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Lit Painting Group

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Landon Diaz
Landon Diaz

The Testosterone Experience


Testosterone's role in bad behavior is largely a myth. What's more, testosterone plays other important roles in health and disease that may surprise you. For example, did you know that testosterone is a key player in prostate cancer? Or, that women need testosterone, too? There's more to testosterone than guys behaving badly.




The Testosterone Experience



Adolescent boys with too little testosterone may not experience normal masculinization. For example, the genitals may not enlarge, facial and body hair may be scant and the voice may not deepen normally.


Signals sent from the brain to the pituitary gland at the base of the brain control the production of testosterone in men. The pituitary gland then relays signals to the testes to produce testosterone. A "feedback loop" closely regulates the amount of hormone in the blood. When testosterone levels rise too high, the brain sends signals to the pituitary to reduce production.


If you thought testosterone was only important in men, you'd be mistaken. Testosterone is produced in the ovaries and adrenal gland. It's one of several androgens (male sex hormones) in females. These hormones are thought to have important effects on:


The proper balance between testosterone (along with other androgens) and estrogen is important for the ovaries to work normally. While the specifics are uncertain, it's possible that androgens also play an important role in normal brain function (including mood, sex drive and cognitive function).


Testosterone is synthesized in the body from cholesterol. But having high cholesterol doesn't mean your testosterone will be high. Testosterone levels are too carefully controlled by the pituitary gland in the brain for that to occur.


Having too much naturally-occurring testosterone is not a common problem among men. That may surprise you given what people might consider obvious evidence of testosterone excess: road rage, fighting among fathers at Little League games and sexual promiscuity.


Part of this may be due to the difficulty defining "normal" testosterone levels and "normal" behavior. Blood levels of testosterone vary dramatically over time and even during the course of a day. In addition, what may seem like a symptom of testosterone excess (see below) may actually be unrelated to this hormone.


In fact, most of what we know about abnormally high testosterone levels in men comes from athletes who use anabolic steroids, testosterone or related hormones to increase muscle mass and athletic performance.


Some men who have a testosterone deficiency have symptoms or conditions related to their low testosterone that will improve when they take testosterone replacement. For example, a man with osteoporosis and low testosterone can increase bone strength and reduce his fracture risk with testosterone replacement.


As surprising as it may be, women can also be bothered by symptoms of testosterone deficiency. For example, disease in the pituitary gland may lead to reduced testosterone production from the adrenal glands disease. They may experience low libido, reduced bone strength, poor concentration or depression.


There are times when low testosterone is not such a bad thing. The most common example is probably prostate cancer. Testosterone may stimulate the prostate gland and prostate cancer to grow. That's why medications that lower testosterone levels (for example, leuprolide) and castration are common treatments for men with prostate cancer. Men taking testosterone replacement must be carefully monitored for prostate cancer. Although testosterone may make prostate cancer grow, it is not clear that testosterone treatment actually causes cancer.


Genetic diseases, such as Klinefelter syndrome (in which a man has an extra x-chromosome) and hemochromatosis (in which an abnormal gene causes excessive iron to accumulate throughout the body, including the pituitary gland) can also affect testosterone.


Women may have a testosterone deficiency due to diseases of the pituitary, hypothalamus or adrenal glands, in addition to removal of the ovaries. Estrogen therapy increases sex hormone binding globulin and, like aging men, this reduces the amount of free, active testosterone in the body.


Currently, testosterone therapy is approved primarily for the treatment of delayed male puberty, low production of testosterone (whether due to failure of the testes, pituitary or hypothalamus function) and certain inoperable female breast cancers.


However, many men with normal testosterone levels have similar symptoms so a direct connection between testosterone levels and symptoms is not always clear. As a result, there is some controversy about which men should be treated with supplemental testosterone.


Testosterone therapy may make sense for women who have low testosterone levels and symptoms that might be due to testosterone deficiency. (It's not clear if low levels without symptoms are meaningful; treatment risks may outweigh benefits.) However, the wisdom and effectiveness of testosterone treatment to improve sexual function or cognitive function among postmenopausal women is unclear.


People with normal testosterone levels are sometimes treated with testosterone at the recommendation of their doctors or they obtain the medication on their own. Some have recommended it as a "remedy" for aging. For example, a study from Harvard Medical School in 2003 found that even among men who started out with normal testosterone results noted loss of fat, increased muscle mass, better mood, and less anxiety when receiving testosterone therapy. Similar observations have been noted among women. However, the risks and side effects of taking testosterone when the body is already making enough still discourages widespread use.


Testosterone is so much more than its reputation would suggest. Men and women need the proper amount of testosterone to develop and function normally. However, the optimal amount of testosterone is far from clear.


Checking testosterone levels is as easy as having a blood test. The difficult part is interpreting the result. Levels vary over the course of the day. A single low level may be meaningless in the absence of symptoms, especially if it was normal at another time. We need more research to know when to measure testosterone, how best to respond to the results and when it's worthwhile to accept the risks of treatment.


Testosterone is responsible for the development of primary sexual development, which includes testicular descent, spermatogenesis, enlargement of the penis and testes, and increasing libido. The testes usually begin the descent into the scrotum around 7 months of gestation, when the testes begin secreting reasonable quantities of testosterone. If a male child is born with undescended but normal testes that do not descend by 4 to 6 months of age, administration of testosterone can help the testes descend through the inguinal canals. [2]


Testosterone is also involved in regulating secondary male characteristics, which are those responsible for masculinity. These secondary sex characteristics include male hair patterns, vocal changes, and voice deepening, anabolic effects, which include growth spurts in puberty (testosterone increases tissue growth at the epiphyseal plate early on and eventual closure of plate later in puberty) and skeletal muscle growth (testosterone stimulates protein synthesis). Testosterone also stimulates erythropoiesis, which results in a higher hematocrit in males versus females. Testosterone levels tend to drop with increasing age; because of this, men tend to experience a decrease in testicular size, a drop in libido, lower bone density, muscle mass decline, increased fat production, and decreased erythropoiesis, which leads to possible anemia.


In puberty, the hypothalamic-pituitary-gonadal axis plays a major role in regulating testosterone levels and gonadal function. The hypothalamus secretes GnRH, which travels down the hypothalamohypophyseal portal system to the anterior pituitary, which secretes luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are two gonadotropic hormones that travel through the blood and act on receptors in the gonads. LH, in particular, acts on the Leydig cells to increase testosterone production. Testosterone limits its own secretion via negative feedback. High levels of testosterone in the blood feedback to the hypothalamus to suppress the secretion of GnRH and also feedback to the anterior pituitary, making it less responsive to GnRH stimuli. [3]


Throughout the reproductive life of males, the hypothalamus releases GnRH in pulses every 1 to 3 hours. Despite this pulsatile release, however, average plasma levels of FSH and LH remain fairly constant from the start of puberty, where levels spike, to the third decade of life, where levels peak and slowly begin to decline. Prior to puberty, testosterone levels are low, reflecting the low secretion of GnRH and gonadotropins. Changes in neuronal input to the hypothalamus and brain activity during puberty cause a dramatic rise in GnRH secretion.


Leydig cells in the testes function to turn cholesterol into testosterone. LH regulates the initial step in this process. Two important intermediates in this process are dehydroepiandrosterone (DHEA) and androstenedione. Androstenedione is converted to testosterone by the enzyme 17-beta-hydroxysteroid dehydrogenase. The majority of testosterone is bound to plasma proteins such as sex-hormone-binding-globulin and albumin. This majority supply of protein-bound testosterone acts as a surplus of testosterone hormone for the body. The small amounts of free testosterone in the blood act at the level of the tissues, primarily the seminal vesicles, bone, muscle, and prostate gland. At the cellular level, testosterone gets converted to dihydrotestosterone by the enzyme 5-alpha-reductase. Testosterone and dihydrotestosterone can bind to cell receptors and regulate protein expression. Both men and women also produce weak acting androgens in the zona reticularis of the adrenal glands. These weak-acting androgens are known as dehydroepiandrosterone and androstenedione. They bind to testosterone receptors with weaker affinity but can also be converted to testosterone in the peripheral tissues if produced at high amounts. [4]


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