Management Of Male Hypogonadism Research Articles

Adult Male Hypogonadism: A Laboratory Medicine Perspective on Its Diagnosis and Management.

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism.

Towards optimising diagnosis and management of male hypogonadism: Commentary on CEN-2023-000285 "Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine".

Towards optimising diagnosis and management of male hypogonadism: Commentary on CEN-2023-000285 "Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine".

Management Outcomes in Males With Hypogonadotropic Hypogonadism Treated With Gonadotropins.

Background Hypogonadotropic hypogonadism is an important cause of male infertility and loss of secondary sexual characteristics. Gonadotropin replacement is mandatory for sexual function, bone health, and normal psychological status. This study is to compare the effectiveness of different gonadotropin therapy modalities in the management of male hypogonadism. Methods A randomized open-label prospective study of 51 patients attended the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) with hypogonadotropic hypogonadism, divided randomly into three groups. The first group was treated with human chorionic gonadotropin (hCG) alone, the second group was treated with a combination of both hCG and human menopausal gonadotropin (HMG), while the third group started with hCG alone then followed by combination therapy after six months. Results All modalities of therapy result in a significant increase in mean testicular volume although no clinically significant difference between the groups, but the combination group had the highest increment. The increment in serum testosterone level was statistically significant among the different groups of treatment (p-value < 0.0001). When comparing groups, a higher mean maximum testosterone level (710.4±102.7 ng/dL) was obtained with the combination group followed by the sequential group, with mean maximum testosterone levels (636.0±68.6 ng/dL) (p-value = 0.031). Factors negatively affecting testosterone level include BMI > 30 kg/m2, initial testicular volume < 5 mL, and duration of therapy < 13 months. Conclusions Induction of puberty using recombinant hCG alone is sufficient to induce secondary sexual characteristics, while for fertility issues combination from the start or sequential therapy has better for spermatogenesis. There was no effect of prior exogenous testosterone treatment on final spermatogenesis.

Expert Opinion on the Diagnosis and Management of Male Hypogonadism in India.

Male hypogonadism (MH) is a clinical and biochemical syndrome caused by inadequate synthesis of testosterone. Untreated MH can result in long-term effects, including metabolic, musculoskeletal, mood-related, and reproductive dysfunction. Among Indian men above 40 years of age, the prevalence of MH is 20%-29%. Among men with type 2 diabetes mellitus, 20.7% are found to have hypogonadism. However, due to suboptimal patient-physician communication, MH remains heavily underdiagnosed. For patients with confirmed hypogonadism (either primary or secondary testicular failure), testosterone replacement therapy (TRT) is recommended. Although various formulations exist, optimal TRT remains a considerable challenge as patients often need individually tailored therapeutic strategies. Other challenges include the absence of standardized guidelines on MH for the Indian population, inadequate physician education on MH diagnosis and referral to endocrinologists, and a lack of patient awareness of the long-term effects of MH in relation to comorbidities. Five nationwide advisory board meetings were convened to garner expert opinions on diagnosis, investigations, and available treatment options for MH, as well as the need for a person-centered approach. Experts' opinions have been formulated into a consensus document with the aim of improving the screening, diagnosis, and therapy of men living with hypogonadism.

Clinical practice update on testosterone therapy for male hypogonadism: Contrasting perspectives to optimize care

US Endocrine Society (ES) published a clinical practice guideline on testosterone therapy in men with hypogonadism, and Endocrine Society of Australia (ESA) a position statement on management of male hypogonadism. Both emphasize the importance of diagnosing men who are androgen deficient due to organic (classical or pathological) hypogonadism arising from disorders of the hypothalamus, pituitary or testes, who assuredly benefit from testosterone therapy. Both recognize that men with an intact gonadal axis may have low testosterone concentrations, for instance older men or men with obesity or other medical comorbidities. ES guidelines classify such symptomatic men as having organic (advanced age) or functional (obesity, medical comorbidities) hypogonadism, giving an option for testosterone therapy as a shared decision between clinicians and individual patients. ESA did not recommend testosterone therapy in these men. ES offers a reference range for total testosterone established in young men, while ESA cites age-standardized reference ranges. ES recommends using free testosterone as well as total testosterone to identify men with hypogonadism in conditions where sex hormone-binding globulin (SHBG) is altered, or when total testosterone is borderline. ESA recommends confirmatory biochemical testing with total testosterone, recognizing that this may be lower than expected if SHBG concentrations are low. Both emphasize the importance of identifying pre-existing prostate and cardiovascular disease prior to initiating testosterone therapy, with ES providing specific recommendations for PSA measurement, deferring testosterone therapy after major cardiovascular events and indications for pituitary imaging. These contrasting approaches highlight gaps in the evidence base where individualized patient management is required.

Diagnosis and management of male hypogonadism

Diagnosis and management of male hypogonadism

Adjunct Management of Male Hypogonadism

While testosterone replacement therapy (TRT) has been the main strategy in the management of male hypogonadism, the significant risks associated with TRT have driven the search for alternative strategies to treat hypogonadism. With the high preponderance of secondary and mixed-dysfunction hypogonadism, medications such as clomiphene citrate, aromatase inhibitors, and human chorionic gonadotropin (HCG), which target the hypothalamus/pituitary portions of the hypothalamus-pituitary-gonadal axis, have increasingly been studied despite not being FDA-approved for treatment of male hypogonadism. While these agents have demonstrated some promise in managing male hypogonadism, the current evidence behind their use remains weak and there is a need for well-designed, prospective trials that can further elucidate the roles for these agents in the management of male hypogonadism.

Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH.

Current Practices of Measuring and Reference Range Reporting of Free and Total Testosterone in the United States

The evaluation and management of male hypogonadism should be based on symptoms and on serum testosterone levels. Diagnostically this relies on accurate testing and reference values. Our objective was to define the distribution of reference values and assays for free and total testosterone by clinical laboratories in the United States. Upper and lower reference values, assay methodology and source of published reference ranges were obtained from laboratories across the country. A standardized survey was reviewed with laboratory staff via telephone. Descriptive statistics were used to tabulate results. We surveyed a total of 120 laboratories in 47 states. Total testosterone was measured in house at 73% of laboratories. At the remaining laboratories studies were sent to larger centralized reference facilities. The mean ± SD lower reference value of total testosterone was 231 ± 46 ng/dl (range 160 to 300) and the mean upper limit was 850 ± 141 ng/dl (range 726 to 1,130). Only 9% of laboratories where in-house total testosterone testing was performed created a reference range unique to their region. Others validated the instrument recommended reference values in a small number of internal test samples. For free testosterone 82% of laboratories sent testing to larger centralized reference laboratories where equilibrium dialysis and/or liquid chromatography with mass spectrometry was done. The remaining laboratories used published algorithms to calculate serum free testosterone. Reference ranges for testosterone assays vary significantly among laboratories. The ranges are predominantly defined by limited population studies of men with unknown medical and reproductive histories. These poorly defined and variable reference values, especially the lower limit, affect how clinicians determine treatment.

AB68. Novel regulators of testosterone production

In recent years, interest in testosterone replacement therapy for the management of male hypogonadism has grown significantly. This development has paralleled increased public awareness of the signs and symptoms of hypogonadism (also known as low T or low serum testosterone) and the opportunity to address this problem with therapeutic interventions. Conventionally, medical treatment of hypogonadism has been met with various formulations of exogenous testosterone therapies, albeit such therapies do carry limitations. Limitations range from challenges with therapeutic delivery to possible adverse effects. As understanding has grown with respect to regulatory mechanisms of testosterone production and possible new targets for endogenous production of testosterone, new avenues are opening for consideration of therapy particularly in males with primary hypogonadism (low intratesticular testosterone, high serum luteinizing hormone (LH) with low serum testosterone). Several novel molecular pathways have received interest recently as potential pharmacologic targets to increase Leydig cell testosterone production. These pathways and/or signaling molecules include phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin. The advantages of these new targets are suggested to be: (I) maintain an intratesticular testosterone environment that allows /promotes normal spermatogenesis, (II) avoid side effects of exogenous testosterone supplementation, and (III) maintain the negative feedback mechanism of luteinizing hormone (LH) that prevents testosterone levels from becoming supratherapeutic. These novel options are perceived to offer a more targeted and efficacious approach than other suggested interventions to stimulate Leydig cell testosterone production in individuals with primary hypogonadism, such as exogenous LH, human chorionic gonadotropin, and clomiphene, which all act conventionally through the LH receptor. The proposed novel targets offer opportunities to promote increased endogenous testosterone production through the Leydig cell directly without reliance upon functional LH receptors. This approach may involve the application of small molecules, dietary supplements, or even currently available FDA- approved medications, that may exploit newly refined understanding of signaling pathways at the Leydig cell level. It will be of interest to study all of these potential therapeutic prospects further both with careful animal model experimentation and subsequently in human clinical trials.

AB04. Novel approaches for testosterone replacement therapy

Surging interest in addressing male hypogonadism in recent years has resulted in the identification and development of novel pharmacotherapeutic approaches that may yield increased serum testosterone levels. Testosterone replacement therapy is controversial with concerns surrounding its proper indications and potential side effects. However, interest remains strong to explore treatment options that may address the signs and symptoms of male hypogonadism. Several testosterone preparations are commercially available at this time, and these encompass assorted routes of delivery with specific generic names and dosage recommendations. Routes of delivery include oral, intramuscular, subcutaneous, transdermal and buccal preparations. The routes of administration confer various advantages and disadvantages with respect to efficacy, physiologic levels, duration of effect, ease of administration, and cost. Besides testosterone formulations, alternative options are in development or are used in an off-label mode such as selective androgen receptor modulators (SARMS), selective estrogen receptor modulators (SERMS; clomiphene citrate, enclomiphene), aromatase inhibitors, dihydrotestosterone and human chorionic gonadotropin. These alternatives are hoped to reduce side effects believed to be associated with exogenous testosterone therapy and may be particularly advantageous in the young male with primary hypogonadism whose interest is to preserve normal spermatogenesis (which may be impaired by feedback control mechanisms resulting from exogenous testosterone therapy). Ongoing investigation may reveal select roles for these therapies in the management of male hypogonadism.

Testosterone Administration in Older Men

The only indication for testosterone administration in older men is testosterone replacement therapy for male hypogonadism. Compared with young hypogonadal men, the diagnosis and management of male hypogonadism in older men is more challenging. Both the clinical manifestations of androgen deficiency and low testosterone levels may be caused or modified by comorbid illnesses that occur and medications taken more frequently by older men, resulting in a greater likelihood for overdiagnosis of hypogonadism and subsequent inappropriate use of and inadequate response to testosterone treatment. It is important to use a systematic, holistic approach to the diagnosis and management of older men with hypogonadism.

The role of accurate testosterone testing in the treatment and management of male hypogonadism

A reduced concentration of serum testosterone resulting in male hypogonadism is a well described endocrine abnormality associated with classical signs and symptoms. This manuscript presents one such patient. However, low serum testosterone is being recognized more commonly associated with aging and chronic disease. It is in this situation in which the signs and symptoms of male hypogonadism can be subtle and non-specific. This manuscript reviews examples of such situations and highlights our need to have a reliable and accurate measure of serum testosterone. Both clinicians and researchers need better assays to better understand basic mechanisms, diagnose, treat, and monitor men with testosterone deficiency.

Review of Testim® gel

Hypogonadism is a medical condition characterised by testosterone deficiency in males, accompanied by numerous clinical symptoms, which can negatively affect quality of life and multiple organ systems. Late-onset hypogonadism describes testosterone deficiency or reduced effect seen in ageing men. The conditions are generally managed using testosterone supplementation. Many formulations of testosterone are available, including deep-muscle injections, buccal formulations, transdermal patches and topical gels. Testim® gel 1% testosterone gel (Auxilium Pharmaceuticals, Inc. and Ipsen) has been shown to restore serum testosterone concentrations to within the normal range in men with hypogonadism. Two randomised, controlled studies showed that Testim gel significantly improved sexual motivation, desire, performance and function, as well as positive and negative mood scores and body composition after 90 days, compared with baseline. The magnitude of improvement seen with Testim gel was similar to that achieved with testosterone patches, but with fewer application-site reactions. In another study, improvements in mood and sexual function were seen within the first 2 weeks of treatment. Long-term, open-label extension studies of Testim gel suggest that clinical benefits are maintained for ≤ 12 months without an additional increase in side effects. Notably, Testim gel treatment for 12 months was associated with a gradual increase in bone mineral density, suggesting that Testim gel may help to prevent osteoporosis. The most common adverse events associated with Testim gel were application-site reactions, increased haematological parameters, and moderately increased prostate-specific antigen levels that remained within the normal range in 96% of subjects. Men on any testosterone therapy will require careful monitoring, including serial digital rectal examination and prostate-specific antigen testing. Overall, the clinical evidence so far indicates that Testim gel is a safe and effective treatment option for daily use in the management of male hypogonadism.

Testim ® Gel: Review of Clinical Data

Late-onset hypogonadism is a medical condition characterized by testosterone deficiency in ageing men, accompanied by clinical symptoms, that can negatively affect quality of life and multiple organ systems. The condition is generally managed using testosterone substitution. Many formulations of testosterone are available, including deep-muscle injections, buccal formulations, transdermal patches, and topical gels. Testim ® Gel 1% testosterone gel (Auxilium Pharmaceuticals – Norristown, Pennsylvania, USA, and Ipsen – Paris, France) has been shown to restore serum testosterone concentrations to within the normal range in men with hypogonadism. Two randomized, controlled studies showed that Testim ® Gel significantly improved sexual motivation, desire, performance, and function, as well as positive and negative mood scores and body composition after 90 days, compared with baseline. The magnitude of improvement seen with Testim ® Gel was similar to that achieved with testosterone patches, but with fewer application-site reactions. Improvements in mood and sexual function were seen within the first 2 weeks of treatment. Long-term, open-label extension studies of Testim ® Gel suggest that clinical benefits are maintained for up to 12 months without an additional increase in side-effects. Notably, Testim ® Gel treatment for 12 months was associated with a gradual increase in bone mineral density, suggesting that Testim ® Gel may help to prevent osteoporosis. The most common adverse events associated with Testim ® Gel were application-site reactions, increased haematological parameters, and moderately increased prostate-specific antigen levels that remained within the normal range. Overall, the clinical evidence indicates that Testim ® Gel is a safe and effective treatment option for use in the management of male hypogonadism.

Testosterone replacement therapy: current trends and future directions.

Male hypogonadism is characterized by abnormally low serum testosterone levels associated with typical symptoms, including mood disturbance, sexual dysfunction, decreased muscle mass and strength, and decreased bone mineral density. By restoring serum testosterone levels to the normal range using testosterone replacement therapy, many of these symptoms can be relieved. For many years, injectable testosterone esters or surgically implanted testosterone pellets have been the preferred treatment for male hypogonadism. Recently, newer treatment modalities have been introduced, including transdermal patches and gels. The development of a mucoadhesive sustained-release buccal tablet is the latest innovation, which will provide patients with an additional option. The availability of new treatment modalities has helped to renew interest in the management of male hypogonadism, highlighting the need to address a number of important but previously neglected questions in testosterone replacement therapy. These include the risks and benefits of treatment in different patient populations (e.g. the elderly) and the need for evidence-based diagnosis and treatment monitoring guidelines. While some recommendations have been developed in individual countries, up-to-date, internationally accepted evidence-based guidelines that take into account national differences in clinical practice and healthcare delivery would optimize patient care universally.

Measurement of total serum testosterone levels using commercially available kits: high degree of between-kit variability

Objective: The measurement of total serum testosterone has an established clinical role in the management of male hypogonadism and female androgen excess disorders. We studied the between-kit variability and precision of six different commercially available testosterone assays and compared them with an established in-house method. Design: Laboratory observational prospective study. Setting: Tertiary university medical center clinical laboratory. Patient(s): Three groups of samples each of men (n = 36) and women (n = 15) who had high, normal, or low levels of sex hormone-binding globulin (SHBG), respectively, were studied. Intervention(s): Individual and pooled (male and female) serum samples were analyzed for total testosterone concentration using six different commercially available assays and one in-house method. Main Outcome Measure(s): The between-kit variability and the effect of the mean (± SD) SHBG level were determined, the results obtained with the use of the kits and the in-house method were compared, and the intraassay variability (i.e., precision) was evaluated. Result(s): Male samples demonstrated a 26.3%-40.8% variance in the results obtained with different kits, which was greatest for samples with the lowest SHBG levels. For female samples, between-kit variability ranged from 57%–115% (average, 77%). The percent deviation of the results obtained with the use of commercial methods from those obtained with the use of our in-house assay was greater for men (mean variance, 194%) than for women (mean variance, 67%). The female pool intraassay coefficient of variation was 3.8% with the use of the in-house method and ranged from 8.9%-21.2% with the use of the commercial kits. The male pool intraassay coefficient of variation was 3.1% with the use of the in-house method and ranged from 3.3%-5.5% with the use of the commercial kits. Conclusion(s): Most commercially available kits for measuring the total serum testosterone level demonstrated significant between-kit variability, which was greatest for female samples. Further, samples with the lowest SHBG levels had the highest between-kit variances. These data strongly suggest that the measurement of total serum testosterone using commercial kits may have limited utility, particularly for the detection of hyperandrogenemia.