Testosterone Replacement Therapy

By: | Tags: | Comments: 0 | August 3rd, 2020

Testosterone ,should be administered only to a man who is hypogonadal, as evidenced by clinical symptoms and signs consistent with androgen deficiency and a distinctly subnormal serum testosterone concentration. In comparison, increasing the serum testosterone concentration in a man who has symptoms suggestive of hypogonadism, but whose testosterone concentration is already normal, will not relieve those symptoms.

Symptoms and signs suggestive of androgen deficiency include low libido, decreased morning erections, loss of body hair, low bone mineral density, gynecomastia, and small testes. Symptoms and signs such as fatigue, depression, anemia, reduced muscle strength, and increased fat mass are less specific

Testosterone can be replaced satisfactorily whether the testosterone deficiency is due to primary or secondary hypogonadism.

The role of Testosterone replacement to treat the decline in serum testosterone concentration that occurs with increasing frequency in men above age 60 years, in the absence of identifiable pituitary or hypothalamic disease, is uncertain.

Testosterone therapy is indicated only for testosterone deficiency, not for impaired spermatogenesis. Testosterone therapy impairs spermatogenesis further by suppressing pituitary gonadotropin secretion.

Testosterone has many different biologic effects, at least in part because it can act as three hormones:

  1. It can act directly by binding to the androgen receptor.
  2. It can also act in tissues that express the enzyme 5-alpha-reductase, via conversion to dihydrotestosterone, which binds more avidly to the androgen receptor than testosterone itself.
  3. Finally, it can act as an estrogen following conversion by aromatase to estradiol, which binds to the estrogen receptor.

Facts you should know

  • Testoterone requires conversion to dihydrotestosterone for its action on the external genitalia (which include the prostate gland) and sexual hair. This mechanism provides the basis for the use of the 5-alpha-reductase inhibitor To treat Benign Prostate enlargement and also male pattern of  baldness.
  • Testosterone requires conversion to estradiol for much of its action on bone. This effect is illustrated by the rare condition of aromatase deficiency in men, which results in failure of epiphyseal closure and severe osteoporosis. Treatment with estradiol corrects both
  • Testosterone also appears to require conversion to estradiol to stimulate normal sexual function and decrease body fat in men, as shown by an experiment in which men 20 to 50 years old were treated with a gonadotropin-releasing hormone (GnRH) agonist to suppress testosterone and estradiol secretion and then replaced with testosterone, with or without an aromatase inhibitor
  • Addition of the aromatase inhibitor partially blocked testosterone from increasing libido and erectile function and from decreasing subcutaneous and intraabdominal fat.

Testosterone should be administered only to a man who is hypogonadal, as evidenced by clinical symptoms and signs consistent with androgen deficiency and a distinctly subnormal serum testosterone concentration. In comparison, increasing the serum testosterone concentration in a man who has symptoms suggestive of hypogonadism, but whose testosterone concentration is already normal, will not relieve those symptoms.

Symptoms and signs suggestive of androgen deficiency include/ Hypogonadism:

  • Low libido,
  • Decreased morning erections,
  • Loss of body hair,
  • Low bone mineral density,
  • Gynecomastia,
  • Small testes.

Symptoms and signs such as fatigue, depression, anemia, reduced muscle strength, and increased fat mass are less specific.

Testosterone can be replaced satisfactorily whether the testosterone deficiency is due to primary or secondary hypogonadism.

Testosterone therapy is indicated only for testosterone deficiency, not for impaired spermatogenesis. Testosterone therapy impairs spermatogenesis further by suppressing pituitary gonadotropin secretion.

Clinical Benefits of TRT

The desirable effect of Testosterone administration include the development or maintenance of secondary sexual characteristics and increases in libido, muscle strength, fat-free mass, and bone density. Undesirable effects related directly to testosterone include acne, prostate disorders (such as benign prostatic hyperplasia [BPH] symptoms), sleep apnea, and erythrocytosis.

  1. Normalization of Serum Testosterone concentration should lead to normal virilization in men who are not virilized and maintenance of virilization in those who already are. Men who become hypogonadal in adulthood and are still normally virilized, but whose hypogonadism is manifested by a decrease in libido and energy, should note a marked improvement in these symptoms. Failure of improvement when the serum testosterone concentration has been restored to normal suggests another cause of the symptom
  2. Testosterone replacement also leads to substantial improvements in muscle strength and fat-free mass in hypogonadal men. In one report, for example, the administration of 100 mg of testosterone enanthate once a week for 10 weeks to hypogonadal men increased their strength in the bench press by 22 percent, their squat strength by 45 percent, and fat-free mass by 5 percent
  3. Testosterone replacement improves bone density in male hypogonadism, as illustrated in a study of 72 such men receiving testosterone replacement therapy

Testosterone should be administered only to an adult male who is hypogonadal, as evidenced by clinical symptoms and signs consistent with androgen deficiency and a subnormal morning (8 to 10 AM) serum testosterone concentration on three separate occasions. Ideally, samples should be drawn fasting; in one report, an oral glucose load suppressed serum testosterone concentrations acutely

The role of Testosterone in replacement to treat the decline in serum testosterone concentration that occurs with aging in men, in the absence of identifiable pituitary or hypothalamic disease, has been unclear. However, results from the Testosterone Trials suggest that testosterone has a beneficial effect on sexual function, mood, possibly walking, bone density, and anemia .

Inappropriate use of testosterone in healthy, middle-aged men — 

There has been a dramatic increase in inappropriate use of Testosterone therapy in healthy, middle-aged and older men. It is important for clinicians to understand that the diagnosis of testosterone deficiency should be made only on the basis of clinical symptoms and signs consistent with androgen deficiency and consistently subnormal serum testosterone concentrations at 8 to 10 AM on three occasions.

For men with vague symptoms that could be the result of low Testosterone  (eg, fatigue) and a single, but not repeatedly, subnormal serum testosterone concentration, I recommend strongly against testosterone use.

The Endocrine Society’s guidelines and others also strongly advocate this approach ,i.e three testing to confirm hypogonadism .

Treatment should not be prescribed on a “trial” basis, because the results are not interpretable and because once men have started treatment, they may find cessation difficult because of the prolonged period of hypogonadism during recovery of the pituitary-testicular axis. In addition, testosterone therapy eventually results in suppression of spermatogenesis and decreased testicular size.

The rise in Testosterone  prescriptions in healthy, middle-aged men is likely due, at least in part, to direct-to-consumer advertising (DTCA) encouraging use of testosterone products for nonspecific symptoms, such as decreased energy and sexual interest .

In one study of 75 designated market areas with high rates of DTCA of specific testosterone products and/or testosterone deficiency (“low T”), approximately 1 million of 17 million men (6 percent) had themselves tested for low testosterone for the first time between 2009 and 2013.

Approximately 280,000 men (1.6 percent) started testosterone therapy during that interval. The study authors calculated that each exposure to DTCA was associated with a 0.6, 0.7, or 0.8 percent increase in testosterone testing, initiation of therapy, or initiation of testosterone therapy without baseline testing, respectively. Although the percentage changes are small, in large populations, the impact is large.

Choice of testosterone regimen 

Choosing among the different Testosterone preparations requires an understanding of their pharmacokinetics. Native testosterone is absorbed well from the intestine, but it is metabolized so rapidly by the liver that it is virtually impossible to maintain a normal serum testosterone concentration in a hypogonadal man with oral testosterone. The solutions to this problem that have been developed over many years involve modifying the testosterone molecule, changing the method of testosterone delivery, or both.

A number of Testosterone preparations are currently available or are under development for treating testosterone deficiency

I usually suggest Testosterone gels because they typically result in normal and relatively stable serum testosterone concentrations, and most patients prefer them to other preparations. However, other factors affect choice of regimen, including patient preference, cost, convenience, and insurance coverage, which varies by plan and regimen. In general, the newest preparations (the gels) cost the most and injectable esters cost the least.

Three gels :

  1. AndroGel is supplied in both 1% and 1.62% concentrations. The 1% concentration was the first to become available. It is still available in 2.5 and 5 g packets, which contain 25 and 50 mg of testosterone, respectively , and a metered-dose pump that delivers 1.25 g of gel (containing 12.5 mg of testosterone) per pump depression (although the metered-dose pump bottle is no longer available in the United States). When this preparation is applied to the skin once a day in doses of 5 to 10 g (delivering 50 to 100 mg of testosterone), the serum testosterone concentrations usually reach the normal male range within a month and remain steady throughout 24 hours .
  2. Testim, (1% Testosterone gel) is supplied in tubes containing doses of 5 and 10 g, which contain 50 and 100 mg of testosterone, respectively, and when applied daily usually results in normal serum concentrations of testosterone
  3. Fortesta  (2% TESTOTERONE gel) is also supplied in a metered-dose pump, with each pump depression delivering 0.5 g of gel (containing 10 mg of testosterone) . The recommended starting dose is 40 mg, applied to the front and inner thighs, and adjusted to a minimum of 10 mg and a maximum of 70 mg, as determined by the serum testosterone concentration. A study in hypogonadal men showed that after 90 days of daily use, the mean serum testosterone concentration before gel application was in the low end of the normal range, after application reached a peak in the midnormal range in approximately four hours, and fell to the baseline level 12 hours after application

Axiron (2% Testosterone solution) is a solution of testosterone that also comes in a metered-dose pump with applicator. Each depression yields 30 mg (1.5 mL) of testosterone. The package insert suggests a starting dose of 30 mg applied to each axilla (total of 60 mg) once a day and adjustment of the dose as low as 30 mg and as high as 120 mg once a day, as judged by the serum testosterone concentration

The serum concentrations of testosterone throughout the 24 hours from one application to the next are similar at one, three, and six months .Occasional local skin irritation occurs but usually does not necessitate discontinuation of therapy.

Transdermal delivery first became available in 1994 with the introduction of a scrotal patch (chosen because drugs are absorbed readily across scrotal skin). Since then, body patches and gels have also become available, but the scrotal patch is no longer available in the United States. The major advantage of transdermal administration is maintenance of relatively stable serum testosterone concentrations, resulting in maintenance of relatively stable energy, mood, and libido

INTRAMUSCULAR INJECTION

An advantage of TESTOTERONE enanthate and cypionate over other testosterone preparations is that :

  • they are biologically effective in initiating and maintaining normal virilization in all hypogonadal men.
  • Another advantage to some men is freedom from daily administration.

The disadvantages are the need for deep IM administration of an oily solution every one to three weeks and fluctuations in the serum testosterone concentration, which result in fluctuations in energy, mood, and libido in many patients. These fluctuations are more pronounced as the dosing interval is increased.

Other form of treatment includer the oral / buccal mucosa administration, but I will advice against this treatment .

Decades ago, investigators discovered that adding an alkyl group in the 17-alpha position of the Testosterone molecule slowed its catabolism by the liver .Many endocrinologists who treat male hypogonadism think that these preparations are not fully effective in producing virilization, although no studies have tested these observations.

In addition, several reports have described hepatic side effects with these preparations, including cholestatic jaundice, a hepatic cystic disease called peliosis hepatis, and hepatoma [. For both of these reasons and because better preparations are available, the 17-alpha alkylated androgens should generally not be used to treat testosterone deficiency.

Contraindications to use — Several possible contraindications to Testosterone therapy should be evaluated before initiating testosterone treatment:

  • Prostate Cancer  man who has a history of prostate cancer should generally not be treated with Testosterone . A possible exception is a hypogonadal man who had a radical prostatectomy for cancer confined to the prostate and has been free of disease and has had an undetectable prostate-specific antigen (PSA) for at least two years.
  • Breast Cancer -Testosterone is aromatized to Estradiol, men who have breast cancer should not be treated with testosterone.
  • Erythrocytosis -Testosterone stimulates erythropoiesis, so the hematocrit should be measured before initiating testosterone treatment, and if it is elevated, the cause should be sought and the condition treated before testosterone treatment is initiated.
  • Sleep Apnea  may be worsen with the Testosterone treatment .
  • Uncontrolled Heart Failure  Testosterone has slight sodium retaining properties, so severe heart failure should be treated before beginning testosterone treatment
  • Testosterone treatment can stimulate erythrocytosis
  • Risk of VTE-  Pulmonary embolism risk
  • Increase risk of Myocardial infarction  and strokes

At 1st class urgent Care center we are interested in your overall well being, we would offer detailed evaluation of you and overall well being, we would also provide you with the right information thereby equipping you .

We would consider risk versus the benefits of taking the TRT, before engaging you in any form of treatment,

We are glad to help , remember we are your neighborhood clinic. Get Wisdom, Get Understanding ! In all thy getting get understanding ..

Dr Joseph Taiwo

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Joseph Taiwo MD

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