Andropause: Myth or Reality
As a result of urbanization, improvement in the medical sciences, and also affordability of medical facilities, we are heading towards a population cohort, which is likely to have more and more elderly individuals. The demographic data as depicted in table 1 is a clear indication of the fact that India is no exception to the global change towards a higher percentage of aging population. In India, there would be around 244,999 men above the age of 40 by the year 2025,which would be an increase of about 68.2% over the145, 657 men in the same group as in 2005. As the age advances, almost all organs of the body get affected and in addition much age related diseases may also set in.
To some extent, organic diseases could be prevented, but there is yet no way to prevent aging. In women, after a certain age, there is cessation of ovarian function resulting in widespread changes in the body and mind, which have been shown to be reversed to certain extent by hormone replacement therapy. This illustrates a very interesting phenomenon that even though one can’t prevent aging, the effects of aging can be minimized by judiciously replacing appropriate vital hormones in correct doses exogenously.
While in case of women it was really never difficult to pin point the correlation of various symptoms with the cessation of ovarian function or the menopause, a similar condition in men has been difficult to localize. It also interesting to note that while all medical schools have gynecology as an essential subject in their curriculum, andrology still continues to be left out in the under graduate level. With advancing age, men also have a gradual reduction in their testosterone levels, which is not as dramatic as in women and hence is hardly ever noticed by the individual himself. This reduction in the serum levels of testosterone has been termed as Late Onset Hypogonadism. Besides, due to aging various body tissues undergo regressive changes, which in the background of reduced testosterone levels adversely affect the quality of life of aging men. It is the responsibility of the family physician to be alert and keep the possibility of this Late Onset Hypogonadism (LOH) while trying to address day-to-day complaints of aging men. Since it has been shown that not all men with low testosterone levels would have symptoms attributable to LOH, it is prudent to be able to diagnose the right indication for testosterone replacement therapy. In the following passages some of the common indications of testosterone therapy have been discussed.
Symptomatic Late Onset Hypogonadism (SLOH)
This clinical condition though not uncommon, is often missed in the practice. High index of clinical suspicion, which should arise out of the following, is the key to diagnosing SLOH.
- Men above 40 years of age, who have recent onset erectile dysfunction
- Decreased libido
- Loss of ejaculation
- Reduction in muscle mass and strength
- Increased abdominal fat distribution
- Mood disturbance, dysphasia, irritability
- Decreased attention span
- Memory loss
- Reduced ability to handle stress
- Reduced bone mineral density
- Vasomotor instability/hot flushes
- Reduced pubic and axillary hair
All the above can also be found in various permutations and combinations in people suffering from a variety of organic disorders. Therefore it is the responsibility of the treating physician to exclude any underlying medical condition resulting in these symptoms. However since SLOH can occur in men suffering from common ailments like diabetes mellitus, cardiac disease, chronic renal insufficiency and practically any known condition, it may be prudent to look for hypogonadism in such situations as quality of life might be improved by adding testosterone replacement therapy in such individuals. There are various questionnaires available to screen men for symptomatic late onset hypogonadism(SLOH) e.g. The Saint Louis University Androgen Deficiency in Aging Males (ADAM) questionnaire or the Aging Males Symptoms questionnaire. Once clinically indicated, biochemical confirmation is must before instituting testosterone replacement. A morning sample of blood is analyzed for the serum concentration of total testosterone. If the serum testosterone (total) is above12 nmol/L then the patient is certainly not a candidate for testosterone replacement therapy, on the other hand if the value of same is less than8 nmol/L then the person definitely has hypogonadism and therefore requires testosterone replacement for sure. However if the serum testosterone (total) is between 8-12 nmol/L, then further confirmation by estimation of serum levels of free testosterone is required. If the facility for estimation of serum free testosterone is not available, the serum levels of sex hormone binding globulin (SHBG) may be obtained to calculate the bioavailable testosterone. Testosterone therapy is indicated if the free testosterone level is below 180 pmol/L or the bioavailable testosterone is less than 2.5 nmol/L.  Once the diagnosis of hypogonadism is clear one must look for associated endocrinological abnormalities like deranged glucose metabolism, thyroid function, lipid profile etc. Also an effort should be made to assess the nature of hypogonadism by evaluating the levels of Leutinising Hormone. Before initiating testosterone replacement therapy one should exclude the following contraindications:
a) Carcinoma Prostate
Carcinoma prostate is an absolute contraindication of testosterone therapy. There is no evidence to suggest that testosterone treatment causes development of de novo cancer of prostate. Also, there is no increase in the incidence of invasive carcinoma prostate in cases of Prostatic Intra epithelial Neoplasm (PIN). Another interesting observation is that the Gleason grade of the carcinoma prostate is inversely related to the serum testosterone levels. As a corollary higher testosterone levels are associated with less aggressive carcinoma of prostate. In all cases, a close watch on serial serum PSA levels must be kept to look for incidental carcinoma prostate. Serum levels of PSA are expected to rise with testosterone replacement therapy in all cases, but if the rise is more than 0.75 ng/ml/year, then a transrectal ultrasound guided biopsy of prostate must be done. It has been recommended that after successful treatment of carcinoma prostate by radical prostatectomy with no evidence of residual or recurrent disease and suitable interval, testosterone may be advised judiciously in symptomatic hypogonadal men [3,4].
b) Carcinoma Breast
Carcinoma of male breast thrives on testosterone and therefore is an absolute contraindication of testosterone replacement therapy.
c) Symptomatic obstructive BPH
Precarious balance of estrogen and testosterone may be affected adversely resulting in sudden aggravation of bladder outlet obstruction. Therefore, before instituting testosterone therapy the bladder outlet obstruction must be treated to prevent sudden deterioration of voiding function.
d) Sleep Apnea
Sleep apnea worsens with testosterone therapy and therefore may add to the discomfort.
e) Polycythemia Vera
Testosterone is expected to increase the packed cell volume of blood secondary to enhanced erythropoiesis. Hence patients with pre-existing Polycythemia Vera must not receive exogenous testosterone. The risk is particularly more with injectable testosterone preparations
f) Decompensated Cardiac Failure
Decompensated cardiac failure can get aggravated as a result of salt and water retention due to testosterone. Hence patients with compromised cardiac contractility must be judiciously selected for testosterone therapy.
SLOH in special circumstances
1) SLOH with Diabetes Mellitus
Type 2 diabetes mellitus is a leading cause of morbidity in urban Indian population. An estimated 17.97million men are suffering from this ruthless disease and the number is expected to rise to 37.2 million in the year 2025(fig.1) making India the diabetic capital of the world . This complex endocrinological entity affects almost all organ systems of the human body. Abundant literature from other parts of world is available correlating frequent occurrence of hypogonadism in men suffering from type 2 diabetes mellitus. In one study the incidence of hypogonadism in type 2 diabetes mellitus has been shown to be almost 33%, majority of them being hypogonadotropic hypogonadism . No correlation has been found between the occurrence of hypogonadism and the duration of diabetes, effectiveness of glycemic control, obesity, or the complications of diabetes mellitus. Most of the clinical features of SLOH like reduced libido, erectile dysfunction, and increased abdominal fat, reduced muscle mass, depression, and endothelial dysfunction were found to be reversed by testosterone replacement . As testosterone has been shown to have anti-inflammatory and anti atherogenic properties, it’s deficiency, as a corollary, may be presumed to be pro atherogenic . Therefore testosterone replacement in hypogonadal diabetic men may be cardio protective.
2) SLOH with obesity.
Testosterone and estrogen are expected to regulate the fat distribution through the lipoprotein lipase and leptin. Deficiency of testosterone causes reduction in the activity of lipoprotein lipase causing accumulation of fat. This has been shown to be reversed by administration of exogenous testosterone .
3) SLOH and Cardiac disease
There are three important determinants of cardiac disease, namely, atheromatous plaques, coronary insufficiency and cardiac contractility.
- Atheromatuos plaques: Assessment of atheromatous plaques as measurement of intima media thickness of carotid arteries has shown to have an inverse relationship with the serum testosterone levels [9,10]. This points to the anti atherogenic properties of testosterone. In addition, testosterone replacement has-been shown to have a favorable effect on lipid profile which further reduces the athermanous process .
- Coronary blood flow: According to a review article based on 39 studies, testosterone has been shown to have an anti-inflammatory and vasodilatory properties . Another study has shown that testosterone replacement in hypogonadal men with coronary insufficiency improves ischemic threshold and quality of life .
- Cardiac contractility: Testosterone replacement therapy has been shown to increase cardiac contractility by reducing after load . Improvement of effort tolerance and functional capacity in hypogonadal men with moderate cardiac failure has been documented in another study .
Thus, testosterone replacement can be expected to benefit and improve the quality of life of selected hypogonadal men with cardiac disease.
4) SLOH with Depression
Depression can occur due to a variety of reasons in aging men. Testosterone deficiency can result in aggravation of depression. Estimation of testosterone levels and suitable replacement in cases of late onset depression has been shown to improve the treatment outcome of such patients. .
5) SLOH in Chronic Renal Failure
Chronic renal insufficiency due to any cause is a debilitating illness. It is associated with reduced testosterone levels secondary to hyperprolactinemia. This is reflected as reduced libido and erectile dysfunction. In addition there is anemia due to deficiency of erythropoietin. Testosterone replacement is expected to improve the effects of hypogonadism as well as increase the hematocrit through its effect on erythropoiesis.
6) SLOH and AIDS
AIDS is associated with muscle wasting and reduced erectile function along with diminished libido. A group of 74 men with symptomatic human immunodeficiency virus illness were studied in a double blind placebo controlled 6-week trial with bi- weekly testosterone injections, followed by 12weeksof open label maintenance treatment. Major outcome measures studied were improvement in libido, mood, energy, erectile function, body composition and depression. It was concluded that testosterone administration in clinical hypogonadal men with AIDS caused an improvement in all the above-mentioned parameters.  Another study has shown weight gain in men with AIDS by using oral testosterone undecanoate 
Symptomatic late onset hypogonadism can be diagnosed with high degree of clinical suspicion and good laboratory back up. It may be associated with commonly seen medical conditions. Replacement of testosterone has been shown to improve the quality of life of hypogonadal men thus adding to the overall therapeutic outcome.
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