The Condition No One Wants to Talk About
Diagnosis and Treatment of Andropause Is Hindered by Stigma
Andropause refers to symptoms men may experience as testosterone levels decrease during the normal aging process. Andropause is also sometimes referred to as testosterone deficiency (Low-T), androgen deficiency, and late-onset hypogonadism (LOH). Not all men experience low testosterone symptoms; however, for those who do, the symptoms can have serious consequences related to how they feel and their quality of life. Unwarranted stigmas associated with the disorder can discourage men from seeking treatment and may make it difficult for some to discuss their symptoms with health care providers. This can result in underdiagnoses and undertreatment, leading to potentially significant risks such as cardiovascular disease, osteoporosis, and diabetes. Despite the significant benefits for some men, testosterone replacement therapy (TRT) carries its own risk, which makes it essential for health care professionals to feel comfortable openly discussing the condition and potential treatment options with patients.
Andropause vs Female Menopause
Hypogonadism symptoms may include the following:
• Mood and mental function changes: anxiety, depression, mood swings, irritability, poor sleep, difficulty concentrating, poor short-term memory, decreased motivation, and low self-esteem.
• Virility changes: decreased physical energy, decreased muscle strength, constant tiredness, and joint pain.
• Alterations in circulatory and nervous systems: sweating, hot flashes, and insomnia or other sleep disorders.
• Sexual function changes: infertility, reduced libido, erectile dysfunction (ED), and impaired ejaculation.
• Changes in physical appearance: abnormal weight gain, gynecomastia, decreased testicle size, loss of body hair, loss of muscle mass, and height loss.
• Changes in body metabolism and chemistry: increased body fat and cholesterol, decreased bone density (osteoporosis), and reduced red blood cells.
Underdiagnoses and Undertreatment
The Endocrine Society defines hypogonadism as a combination of low testosterone levels and the presence of any of these symptoms: drop in sex drive (libido), ED and loss of spontaneous erections, lowered sperm count and infertility, breast enlargement or tenderness, reduced energy, hot flashes (when testosterone levels are very low), increased irritability, inability to concentrate, and depressed mood.6 There should be at least two early morning (7–10 am) blood tests that reveal low testosterone, with low testosterone levels typically noted as being less than 300 ng/dL or free testosterone less than 5 ng/dL should be used.
Depression, hypothyroidism, chronic alcoholism, and use of medications such as corticosteroids, cimetidine, spironolactone, digoxin, opioid analgesics, antidepressants, and antifungal agents should be excluded before making a diagnosis of LOH. Similarly, diagnosis of LOH should not be made during acute illness, which decreases testosterone levels temporarily.7
Testosterone Replacement Therapy
Benefits of Testosterone Replacement
Testosterone replacement in men with testosterone deficiency has been shown to have profound effects on body composition, including reduced body fat and increased lean body mass, along with significant reduction in weight, waist circumference, and BMI.12 Long-term testosterone treatment of hypogonadal men—up to five years in duration—has been shown to produce marked and significant decrease in body weight, waist circumference, and body mass index.13
Metabolic Syndrome, Diabetes, and Cardiovascular Disease
Low testosterone is an independent risk factor for development of metabolic syndrome and type 2 diabetes in men. Conversely, men with metabolic syndrome are at increased risk of developing hypogonadism.14 Testosterone may also protect against type 2 diabetes, as men with higher testosterone levels had a 42% lower risk of type 2 diabetes.14 Several studies suggest that low testosterone may, in fact, be a precursor to the development of diabetes or insulin resistance.14 In hypogonadal men, long-term TRT has been shown to ameliorate the components of the metabolic syndrome, with reductions in waist circumference, total and LDL cholesterol, blood pressure, blood glucose, HbA1c, and C-reactive protein, and increases in HDL cholesterol.15
Fall risk is also associated with lower testosterone levels.17 Furthermore, in hypogonadal men, reduced BMD is associated with a significant increase in bone fractures, including hip and spine fractures.18,19 Despite osteoporosis prevalence among males older than the age of 50 being significantly lower than in females, male osteoporosis and osteopenia have significant consequences. Although men tend to sustain fractures up to 10 years later in life than women do, the mortality and morbidity associated with male hip fractures are higher than those experienced by women, and men with known fragility fractures are less likely than women to receive treatment.20
A number of studies have demonstrated that TRT increases BMD in hypogonadal men with osteopenia and osteoporosis.21 Testosterone appears to produce this effect by increasing osteoblastic activity and, through aromatization into estrogen, reduces osteoclastic activity, with pooled data from a meta-analysis suggesting a beneficial effect on lumber spine density but less certain findings on the femoral neck.22
TRT has been shown to increase BMD in hypogonadal men of all ages.23 Due to potential risks associated with it, the use of testosterone to improve BMD is not recommended unless the patient is experiencing symptomatic hypogonadism.5 Testosterone replacement may be recommended in hypogonadal men with symptomatic low testosterone who are at high risk of fracture, though this should be done in combination with a medication with a proven antifracture effect such as a bisphosphonate.24
Testosterone replacement increases hemoglobin, hematocrit, and red blood cells by stimulating iron-dependent erythropoiesis and has been shown to correct unexplained anemia in the elderly, anemia of inflammation, and anemia of chronic kidney disease.26
Erectile Dysfunction and Libido
Although testosterone is generally considered safe it is not without some risks, including elevated red blood cell count, acne, sleep apnea, and possible prostate and/or breast enlargement.
The FDA requires that patients are made aware that the possibility of cardiovascular events may exist during treatment. Despite this warning, there’s no firm scientific evidence that long-term testosterone replacement is associated with cardiovascular events, and the evidence supporting the drug safety warning remains controversial.
Patients should not receive testosterone therapy if they have the following:
• prostate or breast cancer (or suspected);
There’s no evidence that testosterone causes prostate cancer; however, testosterone can fuel prostate cells and cancer that has already started. For this reason, extra vigilance is required concerning prostate cancer screenings, especially for those patients at increased risk of prostate cancer, including those with a family history of cancer and Black men older than age 45.
— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.
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