International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

BACKGROUND: The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with HSDD. METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS & LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need. Parish SJ, Simon JA, Davis SR, et al. International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women. J Sex Med 2021;18:849-867.

Recommendations on the diagnosis, treatment and monitoring of testosterone deficiency in men.

The relative proportional increase of the elderly population within many countries will become one of the most significant social transformations of the twenty-first century and, for the first time in history, persons aged 65 or above outnumbered children under five years of age globally. One in four persons living in Europe and Northern America will be aged 65 or over. One of the goals of ISSAM is to raise awareness of the special health needs of older men. Since a significant number of aging men will eventually become testosterone deficient, the Hypogonadism panel of ISSAM updates its guidelines.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with hypoactive sexual desire disorder (HSDD). METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS AND LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency.

PURPOSE: Although healthy young men demonstrate a diurnal pattern of serum testosterone, minimal information is available on diurnal variation in young men with testosterone deficiency. MATERIALS AND METHODS: Blood samples were obtained during a 24-hour period at 8 and 11 a.m., 2, 5 and 8 p.m., and 8 a.m. the following morning. Men were categorized with normal or low testosterone if serum testosterone was greater than 300 ng/dl or less than 300 ng/dl at 8 a.m., respectively. RESULTS: We studied 21 volunteers with a mean age of 31.7 years (range 18 to 49). Testosterone was normal in 11 men and low in 10 and all had a normal luteinizing hormone concentration. The low testosterone group was older (mean age 33.4 vs 30.1 years) with a higher body mass index (mean 32.6 vs 27.5 kg/m2) but the differences were not significant. The highest and lowest overall mean testosterone concentrations were observed at 8 a.m. and 2 p.m., respectively. Mean testosterone levels in the normal group declined between 8 a.m. and 2 p.m. from 423 to 358 ng/dl, representing a 15% decrease (p=0.0003). Mean testosterone in the low testosterone group was 228 ng/dl at 8 a.m. and 218 ng/dl at 2 p.m., representing a 4% decline (p=0.54). Calculated free testosterone paralleled total testosterone with a 14% decrease in the normal testosterone group (p <0.001) and a 5% decrease in the low testosterone group (p=0.52). Two of 11 men in the normal group showed no diurnal variation. No subject with baseline testosterone greater than 400 ng/dl had testosterone less than 300 ng/dl at any time point. CONCLUSIONS: Men with low testosterone failed to show diurnal variation on 24-hour blood sampling. We speculate that similar central mechanisms may be involved in the pathophysiology leading to secondary testosterone deficiency as well as the loss of circadian rhythms.

The state of testosterone therapy since the FDA's 2015 labelling changes: Indications and cardiovascular risk.

OBJECTIVE: A label change in testosterone (T) products in March 2015 followed a highly publicized FDA advisory committee meeting in September 2014. Changes included a warning of possible increased cardiovascular (CV) risks and restriction of indicated populations to younger men with a limited set of known aetiologies of testosterone deficiency (TD). These changes greatly impacted clinical practice and public perception of T therapy (TTh). Our aim was to review these changes in the light of subsequently published studies. DESIGN: We identified 23 studies through June 2017, including 12 clinical trials and 11 observational studies. The Testosterone Trials included 790 men aged 65 years and older with TD without known aetiology, assigned to 1-year T gel or placebo. RESULTS: Demonstrated benefits of T included sexual activity and desire, physical activity and mood. There were 9 major adverse CV events (MACE) in the T arm and 16 in the placebo arm. No study reported increased MACE with TTh. A 3-year RCT showed no difference in carotid atherosclerosis. Several large observational studies reported reduced CV events with TTh, including one showing progressively reduced CV and mortality risk with greater duration of TTh. Men whose serum T normalized with TTh had reduced risk of MI and death compared with men whose T levels failed to normalize. CONCLUSION: We conclude that existing evidence fails to support increased CV risk with TTh; on the contrary, there is evidence suggestive of real-world CV benefits. Finally, existing evidence provides benefits of TTh in older men without known aetiology for T deficiency.

Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels.

BACKGROUND: Although delayed ejaculation (DE) is typically characterized as a persistently longer than anticipated or desired time to ejaculation (or orgasm) during sexual activity, a timing-based definition of DE and its association with serum testosterone has not been established in a large cohort. AIM: To examine in an observational study estimated intravaginal ejaculatory latency time (IELT) and masturbatory ejaculation latency time (MELT) in men self-reporting DE, assess the association of IELT and MELT with serum testosterone levels, and determine whether correlation with demographic and sexual parameters exist. METHODS: Men who resided in the United States, Canada, and Mexico were enrolled from 2011 to 2013. Self-estimated IELT and MELT were captured using an Ejaculatory Function Screening Questionnaire in a sample of 988 men screened for possible inclusion in a randomized clinical trial assessing testosterone replacement therapy for ejaculatory dysfunction (EjD) and who self-reported the presence or absence of DE and symptoms of hypogonadism. Additional comorbid EjDs (ie, anejaculation, perceived decrease in ejaculate volume, and decreased force of ejaculation) were recorded. Men with premature ejaculation were excluded from this analysis. IELT and MELT were compared between men self-reporting DE and men without DE. The associations of IELT and MELT with serum testosterone were measured. OUTCOMES: IELT, MELT, and total testosterone levels. RESULTS: Sixty-two percent of screened men self-reported DE with or without comorbid EjDs; 38% did not report DE but did report at least one of the other EjDs. Estimated median IELTs were 20.0 minutes for DE vs 15 minutes for no DE (P < .001). Estimated median MELTs were 15.0 minutes for DE vs 8.0 minutes for no DE (P < .001). Ejaculation time was not associated with serum testosterone levels. Younger men and those with less severe erectile dysfunction had longer IELTs and MELTs. CLINICAL IMPLICATIONS: Estimated ejaculation times during vaginal intercourse and/or masturbation were not associated with serum testosterone levels in this study; thus, routine androgen evaluation is not indicated in these men. STRENGTHS AND LIMITATIONS: This large systematic analysis attempted to objectively assess the ejaculation latency in men with self-reported DE. Limitations were that ejaculation time estimates were self-reported and were queried only once; the questionnaire did not distinguish between failure to achieve orgasm and ejaculation; and assessment of DE was limited to heterosexual vaginal intercourse and masturbation. CONCLUSION: IELT and MELT were longer in men with DE, and there was no association of ejaculation times with serum testosterone levels in this study population. Morgentaler A, Polzer P, Althof S, et al. Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels. J Sex Med 2017;14:1116-1124.

Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. AIM: To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning prevention and management strategies for post-RP erectile function impairment in terms of preoperative patient characteristics and intraoperative factors that could influence erectile function recovery. METHODS: A literature search was performed using Google and PubMed databases for English-language original and review articles published up to August 2016. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) based on a thorough analysis of the literature and committee consensus. RESULTS: Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 1 states that clinicians should discuss the occurrence of postsurgical erectile dysfunction (temporary or permanent) with every candidate for RP (expert opinion, clinical principle). Recommendation 2 states that validated instruments for assessing erectile function recovery such as the International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires are available to monitor EF recovery after RP (LE = 1, GR = A). Recommendation 3 states there is insufficient evidence that a specific surgical technique (open vs laparoscopic vs robot-assisted radical prostatectomy) promotes better results in postoperative EF recovery (LE = 2, GR = C). Recommendation 4 states that recognized predictors of EF recovery include but are not limited to younger age, preoperative EF, and bilateral nerve-sparing surgery (LE = 2, GR = B). Recommendation 5 states that patients should be informed about key elements of the pathophysiology of postoperative erectile dysfunction, such as nerve injury and cavernous venous leak (expert opinion, clinical principle). CONCLUSIONS: This article discusses Recommendations 1 to 5 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:285-296.

Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. AIM: To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning management strategies for post-RP erectile function impairment and to analyze post-RP sexual dysfunction other than erectile dysfunction. METHODS: A literature search was performed using Google and PubMed database for English-language original and review articles published up to August 2016. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 6 states that the recovery of postoperative erectile function can take several years (LE = 2, GR = C). Recommendation 7 states there are conflicting data as to whether penile rehabilitation with phosphodiesterase type 5 inhibitors improves recovery of spontaneous erections (LE = 1, GR = A). Recommendation 8 states that the data are inadequate to support any specific regimen as optimal for penile rehabilitation (LE = 3, GR = C). Recommendation 9 states that men undergoing RP (any technique) are at risk of sexual changes other than erectile dysfunction, including decreased libido, changes in orgasm, anejaculation, Peyronie-like disease, and changes in penile size (LE = 2, GR = B). CONCLUSION: This article discusses Recommendations 6 to 9 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:297-315.

Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Testosterone deficiency (TD), also known as hypogonadism, is a condition affecting a substantial proportion of men as they age. The diagnosis and management of TD can be challenging and clinicians should be aware of the current literature on this condition. AIM: To review the available literature concerning the diagnosis and management of TD and to provide clinically relevant recommendations from the Fourth International Consultation for Sexual Medicine (ICSM) meeting. METHODS: A literature search was performed using the PubMed database for English-language original and review articles published or e-published up to January 2016. MAIN OUTCOME MEASURES: Levels of evidence (LoEs) and grades of recommendations are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Recommendations were given for 12 categories of TD: definition, clinical diagnosis, routine measurement, screening questionnaires, laboratory diagnosis, threshold levels for the biochemical diagnosis of TD, prostate cancer, cardiovascular disease, fertility, testosterone (T) formulations, alternatives to T therapy, and adverse events and monitoring. A total of 42 recommendations were made: of these, 16 were unchanged from the Third ICSM and 26 new recommendations were made during this Fourth ICSM. Most of these recommendations were supported by LoEs 2 and 3. Several key new recommendations include the following: (i) the clinical manifestations of TD occur as a result of decreased serum androgen concentrations or activity, regardless of whether there is an identified underlying etiology [LoE = 1, Grade = A]; (ii) symptomatic men with total T levels lower than 12 nmol/L or 350 ng/dL should be treated with T therapy [LoE = 1, Grade = C]; (iii) a trial of T therapy in symptomatic men with total T levels higher than 12 nmol/L or 350 ng/dL can be considered based on clinical presentation [LoE = 3, Grade = C]; (iv) there is no compelling evidence that T treatment increases the risk of developing prostate cancer or that its use is associated with prostate cancer progression [LoE = 1, Grade = C]; and (v) the weight of evidence indicates that T therapy is not associated with increased cardiovascular risk [LoE = 2, Grade = B]. CONCLUSION: TD is an important condition that can profoundly affect the sexual health of men. We provide guidance regarding its diagnosis and management. Men with TD who receive treatment often experience resolution or improvement in their sexual symptoms and non-sexual health benefits.

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer.

PURPOSE: Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy. MATERIALS AND METHODS: We retrospectively reviewed the records of hypogonadal men treated with testosterone therapy after radiation therapy for prostate cancer at 4 institutions. Serum testosterone, free testosterone, estradiol, sex hormone-binding globulin, prostate specific antigen, prostate specific antigen velocity and prostate biopsy findings were analyzed. RESULTS: A total of 98 men were treated with radiation therapy. Median age was 70.0 years (range 63.0 to 74.3) at initiation of testosterone therapy. Median baseline testosterone was 209 ng/dl (range 152 to 263) and median baseline prostate specific antigen was 0.08 ng/ml (range 0.00 to 0.33). In the cohort the tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median followup was 40.8 months (range 1.5 to 147). Serum testosterone increased to a median of 420 ng/dl (range 231 to 711) during followup (p <0.001). Overall a nonsignificant increase in mean prostate specific antigen was observed from 0.08 ng/ml at baseline to 0.09 ng/ml (p = 0.05). Among patients at high risk prostate specific antigen increased from 0.10 to 0.36 ng/ml (p = 0.018). Six men (6.1%) met criteria for biochemical recurrence. CONCLUSIONS: Testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum prostate specific antigen and a low rate of biochemical recurrence.

Clinical and Demographic Correlates of Ejaculatory Dysfunctions Other Than Premature Ejaculation: A Prospective, Observational Study.

INTRODUCTION: Ejaculatory dysfunctions other than premature ejaculation are commonly encountered in specialized clinics; however, their characterization in community-dwelling men is lacking. AIM: The aim of this study was to evaluate the prevalence, severity, and associated distress of four ejaculatory dysfunctions: delayed ejaculation (DE), anejaculation (AE), perceived ejaculate volume reduction (PEVR) and/or decreased force of ejaculation (DFE) as a function of demographic and clinical characteristics in men. METHODS: Observational analysis of 988 subjects presenting with one or more types of ejaculatory dysfunctions other than premature ejaculation who screened for a randomized clinical trial assessing the efficacy of testosterone replacement on ejaculatory dysfunction. Demographic and clinical characteristics were assessed as potential risk factors using regression analysis. MAIN OUTCOME MEASURES: The main outcome measures used were ejaculatory dysfunction prevalence and scores (3-item Men's Sexual Health Questionnaire Ejaculatory Dysfunction-Short Form [MSHQ-EjD-SF]), and bother (MSHQ-EjD-SF Bother item) and sexual satisfaction/enjoyment (International Index of Erectile Function Questionnaire Q7, Q8) as a function of subject's age, race, body mass index (BMI) and serum testosterone levels (measured by liquid chromatography tandem mass spectrometry). RESULTS: Mean (standard deviation [SD]) age of the participants was 52 years (11). Eighty-eight percent of the men experienced more than one type of ejaculatory dysfunction and 68% considered their symptoms to be bothersome. Prevalence of the ejaculatory dysfunctions was substantial across a range of age, race, BMI, and serum testosterone categories. Prevalence of PEVR and DFE were positively associated with age (<40 years vs. 60-70 years: PEVR: odds ratio [OR], 3.05; 95% confidence interval [CI], 1.32-7.06; DFE: OR, 2.78; 95% CI, 1.46-5.28) while DFE was associated with BMI (≥30 kg/m(2) vs. < 25 kg/m(2) : OR, 1.80; 95% CI, 1.062-3.05). All ejaculatory dysfunctions were more prevalent in black men. CONCLUSION: The majority of the participants experienced multiple ejaculatory dysfunctions and found them to be highly bothersome. Ejaculatory dysfunctions were prevalent across a wide range of demographic and clinical characteristics.

The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men.

INTRODUCTION: In 2014, the International Society for Sexual Medicine (ISSM) convened a panel of experts to develop an evidence-based process of care for the diagnosis and management of testosterone deficiency (TD) in adult men. The panel considered the definition, epidemiology, etiology, physiologic effects, diagnosis, assessment and treatment of TD. It also considered the treatment of TD in special populations and commented on contemporary controversies about testosterone replacement therapy, cardiovascular risk and prostate cancer. AIM: The aim was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of diagnosis and management of TD for clinicians without expertise in endocrinology, such as physicians in family medicine and general urology practice. METHOD: A comprehensive literature review was performed, followed by a structured, 3-day panel meeting and 6-month panel consultation process using electronic communication. The final guideline was compiled from reports by individual panel members on areas reflecting their special expertise, and then agreed by all through an iterative process. RESULTS: This article contains the report of the ISSM TD Process of Care Committee. It offers a definition of TD and recommendations for assessment and treatment in different populations. Finally, best practice treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with TD. CONCLUSION: Development of a process of care is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to new insights into the pathophysiology of TD, as well as new, efficacious and safe treatments. We recommend that this process of care be reevaluated and updated by the ISSM in 4 years.

International expert consensus conference on testosterone deficiency and its treatment held in Prague, Czech Republic.

An international expert consensus conference regarding testosterone deficiency (TD) (also known as hypogonadism) and its treatment was held on 1 October 2015, in Prague, Czech Republic. The impetus for this meeting was to address several key scientific issues that have been misunderstood or distorted during the recent intense media attention to this topic. Eighteen experts from 11 countries participated, from the disciplines of urology, endocrinology, andrology, diabetology, and basic science research. The goal was to identify scientific concepts for which there was broad agreement. It was noted that recent public controversies regarding testosterone therapy have been anchored by two retrospective studies reporting increased cardiovascular (CV) risks. Both these studies contained major flaws, and are contradicted by a large body of evidence suggesting CV benefits with testosterone therapy. Other topics discussed included the negative impact of TD on male health; the questionable validity of restrictions on treatment based on age-specific cut-offs, presence of identified underlying conditions, or application of rigid biochemical thresholds; and the lack of evidence regarding prostate cancer risks. Final consensus statements (resolutions) are under development. It is hoped these will serve as a scientific foundation for further discussion, and will thereby reduce misinformation regarding TD and its treatment.

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men.

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

Bone mineral density and response to treatment in men younger than 50 years with testosterone deficiency and sexual dysfunction or infertility.

PURPOSE: Testosterone deficiency is a known risk factor for osteopenia and osteoporosis in older men. Less is known about the impact of testosterone deficiency on bone mineral density in younger men. MATERIALS AND METHODS: We retrospectively reviewed the charts at an andrology/infertility clinic and identified 399 men younger than 50 years who underwent baseline dual energy x-ray absorptiometry and had total testosterone less than 350 ng/dl or free testosterone less than 1.5 ng/dl. Additional analysis was done in a subgroup of 75 men (18.8%) in whom dual energy x-ray absorptiometry was repeated after treatment at a mean ± SD of 30.4 ± 16.2 months. The determination of osteoporosis or osteopenia was based on T-scores (osteopenia less than -1.0 and osteoporosis less than -2.5) of the lumbar spine and left hip. RESULTS: Of all 399 men 141 (35.3%) had bone mineral density consistent with osteopenia at the lumbar spine (137) and/or the total hip (19). In 11 men (2.75%) bone mineral density was consistent with osteoporosis at the lumbar spine. On multivariate analysis higher body mass index was independently associated with increased bone mineral density at the spine (p <0.0001) as well as the hip (p <0.001). Testosterone treatment in 43 men increased spine bone mineral density (p <0.001). Significant decreases in spine bone mineral density developed in 21 men treated with clomiphene citrate or anastrazole (p = 0.003). No significant change was noted in hip bone mineral density for any treatment. CONCLUSIONS: More than a third of men younger than 50 years with testosterone deficiency and infertility or sexual dysfunction had decreased bone mineral density. Testosterone treatment increased bone mineral density while estrogen modulators such as clomiphene citrate or aromatase inhibitors decreased bone mineral density. These results suggest that dual energy x-ray absorptiometry may be warranted in young men with testosterone deficiency.

Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance.

OBJECTIVE: To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). PATIENTS AND METHODS: Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver-operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan-Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25-14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification. CONCLUSIONS: Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer.

OBJECTIVE: To evaluate the clinical and biochemical effects of long-acting testosterone undecanoate injections in men with prostate cancer treated with brachytherapy, as the use of testosterone therapy (TTh) in men with prostate cancer is highly controversial, with limited published safety data, particularly after brachytherapy treatment. PATIENTS AND METHODS: In all, 20 men treated with brachytherapy for prostate cancer received TTh for symptoms of testosterone deficiency from February 2005 to August 2013. Symptoms of testosterone deficiency included low libido, erectile dysfunction, and fatigue. The mode of TTh was long-acting testosterone undecanoate injections in all cases. Sexual function was assessed by Sexual Health Inventory for Men (SHIM) questionnaire. Serum PSA and testosterone concentrations were recorded monthly for 3 months, then every 3 months for the first year, every 6 months for the second year, and annually then after. RESULTS: The mean (range) age was 62 (49-74) years and the mean (range) serum PSA level at the time of prostate cancer diagnosis was 6.2 (2-11.5) ng/mL. The Gleason score was 2 + 3 in one patient, 3 + 3 in 15 patients, 3 + 4 in three patients and 4 + 4 in one patient. In all, 15 men were stage T1c and five were T2a. The mean (range) baseline total testosterone concentration was 343 (200-592) ng/dL, and 6.9 (2.1-9.7) ng/dL for free testosterone. The mean SHIM scores improved with treatment from 16.1 at baseline to 22.1 with TTh (P = 0.002). There was a decrease in mean PSA level from baseline of 0.7 ng/mL before initiation of TTh to 0.1 ng/mL at last follow-up (P < 0.001), with a median (range) follow-up of 31 (12-48) months. There were no cases of prostate cancer progression or recurrence. CONCLUSIONS: With a median of 31-months follow-up, long-acting testosterone injections in men with prostate cancer treated with brachytherapy produced significant clinical benefits. There were no cases of rising serum PSA, prostate cancer progression or recurrence.

Testosterone, cardiovascular risk, and hormonophobia.

INTRODUCTION: A public outcry against testosterone (T) therapy has suddenly occurred based on two reports suggesting treatment was associated with increased cardiovascular (CV) risks. AIM: To analyze scientific and social bases for concerns regarding T therapy. METHODS: Analysis of recent articles regarding CV risks with T and comparison with events surrounding publication of results of the Women's Health Initiative in 2002. RESULTS: In the first study, the percentage of individuals with an adverse event was lower by half in men who received T compared with untreated men (10.1% vs. 21.2%). However, an opposite conclusion was reached via complex statistics. The second study reported minor increased rate of nonfatal myocardial infarction (MI) up to 90 days after receiving a T prescription compared with the prior 12 months. However, there was no control group, so it is unknown whether this MI rate was increased, reduced, or unchanged compared with untreated men. Neither study provided substantive evidence of risk, yet these were lauded as proof of dangers, despite a substantial literature to the contrary. Similar events followed the publication of the Women's Health Initiative in 2002 when a media frenzy over increased risks with female hormone replacement therapy obscured the fact that the reported excess risk was clinically meaningless, at two events per 1,000 person-years. Stakeholders driving concerns regarding hormone risks are unlikely to be clinicians with real-world patient experience. CONCLUSIONS: The use of weak studies as proof of danger indicates that cultural (i.e., nonscientific) forces are at play. Negative media stories touting T's risks appear fueled by antipharma sentiment, anger against aggressive marketing, and antisexuality. This stance is best described as "hormonophobia." As history shows, evidence alone may be insufficient to alter a public narrative. The true outrage is that social forces and hysteria have combined to deprive men of a useful treatment without regard for medical science.