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).

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

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.

Testosterone Esters and Injections

I was prescribed testosterone cypionate for injection, one shot every 7 days. The shot size is 1ml for delivery of 100mg of testosterone. Naturally, when I found out my prescription, I did some research to figure out what I'd be injecting into my body.

Most testosterone prescribed for testosterone replacement therapy is in the form of a testosterone ester. Esterification is done to improve the solubility of testosterone in oil, which in turn slows the release of the testosterone once it's injected into the body. Testosterone comes in numerous types of injectable esters, including the common testosterone enanthate and testosterone cypionate, as well as the less common esters caproate, propionate, acetate, phenylpropionate, isocaproate, decanoate, and undecanoate. Each of these esters is a molecular chain composed of carbon, hydrogen, and oxygen atoms, the difference being how many carbon and hydrogen atoms make up the chain.

Once an ester group has been added, testosterone becomes more soluble in oil, but less soluable in water. It's also interesting to note that, in general, the more carbon atoms an ester has, the more oil-soluble it becomes. Testosterone propionate, for example, has 3 carbon atoms in the ester group and is less soluble than testosterone cypionate which has 8. The ratio between oil and water solubility is called the "partition coefficient". The higher the oil solubility, the higher the partition coefficient. As far as oils goes, testosterone compounds usually use cottonseed or sesame seed oil.

The partition coefficient is important because it indicates how quickly the testosterone is released into and stays in your system. Generally, the quicker the release, the shorter the stay. If the testosterone is released too quickly, testosterone rises quickly, but then soon starts declining once the dose has been used. So a testosterone solution with a very low partition coefficient is immediately available and used up quickly once it's injected, while a solution with a higher coefficient is released more slowly and lasts longer.

Testosterone cypionate is an example of a slow-acting compound with a high partition coefficient. When injected, the compound slowly dissolves, resulting in a slower release of testosterone with more stable, longer-lasting testosterone levels.

For testosterone replacement therapy, slow-acting compounds are usually prescribed, since a slower releasing compound means fewer injections and more constant testosterone levels. Testosterone enanthate, which has 7 carbons in the ester, and testosterone cypionate, which has 8 carbons, both take around 8-10 days to be fully released. As such, these testosterone esters are usually injected once every 1 to 2 weeks. In contrast, testosterone propionate with only 3 carbons in the ester, is fully released in 3-4 days. Using testosterone propionate would mean smaller doses injected more frequently.

So from the above, you can see that the dosage and frequency of shots depends a good deal on which testosterone ester is prescribed. Testosterone dosages range from 50mg to 300mg per injection, depending on the ester and dosing schedule. A typical dosing schedule might be 200-250mg every 2 weeks, or 100mg every week to 10 days. Blood levels should be monitored and the dosages adjusted according to an individual's response.

My Prescription

The clinic I went to prescribed a 1ml testosterone cypionate once weekly, with each ml containing 100mg of testosterone. I do the injections for a month, then get my levels checked, with adjustments (if required) made according to my individual results.

Below is some more information on the individual testosterone esters:

Testosterone enanthate is one of the two most commonly prescribed testosterone esters in the United States. It's slow-acting with a release time of 8 - 10 days. Testosterone enanthate is usually injected between once a week to once every three weeks.

Testosterone cypionate is the other most common injectable form of testosterone prescribed in the United States. It's also slow-acting, with a release time of 8-10 days. Testosterone cypionate injection schedules run from once every week to once every three weeks.

Sustanon is the brand name for two formulas of injectable testosterone that contain an ester blend. Sustanon 100 contains three testosterone esters: testosterone propionate, testosterone phenylpropionate, and testosterone isocaproate. Sustanon 250 contains four testosterone esters: testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, and testosterone decanoate. Both formulas feature both fast-acting and slow-acting esters, and are typically injected once every week to once every four weeks.

Testosterone propionate is a fast-acting ester with a release time of 3-4 days. To keep blood levels stable, propionate is usually injected one to three times a week.

Testosterone phenylpropionate is a slow-acting ester with a release time of 1-3 weeks. Testosterone phenylpropionate is one of the components of Sustanon and Omnadren.

Omnadren is the brand name for a blend of four testosterone esters: testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, and testosterone decanoate. It is pretty much the blend as Sustanon, featuring both fast-acting and slow-acting esters. It's injected from once every week to once every four weeks.

Injectable aqueous (water based) testosterone is available, but it is very short-acting, being completely released in the system within hours. It's not used for replacement therapy, since it would need to be re-injected multiple times daily to maintain stable blood levels.