The Ultimate Testosterone Replacement Guide for Men AND Women

All your questions answered.

There’ve been a lot of articles in old-school media lately (magazines and newspapers) on the wisdom of testosterone replacement therapy (TRT), but perhaps not surprisingly, they seem to focus on only one aspect of TRT, which is its ability to resurrect a flagging libido in both men and women. That does my favorite hormone a disservice because he’s got much more on his mind than steely erections and loamy loins! Hence this comprehensive guide to TRT for both sexes.

You’ve no doubt heard most of the questions used to diagnose low testosterone:

Do you have less energy? Have you experienced an inexplicable increase in body fat and have trouble losing it? How about a loss of muscle tone, and an inability to make progress in your workouts? Does your erection sometimes falter and wane when taken to task? Do you think more about your lawn than lady parts?

How about premature aging? Difficulty in concentration or memory? Depression? Or maybe a lack of “appropriate aggressiveness” where you don’t take the initiative in matters of business or the heart? Maybe you’re nervous, or always pissed off, ready to tear the head off the pudknocker in line in front of you who bought the last goddam cinnamon roll?

Any of these things could be indicative of low testosterone, including, seemingly paradoxically, that last item on the list about undue anger levels.

Historically, low testosterone, or hypogonadism, has largely been a problem of middle age and beyond. A 2006 study reported that 39% of men over 45 suffer from it. Another study said that while 13 million men in the U.S. may be deficient in testosterone, fewer than 10% get treatment for it.

That’s quite a chunk of human change but consider that these statistics reflect only those men that were clinically deficient, i.e., their lab tests indicated they were low. It leaves out the millions – many who are young or relatively young -- whose lab tests say they may be fine but based on their symptoms are probably deficient.

It also ignores the younger men who don’t typically get their testosterone levels tested. Gawd, I hate finding myself in agreement with the likes of basking-his-balls-in-red-light Tucker Carlson, but millions of them are likely deficient, too. Not because of old age, but because of environmental estrogens, pituitary and testicle stifling chemicals in general, and probably even a soft, cushy, modern, convenience-filled low-testosterone lifestyle. It’s even speculated by some that the testosterone levels of today’s average man are roughly half of what his grandfather’s were at a comparative point in life.

What Kind of Blood Tests Do I Need?

So, let’s assume you’re suffering from one or more of the above symptoms. Or, screw that, maybe you feel okay but you just want to be the same baller you were in your twenties or thirties. Either way, you decide to take the testosterone replacement therapy (TRT) plunge. Assuming you’re going to do this the legal way, your first step is to find a rational, open-minded doctor.

Why rational and open-minded? Because an old-school doc might operate solely on the perception of need. Conventional doctors assume that “no one ever dies from low testosterone,” so they might not see a reason to treat it.

The trouble with all this is, as recent studies have shown, people do end up dying from low testosterone, as low amounts of the hormone have been associated with cardiovascular disease, type II diabetes, metabolic syndrome, a higher death rate from all causes, and death from general system-wide decrepitude.

This is all part of the doctor-patient game. You might have to humiliate yourself and tell them that your libido is flagging, your erections are overcooked-linguini soft, and that you lack energy, even if none of it’s true. Telling them you want TRT for what I call “health extension” or because you simply want to be a better, more sexually proficient you, probably won’t cut it.

Of course, you might be one of the millions of men who actually have low testosterone and are experiencing the aforementioned symptoms.

However, believe it or not, convincing a doc to at least consider giving you TRT is the easy part, or at least the comparatively easier part. Once you convince them to consider it, they’ll order a blood test, and that’s where the real circus begins.

Why Accurate Results are Important

Chew on this: There are no standardized referenced values regarding testosterone levels among different laboratories. Standardized values are important because a lot of men are -- or will become -- genuinely hypogonadal. That diagnosis generally brings a lot of symptomatic baggage, including the aforementioned diminished sex drive and energy, along with impaired cognition and a slow erosion of muscle mass and strength.

However, the way things are, one lab may categorize a man as “low” in testosterone while another may classify him as “normal.” This is problematic because doctors rely heavily on these readings to determine if a patient requires TRT. Too bad the patient is unwittingly forced to participate in this Russian roulette style of clinical diagnosis.

Pick the wrong doctor and, ipso facto, the wrong lab or testing method, and patients are endocrinologically doomed.

The Truth is Ridiculously Bad

Abraham Morgenthaler, MD, is a testosterone-science hotshot who’s well known to those of us who are passionate about the hormone. In 2006, he and his colleagues did a survey of 12 academic laboratories, 12 community medical laboratories, and one national laboratory.

Of the 25 labs they surveyed, there were 17 different sets of values for total testosterone and 13 different sets of values for free testosterone. Reference values for low testosterone ranged from 130 to 450 ng/dl, a 350% difference. Reference values for the upper end of “normal” ranged from 486 to 1,593 ng/dl, a 325% difference.

The widest range for supposedly normal total testosterone levels from a single lab was 262 to 1,593 ng/dl and the narrowest range was 180 to 486 ng/dl.

As far as free testosterone levels, the low value ranged from 5.0 to 13.5 picograms per milliliter, a variation of about 270%. The upper value ranged from 19.0 to 54.7 pg/ml, a variation of about 290%.

Are you getting the implications of this? As Morgenthaler and his colleagues pointed out, a man who had a total testosterone reading of 251 ng/dl would be categorized as hypogonadal by 14 of the labs they surveyed and normal by the other 11 labs.

They noted similar results for free testosterone.

Years Later, More of the Same

Shoot forward in time ten years later. Researcher Margaret Le and her colleagues from the Urology Department of the University of Kansas Medical Center undertook a study similar to Morgenthaler’s, only more comprehensive. They interviewed 120 laboratories from 47 states.

They found a range of 160 to 300 ng/dl for the lower reference value of total testosterone and a range of 726 to 1,130 ng/dl for the upper.

Further, they found that a third of the labs “age stratified” reference values. As an example, 19 of the surveyed labs arbitrarily designated 50 years or greater as kind of a statistical cutoff age, meaning old coots were assigned different definitions of normal total testosterone levels.

Other labs reported ranges by decade of life (i.e., separate ranges for men in their twenties, thirties, forties, etc.). Still others divvied up men into three age groups: 18 to 39, 40 to 59, and greater than 60.

Can you see the problem with this age stratification? Let’s say you just turned 40 and you suspect your T levels are low. You go to the doc to get your levels checked and they come back “normal” for a man your age. However, if you had gotten the test the day before you turned 40, you might have tested low and qualified for TRT.

What a mess.

Another Problem That Has Nothing to Do with Technology or Perceptions

Say you walk into your doctor’s office on a Monday at 9 AM to have your testosterone levels checked. They draw your blood and you venture forth into the world, only to return Wednesday at the same time and have the test repeated.

Studies show that such a scenario could easily result in a 10% variability in your testosterone levels. In effect, you could qualify for TRT on Monday, but test “normal” on Wednesday.

Talk about luck of the draw. This variability has nothing to do with doctor or lab error, though. It’s entirely based on the normal circadian rhythms and biochemical fluctuations that come with being a living organism.

Other Things that Can Muddle the Bloodwork Values

Let’s assume you had your bloodwork done and your total testosterone is 600 ng/dl. That would put you smack-dab in the middle of “normal” ranges, at least according to endocrinology textbooks.

However, that 600 number might be meaningless as to how much testosterone is really in your blood, doing the work it’s supposed to do. For one, your steroid hormone binding globulin, or SHBG, might be too high. It’s a glycoprotein that literally binds up the sex hormones, including, on average, about 60% of your testosterone, and that percentage keeps climbing as you grow older.

The more SHBG you have, the more of your testosterone is bound up, leaving less of it free to do all the good stuff. So, while your testosterone level may be 600, a good portion of it has been hog-tied and thrown into the bed of a pick-up. It can be maddening. It’s like having a genie in a bottle that you can’t uncork.

That’s why, at the very least, when trying to determine your testosterone levels, doctors should ask the lab for your total testosterone levels, your “free” testosterone levels, and your “bioavailable” testosterone levels so you can get a little bit better of an idea of what your testosterone situation is. (Of the three, free testosterone is the most accurate indicator of how much testosterone you have working for you.)

But, you guessed it, nobody does that, at least very few conventionally trained doctors.

And we can’t forget about estrogen, or more specifically, estradiol levels in men. Your testosterone levels may read normal, but if estradiol levels are high, it could thwart testosterone in its efforts to make you the man you’re supposed to be.

Let’s assume, though, that all labs were terrific and shared the same reference ranges. There’d still be a problem with what constitutes “normal” testosterone levels. Normal for you might be towards the upper end of the scale, but since no doctor ever thinks to order a testosterone baseline for someone in their twenties, patients in their 30’s or 40’s are often forced to play this silly, maddening game where they’re ruled by some arbitrary lab values.

This makes it absolutely essential that a responsible physician observe his patient, listen to his symptoms, evaluate him, and, if needed, formulate a treatment based on humanitarian and scientific principles to restore his health and vitality, sometimes regardless of what the numbers say.

In other words, treating patients based on symptoms (or at least alleged symptoms) rather than possibly misleading or inaccurate lab samples.

Get the Right Lab Work Done

As stressed above, it’s important that your doc get the right lab work done. Unfortunately, they probably don’t know what the right lab work is. Additionally, your insurance company doesn’t either. So you’ll have to supplicate your doctor to order the right tests and you might have to pay for them out of your own pocket.

Try to get the tests done in exactly the way specified below (for instance, if you don’t ask for a “sensitive assay” estradiol test for males, they’re going to measure your estradiol the same as if you were a ballerina from the Bolshoi ballet suffering from menstruation problems):

• Testosterone, total

• Testosterone, bioavailable

• Testosterone, free

• Estradiol (sensitive assay)

• Steroid Hormone Binding Globulin

• Follicle Stimulating Hormone (FSH)

• Luteinizing Hormone (LH)

• Dihydrotestosterone (DHT)

• Complete Blood Count (CBC)

• Prostate Specific Antigen (PSA)

• Blood Chemistry Panel

• Metabolic Panel

These tests will give a fairly good baseline reading of where you stand so that when you have follow-up blood testing done three to six months later, you can see if you’re on the right dosage and whether you’re suffering any insidious negative side effects. If you’re forced to pick and choose, at least get Free Testosterone, Estradiol, PSA (only to determine if you need further testing to rule out prostate cancer, which would be incompatible with TRT), the blood chemistry panel, and the metabolic panel (to make sure you’re generally healthy).

Question 3 -- What are Normal Testosterone Blood Values?

Ask 10 different doctors, ask 10 different TRT experts, ask 10 different labs, and you’ll likely get close to 30 different definitions as to what constitutes “normal” testosterone levels.

Let’s generalize and say that low total testosterone is from 200 to 300 nanograms per deciliter of blood and “normal” is anywhere from 300 to around 1100. However, as I went to great lengths to point out, total testosterone doesn’t mean a whole hell of a lot. Further, as I pointed out, labs and doctors tend to “age stratify” reference values.

Here’s how this kind of categorizing could bite you in the ass. Say you’re 50 and the doc prescribed you 100 mg. of testosterone a week. You’re feeling great and all is well in the world, but when you come back for some follow-up blood work, your total testosterone comes back at 800 ng/dl. However, according to this age stratification thing, your levels are too high for a coot your age. The doctor is then compelled to lower your dosage.

But this practice belies common sense. Why would anyone undergoing TRT want to have the testosterone levels of a 50-plus year-old man? The whole point of TRT is bringing your testosterone levels up to those of a younger man, your younger self.

Besides all that, total testosterone really is pretty worthless, at least in my opinion. Most doctors believe that total testosterone correlates pretty well with free testosterone, but I prefer to be more convinced of my hormonal status.

For instance, you could easily have “normal” total testosterone levels but still experience all the symptoms of low testosterone because much of your testosterone is “bound up” and unable to do its thing.

That’s why measuring free testosterone is much more telling of your endocrinological state. However, doctors and labs again tend to assign normality based on age ranges (approximately 2% of total testosterone is free, so don’t be freaked out by these seemingly low numbers):

• 20-<25 years: 5.25-20.7 ng/dL

• 25-<30 years: 5.05-19.8 ng/dL

• 30-<35 years: 4.85-19.0 ng/dL

• 35-<40 years: 4.65-18.1 ng/dL

• 40-<45 years: 4.46-17.1 ng/dL

• 45-<50 years: 4.26-16.4 ng/dL

• 50-<55 years: 4.06-15.6 ng/dL

• 55-<60 years: 3.87-14.7 ng/dL

• 60-<65 years: 3.67-13.9 ng/dL

• 65-<70 years: 3.47-13.0 ng/dL

But forget all these sub-categories, anyone on TRT should be aspiring to free testosterone levels in the upper teens.

Question 4 -- What Are My Choices for TRT Delivery Systems?

Your choice of TRT essentially comes down to one question: Can you handle injecting yourself once or twice a week, or does the thought cause your face to go Zuckerberg pale? Let’s look at the pros and cons of the main types of TRT:

Testosterone Injections -- In my experience, testosterone injections are the crème de la crème of TRT. While it’s true that testosterone gels (see below) create a more natural ebb and flow of testosterone, injections, provided they’re administered properly, give you the most muscle-building, libido boosting, rock-your-world bang for the buck.

You essentially have three injectable choices in America, testosterone enanthate, testosterone cypionate, and testosterone propionate. (A more sophisticated injectable, testosterone undecanoate, is now available in the U.S., but the regs state that it must be injected by a health care professional. Why, I don’t know.) The half-lives of these esters differ slightly, but it’s not that big a deal, especially if your dosing is adequate and you’ve chosen a suitable injection method and schedule.

For most men, 100 mg. a week of any of those esters is enough for effective TRT. However, some men need less and some men need more, possibly up to 200 mg. a week. Beyond that amount and you’re pretty much on a mild bodybuilding steroid cycle instead of testosterone replacement

Even if you’re injecting weekly (always on the same day), you still might suffer a bit of a low-testosterone lull as you get further away from injection day. To remedy this, many men split their dosage in half and inject twice a week instead of once a week. Doing so keeps your blood levels of testosterone fairly stable.

And while many men micromanage their hardest workouts to coincide with the peaks and troughs of their TRT, it’s largely an unnecessary battle, especially when you’re giving yourself two injections a week. Injections given that close together ensure that you’re pretty much always riding a peak.

Additionally, you might want to consider subcutaneous injections rather than intramuscular injections. The late Dr. John Crisler, noted testosterone guru, insisted that sub-Q is much more effective, so much so that 80 mg. of testosterone injected under the skin is equal to 100 mg. injected intramuscularly.

A study conducted by the Department of Urology at University of California (Choi, et al 2022) has, however, given us evidence of how sub-Q shots lead to higher levels of free T, along with evidence of them being physiologically superior to IM shots in several other important ways.

The U of C researchers wanted to compare four effects, or potential effects, of sub-Q and IM injections:

• Total testosterone levels.

• Hematocrit levels (the ratio of red blood cells to total volume of blood; if it’s too high, you’re at a heightened risk of heart attack or stroke).

• Estradiol levels (generally speaking, you don’t want too much of your testosterone to be aromatized into estradiol).

• PSA levels (high levels of PSA are implicated with prostate cancer).

In order to conduct those comparisons, the researchers recruited 232 men. Baseline levels were measured and then were repeated at 6 weeks and 12 weeks post-treatment.

Men who received subQ injections of testosterone exhibited the following:

• 14% greater total testosterone levels than those receiving IM injections.

• 41% lower hematocrit than those receiving IM injections.

• 26.5% lower estradiol than those receiving IM injections.

• No rise in PSA (the IM method didn’t raise PSA either).

To put these findings into action, take a pinch of skin on your glute, thigh, or even belly, and inject a tiny needle into the fold at a 45-degree angle. Fully depress the plunger, release the skin, and you’re good to go.

One thing to consider: Given that the sub-Q method leads to a higher total testosterone level (and presumably higher levels of bioavailable testosterone), you might, as Dr. Crisler pointed out, want to adjust your dosage downwards. Then again, you might just want to ride the higher levels and see how you do.

Testosterone Gels -- As mentioned above, testosterone gels provide a much more natural androgen rhythm and there’s probably some argument to be made that mimicking the body’s natural rhythms is the way to go. However, many believe it doesn’t have the same bang for the testosterone buck as injectable esters.

Besides, gels have their drawbacks. You should only apply gels to freshly showered skin. You should refrain from swimming or working up a sweat for at least an hour. Furthermore, you can’t, under any circumstances, let a child or female (especially a pregnant one) come into contact with the treated area until it’s absolutely dry.

If you do decide to use gels, you must apply them once (or in some cases, twice) a day. Don’t use your hands to apply the gel, though. Any gel on the hands doesn’t soak into the bloodstream; it’s like applying gel onto an old catcher’s mitt, which isn’t very permeable. Instead, squeeze the gel onto your forearms and rub them together like a fly rubs its forelegs together after feasting on some roadkill. That way you won’t waste any.

Everything Else -- Just about everything else, including patches, creams, pellets, nasal delivery, buccal delivery, and sublingual drops, aren’t much worth discussing. Granted, creams can be effective, but they’re messy and they don’t penetrate the skin as well as gels. Pellets and drops, however, are either ineffective or impractical and make accurate dosing all but impossible.

There are, however, other protocols that have proven to be effective in treating secondary hypogonadism (where the hypothalamus, for whatever reason, isn’t telling the pituitary to produce LH and FSH, which in turn cause the testicles to produce testosterone), like selective estrogen receptor modulators, or SERMs. Two of the most common ones are Clomid (clomiphene) and Nolvadex (tamoxifen). They simply trick the pituitary into producing LH, which then tells the testicles to get to work.

Exact protocols are beyond the scope of this already long article, though.

Question 5 – What are the Potential Negative Side Effects of TRT?

There are a small number of undesirable side effects that can happen when on TRT.

Diminutive Testicles -- One of the big fears about undertaking TRT is infertility and shrinking balls. While TRT does reduce the number of sperm that a man produces, it’d be foolish to think that your replacement dosage has rendered you safe from becoming a daddy. In many cases, though, the testicles will shrink and sperm count will drop, but these potential effects can easily be prevented by concurrently administering human chorionic gonadotropin, or HCG.

The drug mimics luteinizing hormone (LH) so that your testicles don’t shut down. As such, they’ll still produce sperm and they’ll still produce testosterone and shrinkage won’t occur. Additionally, there are LH receptors throughout the body, and HCG attaches to these system-wide receptors. Anecdotally, at least, this causes men on TRT and HCG therapy to report feeling pretty damn good.

HCG is administered subcutaneously via an insulin needle and it’s easily available to your doctor through various compounding pharmacies around the country. The generally recommended starting dose is about 100 iu a day, working up to higher daily dose or, alternately, 250 or 500 administered twice a week.

However, it’s not absolutely necessary to use HCG when undergoing TRT. Sane doses of testosterone might cause your testicles to shrink a bit, but by no means will they ever be mistaken for cherry tomatoes…unless they were that size to begin with. And, should you ever stop sane doses of TRT, the testicles should spring back to their mid-season form in a couple of months, even without HCG.

Polycythemia -- It’s also important to monitor both hemoglobin and hematocrit. Those two are thick as thieves and where one goes, the other usually follows. Hematocrit is simply a measurement that indicates what percentage of your blood is taken up by red blood cells, while the hemoglobin test simply measures the amount of hemoglobin in your blood (hemoglobin is an iron-based protein that transports oxygen throughout the body).

If hematocrit goes up, so too, almost always, will hemoglobin. Elevated levels are dangerous because of simple physics. And simple plumbing. If you have too many red blood cells (i.e., high hematocrit, aka polycythemia or erythrocytosis), your blood gets thicker. Imagine replacing the motor oil in your car with maple syrup. The pickup pipe to the oil pump would slow or clog and engine failure would be imminent.

That’s almost identical to what thickened blood could do to your heart. The risk of heart attack or stroke escalate considerably. Engine failure becomes imminent.

Other possible dangers include an elevated risk or dementia and the general oxidative damage to the system that can occur when iron levels are high (you actually rust, in a biological sort of way).

While no one knows for sure why TRT raises hematocrit levels, there are a couple of decent theories. One is that testosterone stimulates red blood cell production by not only kicking up production of a kidney hormone named erythropoietin (EPO), but also by recalibrating EPO’s set point in relation to hemoglobin.

Another theory is that testosterone reduces hepcidin, a liver hormone that’s involved with the absorption of iron (the backbone of hemoglobin) (Bachman et al 2014). When hepcidin levels go down, production of red blood cells goes up, thus thickening the blood.

Following are normal hematocrit and hemoglobin values:

• Normal hematocrit for men: 41% to 50%

• Normal hematocrit for women: 36% to 48%

• Normal hemoglobin for men: 13.2 to 16.6 grams per deciliter

• Normal hemoglobin for women: 11.6 to 15 grams per deciliter.

There’s a little leeway in the men’s values, however. A man, using what doctors refer to as “strict criteria,” isn’t considered to be suffering from erythrocytosis until hematocrit is higher than 52% and hemoglobin is higher than 18.5 g/dl (4).

For some reason, women aren’t granted that same leeway. Using those same strict criteria, a woman is considered to be suffering erythrocytosis when hematocrit is at least 48% and hemoglobin is 16.5 g/dl or higher (5).

There are, however, several ways to reduce erythrocytosis, TRT-induced or otherwise, and not all of them require visiting a doctor. Here are the most common and easiest:

1. Use a lower dose of testosterone – This is the most obvious solution to elevated hematocrit, but it’s probably also the least popular. Hardly any man wants to use less testosterone and give up any of the increased energy, sexuality, and muscularity that the hormone has gifted him, but truth be told, a lot of men are probably taking more than they need.

2. Switch to subcutaneous injections – As detailed above, a srudy conducted by the Department of Urology at University of California found that subcutaneous (subQ) injections (under the skin rather than into the muscle) led to higher levels of free testosterone, but 41% lower hematocrit than those receiving IM injections.

3. Consider another mode of TRT – Studies have shown that testosterone creams and gels raise hematocrit less than intramuscular testosterone injections.

4. Donate blood – This is that standard go-to treatment for high hematocrit as every pint donated has been shown to decrease hematocrit by about 3 points. Unfortunately, you’d likely have to continue to periodically donate blood if you hadn’t adopted any other hematocrit-lowering strategies.

That being said, there’s some evidence that hematocrit levels stabilize after donating blood 5 times. Whether that’s universally true is unlikely.

5. Hydrate – High hematocrit readings sometimes occur because the patient was simply dehydrated, making it appear that the concentration of red blood cells was higher than it really was.

Of course, one simple way to determine whether your high hematocrit was caused by dehydration is to do a little simple math: hematocrit must always be three times the value of hemoglobin. If it’s lower (Hct<3 x Hb), you’re over-hydrated. If it’s higher (Hct>3 x Hb), you’re dehydrated. Either way, you’re getting a false value because of your hydration status.

Gynecomastia – Gynecomastia is common in men as it is, but growing male breast tissue upon beginning hormone treatment is seen almost exclusively in men taking professional bodybuilder levels of testosterone (1,000 to 3,000 mg. a week) or testosterone analogs. The much-dreaded condition is almost unheard of in males receiving TRT (unless they had it before they started.

Hair Loss – Losing hair is a possibility, but it seems to stabilize in your 30’s. If you’ve made it that far without losing your hair, it’s highly doubtful that TRT will make things any worse.

Prostate Worries -- Note that there’s absolutely no evidence -- even after researchers have compiled thousands of studies and patient histories -- that TRT can cause prostate cancer. However, for some reasons that we don’t totally understand yet, TRT can make prostate cancer worse. That’s why it’s important to have digital rectal exams (DREs) every year while continuing to monitor prostate specific antigens (PSA).

Elevated Estrogen Levels – Some men have higher levels of aromatase enzymes. In chemistry-talk, these enzymes catalyze the rate-limiting step of testosterone and androstenedione conversion into estradiol and estrone. In other words, men with higher levels of aromatase, or those that take a lot of testosterone, end up with too much estrogen, the “female” hormone.

The problem is, once estrogen levels rise unchecked, bad things can happen. For one, the risk of degenerative disease skyrockets. Atherosclerosis rates go up. The incidence of stroke increases. The risk of developing Type II diabetes goes up. Emotional disturbances become more prevalent. The risk of prostate cancer increases, and erectile function suffers. Waistlines grow thicker. It becomes harder to put on muscle. And, most seriously, high estrogen significantly increases the risk of flat-out dying.

Clearly, proper estrogen levels play a big part in the health of mens’ hearts, in addition to the health of a whole lot of body parts, body systems, and body functions. It’s in every male’s interest to make sure he’s in an estrogen sweet spot, regardless of age.

Symptoms of high estrogen include the following:

• Increased abdominal fat

• Loss of muscle mass

• Low libido, decreased erectile function

• Tiredness

• Increased fatty tissue around nipples

• Depression, emotional disturbances

• Lower urinary tract symptoms associated with benign prostatic hypertrophy (BPH)

• Sobbing at the end of Hallmark Channel movies.

Let’s not demonize estrogen, though. Men need a certain level of estrogen. Not only does estrogen have innumerable effects on one’s health, but it’s also part of an elegant feedback system where overly high estrogen levels alert the testicles, via the pituitary, to send some testicular workers home and cut back on testosterone production for that day.

In this way, the system keeps a perfect amount of testosterone and estrogen flowing through the body.

Sometimes, though, too much testosterone is converted into estrogen. That amount, combined with the small amounts of estrogen being produced in the testes, adrenals, brain, and fat, can create a hormonal maelstrom of trouble. The feedback loop gets a kink in it. Estrogen levels stay perpetually high and thus keep barking the order to back off on the manufacture of testosterone.

Likewise, too much testosterone, courtesy of TRT can cause an undesired amount of T to be converted into estrogen. That’s why it’s important that every man establish an estrogen baseline, to which he can refer to and compare in coming years. Here’s a list of the median estradiol levels by age, as established by the authors of a study that appeared in the journal Clinical Endocrinology:

• Age 2-29: 28.0 pg/ml

• Age 30-39: 25.7 pg/ml

• Age 40-49: 24.7 pg/ml

• Age 50-59: 22.1 pg/ml

• Age 60-69: 21.5 pg/ml

• Age 70-80: 21.9 pg/ml

The above values are what’s considered optimal in approximately 95% of the male population, however, it’s the rare individual who’s going to hit his age-related bullseye with his estrogen levels. It’s much more useful to say that normal ranges are from 10 to 30 or 40 picograms per milliliter for estrogen and 10 to 50 picograms per milliliter for estrone, a “weaker” type of estrogen.

There are pretty much only two ways to accurately test estrogen levels – via a 24-hour urine test or a blood test. The blood test is easier and less dangerously sloshy, of course, but if you go that route make sure you insist that your doctor order a “sensitive” assay, as mentioned earlier.

By default, most labs use the standard assay, which is designed for women. However, it’s not good enough for males because their normal range is a lot smaller and more restrictive than for females.

While I wrote above that the normal range for males is 10 to 40 picograms per ml, the normal range for women is 15 to 350 picograms per ml. They obviously have a lot more leeway; the test doesn’t have to be as precise.

That’s not to say that high estrogen levels aren’t problematic for women, too. They are. High estrogen can lead to some of the same medical problems in females as they can for men, in addition to fibrocystic lumps, and irregular or heavy menstrual periods.

But comparatively, what’s considered a healthy estrogen range in a woman would likely cause man to have some of the severe problems described above.

Additionally, regarding the veracity of blood tests, most labs use immunoassay techniques to test blood samples, which, when compared to other methods, show a variability rate of up to 53%. That kind of inaccuracy could lead to a physician treating a problem that doesn’t even exist, e.g., treating a man for high estrogen levels when he’s well within normal ranges, which could lead to disastrous consequences.

Labs should instead use Liquid Chromatography/Mass Spectroscopy, which is much more accurate when measuring hormone levels. There are specific lab codes that your ordering doctor should use. If he doesn’t use them or doesn’t know them, tell him what they are:

• LabCorp “Sensitive Estradiol” – Code 140244, 500108

• Quest Diagnostics “Ultrasensitive Estradiol” – Code 30289

• Mayo Clinic “Enhanced Estradiol” – Code EEST

Clearly, estrogen needs to be kept in check. Elevated levels need to be addressed by either adjusting the dosage or by taking a prescription drug known as an “anti-aromatase” (a drug that stops the conversion of T to E).

However, before going the prescription route, make damn sure your levels are indeed high. The consequences are too severe to automatically assume you need treatment, as many doctors who prescribe testosterone replacement therapy routinely do.

You might also consider a natural estrogen-fighting supplement like Diindolylmethane (DIM) or Indole-3-Carbinol (I3C).

Cardiovascular Disease and Heart Attacks -- All the rest of the stuff you may have heard about testosterone causing heart attacks or anything else bad appears to be horribly, horribly wrong. If anything, men with low testosterone levels are much more prone to a host of maladies, including heart disease, diabetes, dementia, and pretty much everything else usually associated with old age, death, or decrepitude in males.

Luckily, we have some corroborating evidence. A solid meta-study (a study that combines results from previous separate but related studies) was recently published and it implies responsible TRT is not only safe but might also exhibit “reverse causality,”, i.e., TRT might actually lower the risk of cardiovascular events instead of raising them.

Jemma Hudson and her 37-member team of researchers (2022), after combing the data bases, found 17 studies comprising 1,750 men who’d been using TRT and 1,681 who were in placebo groups.

The mean age was 65 and the mean BMI was 30 (definitely portly, to be kind). Many had diabetes, angina, or had experienced previous myocardial infarction. The mean duration of testosterone replacement was 9.5 months (the range was 12 weeks to 3 years).

Here’s a rundown of some of their findings:

• 82% of the studies addressed mortality. The testosterone group reported fewer deaths from any cause than in the placebo group, but the difference didn’t reach statistical significance.

• 76% of the studies provided data on cardiovascular or cerebrovascular (loss of blood flow to the brain) events. The testosterone group reported slightly more (120) deaths than the placebo group (110), but again, it didn’t reach statistical significance.

That being said, post hoc (after the fact) sensitivity analyses (an examination of how changes in methods, models, or values of unmeasured variables affected results) implied that the risk of cardiovascular or cardio-cerebral events went down after TRT was brought into what’s considered a high normal range.

• Both serum total cholesterol and triglycerides were significantly lower in the testosterone groups, although, as is usually the case, TRT appeared to modestly lower levels of HDL more than the placebo group.

• There appeared to be no difference in the blood pressure between the two groups. The same was true for glucose sensitivity or A1C (a measure of average blood sugar over the previous 3 months).

• Hemoglobin and hematocrit were higher in the TRT groups and the number was statistically relevant. This is to be expected, though, as testosterone therapy suppresses hepcidin, a regulator of iron levels, and iron levels directly influence red blood cell production. However, only 5 cases of deep-vein thrombosis were reported in the testosterone groups, compared to 7 in the placebo group.

• Lastly, there was no difference in the groups as far as incidence of prostate cancer (meaning that TRT didn’t, contrary to popular belief, raise chances of prostate cancer).

So there.

Question 6 – What Should I Expect from Testosterone Replacement Therapy?

Testosterone does cool stuff to the body, but it usually doesn’t happen overnight. While you might start feeling pretty good, almost elated, after starting therapy, the various physiological benefits take varying amounts of time. Sexual benefits kick in fully at about week 3 and plateau between weeks 19 and 21. Depression, if it’s a factor, often starts to lift by about week 6, but maximum benefits take longer.

Anxiety, sociability, and stimulation of the cerebral cortex (the part that controls attention and even creativity) start to improve at about week 3, plateauing about 3 months after beginning therapy. Insulin sensitivity starts to increase in just a few days, with effects becoming evident (less body fat) in 3 to 12 months, but often continuing for years.

Increased muscularity is highly dependent not only on having adequate testosterone levels, but genetics, diet, lifestyle, and training. However, generally speaking, testosterone therapy can positively affect muscularity in as little as a month, peak at about a year, and then continue at a slower pace for some time.

And then there’s the intangible benefit known as life enjoyment. It’s what you often get when you combine all of testosterone’s benefits, the physiological and the psychological, into one. It can’t really be measured, but it’s oh-so valuable. Just make sure you find a doctor that understands that.

Question 7 -- What About TRT for Women?

Chew on this: Testosterone has long been characterized as the “male hormone” when, in fact, it’s also the most abundant active hormone in women. Sure, men have higher circulating levels of testosterone than women but regardless, testosterone, not estrogen, is the predominant sex steroid in women throughout their entire lifespan, or so say scientists Rebecca Glaser and Constantine Dimitrakakis (2013).

The two scientists, writing in Maturitas, urge us to “look at how women’s estrogen levels are measured -- in mere picograms per deciliter, while their T levels are measured in nanograms per deciliter, a 10-fold higher unit of measurement.”

Beyond estrogen, there are even higher, exponentially higher, amounts of pro-androgens circulating through their bodies, players like dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, each of which supply significant amounts of additional T.

Hell, even the gene for the androgen receptor that testosterone and other sex hormones latch onto is located on the Xchromosome and not the Y, or male chromosome. Glaser and Dimitrakakis lamented the medical establishment’s myopic stance by writing, “Despite any clear rationale, estrogen was assumed to be the hormone of ‘hormone replacement therapy’ in women.”

They point out that this assumption occurred despite testosterone -- as early as 1937 -- being the treatment of choice when it came to ameliorating the symptoms of female menopause.

So why is it that testosterone has been largely dismissed as a viable treatment for women facing pre- and post-menopause? How the hell can the medical establishment freely offers women estrogen and progesterone replacement but waver or dither on doling out testosterone? How can you expect good results by only shoring up two of the three primary legs that support female hormonal health? It’s crazy.

However, when you start to look at all the myths associated with testosterone – some of which have also hindered the acceptance of male testosterone replacement – you begin to understand WTF has been going on.

Myth 1: Testosterone Turns Women into Dudes with Hairy Backs

While some of the decidedly masculine circa 1970 female Olympic athletes from East Germany and the U.S.S.R. played a part in the origin of this myth, it was competitive female bodybuilding that did the most damage.

I personally know women that once had voices like sweet, sweet nightingales who later, after taking stupid amounts of anabolic/androgenic steroids (which are all synthetic derivatives of testosterone), ended up sounding like the guys who do voice overs for Coors Beer and Ford trucks; women who had to start shaving their faces every day.

So yeah, no wonder the medical establishment and their patients fear testosterone, but what they need to know is that all that scary stuff is dose dependent and that the doses used for T replacement in women actually “stimulate femininity” by increasing fertility and promoting ovulation. T was even used safely in the past to treat the nausea that often accompanies early pregnancy.

Still, side effects do sometimes occur, but Glaser and Dimitrakakis write that “true masculinization is not possible [with normal doses].” Even so, the benefits are often so great that some women often choose to treat the side effects rather than lower the dosage.

The authors also admit that, yes, pharmacologic and supra-pharmacologic doses of T are used to transform female-to-male transgender patients and that it may result in increased facial hair growth, hirsutism in general, and slight enlargement of the clitoris, but these effects are often largely reversible by simply lowering the dose.

Even so, an enlarged clitoris is not a medical problem, only a superficial cosmetic one that might invite embarrassment even though, in many cases, the additional length or girth can enhance sexual pleasure.

So no, when used in normal replacement doses, testosterone doesn’t masculinize women; it largely does the opposite.

Myth 2: The Only Reason Women Need Testosterone is to Increase Their Libido

Sure, testosterone replacement therapy (TRT) in women often cranks up a once-flagging libido, but women have androgen receptors (AR) all over the place and not just in their brain and their reproductive parts. They’re found in the heart, breasts, blood vessels, lungs, spinal cord, bladder, peripheral nerves, bone, bone marrow, synovium (soft tissue that lines joint capsules), adipose tissue, muscles, and of course, the uterus, ovaries, and vaginal tissues.

Just as in men, the testosterone levels of women start to decline with age, bringing about anxiety, irritability, depression, physical fatigue, bone loss, muscle loss, insomnia, changes in cognition, memory loss, breast pain, urinary complaints, and yes, sexual dysfunction as well as sexual indifference.

Clearly, testosterone plays a big part in women’s health that goes way beyond just feeding the urge to put on some good “doing it” music when their partner comes home.

Myth 3: Testosterone Can Lead to Female Heart Disease

You can see how this myth started: Men have more testosterone than women and men have more heart attacks than women. That’s an example of what’s called a causal fallacy. It’s like believing that every time you turn on “The Young and the Restless,” it causes the neighbor’s dog to start barking. It’s more likely that the mailman comes around the same time that the soap opera starts rather than the dog having some preternatural connection to Devon, Abby, Chance, Lauren, Victoria, or Billy.

Back to men and their hearts: If T is involved in their heart attacks, it’s more likely to do with low T levels as that condition has been associated with an increased risk of disease and mortality from all causes. Quite the contrary to what is commonly believed, there’s overwhelming evidence that T is cardioprotective, helping men and women with their glucose metabolism and lipid profiles (two factors that play a role in heart disease).

Testosterone also expands blood vessels, making it easier for the blood to surge past any plaque or partial blockages. It also has immune-modulating effects that can inhibit the formation of those same blockages.

This isn’t just conjecture, either. Clinical studies have shown T to improve the functional capacity, insulin resistance, and muscle strength in men and women with congestive heart failure.

Of course, a certain amount of T does aromatize (chemically convert) to estrogen and this excess estrogen can cause adverse side effects in both heart patients and healthy individuals. These side effects would include swelling, anxiety, and weight gain. Furthermore, other medications often used to treat heart disease can increase aromatization, indirectly leading to side effects from T therapy.

The info that you can pocket, though, is that T is largely cardio protective and having normal or adequate levels can decrease the risk of cardiovascular disease.

Myth 4: Testosterone Damages the Female Liver

T doesn’t cause liver damage, but it’s easy to see from where this belief came. Bodybuilders, pro athletes, and pathologically vain people often take staggering doses of oral, synthetic versions of testosterone (steroids), which are then processed by the liver and, over the long run, can cause a significant amount of damage.

T itself, though, isn’t taken orally; it’s either injected, implanted (as a pellet), or absorbed through the skin as a cream or gel. Each of these methods allow testosterone to bypass the liver. The organ avoids the “fight” and hence walks away unscathed.

Myth 5: Testosterone Leads to Female Hair Loss

As Glaser and Dimitrakakis point out, “hair loss is a complicated, multifactorial, genetically determined process that is poorly understood.” There is, however, little or no evidence that T or T therapy is a cause of hair loss in women. It’s true that women with polycystic ovary disease and the accompanying insulin resistance have higher T levels and experience hair loss but that, again, doesn’t prove causation and besides, hair loss is common in women and men with insulin resistance.

What happens is that insulin resistance (and obesity) increases levels of the 5-alpha-reductase enzyme, which can result in some testosterone being “reduced” to dihydrotestosterone, or DHT, which is the androgen involved in balding.

However, this isn’t the case in healthy women, many (about a third) of whom start to experience hair loss with aging, which coincides with a decline in T levels. Remarkably, and contrary to what most people believe, including doctors, two thirds of women who undergo TRT start to experience hair regrowth. And many of those who don’t are more likely to be experiencing some contributing medical problem, like having hypo or hyperparathyroidism, being deficient in iron, or being obese.

As evidence of T’s innocence in causing hair loss in women, none of 285 patients treated for up to 56 months with T therapy complained of hair loss.

Myth 6: Testosterone Turns Women Irritable

Despite the propensity of men who commit acts of aggression to blame it on “testosterone aggression” or “roid rage” instead of their inherent emotional instability, this type of thing is either rare or nonexistent with TRT, especially in women – the doses are just too small.

Besides, there’s significant evidence “in a wide variety of species” that it’s estrogen, not testosterone, that plays a major role in aggression. Of course, some testosterone does aromatize (enzymatically convert to estrogen) in both women and men, but again, the amount of estrogen resulting from conventional doses of TRT wouldn’t lead to any noticeable changes in female Hulk-nicity, i.e., the “you wouldn’t like me when I get mad” factor.

Quite the contrary, studies have found that subcutaneous (under the skin) implantation of T pellets has led to decreased aggression, irritability, or anxiety in 90% of female patients treated for T deficiency.

Myth 7: Testosterone May Increase the Risk of Breast Cancer

Okay, it’s long been known that breast cancer is an estrogen sensitive cancer, but clinical trials have found that T has a beneficial effect on breast tissue in that it decreases breast cancer-cell proliferation and prevents breast cancer-cell stimulation.

It appears that the ratio of T to estrogen (E2), or the balance of these two hormones, deserves some of the credit in making T breast protective. Furthermore, once you activate the androgen receptor (to which estrogen and testosterone latch onto), it “exerts a pro-apoptopic [causes cancer cells to die], anti-estrogenic, growth-inhibiting effect in normal and cancerous breast tissues.”

I’d be remiss, though, in failing to mention that -- as explained earlier -- some testosterone can be aromatized into estrogen, which risks upsetting the hormonal apple cart if not monitored. Regardless, it still appears that T lowers the risk of breast cancer in women who have been treated with estrogen therapy.

Myth 8: Testosterone Replacement in Women is Some New-Fangled Thing and Its Safety Hasn’t Been Established.

England and Australia have been treating women with T for almost 70 years. T implants have been safely used in women since 1938. There’s long-term data on the safety and tolerability of T in women using doses up to 225 mg., which is a really high amount, especially for women.

All that being said, aromatase activity (which converts T into estrogen) increases with age, obesity, alcohol intake, breast cancer, insulin resistance, medications, recreational drugs, a sedentary lifestyle, and the unfettered intake of heavily processed foods. Combine that fact with the potential for even more production of estrogen through T replacement and the risk of a hormonal imbalance increases.

That makes it important for physicians to monitor aromatase levels in women who are being treated with T so that the T to E ratio is maintained within safe boundaries and that patients’ health is assured.

Regardless of all the good news, the main barrier to more widespread use of female TRT, though, at least in the United States, is the mythology that’s grown around the use of testosterone.

Question 8 – What Are Normal Testosterone Levels in Women and What Delivery Systems are Available to Them?

In stark contrast to male TRT, the standard of care in women is to treat testosterone deficiency as a clinical syndrome that’s not tied to specific lab values, i.e., there’s no one-dose-fits-all approach as there often is with men.

That being said, women generally do well with testosterone levels between 150 and 250 ng/dl. This level can be achieved with the same injectable and transdermal preparations used by men, but these methods can cause spikes in testosterone levels and an increased risk of side effects.

That’s not to say that injectable or transdermal preparations are a bad idea, it’s just that additional care has to be taken with dosing.

Sub-cutaneous pellets are a viable alternative for women, but unfortunately, there haven’t been any head-to-head trials comparing transdermal gels/creams with subcutaneous pellets. There was, however, a 7-year study that studied the viability of subcutaneous pellets in women (Donovitz, 2021). Out of 400,000 patients, the overall complication rate was less than 1 percent. Ninety-three percent of women continued to use pellets after the study was completed.

My advice would be to stick with injections or gels, though, as they allow for much more precise dosing. It’s also much easier to “call an audible” and change the dosing than it might be with a pellet that’s been embedded in your arm.

Question 9 -- Is Testosterone Replacement for You?

Traditional medicine has long held the belief that health is defined merely by the absence of disease. Not only is this definition antiquated, it automatically dismisses the millions of people who just don’t feel like they used to, look like they used to, or function like they used to.

These are the men (and women) who might want to consider TRT. If done correctly, if done wisely, the potential health benefits are considerable.

There’s also one benefit that’s extremely difficult to quantify and it’s what you get when you bunch all of the positive attributes of testosterone replacement therapy into one great, big psychological, sexual, health, and cosmetic sandwich.

It’s what the French refer to as joie de vivre, or “joy of life,” and if you feel like you’re not getting your fair share of it, you might want to consider TRT.

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