Doesn’t everyone Know about Low Testosterone Treatment by now?
In a word: no! As a Functional Medicine doctor, about 2/3 of the “hormone therapeutic requests” I receive involve either menopausal symptoms or symptoms of low testosterone. Women read Suzanne Somer’s books. Men don’t seem to have a “go-to” for good information, so, from what I hear, they seem to have many misconceptions about testosterone treatment. In this article, I’ll discuss testosterone replacement therapy risks and benefits, including:
- How testosterone works
- What are the signs/symptoms of low-T A.K.A. male hypogonadism?
- Why do testosterone levels decline?
- What’s the latest on testosterone and heart disease?
- What should my testosterone level be?
- What’s the best way to replace testosterone?
- What about raising testosterone levels without using testosterone?
- Testosterone replacement and future fertility
- Erectile dysfunction
How does Testosterone Work, and What does it do?
Testosterone is the male sex hormone, just as estrogen and progesterone are the primary female sex hormones. Although women do indeed produce testosterone (and at some point might need replacement), this article will focus on men.
In men, testosterone is the main hormone produced in the testicles and secreted by the testes. It promotes libido (sex drive), aggressiveness, and sexual desire. It also stimulates the growth of certain organs, producing sperm, and nourishes all the tissue of the male urinary and reproductive systems. In addition, testosterone promotes protein anabolism which is the use of protein to build muscle, skin, and bone, and mitigates against protein catabolism or breakdown. It also regulates the production of prostaglandins, which (research shows) seems to keep prostate growth under control.
The effects of testosterone are most pronounced during puberty. In fact, it brings on the enlarged larynx, thicker vocal cords, new body hair, increased muscle mass, and increased oil-gland secretion by the skin commonly associated with puberty.
Some telltale signs of hypogonadism (“Low-T”)
Testosterone deficiency can cause memory, mood, and sleep issues, usually resulting in interrupted and unrefreshed sleep and next-day brain fog. Energy is also impacted, with an all-day feeling of sluggishness, which often includes lack of drive, inability to start an exercise regimen, and loss of muscle mass.
In addition, libido is down, and erectile dysfunction is possible, but (believe it or not) E.D. is usually not due to having a low testosterone level. More on this topic to come. Here are the symptoms laid out as bullet points.
- Depressed mood
- Aches and pains in the joints
- Poor sleep
- Cognitive impairment
- Decreased energy
- Decreased libido with or without erectile dysfunction
- Osteoporosis if it goes on for a while
- Loss of weight due to muscle mass loss and fat gain
- Mild regression of secondary sexual characteristics
If you are experiencing the symptoms described above, there is always the possibility of a testicular or pituitary issue. This is the main reason I implore you not to “cheap out” and go to an online source or a “hormone mill” for your testosterone replacement. Now, these two reasons aside, I’ll discuss why (typically) men develop low testosterone levels, which include other primary causes of hormone deficiency syndromes.
What causes low testosterone?
Hormonally and physically speaking, your body peaks around age 25. Unfortunately, we often assume things like a decreased libido, foggy memory, mid-life weight gain, hair loss, and wrinkles are simply a part of “getting older.” Even worse, that’s what most non-functional doctors think too! However, we can relieve these symptoms with the use of bioidentical hormones and peptides.
Before jumping into a discussion about hormone replacement, a thorough workup is necessary to rule out (or diagnose and then treat) excess weight issues, inflammation, tumors, medications, smoking, excess alcohol, diabetes, HGH deficiency, inactivity, toxins, food allergies, head trauma, groin trauma, pituitary or testicular tumors, leaky gut, silent autoimmune disease, and even high cortisol (and then subsequent leaky gut) from excessive stress. Believe it or not, all of these things can cause significant drops in testosterone levels, and oftentimes, testosterone replacement therapy isn’t even needed! In addition, every single mold and mycotoxin illness male patient I see has anterior pituitary involvement and low testosterone that can and should always be resolved without resorting to supplemental testosterone.
A brief note here about chronic pain as a cause of low testosterone and lack of treatment as a further exacerbation of any existing pain. Pain can cause disruptions in the pituitary-hypothalamic axis to lower testosterone physically. Opiates will further lower testosterone. And then, as mentioned, having low testosterone amplifies pain. Just be aware of this phenomenon for yourself or a loved one.
Low testosterone can also be caused by previous use of testosterone for (oftentimes) bodybuilding purposes. Further, a permanent interruption of the pituitary-testicular axis with “unresponsive testes” may be present after normal dosing for only a few months. Again, let me emphasize that a great form of natural hormone balancing is to fix the underlying cause of the hormonal issue(s). When underlying problems are properly addressed, we can assess whether or not testosterone replacement is actually needed.
After a good medical check-up and a visit with a Functional doctor specializing in bioidentical hormones, it’s time to discuss testosterone replacement therapy. What most men think about when they think “Low-T” is “andropause,”; the gradual waning of testosterone levels usually occurring in men in their 50’s, but sometimes as early as the late 30’s. But are there cardiac risks to using HRT? Should men worry about an increased risk of heart disease if they replace their testosterone? Let me show you the data on that.
Testosterone and Heart Disease Risks
Several years ago, there was a big stir with editorials in the Wall Street Journal and New York Times, reporting on a study showing a correlation between testosterone replacement and coronary artery disease. That particular study was farcical, as the diagnosis of low testosterone was based on symptoms, not lab testing, and replacement was performed by primary care doctors who didn’t check post-treatment testosterone levels. Furthermore, cardiac risks pre-testosterone treatment were poorly documented. Indeed, a lot of chaos was created by one study which should not have been published. Here’s the reality.
Positive Cardiac Effects of testosterone replacement
Hundreds of studies since the 50’s show that adequate testosterone helps prevent heart disease. For example, a recent comprehensive study reviewed men who had existing heart disease. Researchers studied 755 male patients, 58-78 years of age, who all had severe coronary artery disease and low testosterone levels. They were separated into three different groups, receiving various doses of testosterone, administered intra-muscularly or by a gel.
At the end of the first year, 64 patients who weren’t taking any testosterone supplements had severe adverse cardiovascular events. This included only 12 who were taking medium doses of testosterone and nine who were taking high doses. After three years, 125 patients who had not received testosterone therapy suffered severe cardiovascular events, whereas only 38 medium-dose and 22 high-patients did.
Patients who were given testosterone as part of their follow-up treatment did much better than patients who had not been given testosterone supplementation. However, the non-testosterone-therapy patients were 80 percent more likely to suffer an adverse cardiac event. This study also confirms the findings of a previous study from the same researchers, which found that testosterone therapy did not increase the risk of experiencing a heart attack or stroke for men with low testosterone levels and no prior history of heart disease.
Mayo Clinic’s Review of the Effects of Testosterone Replacement
The Mayo Clinic published a large 2018 review of the effects of testosterone replacement based on numerous studies. Here is a summary of their summary.
Randomized controlled studies confirm that testosterone replacement improves cardiac blood flow in men with chronic stable angina (chest pain) and chronic heart failure. These effects persist for at least one year. Testosterone is a coronary vasodilator as well as having other positive vascular actions on other arteries.
The same well-done studies have consistently shown that testosterone replacement therapy reduces fat mass and increases lean mass. In addition, the effect of testosterone on BMI plus waist circumference shows that benefits gradually accrue over several years. Testosterone is also beneficial for regulating carbohydrate and lipid metabolism, positively affecting metabolic pathways, all of which contribute to cardiovascular risk benefits. Further, testosterone replacement in men with type 2 diabetes and hypogonadism improves all-cause (including cardiac) mortality.
Results of a 2020 and a 2021 Analysis
In 2020, a large study concluded that testosterone replacement therapy posed no increased cardiac risk in men with no prior coronary artery disease and men with coronary artery disease. In addition, a retrospective, large-scale study published in 2021 showed a far greater risk of low testosterone causing COVID deaths in men than any cardiac risk to all testosterone-replaced men. The bottom line: testosterone “done right” with aromatization (estradiol conversion) controlled properly is (sum-total) “good for you!”
Endocrine and Urological guidelines for replacement of testosterone
There is a consensus of who needs treatment from the Endocrine and Urological medical communities. In short, they recommend therapy for men with symptomatic testosterone deficiency to either induce or maintain secondary sex characteristics such as muscle development, deep voice, and hair distribution on the chest and face and correct symptoms of hypogonadism. They (of course) strongly discourage starting testosterone treatment in patients who have fertility plans. Contraindications to therapy also include prostate cancer, palpable prostate nodule(s), a prostate-specific antigen level in all men of over 4 ng/mL, or a PSA level greater than 3 ng/mL in men at increased risk of prostate cancer without further urological evaluation. Included in the restriction on therapy are an elevated red blood cell count, untreated sleep apnea, uncontrolled heart failure, and even (per Endo guidelines) stroke or heart attack within the last six months.
Regarding actual testosterone levels, it is suggested in the “conventional literature” that treating Physicians aim for testosterone concentrations in the mid-normal range. That would be 590 ng/dL of total testosterone and 12.35 pg/mL of free testosterone. However, most scientific articles don’t discuss free testosterone and recommend a total testosterone level of 350 ng/dL. Wow, that’s a low-ball recommendation in the opinion of most hormone-replacement experts. After prescribing testosterone replacement therapy for many years, I will tell you that men get symptomatic with a Free testosterone of 12 or less as a rule of thumb. So let me clear things up here regarding “how much” testosterone you need.
Adequate Levels of Testosterone
As clinicians, we seek to replace testosterone to levels where our male patients will have good sleep, energy, libido, optimized moods, and optimal metabolic results from testosterone replacement. Too little yields inadequate clinical results; too much might compromise glucose control; the whole “roid rage thing” involves huge doses, which is a lot more than a legitimate doctor would prescribe. Those of us in the Functional Medical community look at symptoms and aim for a free testosterone of about 15-18 pg/mL.
We also take into account a man’s albumin and SHBG (sex hormone-binding globulin) levels, as these will affect the amount of “free and unbound” testosterone, which is the best number to calculate if we’re looking for “the magic number.” Unfortunately, there is not always a good correlation between total T, free T, and free and unbound T, which is why I always say you need a hormone specialist to do any hormone replacement correctly.
What’s the best form of treatment?
There are two types of hormones available for hormone replacement therapy: synthetic hormones and bioidentical hormones. This is important to know because of potential side effects.
Various formulations of exogenous testosterone replacement therapy exist, including oral, buccal, intramuscular, transdermal, subdermal, and nasal preparations. Bioidentical hormones are made to yield products that are biological replicas of the substances produced by our bodies. This is why they do not produce undesirable side effects when administered correctly.
In contrast, synthetic hormones are not biologically identical replicas. As a result, their use can result in severe side effects, as evidenced by clinical studies. Furthermore, bioidenticals have been shown by most clinical studies to be protective when administered properly. This can only be accomplished by a physician who has specialized in this field.
The most commonly prescribed forms of testosterone replacement therapy including commercial gels or compounded creams, injectables, and pellets. Commercially available gels are synthetic but will get men to testosterone levels which are “generally medically acceptable” but not to the levels of optimal symptomatic control as described above. Compounded bioidentical topicals come with the “hassle” of having to air dry plus the concerning factor of transfer to other humans (children and spouses) and even pets. However, this hassle factor has been reduced recently with the advent of special topical compounding formulations, so it’s still a good option.
Then there is the weekly IM or sometimes sub-q injection which is my preferred delivery system. I choose to use testosterone cypionate because after one biochemical “cleavage,” it is considered one of the most bioidentical hormones we use. Lastly, there are pellets, which generally last 3 months. The pellets are implanted into the subdermal fat of the buttocks, lower abdominal wall, or thigh with a tunneling technique using a local anesthetic.
The benefits of this method include guaranteed compliance and lack of transference to persons who may come in contact with it. Adverse effects include pellet extrusion, infection, and fibrosis. Due to the need for a surgical procedure for implantation and the sequela of side effects, this form of HRT is not recommended as a first-line treatment. Now, that said, some doctors want to “make a buck,” and they offer pellet therapy as their only choice. But we don’t always need to use testosterone, either.
Raising Testosterone without Exogenous Testosterone
Selective estrogen receptor modulators
SERMs are pharmaceuticals that act as competitive inhibitors of estrogen receptors in the hypothalamus and pituitary gland. They increase (via stimulation) the release of what is called gonadotrophins. These gonadotropins then increase the production of intra-testicular testosterone. Clomiphene citrate is a SERM that has been used to increase testosterone levels and sperm counts. Although thromboembolic events and carcinogenesis have been reported as (uncommon) adverse effects of SERMs, it appears to be a safe short-term solution for many patients who have (as an example) mold toxin illness and other toxin-related issues.
Gonadotropin therapy (most commonly hCG-human chorionic gonadotropin) is typically used to manage infertile patients with low testosterone concentrations to recover normal sperm production. Additionally, treatment with hCG can usually preserve normal sperm production in men undergoing TRT by maintaining intratesticular testosterone concentrations. However, gonadotropin therapy’s potential side effects include gynecomastia (“man-boobs”), headache, fatigue, and mood changes.
What if I have low T and want a family?
First, you will need a sperm count performed, and if you are lucky enough to have a normal one, you need to deep freeze your sperm. However, if your count is low, then we try to increase your count with Clomiphene citrate and HCG (human chorionic gonadotropin), as discussed above. If you respond favorably, you’ll have a decent count or a “combinable samples count,” and you can freeze your sperm then.
To emphasize, do not start taking testosterone if you are planning to have children. Despite the findings just mentioned, a sizeable percentage of men who are given SERMS or Gonadotropins along with their exogenous testosterone is never able to have their pituitary-testicular connection re-established and are therefore unable to conceive. Therefore, I will not prescribe testosterone to a young man who has not frozen his sperm.
E.D. and the Role of Testosterone
Contrary to popular belief, low testosterone is less of a cause of erectile dysfunction than diabetes, pre-diabetes, or vascular disease. If you have E.D., a thorough check-up and lab testing are necessary. Once the metabolic issues are cleared up, we can focus on erectile function. Chances are, if you are in the age group that is more at risk for metabolic issues, you will also have low testosterone. In this case, testosterone replacement will obviously be of benefit, too. But if it’s “not enough,” what then? You’ve heard about viagra, Cialis and might have even tried one of these drugs. But I’ll bet you haven’t heard about PT-141, which I’ll bet you’ll find quite interesting!
PT-141 is a “peptide,” and more specifically, it’s a natural melanocortin with the following simple amino acid sequence: Asp-His-D-Phe-Arg-Trp-Lys-OH. It was originally studied in men who had not achieved a satisfactory response to viagra. It has been studied and compared to all of the PDe5 inhibitors (viagra, Cialis, and Levitra), and amazingly enough, it is superior to all of them. Therefore, I prescribe it as an intra-nasal spray, a troche (lozenge), or a subQ injection.
I would be remiss if I didn’t address “libido,” which will address female needs and male needs for this one last section. The reason for this is simple; what good is it if you have an amped-up libido if your female partner is never in the mood, right? This is where, unbelievably enough, we again can discuss PT-141, the E.D. peptide discussed above. It seems that a very nice “side effect” researchers discovered was that PT-141 not only improved E.D.; it also made the male study subjects noticeably more, well–horny! It was subsequently studied in men and then in women. Long story very short: it works! Yes, in both men and women.
Another peptide called (seriously) kisspeptin is another way to amp up libido in men and women. It appears to act on the limbic (emotional) system, making it possible to combine therapy with both PT-141 and kisspeptin for those who require it.
Kisspeptin and the control of emotions, mood and reproductive behaviour
Kisspeptin and Testicular Function-Is it Necessary?
Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra
Novel Emerging Therapies for Erectile Dysfunction
Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: current and future prospects
doi: 10.1016/j.jsxm.2020.10.019. Epub 2020 Dec 11.
Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk
doi: 10.1111/andr.12774. Epub 2020 Mar 9.
Testosterone replacement therapy
Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.
Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.
Evaluation and Management of Testosterone Deficiency: AUA Guideline.
Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).
Testosterone Replacement Therapy: for whom, when and how?
Testosterone and Cardiovascular Health.
Benefits and Health Implications of Testosterone Therapy in Men With Testosterone Deficiency.
Randomized controlled trials – mechanistic studies of testosterone and the cardiovascular system.
Testosterone and the Heart.