Written by Dr. Andrew Siegel
There has been an “epidemic” of a clinical syndrome based on low testosterone levels. There is no subject rife with more confusion and misinformation than testosterone deficiency and its treatment. Hopefully, the following 24 questions and answers, pulled from those commonly asked by my patients at office visits, will help enlighten and inform you and clarify misconceptions and falsehoods.
Before we get started, here are some common abbreviations I’ll be using throughout this blog post:
- T = Testosterone (the key male sex hormone)
- TD = Testosterone Deficiency
- TRT = Testosterone Replacement Therapy
- E = Estrogen (the key female sex hormone)
Q: What exactly is testosterone?
A: Testosterone is an “anabolic” hormone, a chemical messenger that promotes growth via protein synthesis, which drives the building of muscle and bone mass as well as strength. Testosterone is equally an “androgenic” hormone, causing masculinization. T is made from cholesterol with most produced in the testes, with a small amount made in the adrenal glands (organs that sit above kidneys). Healthy men produce 6-8 mg testosterone daily, in a rhythmic pattern with a peak in the early morning and a lag in the later afternoon. If you find that you are most amorous in the early morning, now you have a good biochemical explanation.
Q: When does testosterone kick in and what does it do?
A: Testosterone surges around age 12-14 and drives puberty, causing the following:
- Penis enlargement
- Development of an interest in sex
- Increased erections
- Pubic, underarm, facial, chest and leg hair
- Decrease in body fat
- Increase in muscle and bone mass, growth, and strength
- Deepened voice and prominence of the Adam’s apple
- Sperm production
- Bone and cartilage changes, including: growth of jaw, brow, chin, nose and ears (aka: the transition from “cute” baby face to “angular” adult face)
Q: Is testosterone important after puberty?
A: Throughout adulthood, T helps maintain libido, masculinity, sexuality, and youthful vigor and vitality. Additionally, T contributes to mood, red blood cell count, energy, and general “mojo.”
Q: What is Testosterone Deficiency and why does it occur?
A: Testosterone Deficiency (TD) is a clinical and biochemical syndrome characterized by relevant symptoms and signs in conjunction with a deficiency of T or T action. Symptomatic TD occurs in 2-6% of men. There is approximately a 1% decline in T level each year after age 30. Most commonly it is an impaired testicular production of T. It can also happen because of a pituitary issue in which there is not enough production of luteinizing hormone (LH), the hormone that drives the testes to manufacture T. Furthermore, it can happen under circumstances of normal T levels when there are elevated levels of the hormone that strongly binds T (SHBG), reducing the amounts of T available for action. It is important to distinguish TD on the basis of testes impairment vs. pituitary impairment, as the management is different.
Q: Is testosterone going to help my erections, which are not quite what they used to be?
A: Maybe. Although testosterone is important for sexual function and for maintaining the health and vitality of the penis, one does not need high or even normal levels of T to obtain an erection. A good example is a pre-pubertal boy who gets erections all the time, but has no interest in sex. The more compelling role of T is in driving libido.
Q: Testosterone seems like such a vital hormone for men…is it for me?
A: ONLY under the circumstances of a testicular or pituitary problem causing the characteristic symptoms of TD coupled with a blood test that proves that low T levels is it worth pursuing a trial of TRT. It is only beneficial continuing the TRT if it is providing meaningful symptom improvement in the face of a normalized T level.
Q: How does testosterone get to the body tissues where it works?
A: Since T is a hormone – a chemical messenger that is made in one locale but works elsewhere – it needs to be transported to get to those cells where it acts. T circulates in the bloodstream. 60% is inactive as it is tightly bound to SHBG (sex hormone binding globulin), 38% is weakly bound to albumin, and 2% is free. The albumin-bound and free T are the biologically “active” forms of T.
Q: How does testosterone work?
A: Much of T is converted to dihydrotestosterone (DHT), a more potent form, which couples with a special receptor enabling it to move into the nucleus of cells and bind to DNA, where it provides the blueprint for protein synthesis. Some T does so without being converted to DHT and some T is converted to E, the main female hormone.
Q: What about the female hormone estrogen…is it important for men?
A: Yes! More than 80% of estrogen (E) in males is derived from T. When levels of T are low, a decline in E levels will occur. E deficiency is important in terms of osteopenia (bone thinning) in men. As commonly happens with abdominal obesity, E levels become too high as abdominal fat is an active endocrine organ that converts T to E, causing:
- Low T
- High E
- Breast development
- The appearance of a smaller penis and general emasculation.
Q: Why have testosterone levels been dropping over the years?
A: Unhealthy lifestyle and the use of alcohol, steroids (for asthma, arthritis, connective tissue disorders and inflammatory bowel diseases) and opiate pain medications (methadone, tramadol, etc.) are risk factors.
Obesity has played a huge role. Diabetes and metabolic syndrome have contributed to the low T epidemic as well. Physical and psychological stress affect pituitary hormone synthesis, which can give rise to low T levels. Sleep apnea can contribute to TD. Environmental factors such as phthalates, commonly used in plastic products, as well as many other environmental exposures, are associated with low T levels.
Q: How important of a factor is obesity in causing testosterone deficiency?
A: Obesity is the single most common cause of testosterone deficiency in the developed world. More than half of men with TD are overweight or obese. The good news is that it is potentially reversible with weight loss.
Q: What is the issue with diagnosing low T based upon the established ADAM (androgen deficiency in the aging male) screening test?
A: The ADAM screening questions are very general and involve decreased libido, diminished erections, lack of energy, decrease in strength/endurance, loss of height, decreased joy, the presence of sadness or grumpiness, deterioration in sports performance, falling asleep after dinner and deterioration in work performance. These symptoms have an enormous overlap with changes that accompany normal aging, insufficient or poor quality sleep, overworking and/or an unhealthy lifestyle.
For example: a professional athlete of your choice who is at peak performance in his early 20’s. Fast-forward 30 years…how many of the aforementioned questions do you think will be answered positively? Is it low T? Possibly, but certainly not probably.
Q: What are the symptoms that indicate the possibility of testosterone deficiency?
A: 5 domains may be affected by TD: physical, sexual, cognitive, affect and sleep.
- Physical changes are reduced muscle mass and strength, increased body fat and abnormal lipid profiles, frailty, breast development, loss of body hair and central obesity.
- Sexual changes include decreased desire, diminished erection quality and weakened ejaculation and orgasm.
- Cognitive changes that may occur are impaired concentration, diminished verbal memory and altered visual-spatial awareness.
- Changes in affect can be a reduced sense of general wellbeing, decreased energy and motivation, anxiety, depression and irritability.
- Sleep issues include fatigue, tendency to sleep during the day and difficulties falling and staying asleep.
Q: How is testosterone deficiency diagnosed with lab testing?
A: The diagnosis of TD is made via a blood test for total T and free T as well as for the pituitary hormones LH and prolactin. In cases of obese or elderly men, SHBG can be useful. It is important to know that T levels can vary depending on the particular lab and can fluctuate on a day-to-day basis as well as depending on what time of day it is drawn, as T has circadian biorhythms. T can be temporarily suppressed by illness, nutritional deficiency and certain medications. Fasting T levels are generally higher than T levels after a meal. The bottom line is that T should be checked on at least two occasions.
Q: What is the first-line approach to treating testosterone deficiency?
A: Lifestyle improvement measures including:
- Weight reduction
- Exercising regularly
- Management of sleep apnea
- Stopping the use of opioids
Q: When should Testosterone Replacement Therapy (TRT) be used?
A: When TD fails to respond to first-line approaches in a man with characteristic symptoms and laboratory documentation of TD.
Q: What is the goal of TRT?
A: To restore T levels to the mid-normal range of levels observed for healthy men and alleviate the signs and symptoms of TD without causing significant side effects or safety issues.
Q: What are some of the testicular side effects of TRT?
A: Because TRT is an external source of T, it suppresses testes function, resulting in diminished sperm count, decreased fertility and the possibility of testes atrophy (shrinkage) with long-term use. Men who wish to retain fertility should not be put on TRT, but should consider the use of an oral medication that stimulates the testes to produce natural testosterone without suppressing sperm count.
Q: What are some of the other side effects of TRT?
A: Acne, oily skin, breast development, worsening of sleep apnea, hair loss, fluid retention, elevated blood count and aggression.
Q: How is TRT administered?
A: There are many different preparations: buccal (applied to the gums); transdermal (patches and gels); nasal gel; injections; and pellet implants. Each has advantages and disadvantages.
Q: What about treating TD without TRT?
A: Since TRT impairs sperm development and fertility and may result in testes atrophy, an alternative to TRT, called clomiphene citrate, works by stimulating the testes to produce natural T. It is approved by the FDA for both male and female fertility, but not for TD, so must be prescribed “off-label” for TD.
Q: Do men with TD on TRT need follow up?
A: Yes, regular follow up is imperative to ensure that the TRT is effective, adverse effects are minimal, and T blood levels are in-range. Periodic digital rectal exams are important to check the prostate for enlargement and irregularities, and, in addition to T levels, other blood tests are important including a blood count to check for increased hematocrit (thicker, richer blood) and PSA (Prostate Specific Antigen). With the commonly used gel products, absorption rates vary considerably from person to person depending on skin thickness, body hair, preparation, application site, degree of sweating, etc., so dose adjustments need to be made depending on T levels that are periodically checked.
Q: What about TRT in men with cardiac disease or prostate cancer?
A: To quote a review article from the Journal of Sexual Medicine (Dean et al: The ISSM’s Process of Care for the Assessment an Management of TD in Adult Men, 2015;12:1660-1686): “TRT use has been complicated by controversies regarding prostate cancer and cardiovascular risks. Although the absence of large-scale, long-term controlled studies with TRT limits the ability to make definitive conclusions regarding these risks, the weight of evidence fails to support either concern.”
Q: How about testosterone supplements or boosters that can be bought online?
A: The Internet is overrun with male “sexual enhancement” products. They capitalize on male insecurity, which has created a huge market, with hordes of men willing to pay top dollar for products that have misleading claims and are often mislabeled, contaminated and falsely advertised. Unfortunately, such supplements are exempt from the stringent regulatory oversight applied to prescription drugs, which requires reviews of a product’s safety and effectiveness before it goes to market. Do not waste your money!
Bottom Line: Testosterone deficiency (or low T) is a very real entity, but not as common as it’s been made out to be. The symptoms can be devastating, and when accompanied by lab testing confirming the suspected clinical diagnosis, testosterone replacement therapy can be magical. I had one patient who eloquently described his “world of black and white turning into a world of color” after his testosterone level was normalized. For many others with the syndrome, the beneficial effects of TRT are far more subtle. If your T level is normal, it is highly unlikely that your symptoms are on the basis of low T and TRT should not be a consideration.