What is Low T?
Hypogonadism in men is primarily a state involving lower than expected levels of testosterone. Traditionally this condition has been treated almost exclusively with testosterone supplementation.
Just like cholesterol or blood pressure, there is a range of testosterone levels that are considered normal. When hormones, such as testosterone, fall outside of normal levels, there can be consequences that affect the body at cellular, organ, or systemic level.
Blood tests are used to measure testosterone levels. Testosterone sampling is difficult since the levels normally tend to vary throughout the day.
The normal value for total testosterone in males is 270-1070 ng/dl. As people age, the amount of testosterone the body produces gradually falls in both men and women.
What Causes Low T?
The decrease in normal testosterone production is called Hypogonadism.
Low testosterone levels are caused by a number of factors:
- Primary Hypogonadism - The testes do not function normally and do not produce enough testosterone
- Secondary Hypogonadism - Problem with the pituitary gland failing to stimulate the production of testosterone
- Tertiary Hypogonadism - Problem with the hypothalamus gland failing to stimulate the production of testosterone
Causes of primary hypogonadism include the following:
- Undescended testicles: If the testes fail to move from inside the abdomen into the scrotum in the first year or two of life, they may become damaged and unable to produce enough testosterone
- Injury to the scrotum: If the testes are injured, they may not be able to produce adequate testosterone
- Chemotherapy and radiation therapy: Cancer treatment can damage the cells responsible for testosterone production. Cell damage may be temporary or permanent.
- Aging: Testosterone levels decrease with aging. Research suggests that lower testosterone levels can result in bone and muscle loss, and erectile dysfunction.
- 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. 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.
- Decreased blood flow to these glands from other conditions including significant bleeding and shock.
- 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 athletes and body builders, can cause hypogonadism and low testosterone levels.
- Obesity can cause low testosterone: Obesity enhances the conversion of testosterone to estrogen.
- Excess estrogen - Declining testosterone can alter the androgen:estrogen relationship. Changes in this relationship can result in declining prostate health.
What are the Symptoms of Low T?
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.
If low testosterone occurs before or during puberty, there may be a lack of sexual maturation. Signs 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, erectile dysfunction, depression, lethargy, loss of hair, decreased muscle mass, and osteoporosis or decreased bone density.
How is Low T Diagnosed?
Many symptoms that lead to the diagnosis of low testosterone are nonspecific. Dr. Cornell will obtain a history of symptoms and perform a physical exam. Blood tests assess testosterone levels in the body.
The diagnosis depends on the age of the patient. Diagnosis in children occurs when abnormalities or delays in physical development are observed
If a diagnosis of low testosterone or hypogonadism is considered, blood tests to measure testosterone levels are ordered. Testosterone levels vary throughout the day, consequently early morning testosterone levels are most accurate.
Typically the following levels are measured:
- Dehydroepiandrosterone (DHEA)
- Follicle stimulating hormone (FSH)
- Luteinizing hormone (LH)
Further tests may be considered to determine if the low testosterone is due to primary or secondary hypogonadism.
What is the Treatment for Low T?
The primary consideration for treating low testosterone is to identify and treat the underlying cause.
Treatment of Low-T focuses on:
- Lifestyle Changes
- Reducing Estrogen Levels
- Increasing Testicular Output of Testosterone
- Testosterone Supplementation
Dr. Cornell recommends an active exercise program that involves both aerobic and weight-resistant activities, along with a healthy eating plan that promotes loss of excess weight and fat. Many men who follow these tenets of healthy eating, appropriate dieting, and adequate exercise will find that their hormone levels correlate positively with their lifestyles.
Reducing Estrogen Levels
Studies have shown that, instead of actual testosterone supplementation, testosterone levels can be increased by using aromatase inhibitors to decrease the synthesis of estrogen.
High estradiol levels can signal the shut down or slow the production of testosterone. Therefore, decreasing the action of estradiol with an aromatase inhibitor increases the production of testosterone.
Another reason to be aware of estrogen levels is the role that estrogen plays in the level of Sex Hormone Binding Globulin (SHBG). Estrogen elevation contributes to the elevation of SHBG, a protein that binds testosterone and decreases the level of free testosterone. This free form is the active form of testosterone; therefore agents that lower estrogen are proposed to increase the amount of active testosterone available.
For many men, the simplest way to reduce estrogen levels is to lose weight, practice good nutrition and engage in regular exercise. Because aromatase, the enzyme system that is responsible for converting testosterone to estradiol (as well as converting androstenedione to estrone) is more abundant in fatty rather than lean tissue, fat reduction through exercise can improve the relationship of androgen and estrogen levels.
A potent aromatase inhibitor that has been studied for use in men with high estrogen levels is anastrozole. Physicians have found that it can be very effective in oral doses ranging from 0.25 mg three times a week to 0.5 mg every other day.
Another commercially available drug used to block the actions of estrogen is tamoxifen, which is available as a 10 mg tablet and has been studied with good results in men. Suggested dosing ranges from 10 mg to 20 mg daily. As a means of gauging the effectiveness of these agents, one should obtain baseline levels of estradiol, and then compare them with levels 30 to 60 days after initiation of therapy.
Increasing Testicular Output of Testosterone
Increasing testicular output of testosterone may be the desired option in the case of secondary hypogonadism, a condition in which the testes may be fully intact but are not receiving proper or sufficient signals to produce testosterone.
An injection of hCG can often reactivate the testicular secretion of testosterone. Dosage requirements vary from patient to patient, with some responding to injections of 500 units three times weekly and others requiring up to 3000 units three times weekly.
For some men this may be a very effective way of restoring testosterone to physiologic levels while not suppressing the male's ability to produce sperm.
Clomiphene also works to increase testosterone production. At doses ranging from 25 mg every other day to as high as 100 mg daily, clomiphene acts as a selective estrogen receptor modulator (SERM), effectively blocking estradiol from binding to its receptor. With less estrogen binding, GnRH levels increase and lead to increases in LH and FSH secretion.
Clomiphene has been compared in at least one head-to-head study with testosterone supplementation and has been shown to be very effective in both restoring hormone levels and reducing signs and symptoms of hypogonadism. Clomiphene overcomes the previously mentioned problem of decreased sperm production seen with testosterone supplementation. For these reasons, clomiphene is one of the best options for men interested in maintaining their fertility.
While testosterone levels fall with aging, there is no evidence that this condition requires treatment; however studies indicate that Testosterone replacement therapy can boost libido, increase muscle mass, reduce body fat, and improve energy levels.
For many men, this will be the treatment of choice - it is easily understood and, when properly administered, can be very effective in boosting testosterone levels.
In men, low testosterone levels can be supplemented by using various methods. Testosterone replacement therapy can be prescribed:
- as an intramuscular injection
- as a patch
- as a gel
- as a cream
- as an underarm solution placed on the skin
- as subcutaneous pellets
Each treatment has subtle differences such as odor, convenience of use or tendency to irritate the skin.
The decision as to which form of testosterone to use depends largely upon individual preference, which will be discussed with you by Dr. Cornell.
Intramuscular Injection of Testosterone
Administering testosterone by intramuscular (IM) injection is the most common form of dosing for most men. However, a serious and confusing drawback is the erratic release of testosterone; there is no way to provide a steady-state release over the 3 to 4 week intervals at which the injections were usually recommended.
Many times the physician would measure levels after a three week interval and find them, surprisingly low. Not understanding that effective dosing is a matter of finding the proper interval, physicians would increase the dose (e.g., 200 mg up to 300 mg or even 400 mg). This would not lengthen the duration of action, but would rather sharpen the peaks and valleys associated with testosterone injections.
As a result, the patient would experience supraphysiologic levels in the first week, then have declining levels after that. Supraphysiologic levels can cause increased conversion to estradiol and the previously mentioned polycythemia.
Gynecomastia has also been associated with this kind of therapy. It has been proposed multiple times in recent years that a better method of dosing intramuscularly is to give a lower dose at weekly intervals; a suggestion of 75 mg to 100 mg is quite common. In this way, there is a more continuous release of the hormone without the peaks and valleys of the traditional dosing pattern.
Subcutaneous Injection of Testosterone
Subcutaneous (SQ) dosing is being looked at as a potentially more favorably route of dosing, allowing the patient more freedom to dose himself than was possible with the intramuscular injections.
In a pilot study, testosterone enanthate in oil was given by SQ injection on a weekly basis. All of the patients were within the normal range for testosterone following injection. Patients also reported the subcutaneous route was easy to use and well tolerated. In general, subcutaneous injections are preferred over intramuscular injections because they are less painful, more convenient, allow for smoother release of the drug, are patient-controlled, and are associated with better compliance.
Topical administration appears to be the most effective way of dosing testosterone. While creams, gels, solutions, and lotions have been used in the past, the greatest benefit seems to come from topical creams.
At concentrations of 10% to 20%, testosterone creams leave no residue. However, higher concentrations, such as 30% and above, may leave a residue, as the hormone is incompletely dissolved at such concentrations. It has been suggested that creams, unlike gels, depot in the skin dermis allowing a steadier release as opposed to gel's immediate absorption into a patient's system.
Studies performed over the past 10 to 12 years have shown that a topical dosing range of 50 mg - 200 mg daily can be used. An approximate absorption of 5% of testosterone from cream vehicles has been established, suggesting that an application of 100 mg in a topical cream will result in 5 mg net absorption.
For comparison with a patch, 100 mg of a cream equates to about 5 mg from a patch. Some practitioners prefer a topical solution to a cream, using a propylene glycol/alcohol mixture as the base and a suggested concentration of 6% testosterone. At this time there is no known benefit to using a smaller volume of a higher concentration, as high concentrations have the downside of leaving a residue.
A risk associated with topical dosing is the transfer to a child or female, and every precaution should be taken to mitigate that risk. Since testosterone cannot easily penetrate the dermis without the aid of a transdermal vehicle, it is safe to wash off the testosterone cream after the transdermal base has dried 15-20 minutes from the time of application without the concern that the testosterone will be wasted.
Sublingual Or Buccal Administration
Sublingual testosterone is best given three to four times a day to maintain a steady-state release. While absorption is efficient (higher than topical) and rapid (peak levels can be obtained after approximately 30 minutes), metabolism is also rapid due to the short half-life of testosterone. Levels return to baseline after four to six hours.
Effective sublingual or buccal doses can range from 10 mg to 25 mg at six to eight hour intervals. While this is a relatively inexpensive and non-invasive method of dosing, the patient must understand that daily compliance of multiple dosing is necessary to obtain maximum benefit of the hormone.
The use of a high dose once daily (e.g. 100 mg to 200 mg) will simply drive the levels very high into the supraphysiologic levels for several hours, making it an unfavorable route of administration.
Sublingual dosing may be useful for a patients already supplementing testosterone but require an extra testosterone boost to enhance sexual function.
Implantable Pellets (Testopel)
Implantable testosterone pellets are preferred by some physicians because it gives them the ability to control patient dosing with an in-office surgical procedure.
The advantage to the patient is that compliance is not an issue; the patient has the procedure done at three to five month intervals and does not have to be concerned with daily or weekly dosing. A disadvantage is that there is no way to adjust the dose during the life of the pellet in the body.
TESTOPEL® (testosterone pellets) is approved for testosterone replacement therapy in adult males for conditions associated with low or absent testosterone in the body.
Determination of success is made by both serum level measures and satisfaction with subjective symptom improvement. While testosterone replacement to normal physiologic levels as determined by regular monitoring does not cause prostate cancer, testosterone is known to stimulate the growth of existing prostate cancer. For this reason, serum levels of prostate specific antigen (PSA) are measured every 6 months with routine testosterone levels and measures of complete blood count (CBC) to ensure hormone replacement isn’t leading to increased red blood cell or platelet production that can increase stroke risk.
Prior to beginning testosterone supplementation, patients should have some labs drawn in addition to those labs mentioned previously in this review. Hemoglobin and hematocrit, two very commonly measured labs, along with prostate specific antigen (PSA), are important levels to acquire at baseline before beginning testosterone therapy. The importance of hemoglobin and hematocrit measurements is due to the fact that testosterone can raise these levels. Testosterone supplementation can decrease sperm production.
Testosterone replacement is an effective treatment option to replace the body’s natural decline in hormone production. This can lead to more youthful energy levels, physical appearance, sex drive and potency. Your candidacy for testosterone replacement will be discussed with you at your office visit.
Safety of Testosterone Replacement
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