clotting.

The evidence for long-term risks is mixed. Some studies have found that men on testosterone have fewer cardiovascular problems, like heart attacks, strokes, and deaths from heart disease. Other studies have found a higher cardiac risk. For example, in 2010, researchers halted the Testosterone in Older Men study when early results showed that men on hormone treatments had noticeably more heart problems. "In older men, theoretical cardiac side effects become a little more immediate," Dr. Pallais says.

Some physicians also have a lingering concern that testosterone therapy could stimulate the growth of prostate cancer cells. As with the hypothetical cardiac risks, the evidence is mixed. But because prostate cancer is so common, doctors tend to be leery of prescribing testosterone to men who may be at risk.

"Like any treatment, there is risk," Dr. O'Leary says. "I would not give it to a man who is being treated for active prostate cancer, but it's pretty safe under careful supervision for those who need it."

For the time being, the long-term risks of testosterone therapy are "known unknowns." It offers men who feel lousy a chance to feel better, but that quick fix could distract attention from unknown long-term hazards. "I can't tell you for certain that this raises the risk of heart problems and prostate cancer, or that it doesn't," Dr. Pallais says. "We need a large study with multiple thousands of people followed for many years to figure it out."

So, keep risks in mind when considering testosterone therapy. "I frequently discourage it, particularly if the man has borderline levels," Dr. Pallais says.

Take a cautious approach

A large, definitive trial for hormone treatment of men is still to come. Until then, here is how to take a cautious approach to testosterone therapy.

Take stock of your health first

Have you considered other reasons why you may be experiencing fatigue, low sex drive, and other symptoms attributable to low testosterone? For example, do you eat a balanced, nutritious diet? Do you exercise regularly? Do you sleep well? Address these factors before turning to hormone therapy.

If your sex life is not what it used to be, have you ruled out relationship or psychological issues that could be contributing?

If erectile dysfunction has caused you to suspect "low T" as the culprit, consider that cardiovascular disease can also cause erectile dysfunction.
Get an accurate assessment

Inaccurate or misinterpreted test results can either falsely diagnose or miss a case of testosterone deficiency. Your testosterone level should be measured between 7 am and 10 am, when it's at its peak. Confirm a low reading with a second test on a different day. It may require multiple measurements and careful interpretation to establish bioavailable testosterone, or the amount of the hormone that is able to have effects on the body. Consider getting a second opinion from an endocrinologist.

After starting therapy, follow-up with your physician periodically to have testosterone checks and other lab tests to make sure the therapy is not causing any problems with your prostate or blood chemistry.

Be mindful of unknown risks

Approach testosterone therapy with caution if you are at high risk for prostate cancer; have severe urinary symptoms from prostate enlargement; or have diagnosed heart disease, a previous heart attack, or multiple risk factors for heart problems.

Ask your doctor to explain the various side effects for the different
formulations of testosterone, such as gels, patches, and injections. Know what to look for if something goes wrong.

Have realistic expectations

Testosterone therapy is not a fountain of youth. There is no proof that it will restore you to the level of physical fitness or sexual function of your youth, make you live longer, prevent heart disease or prostate cancer, or improve your memory or mental sharpness. Do not seek therapy with these expectations in mind.

If erectile function has been a problem, testosterone therapy might not fix it. In fact, it might increase your sex drive but not allow you to act on it. You may also need medication or other therapy for difficulty getting or maintaining erections.

A Look at Testosterone Replacement Therapy (TRT)

Testosterone replacement therapy (TRT) has surged in popularity over the past decade. Millions of men have turned to TRT to restore hormone levels in hopes of refueling energy and reigniting their sex drive.

Yet TRT remains controversial because of its uncertain benefits and potential health risks. Safety concerns were raised when studies showed a possible association between TRT and an increased risk of cardiovascular disease.

Dr. Frances Hayes, a reproductive endocrinologist with Harvard-affiliated Massachusetts General Hospital, points out that some of these studies had limitations.

"For instance, in one study, TRT doses were much higher than what would usually be prescribed, and the subjects tended to be more frail, with other health problems," she says. "Other studies showed no evidence of increased risk."

The Latest Findings

Recent research has supported this position. 

A study reported at the 2015 American Heart Association Scientific Sessions involved 1,472 men ages 52 to 63 with low testosterone levels and no history of heart disease. Researchers found that healthy men who received TRT did not have a higher risk of heart attack, stroke, or death.

Furthermore, a study in the August 2015 Mayo Clinic Proceedings showed no link between TRT and blood clots in veins among 30,000 men. "Right now, the jury is still out about TRT's influence on cardiovascular disease," says Dr. Hayes.

TRT's relationship with other health issues is also mixed. For instance, TRT has previously been tied to a higher incidence of prostate cancer, but a study published in the December 2015 Journal of Urology found that exposure to TRT over a five-year period was not linked to a greater risk of aggressive prostate cancer.

The bottom line is that the long-term risks of TRT are still unknown, as many of these studies have limited follow-ups. 

That does not mean you should avoid TRT. For a selected subgroup of men, the therapy can be a viable option.

Who is a candidate?

You need to have both low levels of testosterone--less than 300 nanograms per deciliter (ng/dL)--and symptoms to get a prescription for TRT. 

"It is possible to have low levels and not experience symptoms," says Dr. Hayes. "But if you do not have any of the key symptoms, especially fatigue and sexual dysfunction, which are the most common, it is not recommended you go on TRT given the current uncertainty with regard to long-term safety."

A simple blood test measures testosterone levels. Several tests are required, as levels can fluctuate daily and be influenced by medication and diet. 

"In 30% of cases where the first testosterone test is low, levels are normal when the test is repeated," says Dr. Hayes.

Even if your levels are low and you have several symptoms, TRT is not always the first course of action. "If you can identify the source for declining levels, often you can address that problem and increase low levels naturally," says Dr. Hayes.

For instance, the No. 1 contributor to falling levels is weight gain. "Weight has a bigger impact on testosterone levels than aging. As weight goes up, testosterone levels go down," she says. A five-point increase on the body mass index scale is equivalent to adding 10 years to your age in terms of testosterone levels.

"Your doctor should also review any other factors that might influence levels, like medication or medical conditions," says Dr. Hayes. In these instances, your doctor may treat the underlying condition or change your medication or dosage to one that would not affect testosterone levels.

Men also need to understand the limits of TRT, as many envision it as a type of fountain of youth. "Its impact is less than what many men would expect," says Dr. Hayes.

For example, two often-touted benefits of TRT are sexual health and vitality. A double-blind study in the Feb. 18, 2016 issue of The New England Journal of Medicine reviewed the effects of TRT on 790 men ages 65 and older. Those who received TRT for one year, versus those on placebo, saw improvements in sexual function, including activity, desire, and erectile function. 

However, the group experienced only a slight improvement in mood and saw no changes in walking speed, which was used to measure TRT's effect on vitality.

Using TRT

TRT is often given by either gel application or injection. With a gel, you spread the daily dose over both upper arms, shoulders, or thighs. Injections are typically given into the buttocks once every two weeks.

Each method has its advantages. With gels, there is less variability in levels of testosterone. 

With injections, testosterone levels can rise to high levels for a few days after the injection and then slowly come down. This can cause a roller-coaster effect, where mood and energy levels spike before trailing off.

Most men feel improvement in symptoms within four to six weeks, although changes like increases in muscle mass may take from three to six months.

TRT may not always need to be taken for life. 

"If the issue that caused your testosterone levels to drop in the first place resolves, you should have a trial off treatment and be re-evaluated by your doctor," says Dr. Hayes

The Hypothalamic Pituitary Testicular Axis (HPTA) and Chlomid

Clomid works by blocking estrogen receptors at the hypothalamus and also stimulates it to release gonadtropin, aka GnRH. GnRH goes back to the pituitary to stimulate the release of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hhormone). LH, in turn, stimulates the testes to produce and secrete testosterone and perform spermatogenesis.

There is something called the Hypothalamic Pituitary Testicular Axis (HPTA) which encompasses this entire process. This sort of chain reaction sounds good until you get in to the androgenic effects of steroids.

Exogenous androgenic substances (such as injected testosterone) reduce your hypothalamus' ability to release GnRH. This in turn effects your levels of LH and FSH, all of which are necessary to tell your body to produce testosterone. If androgens suppress the release of these hormones, and clomid does such wonderful things to increase the release of these hormones, shouldn't we reach a sort of homeostasis in the middle?

Another underlying problem is that artifical androgens, regardless of external supplementation with other pharmaceuticals, cause our bodies to become desensitized to LH, which is probably the most important hormone in restoring the testes' ability to produce testosterone. Llewellen's research shows almost immediately after the cessation of testosterone supplementation, LH levels start to rise, but testosterone production took much longer to start.

The only hormone shown to have significant impact on maintaining some degree of testosterone production while on cycle is HCG. HCG works by mimicking our own body's natural LH, which we are equally as desensitized to at this point after supplementing with exogenous testosterone. The reason it works though is that we are bombarding our endocrine system with far greater levels of LH than our body is used to seeing. The effect off this is not apparent while on cycle, as our testes are still desensitized to the LH, but upon cessation of exogenous testosterone, the bombardment of LH in our system serves to reduce the time it takes our testes to "wake up" and start producing endogenous testosterone.

An anti-estrogen is needed in compliment the HCG because, post cycle, we still have increased levels of estrogen in our systems. Testosterone and estrogen both have negative and positive feedback signals that our body uses for various purposes. Without the testosterone in our system post cycle to provide its negative and positive feedback singals, we're left with only the ones coming from estrogen. An anti-estrogen, like Nolvadex, serves to block our estrogen receptors so our bodies can longer receive these signals, thus negating the effects of increased estrogen levels without testosterone.

I went a little overboard, moving in to PCT a bit more, but that should give you a pretty decent understanding of just a few of the basics of how testosterone and our endocrine system works in regard to the cessation and restarting of endogenous testosterone production.

source

What is Free Testosterone and Total Testosterone?

Testosterone is a steroid hormone present in both men and women (men have much more). Some testosterone floats about the body in the blood without being attached to anything else. This is called 'free' testosterone.

The rest of the testosterone is attached (called bound), some to a protein called sex hormone binding globulin (SHBG ) and some to a protein called albumin.

'Total' testosterone is the sum of all the testosterone in the blood, no matter whether it is f'free' or bound.

Free testosterone is just the free stuff floating by itself (not bound). Only a small precentage of testosterone is free.

For years, doctos thought only free testosterone was biologically active, meaning it was thought that the free testosterone was doing all the things testosterone is supposed to do, while the bound testosterone attached to SHBG or albumin and doesn't do anything. Some researchers disagree with this and think that the testosterone bound to albumin is also active. The jury is still out.

If someone has normal levels of total testosterone, but a low SHBG, then it's likely there's more free testosterone. Alternatively, someone who has high SHBG would likely have a lower amount of free testosterone, since the SHBG will bind to more of it.

That's why it's useful to know free testosterone levels, rather than just total testosterone.