Implantable Hormone Pellets for Testosterone Deficiency in Adult Men

CHAPTER 124 Implantable Hormone Pellets for Testosterone Deficiency in Adult Men



John Harlan Haynes, III, Terrance S. Hines


Testosterone is responsible for normal growth and development of male sex organs and maintenance of secondary sex characteristics. As the primary androgenic hormone, its production and secretion are the end products of hormonal and biochemical interactions. Gonadotropin-releasing hormone (GnRH) is secreted by the hypothalamus and controls the pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH regulates production of testosterone by the testes, and FSH stimulates spermatogenesis. Testosterone can be converted in the body either to dihydrotestosterone by 5-α reductase or to estradiol by aromatase. Dihydrotestosterone preferentially binds to androgen receptors and becomes the more active form involved in hair growth and sebum production. Estradiol may be important in maintaining libido and bone mass, but may contribute to truncal obesity and feminine characteristics.


Testosterone deficiency is common, occurring in 1 in 200 men. The prevalence increases with age as testosterone levels decrease and sex hormone–binding globulin levels increase (causing a further decrease in free or bioavailable testosterone). More than 50% of men older than 55 years of age may have low testosterone, increasingly referred to as andropause. Treatment should be considered in all men with testosterone deficiency as long as contraindications do not exist.


Abnormally low testosterone levels are associated not only with sexual dysfunction, but with other comorbid conditions such as lipid disorders, cardiovascular disease, insulin insensitivity, osteoporosis, and cognitive and mood changes. Testosterone deficiency may be a cause of sarcopenia, a condition of aging senescence characterized by muscular weakness and atrophy.


In general, there are two basic types of testosterone deficiency:


1 Primary, or hypergonadotropic, hypogonadism results from primary testicular failure. In this situation, testosterone levels will be low and levels of pituitary gonadotropins (LH or FSH) will likely be high-normal or elevated.

2 Secondary, or hypogonadotropic, hypogonadism is the result of inadequate secretion of pituitary gonadotropins. In addition to a low testosterone level, LH or FSH levels will be low or low-normal.

Satisfactory replacement of testosterone is possible regardless of the type of deficiency.


Hypogonadism is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Age-related decreases in free testosterone were once accepted as “normal.” Currently, they are not considered normal. No agreement exists on the exact normal level of testosterone as men age or the serum testosterone level at which a man loses his sexual function.


The definition of relative hypogonadism is also uncertain. Many men have perfectly normal sexual function even if their testosterone levels decline into the age-adjusted lower normal range. Patients with low-normal to subnormal testosterone levels may warrant a clinical trial of testosterone. The threshold of response to and dosage of testosterone vary with age. If LH is increased and the testosterone level is low, the patient will have decompensated primary testicular failure. Testosterone replacement therapy can be essential to maintain physiologically normal levels. Testosterone replacement improves sexual function and mood, increases lean muscle mass and strength, and decreases fat mass in hypogonadal men.


An effect of testosterone on endothelial function in men is supported by a recent study that reported on the effects of intravascular administration of physiologic doses of testosterone on coronary blood flow in men with coronary artery disease. The results showed an increase in coronary vasodilation and blood flow in the testosterone test subjects.



Health Implications of Testosterone Deficiency


Testosterone deficiency can result in the following:


• Anemia

• Decreases in or loss of libido and erectile function

• Absence or regression of secondary sexual characteristics

• Oligospermia or azoospermia

• Decrease in energy, increased fatigue

• Depressed mood

• Increase in fat mass

• Progressive decrease in lean body mass and in muscle strength

• Decrease in bone density and increased risk of osteopenia/osteoporosis

Men with testicular failure may suffer from sexual dysfunction, as well as osteoporosis, muscle weakness, depression, and lassitude, which is the clinical spectrum of hypogonadism. The sexual dysfunction, especially decreased libido and decreased erectile capacity, often reverses with testosterone replacement therapy. Ideally, testosterone therapy should provide physiologic-range testosterone levels (400 to 800 ng/dL). The variability of response in some patients may be related to comorbid medical illnesses, vascular dysfunction causing erectile dysfunction at the penile level, or psychological factors (Box 124-1).



Box 124-1 Testosterone Deficiency Screening Questions


The “low-testosterone syndrome” often seen in healthy older men is thought to play a role in a number of clinical problems seen in the growing elderly male population. A checklist has been developed to help raise awareness of the presence of testosterone deficiency in the older man. Physicians may find the following questions helpful in screening their older patients:


1 Do you have a decrease in libido (sex drive)?

2 Do you have a lack of energy?

3 Do you have a decrease in strength or endurance?

4 Have you lost height?

5 Have you noticed a decreased “enjoyment of life”?

6 Are you sad or grumpy?

7 Are your erections less strong?

8 Have you noted a recent deterioration in your ability to play sports?

9 Are you falling asleep after dinner?

10 Has there been a recent deterioration in your work performance?


Men at Increased Risk for Testosterone Deficiency



• Decreased secondary sexual characteristics

• Erectile dysfunction or reduced libido

• An unexplained decrease in energy, or muscle weakness

• Unexplained osteopenia or osteoporosis

• Testicular atrophy

• Human immunodeficiency virus infection/acquired immunodeficiency syndrome with weight loss

• Long-term systemic glucocorticoids

• Chronic alcoholism or substance abuse

• Chronic systemic diseases (e.g., chronic renal failure, chronic inflammatory diseases)

• Recent-onset gynecomastia

• Morbid obesity

• Family history of endocrine failure

• Hypothyroidism


Diagnosis of Testosterone Deficiency


In symptomatic men, these suggested guidelines may be followed:


• Measure total testosterone (total T) by blood measurement taken between 7 and 10 AM.

• A total T above 400 ng/mL is considered normal.

• If total T is between 300 and 400 ng/mL, use the free or bioavailable testosterone level and clinical judgment to guide therapy.

• If total T is less than 300 ng/dL
• Rule out treatable endocrine causes and transient hypogonadism due to reversible illness, drugs, or nutritional deficiency.

• Repeat the test and measure free or bioavailable testosterone, LH, and FSH levels.

• If repeat total T or free T is confirmed as low, consider initiating testosterone replacement therapy.

• LH, FSH, or both, are measured to distinguish between primary (testicular) and secondary (pituitary hypothalamic) hypogonadism.

• If FSH and LH are low or normal, this is secondary hypogonadism, and in the presence of very low total T (<150 ng/dL), a prolactin level and other pituitary hormones should be obtained. If the prolactin level is elevated or other signs of a tumor mass exist, obtain magnetic resonance imaging of the sellar and pituitary region to rule out a pituitary tumor. Referral to an endocrinologist is indicated for further evaluation.

• With a low total T and a high FSH and LH, Klinefelter’s syndrome must be considered, which is a common identifiable cause of primary testicular failure and may be diagnosed by obtaining a karyotype.

• A dual-energy x-ray absorptiometry (DEXA) scan may considered to evaluate bone mineral density in men with severe androgen deficiency and fracture risk.


Contraindications



• Known or suspected prostate cancer or breast cancer

• Palpable prostate nodule or prostate-specific antigen (PSA) greater than 3 ng/mL without further urologic evaluation

• Severe benign prostatic hypertrophy (BPH) related bladder outlet obstruction or other urinary tract symptoms

• Erythrocytosis (hematocrit >50%)

• Hyperviscosity of blood (hyperviscosity syndrome)

• Treatment for improved athletic performance, body building, or short stature

• Untreated sleep apnea

• Untreated or severe congestive heart failure


Patients in Whom Treatment Requires Careful Monitoring



• Prostate problems and uncorrected obstructive symptoms caused by BPH

• Edema, fluid retention

• Gynecomastia

• Polycythemia or exacerbated erythropoiesis

• Hypogonadal adolescent boys because treatment may increase physical aggression

• Anyone whose epiphyses have not yet closed, because premature closure and permanent short stature can result from treatment

NOTE: It is important to closely monitor those patients with a family history (i.e., presence in a first-degree relative) of prostate cancer, although the relationship between the cancer and testosterone replacement therapy is controversial. A double-blind, randomized, placebo-controlled trial of 237 men 60 to 80 years of age, conducted in the Netherlands from 2004 to 2005 and published in the Journal of the American Medical Association in 2008 (Emmelot-Vonk and colleagues), showed an increase in lean body mass, a decrease in fat mass, increased insulin sensitivity, and no short-term negative effects on the prostate or on cognition. In a review of the literature by Rhoden and Morgentaler in the New England Journal of Medicine in 2004, prospective studies demonstrated a low frequency of prostate cancer in association with testosterone replacement therapy. The conclusion was that there is no compelling evidence at present to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism with exogenous androgens increases this risk. It should be recognized that prostate cancer becomes more prevalent exactly at the time of a man’s life when testosterone levels decline.

Related posts:

  1. Electrical Cardioversion
  2. Umbilical Vessel Catheterization
  3. Knee Braces
  4. Compartment Syndrome Evaluation

Stay updated, free articles. Join our Telegram channel
Tags:
May 14, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Implantable Hormone Pellets for Testosterone Deficiency in Adult Men

Full access? Get Clinical Tree
Get Clinical Tree app for offline access