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.

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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.

How to get Cheap Blood Work Online

Here's a way to get fairly inexpensive blood work performed without insurance. Understanding how testosterone (or any other steroids or prohormone) affects your various hormones and other levels is very important. most people don't get blood work, however, due to the expense or because you need to see a doctor to get it ordered.

Here's a way blood work done by scheduling your blood panel on-line. No need for a visit to the doctor or medical insurance. The blood work is done by Labcorp. Most cities and towns (in the United States) have a Labcorp within driving distance. If you can a Labcorp facility, you do this

Caveat: if you live in NY, NJ, or RI you can't due this due to state medical billing laws.

1. Go to PrivateMDLabs.com and select the hormone panel for females. This test comes with a CMP (liver, kidney values and more), CBC (blood counts), total Testosterone, total Estrogen, LH and FSH. Even though you are selecting the hormone panel for females, later on as you complete entering the information you will indicate you are a male, and the reference ranges will come back correct for males. Loophole!

2. Search for any current discount codes. You can usually find a 15% off. The total should come to around $50.

3. Select the Labcorp facility nearest you. You can make an appointment to have blood drawn. Just go to the Labcorp website after you pay for the blood work to schedule an appointment.

If you go Monday - Thursday, chances are you'll have the results in your email next day!

The basic female hormone panel doesn't include lipid levels, so if you want that you'll have to add it. That costs about another $50.

The trick is selecting female hormone panel to start, because when you complete the patient info you indicate male. Selecting the male hormonal panel costs about $150, three times as much as female for the same tests.

For $50 lousy bucks, you can get everything you'd want tested after a cycle (except lipids, which as mentioned can be added for $47.99 retail, before discounts): liver and kidney function, HPTA, estrogen, etc.

I'm getting my tests through the clinic, and covered by insurance, but I bet many of you aren't. If you're going to use performance enhancing drugs, take out the guess work and spend the money to make sure your health is on track.

TRT Update, 9 Week Blood Test

They call is "cruising" for a reason - I've just been cruising along, doing my test injections 1x per week and the hCG 2x. My initial prescription was for 10 weeks; at 9 weeks I had a Doctor consult scheduled and a blood test taken. Let's do the blood first, since that's probably what you're most interested in. These were my before-therapy levels:

Test	Result	Reference
Serum Testosterone	239 ng/dL	348 - 1197
Free Testosterone	8.0 pg/mL	6.8 - 21.5

And after 9 weeks of therapy (that would be 9 testosterone injections and 18 hCG injections):

Test	Result	Reference
Serum Testosterone	1,128 ng/dL	348 - 1197
Free Testosterone	29.4 pg/mL	6.8 - 21.5

So you can see that's a significant difference from my start numbers.

Serum Testosterone increased 889
Free Testosterone increased 21.4

My weight went from 184 to 196. They have an impedance body tester for body fat, not the most accurate I know, which showed me going from 14.9 to 13.7 percent.

I gotten stronger in bench (from 180x10 first set to 225x7), and the elbow and shoulder discomfort I had is mostly gone now. Unfortunately my back still bothers me, so I haven't been pushing on the squats and deadlifts. I did go from 275x6 on deadlift to 310x6, but that not really going all out.

So physically, there's been a very noticeable change. The more esoteric "mental" benefits have yet to manifest.

I still don't sleep well and frequently suffer from insomnia
No burst of mental clarity or increased motivation or focus
My energy levels do seem a bit higher during my workouts, but not increased overall.

The doctor didn't really have much to say when I pointed this out. She suggested a sleep aid supplement, which I declined.

I'm pretty happy as far as the gains go though, and I've decided to stick with it. So I continued the prescription with only one alteration, that being I decided (after consulting with the doc) to inject 2x a week, .5ml each time (for the same 1ml a week). I'd read this can provide more even test levels, plus it makes the shots a bit quicker and easier.

I'm still doing the shots myself using a 5/8 inch 28g needle in alternating quads on Mondays and Thursdays. No issues there. And the hCG in the stomach on Sundays and Wednesdays.

I did discover something interesting. With insurance, I was paying $78 a month for the testosterone cypionate and hCG, plus an additional $75 for the clinic fee, for a total $158 a month. So three months comes in at $474. If I use insurance, I can ONLY fill my prescription 1 month at a time.

If I "bulk" order from the clinics preferred prescription provider, I can get 3 months of testosterone cypionate and hCG for $425, a savings of about $50. So there you go....

Testosterone Repalcement Therapy, 5 Week Update

I've been meaning to write an update for a week and finally carved the time out today to do it. Yesterday was my sixth shot, marking the end of the fifth week since starting TRT. A good as time as any to give a status update, I suppose.

Energy-wise, I don't feel much different. Still tired, still sleep fitfully for about 6 hours a night. There's been no coalescing of focus, no sharpening of my mental acuity. I might  feel a bit more chipper, but I felt chipper for the most part to begin with. I wasn't depressed, but I still don't like my (admittedly well paying and fairly easy but completely unfulfilling) job.

Maybe a slight change on the sexual side of things. I wasn't having issues before, so no change there, although I have noticed a quality increase. By that I mean where I was maybe hitting an 8 or 9 on the "hardness" scale, I'm now hitting 10. Definitely a noticeable difference, accompanied by a bit more sensitivity as well. Maybe some other TRT users end up running around like randy teenagers, but not me. I'd say my level of desire is about the same as before.

I've gained some weight over the last 5 week, from 188 to 195, no change in waist size, but definitely more muscle. With this has come a cooresponding increase in strength. I don't feel a noticeable energy surge, but the weights float a bit easier, and I'm making gains again after a couple of years fighting to stay at the same place. Very nice to see a bit of muscle being added.

This relates to the above and is undoubtedly the source of my weight gain, but I've been much more hungry since starting the testosterone. Like craving food hungry, sitting down eating huge meals hungry. I'm definitely eating more (hence the weight gain) but it seems to be going to building muscle, not fat. Carb craving is a big part of this hunger, so I find myself eating stuff I'd put aside years ago: chips, candy, peanut butter and jelly sandwiches, pretzels.... I try to limit carbs and was doing so pretty successfully, but these new cravings have me stuffing them down. I need to clamp down a bit on that.

Anyone who's done a steroid or a prohormone is probably familiar with back pumps. Iv'e been gettingthose at a low level for a couple of weeks, to the point where it's difficult for me to run now. I've taken to jum[ping rope for my cardio. Running just cause my back to tighten up too much and is too painful. This si new and definitely related to the testosterone supplementation. I was running fine before, two miles three times a week. So the is for sure a TRT thing.

When it comes to going the bathroom, I've noticed the flow isn't as strong. My PSA levels were fine before hand. I need to do a bit of research on this. I'm not having and problems going, but still.... Related is my (still) waking up at  night to go to the bathroom. I generally wake up once, and occasionally twice. In the past, such nocturnal awakening where sometimes (50/50) accompanied by an erection. Now, every time, I've got to wait for the hydraulics to subside. Really, like every time. Annoying.

Overall, I'm happy with my progress. I especially like getting stronger and putting on some muscle. I don't like the back pumps and night time need-to-pee erections. My first blood test for levels comes at 12 weeks. I intend to continue with the testosterone replacement at least until that point and see how things are.

EDIT: I wrote this post 2 days ago, but didn't have a chance to proof and publish until now. I just finished my Wednesday workout and put up 255 on the bench. Not a lot to some folks, but, due to various shoulder and elbow issues (including elbow surgery a few years back), that's most I've done since I was in my 30s. I'm pretty pleased with that, and after only 5 weeks too!