Testosterone is a steroid hormone which is made in the testes in males and in the ovaries in women (a minimal amount is also made in the adrenal glands). Testosterone has two major functions in the human body.
1.Testosterone is needed to form and maintain the male sex organs and promote secondary male sex characteristics (in both men and women) such as voice deepening and hair growth patterns. This function is related to its androgenic properties.
2.Testosterone is the facilitation of muscle growth as well as bone development and maintenance. This is a result of its anabolic properties
Testosterone production is regulated by hormones released from the brain. The hypothalamus and pituitary gland located in the brain produce hormonal signals that ultimately result in the production of testosterone. The hypothalamus is located just above the brain stem, and among its many functions, it produces gonadotrophin releasing hormone (GRH). GRH then travels a short distance to the pituitary gland, which is located in the base of the brain, and stimulates this gland to release FSH (follicle stimulating hormone) and LH (luteinizing hormone). These hormones travel through the bloodstream to activate the sex organs in both men and women. Subsequently, these hormones have a role in regulating testosterone levels in the bloodstream.
The majority of testosterone circulates in the blood bound to a carrier protein (many hormones that are produced in one area and affect another area have a carrier protein that helps their travel through the bloodstream). In this case the carrier protein is called "sex hormone binding globulin," or SHBG. When testosterone is being carried by SHBG, it is considered "bound". Bound testosterone does not play an active role in the body; only the unbound or "free" testosterone is able to enter the different cells of the body and exert its androgenic and anabolic effects. Thus, anything that affects the function or the amount of SHBG can also affect the total circulating amount of active testosterone.
What is low testosterone?
The human body functions within a relatively narrow range of normal. When chemicals such as hormones fall outside those normal levels, there can be consequences that affect the body at a cellular, organ, or systemic (body-wide) level.
Blood tests used to measure testosterone are usually performed in the morning. Testosterone sampling is difficult since the levels normally tend to bounce around a fair bit during the course of the day. The normal value for total testosterone in males is 270-1070 ng/dl. However, this depends to some extent on the individual laboratory being used, and the range can vary as a result. In women, there is debate about the accuracy of testosterone measurements, because the circulating values are so much lower than in males and are harder to accurately measure.
With advancing age, in both men and women, the amount of testosterone the body produces gradually falls. Free testosterone levels can be measured and normal levels depend upon an individual's age. Interestingly, menopause itself does not seem to play a role in a reduction of testosterone levels in women beyond that of advancing age.
What are the causes of low testosterone?
Low testosterone levels may be caused by a number of factors. For example – there may be a problem at the level of the hypothalamus or pituitary to produce appropriate amounts of LH and FSH to stimulate testosterone production. Another possibility is that the organs that make testosterone do not function normally or are not able to respond to stimulation by the brain. Also, as mentioned, changes in SHBG can account for the amount of testosterone that is available to exert its effects.
•When the problem is in the organs that produce testosterone (the ovaries or testes, for the most part), it is called a "primary" problem". In medical terminology, the decrease in normal testosterone production is called "hypogonadism."
•When the problem is related to the pituitary and its ability to regulate testosterone, it is called "secondary hypogonadism," and
•If the problem is thought to be at the level of the hypothalamus, it is called "tertiary hypogonadism."
Some common causes of primary hypogonadism or failure of the gonads (the medical term for the sex organs, or testes and ovaries) may include the following:
•Undescended testicles: If the testes fail to migrate from inside the abdomen into the scrotum during fetal development or in the first year or two of life, the testes may become damaged and unable to produce adequate amounts of testosterone.
•Injury to the scrotum: If the testes are injured, they may not be able to produce adequate testosterone. Damage to one testicle does not often to lead to low levels if the other testis remains normal.
•Cancer therapy: Chemotherapy and radiation therapy can damage the interstitial cells in the testes responsible for testosterone production. This decrease in testosterone production may be temporary as the cells recover, or it may be permanent.
•Aging: Testosterone levels decrease with aging. Usually, enough testosterone is manufactured to allow for adequate bodily functions.
•Mumps orchitis: The mumps virus can cause inflammation of the testes in males, and if the illness occurs in puberty or adulthood, the damage to the testes may lead to low testosterone production. Immunization against the mumps has significantly decreased the incidence of this illness.
•Chromosomal abnormalities: A normal male has one X and one Y chromosome (a normal female has two X chromosomes). In Klinefelter's syndrome, in males, an extra X chromosome is present and among other anatomic issues, there is abnormal development of the testes and decreased ability to manufacture testosterone.
•Ovary conditions in women: Premature ovarian failure and surgical removal of both ovaries (bilateral oophorectomy) are conditions associated with lower circulating testosterone levels.
Secondary and tertiary hypogonadism may be due to damage of the hypothalamus or pituitary and/or the failure of the production of hormones (GRH, TSH and/or LH) to stimulate the gonads.
Causes of secondary and tertiary hypogonadism include:
•Damage to the pituitary gland may occur because of tumors of the gland itself or because of damage caused by the side effects of treatment of nearby brain tumors.
•Hypothalamus malformations can prevent normal function. Kallman's syndrome is one example.
•Compromised blood flow to these glands from other conditions such as excessive systemic blood loss.
•Inflammation caused by tuberculosis and sarcoidosis may affect the pituitary gland.
•HIV and AIDS may also cause inflammation of both the hypothalamus and pituitary.
•Illegal use of anabolic steroids, for example in body building, can cause hypogonadism and low testosterone levels.
It should be noted that obesity also can be a cause of low testosterone. While it can be associated with other causes, obesity specifically enhances the conversion of testosterone to estrogen. This is a naturally occurring process in both men and women, and this conversion occurs predominantly in fat cells. In the case of obesity, the large amount of fat cells enhances this process, and testosterone levels may fall due to excessive conversion to estrogen.
There are rarer causes of hypogonadism that can occur, dealing with cellular mechanisms and receptor binding. These are beyond the scope of this discussion.
What are the symptoms of low testosterone?
Low testosterone symptoms in males
In males, symptoms of decreased testosterone depend upon when the low levels occur.
If there is inadequate testosterone in the fetus, genital development may be affected. There may be poor development of the penis and scrotum, with an appearance of female genitalia or ambiguous genitalia that are neither male nor female. Remember that the definition of male is based upon the type of chromosomes present and not necessarily upon the outward appearance.
If low testosterone occurs before or during puberty, there may be a lack of sexual maturation. Signs may include failure to develop muscle mass, failure of the voice to deepen, poor growth of body hair, enlarged breasts (gynecomastia), and failure of the penis and testes to enlarge.
In adulthood, low testosterone may lead to decreased sexual function and desire, infertility, and erectile dysfunction. Loss of hair, decreased muscle mass, and osteoporosis or decreased bone density may occur.
Low testosterone symptoms in females
While low testosterone is usually thought of as a male disease, low levels may occur in women and cause significant issues. Symptoms may include hot flashes, irritability, loss of sexual desire (decreased libido), and sleep disturbances. Loss of muscle mass, decreased bone density (osteoporosis), and loss of body hair may also be seen.
When should I contact the doctor for low testosterone?
For infants, routine screening examination is useful in checking for normal placement of the testes within the scrotum.
As puberty approaches in males, it is important that parents and health care practitioners look for the development of secondary sex characteristics such as lowering of voice, development of characteristic hair growth, and increased muscle mass.
In adults, most males will seek help with erectile dysfunction and decreased libido.
In women, a loss of sexual desire and libido are often the presenting complaints
How is low testosterone diagnosed?
Many of the symptoms that lead to the diagnosis of low testosterone are nonspecific, and the health care practitioner may want to take a history of symptoms and perform a physical examination prior to ordering blood tests to assess for low testosterone levels in the body.
The diagnosis also depends upon at what age the concern occurs. Many times the diagnosis in the pediatric age group occurs because of the ability of the parent and health care practitioner to observe abnormalities in physical development that may occur.
If the diagnosis of low testosterone or hypogonadism is considered, blood tests to measure testosterone levels may be ordered. The level of testosterone varies depending upon the time of day, and most often, early morning testosterone levels are measured.
Based upon the clinical situation, further tests may be considered to determine whether the low testosterone is due to primary or secondary hypogonadism.
What is the treatment for low testosterone?
The initial consideration for treating low testosterone is to find the underlying cause and address that issue.
Treatment of low testosterone in men
In men, low testosterone levels in the body can be supplemented by hormone replacement with testosterone. Testosterone replacement therapy can be prescribed as an intramuscular injection usually given on a biweekly basis, as a patch or gel placed on the skin, or as putty that is applied to the gums of the mouth. Each of the treatments has its risks and benefits. The decision as to which form of testosterone to use depends upon the clinical situation. Discussions between the patient and health care practitioner often helps decide which medication to use.
Treatment of low testosterone in women
In women, in the United States there are currently no preparations that are FDA approved for testosterone replacement. Esterified estrogens and methyltestosterone (Estratest), manufactured by Solvay Pharmaceuticals, a combination of estrogen and methyltestosterone that was formerly available, was discontinued by the manufacturer in the spring of 2009.
Some doctors will advise women to cut the patches for men into smaller sizes, or to use the gel in smaller doses; however, the accuracy of these methods is questionable, as is the safety.
What are the complications of low testosterone?
Complications of low testosterone levels depend upon when in life the situation occurs. Low testosterone levels in infants can lead to poor development of sexual organs. Near puberty, it can lead to failure of development of secondary sexual characteristics. In adulthood, osteoporosis, loss of muscle mass, and decreased sexual function including erectile dysfunction and decreased libido may occur.
Can low testosterone be prevented?
Low testosterone is due to the failure of at least one part of the hypothalamus-pituitary- gonadal axis. Many illnesses and diseases that affect these organs are inherited and cannot be prevented. Other causes are unavoidable consequences such as cancer therapy and infection. However, some causes are preventable including obesity and drug abuse.
What is the outlook (prognosis) for a patient with low testosterone?
The ability to treat the condition depends upon recognizing symptoms and seeking medical care. Once the cause for the low testosterone levels is diagnosed, testosterone replacement therapy may be helpful in reversing the symptoms related to those low levels.
Maintaining adequate testosterone levels within the body may minimize future risk of muscle and bone loss.
Low Testosterone At A Glance
•Testosterone is produced by the testes in males and ovaries in females. The testes are under the hormonal control of the hypothalamus and pituitary in the brain and make testosterone in response to stimulation by FSH and LH.
•Primary hypogonadism occurs because of the inability of the testes to produce testosterone.
•Causes of secondary and tertiary hypogonadism are due to a variety of illnesses or diseases that affect the hypothalamus-pituitary-gonadal axis.
•Symptoms of low testosterone depend upon when in the life cycle it occurs.
•Osteoporosis is a significant complication of low testosterone.
•In the United States testosterone replacement therapy is available as an FDA-approved treatment in men only. It may be administered by injection, patch or gel, or gum and cheek putty.