TESTOSTERONE DEFINITION
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1 DEFINITION A hormone that is a hydroxyl steroid ketone (C19H28O2) produced especially by the testes or made synthetically and that is responsible for inducing and maintaining male secondary sex characteristics. Testosterone belongs to a class of male hormones called androgens, which are sometimes called steroids or anabolic steroids. In men, testosterone is produced mainly in the testes, with a small amount made in the adrenal glands. The brain's hypothalamus and pituitary gland control testosterone production. Within the CNS (Central Nervous System), the hypothalamus instructs the pituitary gland on how much testosterone to produce, and the pituitary gland passes the message on to the testes. These communications happen through chemicals and hormones in the bloodstream. The LH (Luteinizing hormone) binds to the Leydig cells in the testes to produce testosterone. The FSH (Follicle-stimulating hormone) helps in production of sperm (Sertoli cells).
2 Testosterone is involved in the development of male sex organs before birth, and the development of secondary sex characteristics at puberty, such as voice deepening, increased penis and testes size, and growth of facial and body hair. The hormone also plays a role in sex drive, sperm production, fat distribution, red cell production, and maintenance of muscle strength and mass. In women, the ovaries and adrenal glands produce testosterone. On average, males testosterone levels are 7-8 times higher than females. During puberty, testosterone is required for the development of male secondary sexual characteristics, stimulation of sexual behavior and function, and initiation of sperm production. In adult males, testosterone is involved in maintaining muscle mass and strength, fat distribution, bone mass, red blood cell production, male hair pattern, libido and potency, and spermatogenesis. Once physical maturity has been achieved, testosterone has a more homeostatic function. It sustains spermatogenesis (production of sperm), maintains muscle bulk, maintains secondary sex characteristics, and aids in erectile function. Endogenous (in the body) testosterone in the circulation can be free (unbound), weakly bound to albumin, or tightly bound to sex hormone binding globulin (SHBG). The free and albumin-bound testosterone is available for use by the body. The largest percentage, however, is bound to SHBG and is unavailable for use in the body. Any condition that increases
3 SHBG will decrease the amount of available testosterone. This includes conditions that elevate estrogens, elevated thyroid hormone, and aging. Testosterone in circulation can also be converted into other hormones. It can be converted peripherally to dihydrotestosterone (DHT) by 5-alpha reductase. DHT has a role in the growth of prostatic tissue and therefore can influence lower urinary tract symptoms. Testosterone is converted to form estradiol (E2) in fatty tissue. In obese men, the increased amount of fat leads to increased conversion activity, resulting in increased levels of estradiol. High circulating levels of estradiol down-regulates the hypothalamic-pituitary axis and decreases the amount of circulating testosterone.
4 As the male body ages, gonadal function slowly declines with a resulting drop in serum testosterone of approximately 1% per year after age 30, a phenomenon that occurs in both males and females.
5 MALE HYPOGONADISM Definition and Prevalence Male hypogonadism is a condition in which the body doesn't produce enough testosterone the hormone that plays a key role in masculine growth and development during puberty or has an impaired ability to produce sperm or both. Although the disorder is exceedingly common, its exact prevalence is uncertain. You may be born with male hypogonadism, or it can develop later in life from injury or infection. The effects and what you can do about them depend on the cause and at what point in your life male hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone replacement therapy. Symptoms Hypogonadism can begin during fetal development, before puberty or during adulthood. Signs and symptoms depend on when the condition develops. Fetal Development If the body doesn't produce enough testosterone during fetal development, the result may be impaired growth of the external sex organs. Depending on when hypogonadism develops and how much testosterone is present, a child who is genetically male may be born with: Female genitals Ambiguous genitals genitals that are neither clearly male nor clearly female
6 Underdeveloped male genitals Puberty Male hypogonadism may delay puberty or cause incomplete or lack of normal development. It can cause: Decreased development of muscle mass Lack of deepening of the voice Impaired growth of body hair Impaired growth of the penis and testicles Excessive growth of the arms and legs in relation to the trunk of the body Development of breast tissue (gynecomastia) Adulthood In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include: Erectile dysfunction Infertility Decrease in beard and body hair growth Decrease in muscle mass Development of breast tissue (gynecomastia) Loss of bone mass (osteoporosis)
7 Hypogonadism can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include: Fatigue Decreased sex drive Difficulty concentrating Hot flashes Causes of Hypogonadism Male hypogonadism means the testicles don't produce enough of the male sex hormone testosterone. There are two basic types of hypogonadism: Primary This type of hypogonadism, also known as primary testicular failure, originates from a problem in the testicles. Secondary This type of hypogonadism indicates a problem in the hypothalamus or the pituitary gland parts of the brain that signal the testicles to produce testosterone. The hypothalamus produces gonadotropinreleasing hormone, which signals the pituitary gland to make folliclestimulating hormone (FSH) and luteinizing hormone (LH). Luteinizing hormone then signals the testes to produce testosterone. Either type of hypogonadism may be caused by an inherited (congenital) trait or something that happens later in life (acquired), such as an injury or
8 an infection. At times, primary and secondary hypogonadism can occur together. Primary hypogonadism Common causes of primary hypogonadism include: Klinefelter syndrome: This condition results from a congenital abnormality of the sex chromosomes, X and Y. A male normally has one X and one Y chromosome. In Klinefelter syndrome, two or more X chromosomes are present in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the sex of a child and related development. The extra X chromosome that occurs in Klinefelter syndrome causes abnormal development of the testicles, which in turn results in underproduction of testosterone. Undescended testicles: Before birth, the testicles develop inside the abdomen and normally move down into their permanent place in the scrotum. Sometimes one or both of the testicles may not be descended at birth. This condition often corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and reduced production of testosterone. Mumps orchitis: If a mumps infection involving the testicles in addition to the salivary glands (mumps orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production.
9 Hemochromatosis: Too much iron in the blood can cause testicular failure or pituitary gland dysfunction affecting testosterone production. Injury to the testicles: Because they're situated outside the abdomen, the testicles are prone to injury. Damage to normally developed testicles can cause hypogonadism. Damage to one testicle may not impair total testosterone production. Cancer treatment: Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and sperm production. These effects are often temporary but can be permanent. Secondary hypogonadism In secondary hypogonadism, the testicles are normal but function improperly due to a problem with the pituitary or hypothalamus. Common causes of secondary hypogonadism include: Normal aging: Older men generally have lower testosterone levels than younger men do. As men age, there's a slow and continuous decrease in testosterone production. Kallmann syndrome: Abnormal development of the hypothalamus the area of the brain that controls the secretion of pituitary hormones can cause hypogonadism. This abnormality is also associated with
10 impaired development of the ability to smell (anosmia) and red-green color blindness. Pituitary disorders: An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Also, the treatment for a brain tumor, such as surgery or radiation therapy, may impair pituitary function and cause hypogonadism. Inflammatory disease: Certain inflammatory diseases, such as sarcoidosis, histiocytosis and tuberculosis, involve the hypothalamus and pituitary gland and can affect testosterone production, causing hypogonadism. HIV/AIDS: HIV/AIDS can cause low levels of testosterone by affecting the hypothalamus, the pituitary and the testes. Medications: The use of certain drugs, such as opiate pain medications and some hormones, can affect testosterone production. Obesity: Being significantly overweight at any age may be linked to hypogonadism. Obesity and low testosterone are tightly linked. Obese men are more likely to have low testosterone. Men with very low testosterone are also more likely to become obese.
11 Fat cells metabolize testosterone to estrogen, lowering testosterone levels. Also, obesity reduces levels of sex hormone binding globulin (SHBG), a protein that carries testosterone in the blood. Less SHBG means less testosterone. Losing weight through exercise can increase testosterone levels. Testosterone supplements in men with low testosterone can also reduce obesity slightly. Diabetes Mellitus (Type 2): A link between diabetes and low testosterone is well established. Men with diabetes are more likely to have low testosterone. And men with low testosterone are more likely to later develop diabetes. Testosterone helps the body's tissues take up more blood sugar in response to insulin. Men with low testosterone more often have insulin resistance: they need to produce more insulin to keep blood sugar normal. As many as half of men with diabetes have low testosterone, when randomly tested. Scientists aren't sure whether diabetes causes low testosterone, or the other way around. More research is needed, but short-term studies show testosterone replacement may improve blood sugar levels and obesity in men with low testosterone.
12 Concurrent Illness The reproductive system can temporarily shut down due to the physical stress of an illness or surgery, as well as during significant emotional stress. This is a result of diminished signals from the hypothalamus and usually resolves with successful treatment of the underlying condition. The rate at which testosterone declines, varies greatly among men. There is also a varying degree of opinions, regarding testosterone decline in regards to age and the rate it occurs, amongst Health Care Providers. Men s testosterone levels peak in their teens and twenties. From there, testosterone levels slowly decrease. After age 30, most men begin to experience a gradual decline in testosterone by approximately 1% a year. (Dr. David Samadi, Chairmen of Urology Department, Lenox Hill Hospital, NY City).
13 Progress Check 1. The brain s & control testosterone production. 2. What are some roles testosterone is involved with in the adult male? 3. Which type of testosterone is available for the body to use? (choose all the apply) a. SHBG b. Free Testosterone c. Albumin-bound d. All of the above 4. The largest percentage of the circulating hormone testosterone is, which is unavailable for use in the body. 5. What is the definition of hypogonadism? 6. What are some symptoms seen with male hypogonadism? 7. What are the two main causes of hypogonadism? & 8. Which cause of hypogonadism is a result of testicular failure? a. Primary b. Secondary 9. True or False. Testosterone declines with the aging male.
14 Progress Check Answers 1. Hypothalamus & Pituitary Gland 2. Maintaining muscle mass and strength, fat distribution, bone mass, red blood cell production, male hair pattern, libido and potency, spermatogenesis to name a few 3. B and C 4. SHBG (Sex hormone binding globulin) 5. Male hypogonadism is a condition in which the body does not produce enough testosterone 6. Erectile dysfunction, infertility, decreased body hair, decrease muscle mass, loss of bone mass, gynecomastia, fatigue, decreased sex drive, difficulty concentrating, hot flashes (to name a few) 7. Primary & secondary 8. A 9. True
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