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PubMed2003

Hormone treatments and preventive strategies in the aging male: whom and when to treat?

Sex hormones have a broad range of actions in regulating very diverse systems throughout life. Testosterone and other related hormones change with age to varying degrees and may induce pathophysiological changes and the clinical condition known as andropause. Androgen replacement is the accepted but not the only possible treatment for andropause. The presence of clinical symptoms, including a loss of sexual function, intellectual capacity, lean body mass, or bone mineral density; alterations in body hair, skin, or sleep pattern; or increases in visceral fat, together with low levels of serum testosterone characterize andropause. An appreciation of the potentially undesirable impact of androgens on the biology of prostate cancer, as well as possibly the cardiovascular system, is necessary. However, proper evaluation of aging men with symptoms of andropause will result in a decision to initiate androgen therapy in some aging men.

Journal Article↗
PubMed2003

Androgen replacement therapy in the hypogonadal ageing man.

In men, gonadal function is affected in a slow, progressive way as part of the normal ageing process. Recently, however, significant interest has developed on the importance of this condition, which is variously known as male climacteric, andropause or, more appropriately, androgen decline in the ageing male (ADAM). The term andropause is biologically wrong and clinically inappropriate but, it adequately conveys the concept of emotional and physical changes that, although related to ageing in general, are also associated with significant hormonal alterations. The inappropriateness of the term is based on the fact that in women, the reproductive cycle invariably ends with ovarian failure. In men, this process is not universal and when it occurs it is normally subtle in its clinical manifestations. This has led to a tendency to ignore the syndrome as an unavoidable and untreatable result of the ageing process. For the sake of simplicity and directness, this review will use the terms ADAM and andropause to denote the global hormonal alterations associated with ageing.

Aging↗
PubMed2005

Measurement of testosterone and its sub-fractions in Canada.

Interest in measuring bioactive testosterone in aging males has increased considerably in the last 5 years in Canada. Emerging andropause clinics have submerged our laboratories with requests for bioavailable testosterone (BAT) testing in replacement or addition to the traditional total testosterone (TT) and direct free testosterone (FT) assays. Beginning with a brief explanation of the bioavailability concept of Pardridge, this review examines the technical characteristics of various approaches currently available to measure TT and its sub-fractions. First, limitations in the measurement of TT, SHBG, and particularly direct (analog) FT assays are extracted from the scientific literature and recent external and internal QC reports. It is concluded that the free direct T assay is useless in the clinical context of andropause. The impact of the observed limitations of TT and SHBG measurements on calculated FT and BAT or BAT obtained by precipitation with ammonium sulfate is then discussed. A comparative evaluation of the advantages and disadvantages of calculated FT or BAT vs. precipitated BAT is presented before concluding that doing a TT as a first line test remains overall the most cost-effective measurement in the diagnosis of hypogonadism in males, and that this sole determination will be sufficient in over 75% of the cases.

Biological Assay↗
PubMed2006

Aging Males' Symptoms scale in Japanese men attending a multiphasic health screening clinic.

OBJECTIVES: The Aging Males' Symptoms (AMS) scale is a health-related quality-of-life scale. The AMS scale has been used worldwide for the evaluation of andropause symptoms, but its standardized values have only been published for Germany. We sought to evaluate the prevalence of andropause symptoms in the male Japanese population using the AMS scale. METHODS: Of a consecutive series of 2833 men who underwent multiphasic health screening at Kurashiki Central Hospital, we analyzed the results for 2211 men who responded to all questions on the AMS scale. RESULTS: The severity of the total score and the sexual subscore of the AMS scale increased significantly with age, but no significant age relationships were observed in the psychological and somatic subscores. Approximately 50% of men in their 40s had moderate or severe symptoms in the sexual subscore. The total scores and all subscores for the Japanese population were significantly greater than those for the German population. CONCLUSIONS: A decline in sexual function with age was demonstrated in healthy Japanese men, but the somatic and psychological subscores were not influenced by age. The present study has provided standardized values for the AMS scale for the Japanese population.

Adult↗
PubMed2001

Patterns of Leydig cell insufficiency in adult males following bone marrow transplantation for haematological malignancies.

Gonadal and sexual function are key to quality of life following bone marrow transplantation (BMT), but no large studies have been published on Leydig cell (LC) function in adults. LC insufficiency (LCI) can cause premature andropause with its consequences including sexual morbidity from diminished libido and erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and even osteopenia. We reviewed gonadal function pre-transplant (immediately prior to BMT) and at 3-18 months post BMT in 117 patients who underwent BMT for a variety of haematological malignancies. The patients presented with variable degrees of symptoms of LCI, such as fatigue, diminished sex drive and libido or ED. The results suggest that the patients sustained severe gonadal damage to both their germ cells (GC) as well as the LC compartment (P < 0.001). We characterised two distinct functional subsets of LC insufficiency: Type I: compensated type with high LH and normal T levels and low T/LH ratio: (n = 102); and type II: uncompensated type (premature andropause) with high LH and low testosterone levels with low T/LH ratio (n = 15). Although type II patients had more severe LC damage than type I, patients in both groups were symptomatic. We recommend that symptomatic patients in both groups may benefit from a therapeutic trial with testosterone replacement treatment (TRT) for 3-6 months.

Adolescent↗
PubMed2003

Declining testicular function in aging men.

Age-related decline in male sex hormones, particularly testosterone, is referred to as andropause. Like menopause, andropause is associated with physical and emotional changes that may be alleviated by hormone replacement therapy. Hypogonadism in aging men, as defined by a low free testosterone index, is due to declining testosterone production and increased sex hormone-binding globulin levels. About 30% of men in their 60s and more than 80% of men over 80 y may have a low free testosterone index. Diagnosis of hypogonadism is based on clinical symptoms (eg, decreased muscle mass, fractures, loss of libido) and laboratory determinations of serum testosterone-usually total testosterone levels. Measuring bioavailable testosterone, or free testosterone, is expensive and time-consuming, but may more accurately detect hypogonadism. Testosterone replacement therapy is generally safe in aging men and may improve libido, cognition, bone mineral density, body mass composition, and serum lipoproteins. Although contraindicated in men with prostate or breast cancer, testosterone replacement therapy in aging men warrants examination. Any of the available testosterone formulations can be used, but injectable forms have certain advantages, including excellent dose adjustability, lack of skin irritation, and low cost.

Aged↗
PubMedDate not supplied

Androgens and the ageing male.

Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial in some elderly males with low-normal testosterone levels. However, at this point in time, widespread use of testosterone in an elderly male population outside controlled clinical trials seems inappropriate.

Aging↗
PubMed2003

Transdermal estradiol therapy for advanced prostate cancer--forward to the past?

PURPOSE: Current hormonal therapies for prostate cancer are associated with significant morbidities, including symptoms of andropause and osteoporosis. Oral estrogens prevented many of these problems but were abandoned due to cardiovascular toxicity attributed to hepatic effect. In contrast, parenteral estrogens prevent first pass hepatic metabolism and substantially reduce cardiovascular risk, and long-term transdermal estradiol therapy is believed to be cardioprotective. We report preliminary results of a pilot study using transdermal estradiol therapy to treat men with advanced prostate cancer. MATERIALS AND METHODS: A total of 20 patients with advanced prostate cancer were enrolled in a before and after study that examined the impact of estradiol patches on hormones, disease, thrombophilia, vascular flow, osteoporosis and quality of life. RESULTS: Median followup is 15 months. Estradiol levels greater than 1,000 pmol./l. were achieved using 2 patches and higher levels were obtained by increasing the number of patches. All patients achieved castrate levels of testosterone within 3 weeks and had biochemical evidence of disease regression. One patient died of disease at 14 months and 1 cardiovascular complication occurred. Thrombophilic activation was avoided and vascular flow improved. Bone mineral density was significantly increased. Mild or moderate gynecomastia occurred in 80% of patients but no patient had hot flushes. All other functional and symptomatic quality of life domains improved. CONCLUSIONS: Transdermal estradiol therapy produced an effective tumor response. Cardiovascular toxicity was substantially reduced compared with that expected of oral estrogen, and other morbidity (gynecomastia) was negligible. Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies.

Administration, Cutaneous↗
PubMed2005

The gonadotropin connection in Alzheimer's disease.

Although not traditionally thought of as regulators of neuronal function, the hypothalamic-pituitary-gonadal (HPG) hormones luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), and activins possess neuronal receptors. These receptors are found throughout the limbic system on a number of different cell types, and, like reproductive tissues, the expression of these receptors is regulated by hormonal feedback loops. These hormones and their receptors regulate structure and a diverse range of functions in the brain. Therefore, it is not surprising that the dysregulation of the HPG axis with menopause and andropause (leading to elevated LH, GnRH, and activin signaling but decreased sex steroid signaling) might promote alterations in both the structure and function of neuronal cells. To date, most evidence has accumulated for a role of LH in promoting neurodegenerative changes. LH is known to cross the blood-brain barrier, receptors for LH are most concentrated in the hippocampus, that region of the brain most vulnerable to Alzheimer's disease (AD) and LH is significantly elevated in both the serum and the pyramidal neurons of AD subjects. LH promotes the amyloidogenic processing of the amyloid-beta precursor protein in vitro, and the antigonadotropin leuprolide acetate decreases amyloid generation in mice. Moreover, leuprolide acetate improves the cognitive performance and decreases amyloid-beta deposition in aged transgenic mice carrying the Swedish AbetaPP mutation. Therefore, the elevation of LH with the dysregulation of the HPG axis at menopause and andropause is a physiologically relevant signal that could promote neurodegeneration. Epidemiological support for a role of LH/GnRH in AD is evidenced by a reduction in neurodegenerative disease among prostate cancer patients a group known to GnRH agonists. Clinical trials are underway for the treatment of AD using GnRH analogs and should provide further insights into the gonadotropin connection in AD.

Activins↗
PubMed2005

Male hypogonadism : an update on diagnosis and treatment.

Male hypogonadism is one of the most common endocrinologic syndromes. The diagnosis is based on clinical signs and symptoms plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions. Serum luteinizing hormone and follicle-stimulating hormone levels distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism. Hypogonadism associated with aging (andropause) may present a mixed picture, with low testosterone levels and low to low-normal gonadotropin levels. Androgen replacement therapy in hypogonadal men has many potential benefits: improved sexual function, an enhanced sense of well-being, increased lean body mass, decreased body fat, and increased bone density. However, it also carries potential risks, including the possibility of stimulating the growth of an occult prostate cancer. The benefits of androgen therapy outweigh the risks in men with classic hypogonadism. However, for men with mild hypogonadism or andropause, the balance between benefits and risks is not always clear. Unfortunately, studies to date have included too small a number of patients and have been too short in duration to provide meaningful data on the long-term risks versus the benefits of androgen replacement therapy in these populations. Several products are currently marketed for the treatment of male hypogonadism. Weekly-to-biweekly injections of testosterone cypionate (cipionate) or testosterone enanthate (enantate) are widely used, as they are economical and generally well tolerated. However, once-daily transdermal therapies have become increasingly popular and now include both patch and gel systems. Intramuscular injection of testosterone undecanoate is an attractive new therapy that can be administered quarterly. To confirm an adequate replacement dosage, assessment of clinical responses and measurement of serum testosterone levels generally suffice. For selected men, serial measurement of bone mineral density during androgen therapy might be helpful to confirm end-organ effects. For men aged >50 years, we advocate measurement of hematocrit for detection of polycythemia and a digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening during the first few months of androgen therapy. Subsequently, a hematocrit should be obtained yearly or after changes in therapy, and annual prostate cancer screening can be offered to the patient after a discussion of its risks and benefits.

Hormone Replacement Therapy↗
PubMedDate not supplied

Recent advances in clinical/molecular andrology.

During the last decade there were extensive investigations in clinical and molecular andrology with emphasis on assisted reproduction, micromanipulation techniques of gametes, sperm/egg interaction, male contraception, diabetes mellitus, varicocele, andropause versus menopause, sexual dysfunction, associated hypertension/stress, prostatic carcinoma and molecular parameters of male reproduction. Sperm hyperactivation is a required step in capacitation sequence. Sperm motility is measured by videotape to evaluate the Straight Line Velocity (microm/s) (VSLI). Fertilization/embryonic development results from single sperm transfer (S-MIST) and multiple sperm transfer. Fertilization/embryo development is achieved by injection of immotile sperm into the perivitelline space. To assess sperm viability, a supravital stain suitable for use in combination with immunofluorescent assay, Hoeschst 33258, is used. The dye fluoresces with an intense blue when bound to DNA. To assess sperm plasma membrane integrity, a hypo-osmotic swelling test (HOST) is performed, using fluoresceinated D-mannose enriched albumin (FITC-DMA). The ability of sperm to swell under hypo-osmotic conditions indicates an intact membrane. A human protein, C-peptide, thought to be a useless byproduct of insulin may protect against devastating heart and nerve damage that diabetes causes. Human diabetics may benefit from the substance. Over 15 million Americans have diabetes, in which blood sugar levels rise out of control. There are two types of diabetics: Type I diabetics produce no insulin, the hormone that regulates blood sugar. Type II diabetics are unable to use their insulin properly. Diabetics are at great risk of heart disease and nerve damage, as arteries throughout the body leak and nerve-cell impulses fail. C-peptide is a byproduct of insulin production; it can be produced by the body or synthetically. Production of this protein is not induced by insulin, so diabetics who take insulin do not get C-peptide with it. Varicocele occurs unilaterally on the left side in 78% to 93% of men. Typically the presence of a varicocele is associated with an abnormal semen analysis (sperm density and morphology) and a decreased testicular volume on the affected side. Impaired sperm motility occurs in 89.5% of all varicocele patients. Varicocele ligation improves semen parameters in two thirds of patients. A few studies on andropause included sexual dysfunction, hormonal changes, medical/psychological correlates of impotence, ostenopenia/osteoporosis and bone loss; indices of bone remodeling, testosterone supplementation, androgen, negative feedback and hypothalamo-pituitary-testicular axis. Prostatic cancer is the second leading cause of cancer death for men between the ages of 60 and 80. Early detection involves a simple blood test for prostate specific antigen (PSA). Regular screening and early detection are essential. This is an important test because a high antigen count can be the only symptom. Since no screening is 100% accurate, physicians recommend both a PSA blood test and a physical examination. Although heredity plays a major role in whether a man will develop prostate cancer, men who lead healthy lives can dramatically reduce their chances of cancer: low-fat diet, eating plenty of fruits and vegetables and not smoking. Recent advances in molecular andrology include peptide hormone binding proteins; gonadotropin-releasing hormone (GnRH) agonists/antagonists analog; gonadotropins/their receptors; growth factors/reproduction; peptides as intratesticular regulators; molecular cloning of reproductive proteins/peptides. Gene cloning is applied for characterization/expression of genes coding. The interaction of gp120 with CD4 receptor plays a role in syncytium formation, apoptosis and CD4 cell deletion in human immunodeficiency virus (HIV) infection. The recombinant V3 peptide of fragment 307-330 of HIV-1 can induce sperm head agglutination. The generation process of react

Contraception↗
PubMed2002

Oral testosterone replacement in Korean patients with PADAM.

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.

Administration, Oral↗
PubMed2003

Self-referred patients in an aging male clinic: much more than androgen deficiency alone.

Following an information campaign through the media on the subject of 'andropause', 81 consecutive self-referred patients were evaluated. At presentation these patients had complaints possibly related to partial androgen deficiency in the aging male. Hormonal parameters were measured and specific aging male questionnaires, such as Androgen Deficiency in Aging Male (ADAM) and Aging Males' Symptoms (AMS) scale questionnaires were completed. The median age was 59 (range 53-66) and mean body mass index (BMI) was 26.4 +/- 3.3 kg/m2. Mean testosterone was 479.8 +/- 149.0 ng/dl and mean free testosterone was 10.0 +/- 3.0 ng/dl. Only 7.1% of all patients were diagnosed with 'idiopathic' ADAM. The majority of patients presented with erectile dysfunction. A wide variety of conditions were diagnosed, including hemochromatosis, micro- and macroprolactinoma, hypothyroidism, benign prostate hypertrophism and prostate carcinoma. The scores of AMS psychological, somatovegetative and sexual subscales were 12, 16 and 13, according to AMS classification corresponding to severe, moderate and severe complaints, respectively. There was no correlation between AMS (total and subscales) and testosterone levels. A positive correlation between the somatovegetative subscale of the AMS and both BMI and insulin was found. In conclusion, we observed that in a group of self-referred men andropause is not a frequent diagnosis, and other pathology needs to be addressed requiring a multi-disciplinary approach.

Aged↗
PubMed2004

Rising PSA during Testosterone Replacement Therapy.

Although testosterone replacement therapy (TRT) is indicated for the management of symptomatic hypogonadism, there is still controversy over whether TRT should be administered to middle-aged men for the clinical manifestations of andropause, regardless of whether the serum testosterone levels are depressed or not. Side effects of TRT may include fluid retention, gynecomastia, polycythemia, and exacerbation of existing prostate cancer. As a result, patients on TRT require meticulous surveillance including regular digital rectal examination and serum prostate-specific antigen (PSA) testing. Herein, we present the case of a middle-aged man with andropause and a rising PSA on TRT.

Case Reports↗
PubMed2006

Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy.

Oral estrogens were the treatment of choice for carcinoma of the prostate for over four decades, but were abandoned because of an excess of cardiovascular and thromboembolic toxicity. It is now recognized that most of this toxicity is related to the first pass portal circulation, which upregulates the hepatic metabolism of hormones, lipids and coagulation proteins. Most of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration, which avoids hepatic enzyme induction. It also seems that a short-term but modest increase in cardiovascular morbidity (but not mortality) is compensated for by a long-term cardioprotective benefit, which accrues progressively as vascular remodeling develops over time. Parenteral estrogen therapy has the advantage of giving protection against the effects of andropause (similar to the female menopause), which are induced by conventional androgen suppression and include osteoporotic fracture, hot flashes, asthenia and cognitive dysfunction. In addition, parenteral estrogen therapy is significantly cheaper than contemporary endocrine therapy, with substantive economic implications for health providers.

Administration, Cutaneous↗
PubMed2006

Mechanisms of disease: late-onset hypogonadism.

Late-onset hypogonadism (formerly called the andropause) is a clinical and biochemical syndrome associated with advancing age, which is characterized by typical signs and symptoms and a deficiency in serum testosterone levels. Age-related hypoandrogenism in the male is a result of the interaction of hypothalamopituitary and testicular factors. The hypothalamic pulsatile secretion of gonadotropin-releasing hormone is blunted, due to increased hypothalamic sensitivity to inhibition by steroids, but the responsiveness of the pituitary gonadotrophs seems to be intact. In addition, testicular volume as well as Leydig cell mass and reserve function are diminished. Taken together, these mechanisms result in reduced testosterone secretion and the loss of nycthemeral variability.

Age Factors↗
PubMed2004

Hormone profiles, body mass index and aging male symptoms: results of the Androx Vienna Municipality study.

Aging in the male is accompanied by steroid hormonal decline, and men may develop symptoms associated with hypogonadism. Increased awareness of 'andropause' in recent years has led to greater demand for hormonal assessments, resulting in a rising burden for health economics. We conducted a cross-sectional study to define men at risk for hypogonadism, in whom further hormonal investigation should be performed. We examined 664 blue-collar workers aged 40-60 years at their workplace and determined hormonal status and body mass index (BMI). Men with an abnormal urogenital status and those on medication that might affect endocrine status were excluded from the study. All participants completed the validated Aging Male Symptom (AMS) questionnaire and obtained scores for psychological symptoms, somatovegetative symptoms, and sexual symptoms. Multiple logistic regression analyses revealed a significantly increased risk (represented by the odds ratio) of psychological symptoms for men with low levels of testosterone and/or bioavailable testosterone (BAT). Increased BMI as well as low testosterone levels and/or low BAT levels raised the risk of somatovegetative symptoms. Each decrease of BAT by 1 ng/ml caused an approximately 1.8-fold increase of the risk (odds ratio = 1.832, p = 0.005). Additional independent risk factors were increased age and low luteinizing hormone (LH) level. Men aged 55 years with BMI > 28 kg/m2 and with somatovegetative symptoms and moderate or severe psychological symptoms had a 7.2-fold increase in the risk of a BAT level < 1.5 ng/ml compared to men without these risk factors (p < 0.001). Sensitivity and specificity were 75% and 71%, respectively. The AMS score combined with age and BMI provides an easy and convenient method to identify men with probable androgen deficiency who require hormonal assessment.

Adult↗
PubMed2005

The laboratory assessment of partial androgen deficiency of the aging male.

The diagnosis of andropause, currently named partial androgen deficiency of the aging male (PADAM), by the International Society for the Study of Aging Male (ISSAM), is based on the presence of clinical symptoms together with a biochemical evidence of hypogonadism. Thus, the definition of specific diagnostic criteria, both as clinical manifestations and laboratory findings, is fundamental to identify those men for whom androgen replacement therapy should be warranted. Clinical manifestations suspected to be caused by androgen deficiency are numerous (decreased libido and erectile dysfunction, decreased muscle mass and strength, decreased bone mineral density, increased fat mass, depression, fatigue, irritability, etc) and, for these, the linkage to a real hypogonadal state must be confirmed on an individual basis. In this regard, the exact list of reproductive hormones to be evaluated, for screening or for diagnosis confirmation, together with eventual dynamic endocrine test (GnRH, hCG, clomiphene, etc) must be adjusted. Furthermore, the clinician must be aware of the methods and limits of androgen assays in order to be able to specifically select, where possible, those which are validated by comparison to a "gold standard" or accepted method of measurement.

Andropause↗