Androgen Replacement

[Michael Scally MD]

Alukal J.P., Lamm S., Walsh T.J. (eds) Design and Implementation of the Modern Men’s Health Center. Springer, Cham. Design and Implementation of the Modern Men’s Health Center | SpringerLink

This book outlines the approach to comprehensive men’s health deployed at three of the most successful American men’s health centers. It demonstrates the ways in which multidisciplinary care allows patients to easily access their doctors via coordination of care, same day add-on visits, and streamlining of office logistics such as sharing of charts, reports, and results. Guiding readers in establishing an evidence-based, multidisciplinary approach to the management of male patients of all ages, this volume shows how prevention, rapid intervention, cost efficiency, and coordinated care are at the forefront of a health center’s care strategy. The authors of this volume are thought leaders in the disciplines of cardiology, gastroenterology, dermatology, psychiatry, and preventative medicine.

Design and Implementation of the Modern Men’s Health Center: A Multidisciplinary Approach enables urologists, medical subspecialists, and surgical subspecialists to both manage basic patient issues and also to understand how multidisciplinary care enables the success of a men’s health center.

· The Multidisciplinary Men’s Health Center: A Modern-Day Necessity

· Urologic Disease in the Aging Male: A Look Across the Lifespan

· Approach to Primary Care of the Male Patient

· Cardiometabolic Diseases in the Adolescents, Young Adults, and the Elderly

· Male Infertility

· Evaluation and Management of Erectile Dysfunction

· Management of BPH and LUTS

· Management of Testosterone Deficiency in the Aging Male

· Controversies in Prostate Cancer Diagnosis and Management

· Gastroenterology in the Aging Male

· Dermatology in the Aging Man

· Men’s Health and Psychiatry

· Billing and Coding for Infertility Services

· The Role for Nurse Practitioners and Physician Assistants in Men’s Health

· Future Directions in Men’s Health Technology

 

[Michael Scally MD]

Alukal J.P., Lamm S., Walsh T.J. (eds) Design and Implementation of the Modern Men’s Health Center. Springer, Cham. Design and Implementation of the Modern Men’s Health Center | SpringerLink

This book outlines the approach to comprehensive men’s health deployed at three of the most successful American men’s health centers. It demonstrates the ways in which multidisciplinary care allows patients to easily access their doctors via coordination of care, same day add-on visits, and streamlining of office logistics such as sharing of charts, reports, and results. Guiding readers in establishing an evidence-based, multidisciplinary approach to the management of male patients of all ages, this volume shows how prevention, rapid intervention, cost efficiency, and coordinated care are at the forefront of a health center’s care strategy. The authors of this volume are thought leaders in the disciplines of cardiology, gastroenterology, dermatology, psychiatry, and preventative medicine.

Design and Implementation of the Modern Men’s Health Center: A Multidisciplinary Approach enables urologists, medical subspecialists, and surgical subspecialists to both manage basic patient issues and also to understand how multidisciplinary care enables the success of a men’s health center.

· The Multidisciplinary Men’s Health Center: A Modern-Day Necessity

· Urologic Disease in the Aging Male: A Look Across the Lifespan

· Approach to Primary Care of the Male Patient

· Cardiometabolic Diseases in the Adolescents, Young Adults, and the Elderly

· Male Infertility

· Evaluation and Management of Erectile Dysfunction

· Management of BPH and LUTS

· Management of Testosterone Deficiency in the Aging Male

· Controversies in Prostate Cancer Diagnosis and Management

· Gastroenterology in the Aging Male

· Dermatology in the Aging Man

· Men’s Health and Psychiatry

· Billing and Coding for Infertility Services

· The Role for Nurse Practitioners and Physician Assistants in Men’s Health

· Future Directions in Men’s Health Technology

Corradi P.F., Corradi R.B., Greene L.W. (2021) Management of Testosterone Deficiency in the Aging Male. In: Alukal J.P., Lamm S., Walsh T.J. (eds) Design and Implementation of the Modern Men’s Health Center. Springer, Cham. Management of Testosterone Deficiency in the Aging Male

Serum testosterone concentrations decrease as men age. The age-related decline in testosterone levels, confirmed in several studies, results from defects in both testicular and hypothalamic-pituitary function.

In some cases, it is unclear whether coexisting nonspecific signs and symptoms, such as decreases in energy and muscle mass, are a consequence of the age-related decline in endogenous testosterone or whether they are a result of other factors, such as coexisting conditions, concomitant medications, or perhaps aging itself.

There is a widespread belief that undesirable changes in body composition and sexual dysfunction in men with hypogonadism are due to androgen deficiency. However, studies have shown that the amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varies widely in men.

Therefore, benefits of raising testosterone levels in older men have not been established. In addition, metabolic and cardiovascular benefits or risks from testosterone therapy are still being debated.

 

[Michael Scally MD]

[OA] Short-Acting Testosterone: More Physiologic?

Short-acting T therapy, consisting of several doses of T with a shorter half-life throughout the day, minimizes inhibition of the HPG axis and reduces the impairment of spermatogenesis.

Utilizing FDA approved, shorter acting forms of T therapy to maintain homeostasis that more closely reflects normal physiology offers great promise for the treatment of men with hypogonadism—an advantage over long-acting formulations.

This therapy would allow use of FDA approved testosterone supplementation exogenously as opposed to using off-label treatment strategies, while also preserving what fertility the treated subject has.

Support of this hypothesis is needed from additional, longer duration studies utilizing short-acting testosterone. However, it is encouraging that studies performed to date tend to support the hypothesis.

The literature is well established that long-acting testosterone results in HPG suppression and resulting changes in physiology. Short-acting T therapy may be paradigm-changing for the treatment of T deficiency.

Westfield G, Kaiser UB, Lamb DJ, Ramasamy R. Short-Acting Testosterone: More Physiologic? Front Endocrinol (Lausanne). 2020 Sep 30;11:572465. doi: 10.3389/fendo.2020.572465. PMID: 33117287; PMCID: PMC7561367. Short-Acting Testosterone: More Physiologic?

 

[Michael Scally MD]

[OA] Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs.

We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. Long-term safety and efficacy of TRT for puberty completion and maintenance have not been established.

Current TRT regimens are based on consensus and expert opinion, while evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are FDA approved for use in adolescent males in the US. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents.

In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

Vogiatzi M, Tursi JP, Jaffe JS, Hobson S, Rogol AD. Testosterone Use in Adolescent Males: Current Practice and Unmet Needs. Journal of the Endocrine Society 2020. Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

 

[Michael Scally MD]

Male Reproductive Aging

As men age, their reproductive functions, both spermatogenesis and testosterone production, diminish, but slowly and to a relatively small degree. The fall in testosterone appears to be the result of primary hypogonadism in some men and secondary hypogonadism, associated with concomitant illness, in others.

The fall in testosterone production may have some consequences, including decreased sexual function, energy, mood, muscle mass, and bone density. Increasing the serum testosterone of older men with low testosterone to that of young men does improve sexual function, mood, walking, anemia, and bone density, but not energy or cognitive function. The cardiac and prostate risks of increasing testosterone in older men are not yet known.

Snyder PJ. Chapter 15 - Male Reproductive Aging. In: Strauss JF, Barbieri RL, eds. Yen and Jaffe's Reproductive Endocrinology (Eighth Edition). Philadelphia: Elsevier; 2019:357-64.e2. Male Reproductive Aging

 

[Michael Scally MD]

Hypothalamo-Pituitary Unit, Testis, and Male Accessory Organs

The function of the hypothalamo-pituitary-testicular-accessory organ axis is to ensure normal androgenization (including embryonic, infantile, pubertal, and adult sexual maturation), male sexual behavior, and reproductively competent sperm output. Thus the system is important for both the health of individuals and preservation of humankind.

All elements in the system acting together as an integrative regulatory network are critical for male reproductive health. Dysfunction may result in ambiguous genitalia, sex reversal, pubertal delay, eunuchism, impaired spermatogenesis, and reduced systemic androgen exposure.

Furthermore, partial deficiency of reproductive hormones may contribute to some of the features of male aging, impair recovery from protracted critical illness, and induce visceral adiposity with insulin resistance.

This chapter reviews the hypothalamo-pituitary-testicular axis, its components, and their joint regulation. Where practicable, emphasis is on newer discoveries in humans. Hormonal methods to regulate male fertility and to limit age-associated frailty constitute examples of how knowledge of male reproductive physiology is being translated into clinical practice.

Liu PY, Veldhuis JD. Chapter 12 - Hypothalamo-Pituitary Unit, Testis, and Male Accessory Organs. In: Strauss JF, Barbieri RL, eds. Yen and Jaffe's Reproductive Endocrinology (Eighth Edition). Philadelphia: Elsevier; 2019:285-300.e8. Hypothalamo-Pituitary Unit, Testis, and Male Accessory Organs

 

[Michael Scally MD]

Is there a place for anabolic hormones in critical care?

Critical illness is characterized by redistribution of energy and anabolic processes toward favoring vital functions and self-defense against danger. Prolonged critical illness is associated with uncompensated catabolism with major nitrogen loss, muscle wasting, and decreased endocrine responses.

If the whole endocrine system takes part in the acute and chronic responses to critical illness, androgens, insulin, growth hormone, and thyroid hormone are the most important players in the anabolic/catabolic balance.

Levels of sulfate-dehydroepiandrosterone and testosterone are commonly inappropriately low in critically ill patients, with lower levels in sickest patients. These findings have formed the rationale for several trials on replacement therapy with various androgens. Albeit conflicting conclusions from these trials, synthetic androgens such as oxandrolone may be considered as adjunct treatment in selected critically ill patients.

Insulin has become a routine treatment in ICU patients to maintain blood glucose levels of less than 180 mg/dL. During the chronic phase of critical illness, growth hormone (GH) and insulin growth factor (IGF)-1 levels decrease partly as the result of decreased ghrelin levels. Yet so far, trials of GH supplementation have suggested that critically ill patients may not benefit from this treatment. Likewise, albeit promising findings in animal models of critical illness, there is no evidence from clinical trial to supplement ICU patients with thyroid hormones.

Heming N, Maxime V, Ha Vivien HT, Annane D. 71 - Is there a place for anabolic hormones in critical care? In: Deutschman CS, Neligan PJ, eds. Evidence-Based Practice of Critical Care (Third Edition): Elsevier; 2020:512-8.e1. Is there a place for anabolic hormones in critical care?

 

[Michael Scally MD]

[OA] Prevalence of Late-Onset Hypogonadism Among Middle-Aged and Elderly Males in China

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China.

A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis.

The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03).

The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l-1 combined with the presence of ≥ 3 sexual symptoms was used as the criterion of LOH. Among them, 26.1% (103/395) and 73.9% (292/395) had primary and secondary hypogonadism, respectively.

After adjustment for confounding factors, primary and secondary hypogonadism was positively related to age and comorbidities. Body mass index was an independent risk factor for secondary hypogonadism.

The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone, and that the cFT level is more reliable than TT for LOH diagnosis. Secondary hypogonadism is the most common form of LOH.

Liu YJ, Shen XB, Yu N, Shang XJ, Gu YQ, Zuo LD, Xiong CL, Ye Z, Zhou YZ. Prevalence of late-onset hypogonadism among middle-aged and elderly males in China: results from a national survey. Asian J Androl. 2020 Nov 3. doi: 10.4103/aja.aja_59_20. Epub ahead of print. PMID: 33154202. Prevalence of late-onset hypogonadism among middle-aged and elderly males in China: results from a national survey Liu YJ, Shen XB, Yu N, Shang XJ, Gu YQ, Zuo LD, Xiong CL, Ye Z, Zhou YZ, - Asian J Androl

 

[Michael Scally MD]

Clinically Important Differences for Mobility Measures Derived from the Testosterone Trials

Background/Objectives - Accurate estimates of clinically important difference (CID) are required for interpreting the clinical importance of treatments to improve physical function, but CID estimates vary in different disease populations. We determined the CID for two common measures of walking ability in mobility‐limited older men.

Design - Longitudinal, multisite placebo‐controlled trial.

Setting/Participants - Men enrolled in the Testosterone Trials who had self‐reported mobility limitation and gait speed less than 1.2 m/second (n = 429). Testosterone‐ and placebo‐allocated participants were combined for this study.

Results - Mean changes from baseline, adjusting for time‐in‐intervention and site, were 29.6, 13.2, 12.5, −2.4, and −32.6 m for 6MWD, and 15.4, 7.2, 2.1, −3.4, and −7.2 for PF10 in men who reported their mobility was “very/much better,” “little better,” “no change,” “little worse,” or “much worse,” respectively. CID estimates using regression, ROC, and eCDF varied from 5.0–29.6 m for 6MWD, and 5.0–15.2 points for PF10.

Conclusion - CID estimates vary by the population studied and by the method and precision of measurement. Increases of 16 to 30 m for 6MWD and 5 to 15 points for PF10 over 12 months appear to be clinically meaningful in mobility‐limited, older hypogonadal men. These CID estimates may be useful in the design of efficacy trials of therapies to improve physical function.

Stephens-Shields AJ, Farrar JT, Ellenberg SS, et al. Clinically Important Differences for Mobility Measures Derived from the Testosterone Trials. Journal of the American Geriatrics Society 2020. https://doi.org/10.1111/jgs.16942

 

[Michael Scally MD]

[OA] Canadian Trends In Testosterone Therapy

Introduction: Rates of testosterone therapy (TT) prescribing dropped dramatically following the FDA and Health Canada warning regarding potential cardiovascular morbidity in 2014. Since then, prescription rates appear to be increasing in the U.S., however, data on TT use in Canada is lacking. Current database studies suffer from incomplete prescription capture, lack of information on continued use, and confounding from concurrent population growth.

Nova Scotia (NS) is a Canadian province with minimal population growth over the past decade. NS tracks every testosterone prescription and refill through their prescription monitoring program (NSPMP).

All testosterone prescriptions must be written on triplicate forms, allowing for comprehensive tracking. The purpose of this study is to describe the long-term prescription trends of testosterone in a mid-sized Canadian province, using a database that captures 100% of all TT prescriptions written and filled.

Methods: Data were extracted from the NSPMP database on all prescriptions and prescription refills of androgens for men over 18 years of age from 2007-2019. Population statistics were gained using publicly available data from Statistics Canada. Analysis of patterns on individual years and over time were examined for number of patients, prescriptions, and prescribers, as well as formulation.

Results: The male population of Nova Scotia remained relatively stable throughout the study period (2007: 455 064; 2019: 475 478; population increase of 4.3%). A total of 7883 men (1.7% of the male population) received a prescription for TT during the study period; 1673 men received only one prescription in the entire study period and 5446 men remained on TT for longer than six months.

Of the 1730 men under 45 who were prescribed TT, 75% (n=1298) of them stayed on it for more than six months; 1856 men (24%) switched the type of testosterone they were on during the study period.

The number of men receiving TT yearly increased by 98%, from 1235 in 2007 to 2448 in 2019. The number of men receiving TT plateaued in 2014, except for men under age 35, in whom it has steadily increased every year since 2007. Interestingly, primary care providers (PCPs) wrote 92% of all prescriptions on average (interquartile range 90-93).

Conclusions: In a mid-sized Canadian province with stable population growth, prescriptions of testosterone increased until 2014, and then either stabilized or decreased. TT prescriptions in young men have continued to increase yearly. Injectable and gel-based formulations have increased in popularity over the past decade. Future efforts to educate prescribers, especially surrounding the effects on fertility in young men, should be largely focused on PCPs.

Ory J, White JT, Moore J, Grantmyre J. Canadian trends in testosterone therapy. Can Urol Assoc J. 2020 Nov 17. doi: 10.5489/cuaj.6892. Epub ahead of print. PMID: 33212007. Canadian trends in testosterone therapy | Canadian Urological Association Journal

 

[Michael Scally MD]

 

[Michael Scally MD]

Determination of Testosterone in Serum and Saliva By Liquid Chromatography-Tandem Mass Spectrometry

Highlights

An accurate and generic LC-MS/MS method for determination of testosterone in serum and saliva.

Low testosterone measurement in biological matrices.

Clinical and forensic applications over a wide range of concentrations.

A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC-MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids.

Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification.

The standard curve was linear within the range of 4-1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99-101% and 93-95% with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2%.

The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.

Lood Y, Aardal E, Ahlner J, et al. Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: an accurate and sensitive method applied on clinical and forensic samples. Journal of Pharmaceutical and Biomedical Analysis 2020:113823. Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: an accurate and sensitive method applied on clinical and forensic samples

 

[Michael Scally MD]

Controversies in Testosterone Therapy

Introduction Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.

Objectives This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.

Methods A systematic review of literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.

Results Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with increased risk of PCa incidence or recurrence.

Conclusions Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories.

Twitchell DK, Pastuszak AW, Khera M. Controversies in Testosterone Therapy. Sexual Medicine Reviews 2020. Controversies in Testosterone Therapy

 

[Michael Scally MD]

Efficacy of Testosterone Replacement Therapy Plus Alternate-Day Tadalafil for Patients with Late-Onset Hypogonadism

Objective: To examine the efficacy and safety of combination treatment with testosterone replacement therapy plus alternate-day tadalafil (10 mg) in patients with late-onset hypogonadism.

Methods: In this open-label, randomized, crossover study, 29 patients with late-onset hypogonadism were randomly assigned to receive testosterone replacement therapy for 12 weeks followed by combination treatment for 12 weeks (Group 1) or combination treatment for 12 weeks followed by testosterone replacement therapy (Group 2). Symptom questionnaires were administered and blood tests were performed prior to and following each treatment to assess safety and efficacy. At the end of the study, participants were asked about their treatment preferences.

Results: An adverse effect, a rheum symptom, occurred in only one participant, and 26 participants completed the study without any toxicity. Scores on the Aging Male Symptoms scale and the modified short version of the International Index of Erectile Function, and Overactive Bladder Symptom scores were significantly improved in the combination treatment phase of Group 2, whereas no significant difference between the phases were observed in Group 1. In total, 12 out of the 14 participants in Group 1 and 11 out of the 12 participants in Group 2 preferred combination treatment, which reached statistical significance (P = 0.008 and 0.004 for Groups 1 and 2, respectively).

Conclusions: Testosterone replacement therapy with add-on alternate-day tadalafil is a safe and satisfactory treatment for patients with late-onset hypogonadism.

Narukawa T, Soh J, Kanemitsu N, Harikai S, Fujihara A, Ukimura O. Efficacy of testosterone replacement therapy plus alternate-day tadalafil for patients with late-onset hypogonadism: An open-label, randomized, crossover study. Int J Urol. 2020 Dec 19. doi: 10.1111/iju.14468. Epub ahead of print. PMID: 33342003. https://onlinelibrary.wiley.com/doi/10.1111/iju.14468

 

[Michael Scally MD]

Human Chorionic Gonadotropin Treatment: A Viable Option for Management of Secondary Hypogonadism and Male Infertility

Introduction: Low testosterone and its symptoms is a condition affecting many males with severe repercussions on health. Testosterone affects metabolism, bones, joints, and ligaments, the cardiovascular system, liver, sexual functions, muscle mass, and the nervous system. Nowadays, due to recent research showing the benefits of testosterone replacement therapy, this treatment is gaining in popularity among aging men. However, testosterone replacement can increase the risk of infertility.

Areas covered: Human chorionic gonadotropin (HCG) is used in the treatment of male infertility due to its luteinizing hormone (LH)-like action triggering testosterone and sperm production. Due to these positive effects on testosterone production, HCG has also been used to treat secondary hypogonadism.

In this review, based on a literature review for the years 1977-2020 via Google Scholar, we summarize the current research on HCG as treatment for patients suffering from low testosterone and provide an overview of the pros and contras for HCG therapy as compared to testosterone replacement therapy for the treatment of secondary hypogonadism.

Expert opinion: The testosterone and sperm production triggering effects of HCG without the side effects on fertility seen in testosterone replacement therapy make HCG therapy a prime candidate for patients suffering from secondary hypogonadism.

Fink J, Schoenfeld BJ, Hackney AC, Maekawa T, Horie S. Human chorionic gonadotropin treatment: a viable option for management of secondary hypogonadism and male infertility. Expert Rev Endocrinol Metab. 2020 Dec 21:1-8. doi: 10.1080/17446651.2021.1863783. Epub ahead of print. PMID: 33345656. https://www.tandfonline.com/doi/abs/10.1080/17446651.2021.1863783?journalCode=iere20

 

[Michael Scally MD]

[OA] Prevalence of Low Testosterone According to Health Behavior

Testosterone is a representative sex hormone for men, and low testosterone causes erectile dysfunction and cardiovascular disease. The purpose of this study was to investigate the association between low testosterone (LTT) and health behaviors, such as alcohol, smoking, and exercise habits.

We included 2980 men aged 65 to 80. Total serum testosterone and body composition were measured. A testosterone level less than 300 ng/dL was defined as low testosterone. A questionnaire on smoking, alcohol, and exercise was included. The odds ratio (OR) of LTT was calculated through logistic regression.

Model 1 only used age as the adjustment variable, whereas Model 2 adjusted for age, waist circumference, and smoking. The prevalence of LTT was 626 (21.0%). The prevalence of LTT was significant in fat mass (Model 1: OR, 2.133) and muscle mass (Model 1: medium OR, 2.130 and low OR, 3.022; Model 2: medium OR, 1.638 and low OR, 1.740). The prevalence of LTT was also different based on smoking (Model 1: OR, 1.590; Model 2: OR, 1.629) and strength exercise (Model 1: OR, 0.849; Model 2: OR, 0.923).

In conclusion, high frequency strength exercise and smoking cessation lower the prevalence of low testosterone, and obesity and low muscle mass increase the prevalence of low testosterone.

Ko DH, Kim SE, Lee JY. Prevalence of Low Testosterone According to Health Behavior in Older Adults Men. Healthcare (Basel). 2020 Dec 24;9(1):E15. doi: 10.3390/healthcare9010015. PMID: 33374470. https://www.mdpi.com/2227-9032/9/1/15/htm

 

[Michael Scally MD]

[OA] Sensitivity, Specificity and Accuracy of Androgen Deficiency in Ageing Male (ADAM) Questionnaire

Introduction: Androgen deficiency in relation to the increasing age is quite prevalent worldwide. However, diagnosing it in low-income countries is quite a challenge due to cost concerns. Through this study, we plan to measure the sensitivity and specificity of the Androgen Deficiency in Ageing Male (ADAM) questionnaire in the Pakistani population.

Methods: A cross-sectional survey study was conducted from September 2019 to November 2019 in a Pakistani tertiary care hospital. Two hundred and fifty-five participants belonging to ages 30-69 years completed the ADAM Questionnaire in the out-patient department. Venous blood samples were taken to check serum total testosterone levels.

Results: The ADAM questionnaire revealed 90.12% sensitivity, 41.3% specificity, 45.34% positive predictive value, 90.80% negative predictive value, and 61.29% accuracy in the Pakistani population.

Conclusion: Low specificity and positive predictive value have been shown by the ADAM questionnaire. Hence, it cannot be used as a diagnostic tool to detect androgen deficiency, replacing the blood sample.

Naz S, Mandhan N, Shankar P, Raj K, Memon S. Sensitivity, Specificity and Accuracy of Androgen Deficiency in Ageing Male (ADAM) Questionnaire for the Clinical Detection of Androgen Deficiency in the Male Population in Pakistan. Cureus. 2020 Nov 30;12(11):e11788. doi: 10.7759/cureus.11788. PMID: 33409035; PMCID: PMC7779182. Sensitivity, Specificity and Accuracy of Androgen Deficiency in Ageing Male (ADAM) Questionnaire for the Clinical Detection of Androgen Deficiency in the Male Population in Pakistan

 

[Michael Scally MD]

[OA] Design and Conduct of a Real-World Single-Center Registry Study on Testosterone Therapy of Men with Hypogonadism

Aims: Despite the prevalence of hypogonadism (testosterone deficiency [TD]) and widespread use of testosterone therapy (TTh), the effectiveness and safety of long-term testosterone use remains highly contested. Over the past 15 years, we have conducted a registry study of men with TD with a focus on several health outcomes associated with TTh.

Design: Observational patient disease registry study.

Materials and Methods: Noninterventional disease registry with prospective longitudinal data on a large sample of adult hypogonadal men (n = 858) who were treated in a single Urology Clinic. The registry evaluates men with symptomatic TD during a urological exam of patients who have not been previously treated with TTh. There were no inclusion/exclusion criteria. All hormone assays are carried out in a single laboratory.

Standard-of-care treatment of each patient is the sole responsibility of the attending clinician. The registry data consist of comprehensive medical records and questionnaire data collected during patient visits. The registry has a dedicated statistician to ensure adequate statistical analyses of all outcome measures assessed.

Main Outcome Measures: We measured the following parameters: height, weight, waist circumference, hemoglobin, hematocrit, fasting glucose, glycated hemoglobin, insulin, systolic and diastolic blood pressure, heart rate, lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides), highly sensitive C-reactive protein, and total testosterone (T). We assessed quality of life, erectile and urinary function. Clinical parameters were measured two to four times a year. Data are analyzed in regular intervals.

Results: As of 2019, 858 men have been enrolled, of whom 85 patients exhibited primary hypogonadism, and the remaining 773 exhibited secondary or functional hypogonadism. Findings from this registry study on the benefit of TTh on anthropometric parameters, cardiometabolic function, diabetes, and prostate health have been reported.

Conclusions: This registry study has provided real-world clinical evidence and produced new important findings regarding the effectiveness and safety of long-term TTh in hypogonadal men.

Haider KS, Haider A, Doros G, Saad F. Design and Conduct of a Real-World Single-Center Registry Study on Testosterone Therapy of Men with Hypogonadism. Androgens: Clinical Research and Therapeutics 2021;2:1-17. https://doi.org/10.1089/andro.2020.0011

 

[Michael Scally MD]

[OA] “Age-Related” Testosterone Deficiency Should not Be Treated: CON

The negative effects of testosterone deficiency (TD) on human health and quality of life are well demonstrated, including signs, symptoms, metabolic syndrome, obesity, and increased mortality. Recently, substantial evidence emerged, demonstrating the benefits of testosterone therapy in men with classical and “age-related” hypogonadism.

The US Food and Drug Administration (FDA) opposes testosterone therapy in men with age-related hypogonadism but not in men with classical hypogonadism. The FDA acknowledges that TD merits treatment, but the FDA made an artificial distinction between diagnoses where T treatment is warranted and others where the underlying diagnosis is unknown, and treatment is unwarranted. The FDA labeled the unknown category as “age-related.” Since the FDA is unable to demonstrate that one group differs in benefits or risks from the other, there are no bases for this distinction. This action by the FDA is not based on scientific or clinical evidence.

There is no evidence that the response to testosterone therapy of “age-related” hypogonadism occurs via different physiological or biochemical mechanisms than those historically recognized conditions. Also, there is no evidence that “age-related” hypogonadism responds less well to testosterone therapy than “classical” hypogonadism.

More importantly, there is no scientific or clinical evidence to suggest that the risks of testosterone therapy in men with “age-related” hypogonadism are worse or different for men with “classical” hypogonadism. For these reasons, we disagree with the FDA position on testosterone therapy in age-related hypogonadism.

Traish AM. “Age-Related” Testosterone Deficiency Should not Be Treated: CON. Androgens: Clinical Research and Therapeutics 2021;2:46-55. https://doi.org/10.1089/andro.2020.0019

 

[Michael Scally MD]

[OA] Testosterone Replacement and Improved Memory

Clinical Inquires question

Does testosterone replacement improve cognition in memory-impaired older men with low testosterone?

Evidence-based answer

Testosterone therapy does not appear to improve cognition in older men with low testosterone and memory impairment (strength of recommendation B, based on systematic reviews of small, low-quality randomized controlled trials [RCTs] and individual, small RCTs).

Lyon C, Wong A, DeSanto K. Testosterone replacement and improved memory. Can Fam Physician. 2021 Jan;67(1):e9. doi: 10.46747/cfp.6701e9. PMID: 33483406. Testosterone replacement and improved memory