Hypogonadism: Why is Hormone Therapy Recommended for Some Men?
A surprising number of older men suffer from low levels of testosterone. Approximately 30% of men aged 60-70 years and 70% of men aged 70-80 have low levels of testosterone in forms that the body can actually use (this is often referred to as bioavailable; unbound; free). Hypogonadism is the name of the clinical condition in which low levels of serum testosterone (that is, bioavailable testosterone less than 60 ng/dl) are found in association with specific signs and symptoms. These symptoms can include diminished sex drive and sense of vitality, erectile dysfunction, depression, anemia, reduced muscle mass and bone density, increased fat mass, frailty, and osteoporosis.
When is a Man Considered Hypogonadal?
It is important for men to understand what is medically considered to be “low testosterone”. A man may be considered hypogonadal at any age if total testosterone (bound and free) is less than 200 ng/dl. It is recommended that elderly men with symptoms of hypogonadism and a total testosterone level less than 300 ng/dl be started on hormone replacement.1
What is Andropause and What is it Associate With?
When hypogonadism occurs in an older man, the condition is often called andropause, or Androgen Deficiency of the Aging Male (ADAM), because testosterone is in a class of hormones known as androgens. Bioavailable testosterone levels are significantly lower for depressed men, perhaps because an associated decrease in sexual function results in depression, irritability, and mood swings. Testosterone therapy might improve depressed mood in older men who have low levels of bioavailable testosterone.2,3
The Link Between Osteoporosis and Low Testosterone
Osteoporosis a medical condition in which the bones become brittle and fragile from loss of tissue, typically as a result of hormonal changes, or deficiency of calcium or vitamin D. Osteoporosis-related fractures occur in 12% of all men over 50 years of age. Twenty-five percent of all hip fractures occur in men, and 33% of these patients die within one year of fracture. Gradual loss of testosterone is one of the major causes of osteoporosis in elderly men. Studies have reported beneficial effects of testosterone therapy on bone in older men, showing an increase in bone mineral density (BMD) and slowing of bone degeneration. Testosterone therapy in older men with low serum testosterone levels also increases lean body mass and decreases fat mass, improving physical performance and strength.4
The Benefits of Testosterone Replacement Therapy (TRT)
Testosterone replacement therapy (TRT) has relieved symptoms and improved the quality of life for many men. TRT is well tolerated, and long term TRT appears to be a safe and effective means of treating hypogonadal elderly males, provided that laboratory values and clinical response are frequently monitored.
Advantages of Compounded Testosterone
Testosterone is well-absorbed from transdermal creams, gels, and lotions. Compounded preparations can have many advantages. For example:
- the exact amount of hormone needed by each man can be applied as a single dose
- there is no need to shave the scrotum to apply one or more patches
- there is no skin irritation from patch adhesive.
- the cream or gel can be applied two or three times daily to simulate the normal circadian rhythm.
A healthy lifestyle is associated with higher hormone levels, and higher hormone levels seem to induce a more active, healthier lifestyle. For optimal results, it is vital that hormone replacement therapy be combined with adequate exercise, proper nutrition, and appropriate use of supplements.
What are the Contraindications or When Should TRT not be Considered?
Testosterone replacement therapy should not be prescribed for patients diagnosed with certain cancers. The only absolute contraindication to androgen replacement therapy is the presence of prostate or breast cancer.
- Guidelines recommend that TRT should not be initiated in older men with PSA serum levels above the normal range.
- Testosterone should be used with caution in men with severe heart, kidney or liver disease, increased red blood cell counts, and sleep apnea.5
What are the Potential Side Effects?
Side effects of testosterone therapy can include mood swings, leg swelling, skin reactions, acne, alopecia, breast enlargement, and infertility. Liver toxicity has not been reported following testosterone administration using transdermal gels in physiologic doses.6 (Toxicity has occurred with methyltestosterone.)
- Am J Med. 2001 May;110(7):563-72.
- J Clin Psychiatry. 2009 Jul;70(7):1009-16.
- J Clin Psychopharmacol. 2009 Jun;29(3):216-21.
- J Clin Endocrinol Metab. 2005 Mar;90(3):1502-10.
- Ther Clin Risk Manag. 2009 Jun;5(3):427-48.
- Expert Opin Drug Saf. 2004 Nov;3(6):599-606.
Testosterone vs. Synthetics: What is the Optimal Form of Testosterone for Replacement Therapy?
Testosterone USP is natural bio-identical testosterone that has been approved by the United States Pharmacopoeia and is available as a bulk chemical. Upon a prescription order, compounding pharmacists can use Testosterone USP to prepare numerous dosage forms.
Natural Testosterone Replacement is Central to the Treatment of All Facets of Andropause.
The term “testosterone” is often used generically when referring to numerous synthetic derivatives, as well as natural bio-identical testosterone. Confusion is responsible for conflicting data in the medical literature about the benefits and risks of testosterone therapy. Studies must be reviewed carefully to determine the form of testosterone that was used. Natural testosterone must not be confused with synthetic derivatives or “anabolic steroids,” which when used by athletes and body builders have caused disastrous effects. For example, administration of synthetic non-aromatizable androgens, like stanozolol or methyltestosterone, causes profound decreases in HDL-C (“good cholesterol”) and significant increases in LDL-C (“bad cholesterol”). Yet, hormone replacement with aromatizable androgens, such as testosterone, results in lower total cholesterol and LDL cholesterol levels while having little to no impact on serum HDL cholesterol levels. Proper monitoring of laboratory values and clinical response are essential when prescribing testosterone replacement therapy.
A healthy adult male secretes 8-15mg/day of testosterone. This “physiologic dose” should be considered when prescribing replacement therapy. Excessive doses leading to high serum levels of testosterone can result in a greater conversion to estradiol (and side-effects resulting from abnormally high estradiol levels), because the body cannot effectively store excess testosterone. This may be a reason to administer testosterone on a daily basis, rather than using long-lasting injections.
Transdermal drug administration allows application of a specific dose of a hormone to be applied to the skin and then be absorbed into the systemic circulation. Transdermal medications have the advantage of high bioavailability, absence of hepatic first pass metabolism, increased therapeutic efficacy, and steadiness of plasma concentrations of the drug. Testosterone is well-absorbed from transdermal creams/gels. Dosage forms also include sublingual drops or troches.
Natural testosterone must not be confused with synthetic derivatives or “anabolic steroids,” which when used by athletes and body builders have caused disastrous effects, such as heart problems and cancer. Use of synthetic androgens, like stanozolol or methyltestosterone, causes profound decreases in HDL-C and significant increases in LDL-C, and has been associated with serious heart disease. However, natural testosterone lowers total cholesterol and LDL cholesterol levels while having little to no impact on serum HDL cholesterol levels.
Screening for potential risks of androgen therapy should be performed prior to the initiation of treatment. Contraindications to testosterone replacement therapy include an elevated level of Prostate-Specific Antigen (PSA), or history or presence of prostate or breast cancer. There is a risk of worsening symptoms of benign prostatic hypertrophy (enlarged prostate), sleep apnea, congestive heart failure, gynecomastia (breast enlargement), infertility and skin diseases.
Drug Design, Development and Therapy 2014:8 101–112
Transdermal testosterone replacement therapy in men
Click here to access the PubMed abstract of this article.
Drugs Aging. 1999 Aug;15(2):131-42.
Risks versus benefits of testosterone therapy in elderly men.
Click here to access the PubMed abstract of this article.
When to Seek Immediate Medical Attention
Patients using testosterone should seek medical attention immediately if symptoms of a heart attack or stroke are present, such as:
- Chest pain
- Shortness of breath or trouble breathing
- Weakness in one part or one side of the body
- Slurred speech