Andropause (also referred to as male menopause, male climacteric, viropause, low-testosterone syndrome, and sometimes “man-opause”) is a name used to describe a collection of symptoms in some aging men, symptoms of which have some superﬁcial similarities to menopause effects in women. Unlike “menopause,” the word “andropause” is not currently recognized by the World Health Organization. The terms andropause and “hypogonadism” are sometimes used interchangeably. Some experts say that about 25% of men go through andropause, the male version of menopause, in which levels of testosterone (T) drop signiﬁcantly with age. Men who are excessively obese have an increased risk of andropause. Sadly, for many years men have accepted and lived with the misconception that nothing can be done to treat the symptoms of andropause.
T is a powerful natural anabolic androgenic steroid that increases bone density, muscle mass, protein anabolism, and nitrogen retention and modulates immune system function. With respect to aging individuals, the effects of T involve improving quality of life; preventing progressive skeletal muscle loss and strength falls, fractures; prolonging independent living, and reducing the need for medical care, all of which remain topics of clinical investigation.
About 60% of circulating T is bound to sex hormone-binding globulin (SHBG), 38% is bound to albumin, and the remaining 2% is free T. Since T is strongly bound to SHBG, only albumin-bound T and free T are bioavailable. In effect, albumin and SHBG tend to function as storage vehicles for T; SHBG appears to store T permanently, and albumin functions as a bioavailable reservoir. The reservoir of available T should include measurements of both albumin-bound and free T. In men, the reservoir of T begins to decline at about the age of 30 years and continues at the rate of about 1% per year. SHBG levels, however, increase with age, and this increases the decline in serum levels of free and bioavailable T. Men that are in their 70s and 80s usually have serum levels of T that are about half to two-thirds that of men in their 20s. Factors affecting T levels in elderly men have been attributed to hereditary, psychosocial (e.g., depression, drugs, smoking), environmental (e.g., obesity, stress) or socioeconomic. Table 1 lists many symptoms associated with andropause.
There are two types of T deﬁciencies; those of testicular origin (primary hypogonadism) and those of hypothalamic-pituitary origin (secondary hypogonadism). As a preliminary screening tool, Table 2 is the A.D.A.M. Questionnaire that can be used as a preliminary screening tool.
1. A physical examination that includes determining the levels of total and free T, estradiol, prostate-specific antigen (PSA), lipids, glucose, and a complete blood count (CBC). Normal T levels in men range widely, with a low end of 300 ng/dL and a high of 1050 ng/dL for serum total T. Bioavailable T can be measured in both serum and saliva with similar accuracy.
2. If T is low, consider other lab tests to determine the level of follicle-stimulating hormone (FHS), luteinizing hormone (LH), and possibly prolactin. Also, thyroid function and iron status should be evaluated.
3. After diagnosis is made, begin the process of correcting the T deficiency
Ways to increase and/or maintain T levels include:
1. Lifestyle changes (active exercise program of both aerobic and weight-resistant activities and a healthy eating plan that promotes loss of excess weight and fat).
2. Reduce estrogen levels by losing weight, practicing good nutrition, and engaging in regular exercise or the use of the following:
• Anastrozole (0.1 mg daily to 0.5 mg every other day)
• Letrozole (0.1 mg daily or 2.5 mg 3 times per week to 2.5 mg daily) Estradiol and estrone are the so-called female hormones. The primary source of estradiol is the aromatization of T; estrone comes primarily from the aromatization of the adrenal hormone androstenedione. With less weight, there is generally less fat, and, therefore, less aromatization of T to estradiol.
3. Increase the testicular output of T (human chorionic gonadotropin [hCG]:
• hCG (500 units to 1500 units three times weekly)
• Clomiphene (25 to 100 mg daily)
4. T supplementation:
• T intramuscularly (IM) (75 to 100 mg weekly)
• Topical gel (40 mg to 120 mg; initially 50 mg/mL)
• Topical cream (5%)
• Sublingual or buccal (10 mg to 25 mg per dose up to 3 times daily)
• Oral 400 mg to 500 mg daily
T can minimize several important risk factors for heart attack, including:
• Reducing cholesterol and triglycerides
• Reducing blood glucose levels
• Decreasing visceral fat mass
• Normalizing blood clotting
Both low T and high estradiol levels have been linked to cardiovascular disease. The dehydroepiandrosterone replacement has also been shown to be associated with beneficial T-like effects. Treatment of andropause patients should be based on knowledge of the physiologic effects of T in the elderly, effective screening for T deficiency, accurate measurement of bioavailable levels
of the hormone, and safe and effective treatment options. Achieving hormonal balance is at the heart of therapy, and the most prevalent treatment is T supplementation.
The benefits of T supplementation in older men include a decrease in body fat, increased libido, improved erectile capacity, increased muscle mass and muscle protein synthesis, improved cognitive function, and increased bone mineral density. T is a primary factor in the health of the heart and blood vessels. Table 4 lists example compounded preparations of T.
Routes of Administration of Testosterone
The background and skill of a compounding pharmacist can be used to customize the dose and dosage forms for individual
patient medical needs. The various dosage forms, which are discussed briefly below, that can be compounded are shown in
This route of administration is very inefficient because of the high first-pass effect in the liver, resulting in loss of T activity.
IM injections are the most common route of administering T and results in a widely fluctuating serum T level.
Topicals consist of creams, lotions, gels, and transdermal patches. Many consider this to be the most effective method of administering T. Suggested gel dosage is 50 to 100 mg/day. Transdermal patch dosage is suggested at 5 mg/day. It is believed that percutaneous hormone therapy acts by loading the stratum corneum layer of the epidermis with an active hormone, where it is then leached out slowly into the capillary circulation.
Sublingual or Buccal
These routes of administration are generally given 3 to 4 times daily; between 10 and 40 mg/day.
This route of administration (pellets are inserted into the buttocks of the patient) gradually releases T over 3 to 5 months. Adjusting the dose is difficult.
Contraindications to Testosterone Replacement Therapy
The following may serve as contraindications to T replacement therapy:
1. Presence or history of prostate cancer
2. A baseline PSA of 4 ng/mL or a palpable abnormality of the prostate without urologic evaluation to rule out prostate cancer
3. Evidence of hereditary prostate cancer, which is defined as three or more affected relatives within a nuclear family, prostate cancer within each of three generations (paternal or maternal), or two relatives affected with that type of cancer at 55 years of age or younger.
4. Severe symptoms of lower urinary tract obstruction as indicated by an International Prostate Symptom Score or an American Urological Association symptom score of 21 or higher.
Some have recommended that PSA levels and a digital examination of the prostate be performed 3, 6, and 12 months after the initiation of T replacement therapy and annually thereafter. T may have a protective effect on the prostate versus the inflammatory actions of estradiol. Nutraceuticals such as omega-3 fatty acids, vitamin D, zinc, and selenium all play an important role in prostate health, as these agents have 5α-reductase inhibiting and anti-inflammatory properties. summary Many clinicians now realize that andropause is a significant condition that a large percentage of men experience. As a result of education and the proper selection of therapeutic options, andropause may one day be the least concern of aging men.
Loyd V. Allen, Jr., PhD, RPh
International Journal of Pharmaceutical Compounding