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What You Don’t Know About Testosterone

But Should

Many brilliant men have experienced their demise that can be explained by the influence of testosterone (T) on their psyche. Bill Clinton, Eliot Spitzer, Anthony Weiner, John Edwards, Mark Sanford, Arnold Schwarzenegger and San Diego Mayor Bob Filner are all members of the “Tainted by Testosterone Club,” men who have had their careers derailed, arguably attributed (at least partially) by the effects of this powerful chemical.

T can be thought of as “kerosene” for the “fire” within the brain that governs what one does with one’s penis. T has undoubtedly played a major role and influence in terms of male aggressiveness, violence, homicides, destruction, power struggles, wars, and death that run rampant in our civilization. The male gender has been both blessed and cursed by this powerful elixir.

Many of us who enjoy canine company can attest (unintended pun) to the dramatic behavioral change of our male pets after they are surgically castrated. Man’s best friends become less aggressive, more docile, less alpha, and less likely to hump your leg. Extrapolate to human beings and one can understand how, with brains bathed in T, thoughts, behaviors, and actions are influenced and modulated.

Ven der putz shteht, ligt der sechel in drerd.” (“When the prick stands up, the brains get buried in the ground.”)

–Yiddish proverb from Phillip Roth’s ‘Portnoy’s Complaint’

God gave every man a brain and a penis, but only enough blood to make one work at a time.”

— Robin Williams

T: Q & A

What role has Big Pharma had in the awareness and management of low T?

Big Pharma is responsible for clever marketing phrases, e.g. relabeling “impotence” as “erectile dysfunction,” “spastic bladder” as “overactive bladder,” and “hypogonadism” as “low T.” As a result, these shrewd terms have become household words and sales of drugs aimed to manage these problems have skyrocketed.

What kind of hormone is T?

T (testosterone) is an “anabolic” and an “androgenic” hormone, anabolic referring to its capacity to build muscle, bone mass and strength, and androgenic referring to its ability to induce male characteristics (masculinize).

Where is T made?

Most T is 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 of secretion 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 and need a nap at 4PM now you know why!

What actions does T have?

T levels surge around 12-14 years of age, inducing puberty. T is responsible for penile enlargement, development of an interest in sex (libido), increased erections, body hair (pubic, underarm, facial, chest and leg), decreased body fat, increased muscle, bone mass, and strength, deepening voice, Adam’s apple prominence, sperm production, and bone and cartilage changes (growth of the jaw, brow, chin, nose and ears) with the transition from “cute” baby face to “angular” adult face. 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.”

What is testosterone deficiency (TD) and why does it occur?

TD is a clinical and biochemical syndrome characterized by symptoms and signs and 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 due to impaired testicular production of T. It can also happen because of a pituitary issue in which there is not enough production of the hormone that drives the testes to manufacture T (LH or luteinizing hormone). It can also occur under circumstances of normal T levels when there are elevated levels of the SHBG (sex hormone binding globulin) that strongly binds T, reducing the amounts of T available for action. It is important to distinguish testes impairment TD vs. pituitary impairment TD, as the management is different.

What is the role of T with respect to erections?

Although T is important for sexual function and for maintaining the health and vitality of penile tissues, one does not need high or even normal levels of T to obtain an erection. A good example is a pre-pubertal boy who frequently gets erections, but has no interest in sex. The more compelling role of T is in driving libido.

Is testosterone replacement therapy (TRT) a consideration for me?

Yes, but only under the circumstances of a testicular or pituitary problem causing the characteristic symptoms of TD coupled with a blood test that demonstrates low T levels. Continuing TRT on an ongoing basis is only beneficial if it results in meaningful symptom improvement.

How does T get to the body tissues where it works?

T is a hormone–a chemical messenger that is made in one locale but works elsewhere–and as such it needs to be transported via the circulatory system to get to those cells where it acts. 60% of T is inactive (tightly bound to SHBG), 38% is weakly bound to albumin, and 2% is free. The albumin-bound and free T are the biologically “active” forms of T.

How does T actually work?

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 estrogen (E), the main female sex hormone.

Why have T levels been decreasing?

Obesity is the single most common cause of low T in the developed world. Diabetes and metabolic syndrome have contributed to the low T epidemic as well. Unhealthy lifestyles 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. Physical and psychological stress may affect pituitary hormone synthesis, which in turn can give rise to low T levels. Obstructive sleep apnea may contribute to low T levels. Environmental factors such as phthalates, commonly used in plastic products, as well as many other environmental exposures are associated with low T levels.

What are the symptoms of low T?

5 domains may be affected: physical, sexual, cognitive, affect and sleep. Physical changes include 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 libido, 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 include the possibilities of a reduced sense of general wellbeing, decreased energy and motivation, anxiety, depression and irritability. Sleep issues include fatigue, daytime sleepiness and difficulties falling and staying asleep. One can think of low T as an accelerant to the aging process.

How is low T diagnosed?

The diagnosis 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 may 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. 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 and preferably in the morning when levels peak.

What is the first-line approach to treating low T?

Lifestyle improvement measures including weight reduction, exercising regularly, management of obstructive sleep apnea and stopping the use of opioids.

When should TRT be used?

When low T fails to respond to first-line approaches in a man with characteristic symptoms and laboratory documentation of low T.

What is the goal of TRT?

To restore T levels to the mid-normal range of levels observed for healthy men and alleviate the signs and symptoms of low T without causing significant side effects or safety issues.

What are some of the testicular side effects of TRT?

When using an external source of T, the body recognizes the presence of the external T and turns off testes function, resulting in diminished sperm count, decreased fertility, diminished natural T production, 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 medications that stimulate the testes to produce natural testosterone without suppressing sperm count.

What are some other side effects of TRT?

Acne, oily skin, breast development, worsening of sleep apnea, hair loss, fluid retention, elevated blood count and aggression. T is rocket fuel that can make a man all “piss and vinegar” if T levels are too high.

How is TRT administered?

There are many different preparations: oral; buccal (applied to the gums); transdermal (patches and gels); nasal gel; injections; and pellet implants. Each has advantages and disadvantages.

How about treating low T without TRT?

TRT impairs sperm development and fertility, turns off natural T production, and may result in testes atrophy. An alternative to TRT–clomiphene citrate–works by stimulating the testes to produce natural T. It is approved by the FDA for both male and female infertility, but not for low T, so must be prescribed “off-label.”

Do men on TRT need follow up care?

Regular follow up is imperative to ensure that 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. Blood testes include T levels, a complete blood count (CBC) to check for increased hematocrit (that can cause more viscous blood), and PSA (prostate specific antigen).

Is TRT use dangerous in men with prostate cancer or cardiac disease?

To quote a review article from the Journal of Sexual Medicine (Dean et al: The ISSM’s Process of Care for the Assessment and Management of Testosterone Deficiency 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.

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