The life expectancy of men is slated to witness a dramatic rise over the next two decades. While this is great news, it also brings with it several health-related issues such as strokes, cancer, heart disease, as well as hormone deficiency.
There is a growing realization that men could have significant health issues associated with age-related hormonal decline . Testosterone peaks in a male around the age of 18 or 19. After this, one starts witnessing a gradual decline in the testosterone levels with the peak reaching after 60 years of age.
Almost half of the male population above the age of 50 are said to suffer from low testosterone levels. Studies have shown that an elderly male will witness an annual decrease of 1% in testosterone levels after age 50.
This decrease in testosterone levels has been termed male climacteric, andropause, male menopause, or PADAM (partial androgen deficiency in the aging male).
Serum testosterone levels decrease progressively, primarily due to reduced production of testicular cells (Leydig cells) that produce testosterone. The decline can also be due to changes in levels of protein (albumin, SHBG) and hormones (LH, GnRH) regulating the production of testosterone.
Normal Testosterone Levels
So what is normal testosterone level?
The main problem with determining the right level of testosterone is it’s presence in several forms in the blood, each with different hormonal activity.
While free testosterone is an active hormone, protein-bound testosterone is partially or sometimes totally inactive. What is generally measured during a blood draw is total testosterone (a combination of protein-bound and free forms).
According to the guidelines of the American Urological Association (AUA), a man is said to have normal testosterone levels if he has levels of 300 ng/dL (nanograms per deciliter). Anything below that is said to be low.
According to the Endocrine Society, the range for normal testosterone levels in a non-obese male aged between 19 to 39 years is 264-916 ng/dL.
The US FDA has also come out with its testosterone range. According to the US FDA, a normal testosterone range is between 300 ng/dL to 1, 000 ng/dL.
As noted, while there is no specific standardization of the testosterone levels, the typical range is around 300 ng/dL.
Testosterone and Men
Testosterone plays an essential role in the male human body. It impacts the brain, muscles, liver, kidney, bones, male reproductive organs, and even body hair growth. It essentially makes men what they are.
The following table throws light on the influence of testosterone on various organs and functions.
Table 1. Testosterone effects in a healthy male.
| TARGET | EFFECTS |
| Behavior | Improved mood, libido, energy, and memory |
| Bone | Linear growth, epiphyseal closure, increased bone mineral density |
| Muscle | Increased muscle volume and strength |
| Fat tissue | Abdominal and body fat reduction |
| Liver | Increased serum protein production |
| Heart | Dilation of blood vessels present in the heart |
| Male Sex Organs | Sperm production, growth, development, as well as maintenance of secondary sex traits, prostatic function, and erections |
| Kidney | Stimulate erythropoietin production |
| Bone Marrow | Increased stem cell production |
| Blood | Low HDL-cholesterol, better control of clotting factors (II, V, VII) |
| Hair | Body hair growth, mainly facial hair |
As mentioned above, testosterone levels in a male usually peak by the time he turns 19. Once he reaches 30, the testosterone levels start decreasing naturally. However, these levels decrease at an alarming level in few men.
According to a study conducted in 2006, approximately 40% of males aged 45 and above are said to suffer from abnormally low testosterone levels.
Symptoms
Several symptoms can manifest if the levels fall drastically. Low testosterone signs are often very subtle. It can be very bothersome and impact the quality of life. Some of the common symptoms on account of low T include:
- Fatigue
- Memory changes
- Mood changes
- Low sex drive
- Difficulty having an erection
- Smaller testicles
- Low blood counts
- Loss of muscle mass
- Low semen volume
- Hair loss
- Decreased bone mass
- Increased body fat
Tests to Determine Testosterone Levels
Since testosterone is found in different forms, there is no clear test to determine the testosterone levels. Many healthcare providers order the serum testosterone test to check for total testosterone.
Testosterone byproducts like estradiol, dehydroepiandrosterone (DHEA), and dihydrotestosterone (DHT) make it a little tricky in making an accurate diagnosis.
Various national guidelines report that any level below 300 ng/dL is considered as low level; however, this can vary in men.
If a man has undergone previous testosterone level test and the reading is higher than the present test, then the person might be considered to have a declining testosterone level.
Other Tests
Besides serum testosterone tests, few other tests can also help in making a diagnosis of low testosterone levels.
Tests for anemia and DEXA scan for measuring bone density and bone loss can also assist in diagnosing the problem. Also, PSA, as well as rectal examination for prostate cancer, can help diagnose.
Advantages of Testosterone Replacement Therapy
To replace the low testosterone levels, doctors advocate testosterone replacement therapy (TRT). Some of the benefits of TRT include:
Leaner Body
TRT helps in increasing the lean body mass, decrease fat mass, and possibly increase strength. It helps in improving the blood counts by stimulating erythropoietin.
TRT is also known to dilate blood vessels in the heart as well as improve lipid profiles. However, it is not very clear if the use of TRT can help in reducing strokes or heart attacks, nor is it clear if it can alter the total cholesterol or LDL levels.
Better Bones
Studies have shown that TRT helps in improving bone mineral density in men with reduced testosterone levels. TRT also helps in reducing bone fractures, akin to postmenopausal women placed on estrogen replacement.
Increased bone mineral density is critical because studies have shown that the chances of hip fractures increase two to -three-fold in men with low testosterone levels. Around 40% of elder males suffering from hip fractures end up dying within a year of the fracture.
Better Sexual Health
Testosterone Replacement Therapy helps in improving sexual function. A majority of the studies have shown that increased testosterone levels help in enhancing the sexual drive.
Increased testosterone levels assist in better erections. It is important to note that isolated low testosterone is however not the usual suspect in erectile problems in older adult men. Erectile problems are common due to age-related changes and lower sex drive.
Types of Testosterone Replacement Therapy
An ideal testosterone replacement therapy maintains the normal level of the hormone, making sure there are no notable side effects. There are different types of hormone replacement currently available.
The following table shows some common testosterone therapy available in the US.
Table 2. Common testosterone therapy types
| PREP | DOSE | FORMULA | COMMENTS |
| Oral | 10-50mg/day | Methyltestosterone Fluoxymesterone | Multiple daily doses. Increased chances of liver problems |
| Intramuscular | 50-400 mg/two to four weeks | Testosterone enanthate Testosterone cypionate | Deep intramuscular injection. Daily regime not given. Mood fluctuations. |
| Subdermal implant | 5-10 g | Testopel | Nonsurgical procedure. Lasts up to six months |
| Transdermal patch | 4-6mg/day 5mg/day
2.5-5mg/day |
Testoderm (scrotal) Testoderm TTS Androderm | Scrotal and non-scrotal patch: variable absorption. Can produce skin welts at the site |
| Transdermal gel | 5 g/day | Androgel Testim | Highly convenient. Has odor. Can rub off |
| Transbuccal pill | 30mg buccal tablet | Striant | Taken twice daily. Can result in mouth or gum irritation. Can result in taste perversion |
Monitoring
Testosterone replacement is not a quick fix solution. The benefits of testosterone therapy only start showing over a longer period. Hence, there is need for constant monitoring as outlined in the below table.
Table 3. Monitoring timeline for testosterone treatment.
| TIMELIME | INDICATED ASSESSMENT |
| Baseline (prior to treatment) | PSA, blood counts, and rectal exam. Check for sleep apnea, and voiding symptoms. DEXA scan |
| 1-2 months after treatment initiation | Assess efficacy: symptoms and testosterone levels. Dosage adjustment as per the results |
| 3-6 months interval (during the first year) | Assess voiding symptoms, symptomatic response, and sleep apnea. Undertake physical exam, rectal examination, lipid profile, liver function, and testosterone test. Blood count and PSA is also checked based upon the formulation |
| Annually (after first year) | Assess symptomatic response: voiding, treatment, and sleep apnea. Undertake physical exam, rectal examination, lipid profile, liver function, and testosterone test. Blood count and PSA is also checked based upon the formulation |
Prior to initiating the treatment, the healthcare provider will do a serum PSA and a digital rectal examination. After a month or two, the symptoms, as well as testosterone levels, are assessed.
The patient has to be followed regularly in the first year of treatment. Once the patient touches the one-year mark, he is monitored on an annual basis.
Annual tests include liver function tests, hemoglobin, testosterone levels, PSA, and lipid profile. Depending on the patient, the provider can also offer psychological assessment or bone density.
Alternative Treatment Options
Dehydroepiandrosterone (DHEA)
Available in OTC formulation, DHEA is a steroid hormone produced by the adrenal gland. DHEA levels start declining after one reaches 30 years and beyond.
Many studies have tried to correlate decreased DHEA as well as DHEA-sulfate with several health conditions.
Placebo-controlled studies have suggested that an oral DHEA dose in the range of 30-50mg could result in increased physiologic androgen levels.
For those with poor adrenal functioning, a 50mg dose can result in an increase of serum androgen levels to that of normal levels in young adults.
It can improve sexual function, self-esteem, mood, and decrease exhaustion/fatigue. However, benefits in older men are still not firmly established.
Dihydrotestosterone (DHT)
A metabolite of testosterone, the natural androgen DHT is a selective androgen since it cannot be converted into estrogens. DHT is also a very potent androgen and binds to receptors more keenly than testosterone.
DHT affects skin, prostate, and external genitalia. Men deficient in DHT are not osteoporotic and have normal muscle mass. In normal males, DHT supplements suppress the production of FSH and LH secretion, which can likely result in infertility.
In its androgen role, DHT is “prostate sparing.” As a result of its potential and potency, various studies are being undertaken with DHT supplements.
Growth Hormone
As a person ages, there is a decrease in the growth hormone as well as growth factor-I. Treatment of GH-deficiency in young adults with growth hormone has been shown to improve body composition, physical function, muscle strength, and bone density.
It is also known to decrease the risk of cardiovascular disease as well as blood cholesterol. In older individuals, GH treatment is known to reduce body fat and improve lean body mass.
However, the use of growth hormones is not without risks. Patients being treated with growth hormones have often complained of peripheral swelling, carpal tunnel syndrome, joint swelling and pain, glucose intolerance, breast tenderness, and in rare cases, increased cancer risk.
As with younger individuals, treatment with growth hormone in older individuals is fraught with dangers. Healthcare providers do not recommend growth hormone treatment in older individuals until more research is conducted and the risk/benefit relationships is properly defined.
Risks of Testosterone Therapy
Testosterone therapy could have risks involved some of which are given below:
Infertility
TRT is known to reduce sperm production. More than 90% of TRT patients report low sperm counts within ten weeks of therapy initiation. Sperm counts rebound six months to a year after the stoppage of therapy.
Prostate health
A worrying risk of TRT is its potential to worsen prostate cancer. However, no direct link has been established to show that TRT can cause prostate cancer.
While on TRT therapy, a close follow-up of those patients who are at increased risk for prostate cancer is warranted. The US FDA does not recommend testosterone therapy for men at increased risk for breast and prostate cancer.
Another concern with regards to prostate health is the possibility that TRT can worsen urinary symptoms in patients with enlarged prostate. Healthcare providers advocate regular monitoring of any voiding symptoms to ensure there is no adverse impact.
Water retention
TRT can result in leg swelling, hypertension, or aggravating heart failure. Control of blood pressure and weight is essential for those who are at increased risk.
Altered cholesterol balance
While testosterone therapy has not shown to impact LDL or total cholesterol, the effects of it on HDL levels remains unclear. The monitoring of lipid levels during treatment is essential.
Polycythemia
Polycythemia (excessive RBC) was a common side effect observed during clinical trials. A hematocrit count of 50 and above is known to increase the chances of stroke.
Testosterone therapy has also been known to suppress clotting factors (II, V, and VII). It can also worsen bleeding in patients who are on anticoagulation. Constant monitoring of blood counts is vital for at-risk patients.
Sleep apnea
Even though TRT does not cause sleep apnea, it is known to add to existing sleep apnea problems.
Liver damage
TRT can also result in liver damage. It is more common with oral treatments and rare with transdermal, injectable, and transbuccal formulations.
Breast tenderness
TRT can also cause gynecomastia (abnormal breast enlargement with pain) on account of the increased estrogen levels. This can be tackled using estrogen receptor blockers.
Dr Harshi Dhingra is a Medical Doctor and specialized Pathologist with clinical, teaching and research experience of over a decade, currently employed as Assistant Professor, Pathology in a medical school and research center.
Her specialties include Histopathology, Haematology, Cytology and Clinical Pathology. Her research papers on sperm characteristics, testicular malignancies and endometrium lesions were well received.
