Testosterone therapy - what,when and to whom?

Testosterone therapy has been used for more than 60 years in the treatment of male hypogonadism. The classical forms of hypogonadism are comprised of primary testicular failure or insufficient testicular stimulation due to the lack of pituitary gonadotropins. Typical causes of primary hypogonadism are Klinefelter's syndrome, anorchia or acquired disturbances of testicular function. Secondary hypogonadism is characterized by insufficient production of pituitary gonadotropins, due either to pituitary failure or defects at the hypothalamic level. It is unequivocally accepted in clinical practice that any male with inadequately low testosterone production for his age will require androgen therapy. In addition to the classical forms of hypogonadism, the past decade of research has clearly demonstrated that, with increasing age, many men will suffer from decreasing testosterone production. About 15-25% of men over the age of 50 years will experience serum testosterone levels well below the threshold considered normal for men between 20 and 40 years of age. Studies substituting testosterone in elderly men with low serum testosterone have shown that men with clinical symptoms identical to the symptomatology of classical hypogonadism will benefit most from such therapy. Therefore, it is the general consensus to treat men with age-related hypogonadism only when clinical symptoms are present that can be potentially corrected by testosterone administration. Until recently, intramuscular injections of esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. The introduction of testosterone patches has not challenged this approach, since many users of patches suffer from moderate to severe skin reactions. Some oral testosterone formulations have proven to be problematic, as absorption can be variable, bioavailability is frequently poor, due to the first-pass effect of the liver, and frequent administration is often required<citeref rid="b1"><emph>¹</emph></citeref>. Oral testosterone undecanoate avoids, at least partially, the first-pass effect of the liver. However, plasma testosterone levels generally undergo large fluctuations<citeref rid="b2"><emph>²</emph></citeref>. The large fluctuations in serum testosterone levels caused by conventional intramuscular injections result in unsatisfactory shifts in mood and sexual function in some men, which, combined with the frequency of injections, make the intramuscular mode of delivery far from ideal. Recently, a hydroalcoholic gel containing 1% testosterone has proven to be as efficient as a testosterone patch, but with fewer side-effects and a higher grade of patient satisfaction<citeref rid="b3"><emph>³</emph></citeref>^-<citeref rid="b4"></citeref><citeref rid="b5"><emph>⁵</emph></citeref>. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and correct the signs and symptoms of hypogonadism. The gel has been shown to be effective and successful in patients in the United States, who have benefited from its availability for almost 3 years. In the near future, intramuscular injections of testosterone undecanoate will become commercially available. Such injections have a very favorable pharmacokinetic profile, with one injection every 3 months maintaining serum testosterone well within the normal range. In phase III studies, intramuscular testosterone undecanoate proved to be as efficient as testosterone enanthate, with only one-quarter of the number of injections required and more stable serum testosterone levels. Thus, the new application modes - hydroalcoholic gel (for example, Testogel®, Schering AG, Germany) and intramuscular testosterone undecanoate (Nebido®, Schering AG, Germany) - appear to be the methods of choice in the near future, one being very suitable for hormone therapy in elderly men, the other for long-term substitution in classical forms of hypogonadism.     

An audit of testosterone measurement in men attending with impotence

As part of the routine assessment of 185 unselected men with undiagnosed impotence, testosterone was measured on a single serum sample to try to detect a subset of men with androgen deficiency who might benefit from testosterone replacement therapy. Those with low levels of testosterone were investigated further with repeat measurements of testosterone and luteinizing hormone (LH). In addition, prostatic specific antigen (PSA) was measured in all the men to exclude concomitant prostate cancer. Testosterone replacement therapy was offered to 20 men with consistently low levels of the hormone but few of the men continued with the therapy because of lack of benefit. It was concluded that either testosterone deficiency is rare in unselected men who actually seek help for impotence orebe our protocol of androgen assessment was not helpful for this group of men. There was correlation between PSA results and testosterone and this may have implications for the investigation of prostate cancer. The results presented here are an audit of a clinical practice and call into question the benefit of routine testosterone measurement in the investigation of all men complaining of impotence.     

Increase in the prevalence of metabolic syndrome among workers according to age

Androgen levels decline over a man's lifetime. In a proportion of men (increasing with age), levels fall below values that have been established by conventional laboratory criteria as indicative of hypogonadism. Testosterone has a wide range of non-reproductive actions: it preserves bone and muscle mass, it acts on non-sexual mental functioning and it stimulates red blood cell formation. Long-term androgen deficiency has a great impact on quality of life. The first intervention studies provide indications that androgen treatment of men with true androgen deficiency is helpful. Obviously, only men who are testosterone-deficient will benefit from androgen supplementation. The diag nosis of testosterone deficiency in old age is not unambiguous. Signs and symptoms of aging sometimes clinically overlap with those of testosterone deficiency. The groups that are at higher risk of testosterone deficiency are those men with disease (pulmonary disease, gastrointestinal disease, rheumatoid disease, etc.). Usually, sex hormone binding globulin levels increase with aging, leading to lower levels of free, biologically available testosterone. For the time being, arbitrary criteria for testosterone deficiency in aging men have to be adopted. The best practical approach is to calculate the free testosterone level. The calculation can be found at www.issam.ch under 'Tools'.     

The effect of androgen supplementation therapy on the prostate

With the recent availability of transdermal formulations, androgen supplementation therapy is increasingly being prescribed for men in their 50s and 60s. With the growing use of testosterone products, there is concern about the long-term risks of androgen supplementation therapy, particularly on the prostate. This article reviews what is known about the safety of testosterone replacement therapy in terms of the potential risks for development of symptomatic benign prostatic hypertrophy (BPH) and prostate cancer. Androgens are undoubtedly involved in the growth of benign prostatic nodules, as a permissive factor in the etiology of prostate carcinoma and in the enhancement of the growth of active prostate cancer. Their role in the initiation of either disease is less clear. Available data support the safety of such treatment in the short term. Caution is still advised in the interpretation of these findings, as the studies producing the data have involved relatively small numbers of participants. Until large, long-term, placebo-controlled studies have been conducted and analyzed, questions about the long-term safety of testosterone supplementation therapy in older men will remain.     

Practical consequences of the validation of a mathematical model in assessment of partial androgen deficiency in the aging male using bioavailable testosterone

Partial androgen deficiency or the andropause in the aging male is a complex clinical and biochemical entity that needs to be analyzed at two levels of the constituent structure: the 'deep structure' should come to light with more intensive research, while the 'surface structure' holds the attention of investigators who focus on hormone measurements in the blood to help diagnose the andropause. In this study, it is recognized that bioavailable testosterone decreases progressively during the aging process. This physiological decline may be so important, or so close to castration levels, that aged men may experience numerous symptoms of hypogonadism. The assay for bioavailable testosterone was indirectly validated with a set of equations derived from our knowledge of the law of mass action at equilibrium, as proposed by Vermeulen and colleagues in 1999. With this mathematical model, we have shown that calculated free testosterone was highly correlated with bioavailable testosterone. It is therefore concluded that the evaluation of aged men's androgenicity should rely on at least one of these free testosterone assessments (bioavailable or calculated free testosterone) for the sake of reproducibility in the construction of the 'surface structure' of the andropause in the coming years.     

Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency

In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol^®) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculo-skeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency.     

The aging male in the literature

The diagnosis of hypoandrogenism in the aging male is still difficult, since the symptomatology is aspecific and multifactorial, and it is unknown whether the androgen requirements of elderly men are the same as those of young men. Indeed, there are arguments for decreased (increased androgen feed-back sensitivity) as well as for increased (decreased concentration of androgen receptors) requirements in elderly men. In the absence of a reliable, clinically useful, parameter of androgen activity, we have to rely on plasma androgen level, an indirect parameter. In the absence of convincing arguments for altered requirements with age, we consider that the normal range of (free) testosterone levels in young adults is also valid for elderly men, the lower normal limit being 11 nmol/l for total testosterone and 0.225 nmol/l for free testosterone. There are indirect, suggestive clinical arguments for accepting these limit values. The diagnosis of hypoandrogenism in elderly males requires both the presence of clinical symptoms and decreased (free) testosterone levels. The best methods for determining free or bioavailable testosterone, are equilibrium dialysis and ammonium sulfate precipitation, respectively. They are, however, time-consuming techniques which are not easily automated. Calculation of the free androgen index (testosterone/sex hormone binding globulin (SHBG)) is not a valid method for male serum. Calculation of free testosterone from total testosterone, SHBG and albumin concentration, yields values that are in good agreement with values obtained by dialysis or ammonium sulfate precipitation. Several conditions should, however, be fulfilled: reliable methods for the determination of testosterone and SHBG, SHBG measurement in serum and not in plasma, use of fresh serum (not repeatedly frozen and thawed), absence of (exogenous) steroids competing for binding sites on SHBG and blood samples taken between 08.00 and 10.00 in the fasting state. Under these conditions an excellent correlation with dialysis and bioavailable testosterone (ammonium sulfate precipitation) is generally obtained.     

Aging androgens and the metabolic syndrome

Objective: To assess the responses of a symptom complex related to partial androgen deficiency in the aging male (PADAM) to androgen supplementation. Subjects and methods: Eighty-six men from five hospitals in Beijing aged 50-70 years with symptoms related to PADAM received oral testosterone undecanoate for 2 months, and the effects of the therapy were evaluated. Results: After treatment, the symptom scores were significantly improved (all p < 0.001). Serum levels of luteinizing hormone and follicle stimulating hormone were suppressed, and free testosterone and albuminbound testosterone levels were elevated. However, they were not significantly different from the pretreatment values. Waist/hip ratio and blood pressure were markedly decreased, but no changes were found in serum levels of total cholesterol, triglyceride, albumin and prostate specific antigen. Conclusions: Two months of treatment with oral testosterone undecanoate clearly improved the symptoms related to PADAM. No statistical relationship was found between symptom improvement and androgen levels. Androgen therapy for 2 months was beneficial to the waist/hip ratio and blood pressure, and no harm was done to the prostate gland or lipid metabolism.     

Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction

The prevalence of erectile dysfunction rises rapidly with age and is a frequent complaint presented in clinical practice. Although the etiology of erectile dysfunction is multifactorial, 10-20% of evaluations demonstrate testosterone deficiency. Testosterone deficiency due to secondary hypogonadism increases with age. Despite a higher prevalence of secondary hypogonadism in the elderly, there are no studies addressing hypothalamic-pituitary structural abnormalities in elderly impotent men with testosterone deficiency. We retrospectively reviewed the records of all elderly men who presented for general outpatient evaluation of erectile dysfunction from 1996 to 1999. To obtain a cohort control population, the records of 300 patients without erectile dysfunction were also reviewed. Amongst the erectile dysfunction patients, 225 were found to be testosterone deficient (testosterone < 300 ng/dl). Of these patients, 29 were additionally diagnosed with secondary hypogonadism based on a luteinizing hormone (LH) < 13 mIU/ml. Magnetic resonance imaging (MRI) or computed tomography (CT) imaging was available and reviewed in all patients diagnosed with secondary hypogonadism. Ten per cent of these patients had hypothalamic-pituitary imaging abnormalities. The prevalence of pituitary tumors within our population was not significantly elevated compared to the previous general population studies. Small-vessel white matter disease, hyperlipidemia and history of compression fractures were significantly increased in both univariate and multivariate analysis in the erectile dysfunction group compared with the control cohort. This study does not suggest that the use of hypothalamic-pituitary imaging in the evaluation of impotence in elderly men, in the absence of clinical characteristics of other hormonal loss or sella compression symptoms, will increase diagnosis of structural hypothalamic-pituitary abnormalities over that of the general population. However, the yield may increase with very low testosterone levels. These data suggest that there is an increase in ischemic white matter disease in elderly men with hypogonadism that may reflect microvascular injury to the hypothalamic-pituitary. Furthermore, these data confirm that low testosterone is associated with hyperlipidemia in the elderly. Future studies are required to assess the role of hypogonadism and hyperlipidemia, and to determine if treatment of the hormone deficiency improves the lipid profile.     

Testosterone and the brain

Gender differences in spatial recognition, and age-related declines in cognition and mood, point towards testosterone as an important modulator of cerebral functions. Testosterone appears to activate a distributed cortical network, the ventral processing stream, during spatial cognition tasks, and addition of testosterone improves spatial cognition in younger and older hypogonadal men. In addition, reduced testosterone is associated with depressive disorders. The relationship between depression and testosterone appears to partly depend upon the androgen receptor genotype of the patient, and in appropriate patients with low testosterone levels, testosterone substitution can increase positive mood and decrease negative mood. The much publicized link between testosterone and aggression is probably only of importance in athletes who supplement their testosterone levels to excessively high levels, whereas in hypogonadal men, testosterone supplementation only enhances the positive aspects of aggression such as vigour and energy. Current data suggest that testosterone supplementation in hypogonadal men of all ages will enhance many aspects of mood and cognition.     

Testosterone metabolism,dose–response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men

In this review selected toxicological problems related to testosterone therapy in hypogonadal men are discussed. Applying ‘classical’ pharmacological/toxicological findings (e.g. animal studies on short- and long-term toxicity) to clinical situations is not very helpful. Molecular biological knowledge and especially evaluation of epidemiological studies, as well as intervention studies, on testosterone therapy in hypogonadal men are more useful. Potential risks include overdosage for lifestyle reasons, e.g. excessive muscle building and reduction of visceral obesity, when erythrocytosis occurs concomitantly. Modern galenic formulations of testosterone administration (e.g. transdermal gel, suitable testosterone esters for intramuscular application and newer oral preparations) avoid supraphysiological serum concentrations, therefore significantly reducing the toxicological risk. A hypothetical model of the toxicological risks of testosterone therapy is given that is based on the influence of testosterone metabolism (aromatization vs. reduction) of the respective parameter/target chosen. Finally, the great influence of polymorphisms of the androgen receptor on the assessment of toxicological risk and on the individualization of androgen therapy is shown. Already existing national, continental and international guidelines or recommendations for the testosterone therapy should be harmonized.     

Diagnosis,pathogenesis and treatment of erectile dysfunction

Introduction: After middle age, some men show androgen-deficiency symptoms leading to so-called PADAM (partial androgen deficiency in aging males). We tested the oral form of testosterone, testosterone undecanoate (Andriol^®, NV Organon, The Netherlands), in men with PADAM and evaluated its efficacy and safety in Korean male patients. Methods: We included those patients with the clinical symptoms of PADAM who had decreased levels of serum total testosterone (< 2.8 ng/ml) or free testosterone (< 13 pg/ml). We excluded patients with biopsy-confirmed prostrate cancer, abnormal findings in digital rectal examination or prostate specific antigen testing (until prostrate cancer was ruled out), breast cancer, severe voiding symptoms and secondary hypogonadism. At the first visit, the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) and Korean Andropause Questionnaires were administered; complete blood count, the lipid profile, and levels of total and free testosterone, prolactin, luteinizing hormone, follicle stimulating hormone and prostate specific antigen were measured and a digital rectal examination was given. Patients were administered oral testosterone undecanoate 160 mg daily for 3 weeks. The dosage was then decreased to 80 mg daily and changes in symptoms were assessed at every visit. After 3 months, serum tests, including testosterone, were repeated. Results: We evaluated 28 patients who had received testosterone undecanoate for more than 3 months. The patients' mean age was 56.1 (48-68) years. The score of the Korean Andropause Questionnaire changed from 56.2 ± 21.7 at baseline to 52.9 ± 21.3 (p = 0.03) after 3 weeks, to 49.3 ± 19.3 (p = 0.03) after 8 weeks, and to 46.5 ± 25.6 (p = 0.028) after 12 weeks. With respect to sexual function, mean IIEF scores were 37.2 ± 19.6 at baseline and 38.7 ± 19.2 and 40.2 ± 22.0 (p = 0.033) after 3 and 12 weeks, respectively. Serum total testosterone increased from 2.13 ± 1.20 ng/ml at baseline to 6.04 ± 3.08 ng/ml (p = 0.005) after 12 weeks, and free testosterone was marginally significantly changed from 8.60 ± 2.25 pg/ml to 11.40 ± 3.81 pg/ml (p = 0.13). However, there were no significant changes in liver function tests, red blood cell count or lipid profiles. There were no significant adverse reactions that led to the cessation of the administration of oral testosterone. Conclusion: Oral administration of testosterone undecanoate can improve symptoms of PADAM in Koreans. It may, therefore, be an appropriate treatment option with few adverse effects for PADAM patients.     

Speaker abstracts

Purpose: There is no consensus on possible benefits and risks of testosterone supplementation. Here we review various controlled studies of testosterone supplementation in aging males.

Methods: We performed a PubMed search using the terms “testosterone/therapeutic use” with the limits “>65 years of age”, “randomized controlled clinical trials”, and “male gender”, starting in 1999.

Results: Forty-three articles have been published since 1999. Some of these studies also included patients in middle-age or younger. Findings reported in these articles were not entirely consistent. After weighting studies by the number of patients, hints are found that testosterone supplementation increases bone mass, lean body mass, muscle mass and hematopoiesis, and improves sexual functioning and perhaps mood, but does not affect serum lipids, cardiovascular parameters, prostate-specific antigen level, or cognition. Considering studies including only men older than 65 years, and in which testosterone supplements were compared with placebo treatment, slightly different results are obtained. In these patient groups, testosterone does not improve sexual function or mood.

Conclusion: The overall benefit of testosterone supplementation for the aging male remains unclear. Any supplementation in men with age-normal testosterone levels only on grounds of subjective symptoms is not advisable.     

Three-year follow-up of androgen treatment in hypogonadal men: preliminary report with testosterone gel

Transdermal testosterone gels represent an effective alternative to injectable testosterone preparations. Shortterm (6 months) data demonstrated positive effects on muscle, bone, fat, libido and mood. This report provides a preliminary analysis of longer-term treatment with a testosterone gel (AndroGel ? or Testogel®) in a group of men aged 19-67 years of age. The positive effects of testosterone treatment on all of the above parameters persisted in this 3-year follow-up. The benefits occurred independent of age (equally in the older and younger subjects). The positive effects of transdermal testosterone gel on bone mineral density previously identified at 6 months of treatment, continued with time. The positive effects on bone mineral density were greater in the spine than the hip. There were minimal effects on lipid levels. Levels of prostate-specific antigen (PSA) increased with testosterone treatment but, in general, remained in the normal range. Three subjects (1.8%) were shown to have elevated PSA and biopsy-proven prostate cancer. It was not possible to determine if this incidence is above the background rate. Monitoring for prostate disease through PSA measurements and digital rectal examination is recommended for hypogonadal men in the older age groups when treated with testosterone.     

Testosterone and erectile physiology

The role of testosterone deficiency in sexual dysfunction is an important aspect of aging, because it affects such a large proportion of men over 50 years old. A number of age-related factors can cause sexual dysfunction (in particular erectile dysfunction) and testosterone deficiency, such as chronic illness and multiple medications, and the causative link between hypogonadism and erectile dysfunction is still debated. However, studies in castrated animals have proven that addition of testosterone, and its conversion to dihydrotestosterone, can restore erectile function. It appears that testosterone achieves this by peripheral mechanisms (endothelial dependent and independent) and central mechanisms. Testosterone replacement therapy is therefore effective for erectile dysfunction in men with hypogonadism, with success rates of 35–40%. Testosterone supplementation is also important in men who fail on phosphodiesterase type-5 inhibitors, because a minimum plasma concentration of testosterone is required for the successful restoration of erectile function with these agents. Testosterone gels are now the preferred formulation for testosterone supplementation and they can be highly beneficial in a proportion of men with erectile dysfunction.     

Effects of long-term testosterone replacement therapy,with a temporary intermission,on glycemic control of nine hypogonadal men with type 1 diabetes mellitus – a series of case reports

Abstract

Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone?≤?12?nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA_1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.     

Clinical experiences with testosterone therapy: prostate safety

Due to a decrease in Leydig cell function, a considerable proportion of men over 50 years of age will develop hypogonadism. Consequently, loss of libido and several other testosterone-dependent symptoms may become evident. When decreased levels of biologically available testosterone are found, and corresponding symptoms are present, these men could be eligible for testosterone substitution therapy. Testosterone treatment in testosterone-deprived men has been shown to improve general well-being, osteoporosis, muscle atrophy, libido and - if present - anemia. Despite these positive effects, testosterone treatment has to be performed with caution. Although it has not been proven that elevation of the serum testosterone level to the normal range results in a greater risk of developing prostate cancer, the effects of testosterone on a prostate cancer already present are well established. Several studies have demonstrated that testosterone treatment does not result in a significant increase in serum levels of prostate-specific antigen (PSA) or prostate volume. The long-term effects, however, are currently unknown. For these reasons, testosterone treatment should be performed only when the presence of prostate cancer is unlikely; i.e. when PSA levels are within normal limits and digital rectal examination does not reveal any suspicious findings. These examinations may still miss some small prostate cancers that could be promoted by testosterone treatment. The determination of PSA levels under testosterone treatment is necessary every 3 months, at least for the first year. Steadily rising PSA levels require immediate cessation of testosterone administration and the initiation of further diagnostic procedures (prostate biopsy), to rule out prostate cancer.     

LOH–pitfalls of an ambiguous abbreviation

Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx?+?El) and orchidectomised and given testosterone (Orx?+?T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.     

How to help the aging male? Current approaches to hypogonadism in primary care

Hypogonadism is a common condition which occurs more frequently in older men. It is characterized by low testosterone (T) and is associated with symptoms which are often nonspecific. A key symptom is low libido, but it can also be associated with erectile dysfunction, reduced muscle mass and strength, increased body fat, reduced bone mineral density and osteoporosis, reduced vitality, and depressed mood. Hypogonadism is linked with a variety of comorbid conditions including erectile dysfunction, metabolic syndrome, diabetes, obesity, and osteoporosis. However, the condition is often underdiagnosed. T supplementation in hypogonadism is associated with a range of benefits including improved sexual function, increased lean body mass and/or reduced fat mass, and improved bone mineral density. A variety of T supplementation formulations are available. Although there is no evidence of increased risk of initiating prostate cancer with T supplementation, it is contraindicated in men with prostate cancer. It is important that primary care physicians are aware of both the signs and symptoms of hypogonadism, the monitoring and testing that is required and the merits and advantages of the various T preparations to ensure optimal management of the condition with a treatment approach that best suits patients’ needs.