Treatment Of Hypogonadism In Men Research Articles

P-063 Effect of varicocelectomy on serum testosterone levels of hypogonadal men above 40 years of age

Abstract Study question Can varicocelectomy be indicated for the treatment of hypogonadism in men above 40 years of age? Summary answer Varicocelectomy improves serum testosterone (T) levels in men with preoperative hypogonadism. This improvement can be anticipated in men above the age of 40 years. What is known already Varicocele ligation is a common intervention used to restore male fertility potential and enhance conception rates. Few studies reported a favorable effect for varicocelectomy on serum T levels stirring some scientists to indicate treatment for men with late onset hypogonadism. Nonetheless, data is still scarce for such a recommendation highlighting the importance of this work Study design, size, duration The charts of 1696 patients who underwent microsurgical subinguinal varicocelectomy for clinically palpable disease between 2011-2023 were retrospectively reviewed. Patients with available pre- and post-operative serum hormone levels were included in the study while those receiving any form of androgen replacement or induction treatment or with known secondary causes of hypogonadism were excluded. Participants/materials, setting, methods Medical charts were reviewed to collect demographic and clinical data. Patients were classified into 2 groups according to preoperative T levels: hypogonadism group (serum T < 10.4 nmol/L) (n = 226) and eugonadal group (serum T ≥ 10.4 nmol/L) (n = 1469). The hypogonadism group was subclassified according to age into less (n = 161) or ≥ (n=66) 40 years of age. Changes in hormone levels were analyzed using Wilcoxon Signed Ranked. A p value <0.05 was considered significant. Main results and the role of chance The patients mean age was 33.6 ± 8.5 years. Their mean BMI was 27.2 ± 5.8 Kg/m2, mean left testis size was 13.4 ± 3.5 cm3 and right testis size 14.4 ± 4.5 cm3. The maximum left and right vein diameters was 3.9 ± 1.3 mm and 2.46 ± 0.73 mm. Unilateral and bilateral microsurgical varicocelectomy were performed in 82% and 18% of cases, respectively. Post-operatively, no significant changes were observed in hormone levels in comparison to preoperative values in the eugonadal group. However, patients with preoperative hypogonadism had significant increase in serum T (7.7±2.2 vs 11.7±6.6, p < 0.001) and E2 (72.5±31.3 vs 94.8±42, p < 0.001) levels following the intervention. These significant improvements were observed in both men < 40 years of age (p < 0.001 for both T and E2) and ≥ 40 years of age (T: p = 0.027, E2: p = 0.024). Limitations, reasons for caution Results were obtained from a retrospective chart review. The majority of these patients performed surgery for fertility reasons and data regarding hypogonadism symptoms is lacking. Wider implications of the findings Results of this study further confirm that an increase in serum testosterone is likely to be anticipated in patients undergoing varicocelectomy who have low serum testosterone levels pre-operatively Trial registration number not applicable

Diagnosis and treatment of hypogonadism in men seeking to preserve fertility - what are the options?

Male hypogonadism is a clinical syndrome that results in low testosterone levels and frequently leads to infertility. The syndrome occurs due to disruption at one or more levels of the hypothalamic-pituitary-gonadal axis. Testosterone replacement therapy (TRT) is the most common treatment utilised for male hypogonadism. However, long-acting forms of TRT leads to infertility and so is inappropriate for patients wishing to conceive. For patients who wish to remain fertile, nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone and aromatase inhibitors have been used as alternative treatment options with different degrees of success. A review of the literature was performed to identify the safety and efficacy of alternative treatment options. Gonadotropin releasing hormone can successfully induce spermatogenesis but is impractical to administer. Likewise, aromatase inhibitors have limited use due to inducing osteopenia. Nasal TRT may be a good treatment option for these patients, but its efficacy has so far only been demonstrated in small sample sizes. However, clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control and can successfully induce fertility in hypogonadism patients.

Trazodone associated with Clomiphene a proposal treatment for post finasteride syndrome

Erectile dysfunction caused by medications are probably caused by the disconnection of synaptic circuits responsible for linking libido to erection. For instance, it is well known that sexual dysfunction may occur in patients treated with finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for androgenetic alopecia and benign prostatic hyperplasia. Interestingly, sexual dysfunction persists after drug discontinuation. Clomiphene citrate is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men. It acts centrally to increase secretion of luteinizing hormone. Trazodone is a multifunctional drug with hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors, therefore this drug can cause severe priapism and in many cases causing penile necrosis or permanent loss of erectile function. Therefore, we propose that trazodone and clomiphene can restore libido synaptic circuits, thus these associated drugs can be a treatment for post-finasteride syndrome.

MP43-06 TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME: ANALYSIS OF A GLOBAL FEDERATED RESEARCH NETWORK

You have accessJournal of UrologyCME1 Apr 2023MP43-06 TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME: ANALYSIS OF A GLOBAL FEDERATED RESEARCH NETWORK Katherine Campbell, Justin Loloi, Chase Carto, and Ranjith Ramasamy Katherine CampbellKatherine Campbell More articles by this author , Justin LoloiJustin Loloi More articles by this author , Chase CartoChase Carto More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Klinefelter Syndrome (KS, 47 XXY) represents the most common genetic form of male hypogonadism. Given the degree and prevalence of hypogonadism in these men, it is recommended that patients with KS and testosterone deficiency should be treated with lifelong testosterone supplementation (TRT) that begins at puberty to secure the development of sexual male characteristics and prevent long-term sequelae. Primary hypogonadism (including KS) is an on-label indication for TRT. The objective of this study was to determine the rates of hypogonadism and prescription of TRT in men with KS. We hypothesized that men with KS are under treated for testosterone deficiency with TRT because of the relationship between KS and neurocognitive impairment. METHODS: We queried TriNetX, a large, multicenter electronic health record database, to identify all men with a diagnosis of Klinefelter syndrome (ICD-10-CM Q98.4). We collected data on comorbidities including cognitive impairment, type 2 diabetes mellitus, obesity, hyperlipidemia, hypertension, osteoporosis in addition to demographic characteristics. Prevalence of testosterone deficiency was determined as defined by testosterone level <300 ng/dl. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later. RESULTS: There were 5,437 total men with diagnosis of KS. A total of 1,581 men with KS received laboratory measurement of testosterone level, 1,113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50–658]. Of the 1,113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT. CONCLUSIONS: Despite the recent addition of KS as an indication for treatment to the FDA-approved label for TRT, in this large, retrospective study, TRT was under-prescribed in men with KS. Under treatment of hypogonadism in men with KS can lead to long-term consequences such as metabolic syndrome and cognitive impairment. This is the first study to evaluate TRT prescribing patterns in men with KS. Future research is needed to corroborate these findings and to evaluate barriers, especially as related to to receiving care in this population. Source of Funding: This work was supported by NIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to Ranjith Ramasamy © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e603 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katherine Campbell More articles by this author Justin Loloi More articles by this author Chase Carto More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Male Hypogonadism (According to the Materials of the European Association of Urology)

Male hypogonadism is a clinical syndrome which is the result of insufficient production of the sex hormone testosterone by the testicles and the number of spermatozoa. The article reveals modern views on the physiology and pathophysiology of testosteroneogenesis in the male organism, provides information on the etiology, pathogenesis, classification, diagnosis and modern treatment of hypogonadism in men. Literature on the results of global and European researches in recent years, as well as materials of the Guideline of the European Association of Urology for 2022, were used in the article. An individual therapeutic approach to each patient with hypogonadism was demonstrated. The importance of diagnosis of chronic and systemic comorbid diseases that cause the risk of hypogonadism, the need to determine the body mass index and the measurement of waist circumference, the size of the testicles, the penis and the presence of secondary sexual characteristic was established. The article includes necessary biochemical and instrumental studies for the diagnosis of hypogonadism. Specific contraindications for hormone replacement therapy are identified. Absolute contraindications for testosterone therapy are indicated: topically widespread or metastatic prostate cancer (PC), breast cancer of men; men who desire to have children; hematocrit level &gt;54%; uncontrolled or poorly controlled stagnant heart failure. Relative contraindications include IPSS&gt;19, initial hematocrit of 48-50 %, venous thromboembolism in a family history. The article also provides recommendations for testosterone therapy. It has been proven that testosterone therapy improves mild forms of erectile dysfunction (ED) and libido in men with hypogonade states; improves the frequency of sexual intercourses, orgasm and general pleasure; increases low-fat mass, reduces fat and improves insulin resistance; normalizes body weight, waist circumference and lipid profile; relieves the symptoms of depression in men with hypogonadism; improves bone mineral density. It has been demonstrated that the use of testosterone therapy in eugonadal men is not indicated. Testosterone therapy should be used as first-line treatment in patients with symptomatic hypogonadism and moderate ED. In addition, it is necessary to use a combination of type 5 phosphodiesterase inhibitors and testosterone treatment in more severe ED forms. It is also necessary to use standard medical treatments for severe symptoms of depression and osteoporosis. The therapy of hypogonadism, non-medication and medication, the necessary medicines and the peculiarities of their use are widely described. The article shows that weight loss due to low calorie diet and regular physical activity leads to a slight improvement in testosterone levels, testosterone gels and prolonged injection drugs are testosterone drugs have the best safety profile, and gonadotropin treatment can be used in men with secondary hypogonadism. It is noted that before the treatment with testosterone, it is necessary to treat organic causes of hypogonadism (for example, pituitary tumors, hyperprolactinemia, etc.), improve lifestyle and reduce body weight in persons with obesity; cancel drugs that can impair testosterone production. Much attention is paid to the risk factors by the treatment with testosterone. Testosterone therapy is contraindicated for men with secondary hypogonadism who wish fertility, men with active PC or breast cancer. Restoration of testosterone concentration in serum relieves the symptoms and signs of hypogonadism in men after 3 months of treatment. Therefore, testosterone therapy leads to improvement of the quality of patient’s life.

Are SERMs safe and effective for the treatment of hypogonadism in men?

YES. For both normal-weight and obese men with low testosterone levels and hypogonadal symptoms, selective estrogen receptor modulators (SERMs), such as clomiphene citrate (CC) and enclomiphene citrate (EC), appear to be effective and safe for improving serum testosterone levels (strength of recommendation [SOR]: C, disease-oriented outcomes from randomized controlled trials [RCTs] and cohort studies). Studies also show that symptom improvement is comparable to that with exogenous testosterone replacement and similar to eugonadal men (SOR: B, patient-oriented outcomes from retrospective cohort studies).

Impact of Testosterone Therapy on Hematocrit and Polycythemia: Evaluation of Data From Two Ongoing Open-Label Randomized Single-Center Clinical Trials

Introduction & Objective: Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC) (short-acting). Subject and Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: Trial 1: 800mg subcutaneous Testopel T pellets; Trial 2: 11mg TID Intranasal testosterone (Natesto) or 200mg x 2 weeks TC for 2 months. Serum T, Hematocrit (HCT), and prevalence of polycythemia (as defined as HCT >50%) were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon rank test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL. T pellets showed a statistically significant increase in HCT from 44.6 [42.0-46.6] to 46.7 [42.6-48.9] (p<0.001), with a prevalence of 7/47 (14%) men developing polycythemia. A safety trigger for HCT greater than 54% occurred in 2/47 (4%). The treatment effect was independent of baseline serum testosterone. TRT with Natesto decreased HCT, from 43.4 [41.6-46.1] to 43.4 [40.6-46.5], however not statistically significant (p=0.262). TC statistically increased HCT from 41.6 [40.3-43.1] to 43.8 [43.5-47.4] (p=0.018), with 0% of men developing polycythemia in both groups. Conclusions: Long acting TRT appears to increase hematocrit compared to short-acting testosterone therapies. Treatment of hypogonadal men with Intranasal T Natesto and testosterone cypionate successfully achieved target serum T level and maintained HCT levels. Longer-term durability and safety effects of the intervention remain to be further investigated.

Updated Review of Testosterone Replacement Therapy in the Setting of Prostate Cancer

Since the 1940s, elevated serum testosterone (T) levels have been infamously suggested as a causal factor in the development of prostate cancer (PCa); this time was also the dawn of both surgically and pharmacologically induced castration. However, men suffering from primary or secondary hypogonadism and who are concomitantly paradoxically at risk for developing PCa cited the adverse effects of T deficiency. In the past 25 years, researchers have published on the genetic, biochemical, and clinical outcomes of testosterone replacement therapy (TRT) in hypogonadal men. The longstanding dogma of the deleterious effects of TRT has recently been challenged, and it now appears that TRT may have an important therapeutic role in the treatment of hypogonadism in those men with either low-risk, active, or previously treated PCa. This review summarizes the latest findings on the treatment of hypogonadal men with a history of PCa, emphasizing results of clinical research studies.

Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis.

Background Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P=0.006) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P=0.002) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P=0.0005). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

SAT-044 Treatment of Hypogonadal Men with a New Oral Testosterone Undecanoate (TU) Formulation Improves Psychosexual, Well-Being and Body Composition and Bone Density Parameters

Introduction and Objective: A new, first-in-class oral testosterone (T) replacement therapy product [T-undecanoate (TU) capsules] was recently approved by FDA to treat hypogonadal men. Clinical trials were conducted to evaluate, in part, the impact of oral TU therapy on important secondary efficacy endpoints: Psychosexual and/or general well-being (Trial I and II); and body composition and bone mineral density (BMD) (Trial II). Subject and Methods: Hypogonadal men (AM serum T ≤ 300 ng/dL) age 18 to 65 (Trial I) or 75 years old (Trial II) were randomized into open-label, active-comparator (T-gel/solution) trials. Subjects received: Trial 1: Oral TU (n=166) or a topical T solution (n=55) for 4-6 mos.; or Trial II: Oral TU (n=162) or T-gel (n=163) for 12 mos. The starting oral TU dose (with food) was 237 mg, BID in Trial I and 316 mg, BID in Trial II; up to 2 dose-titration opportunities were available to achieve eugonadal T concentrations (assayed by LC-MS/MS). In Trial I, Psychosexual Daily Questionnaires (PDQ) were completed by study subjects for 7 days at baseline and prior to final clinic visit (Day 105-180). In Trial II, the SF-36 well-being questionnaire was completed on Days 0, 30, 90, 180, 270 and 365 and PDQs were completed for 7 days prior to clinic visits on these same days. In Trial II body composition and BMD was assessed by DEXA scan on Days 0, 180 and 365. Safety was monitored by physical exam and standard clinical lab tests. Results: Mean serum T in response to oral TU was 489 ± 155 ng/dL (mean ± SD) (Trial I) and 628 ± 342 ng/dL (Trial II); 84% of subjects in each trial achieved mean T concentrations in the eugonadal range. Statistically significant mean changes from baseline (p<0.0001) for most SF-36 well-being parameters were observed in both oral TU and T-gel groups. Psychosexual questionnaire results also demonstrated statistically significant improvement over baseline (p<0.0001) in most parameters at Day 30 and all timepoints thereafter in both trials. On Days 180 and 365 (v. baseline) oral TU was associated with a significant reduction in fat mass [-1.92 ± 2.79 (SD) and -2.4 ± 3.6 kg, respectively] (p<0.0001) and an increase in lean body mass [+2.87 ± 2.73 and +3.15 ± 2.69 kg, respectively] (p<0.0001). Oral TU increased mean BMD over baseline on Days 180 and 365 in spine [+0.013 ± 0.035 and +0.018 ± 0.042 g/cm2, respectively (p<0.0001)] and hip [+0.006 ± 0.019 and +0.012 ± 0.023 g/cm2, respectively (p<0.0001)]. Oral TU exhibited a safety profile consistent with commonly prescribed topical T-comparators. Modest increases in cuff sBP of 2.8 ± 11.84 (SD) mm Hg and 1.8 ± 10.76 mm Hg were observed in Trial I for both oral TU and the comparator T-solution. Conclusions: Treatment of hypogonadal men with oral TU yielded circulating mean T concentrations in the mid-eugonadal range and significantly improved psychosexual, general well-being, body composition and BMD parameters comparable to transdermal T administration.

Effect of Varicocele and Its Treatment on Testosterone in Hypogonadal Men with Varicocele: Review of the Literature

Varicocele might cause deterioration in Leydig cell functions, and it is a significant risk factor for hypogonadism. Some controversial issues have been raised in the treatment of hypogonadal men with varicoceles. Symptomatic hypogonadal men with varicoceles have two options: testosterone replacement therapy or varicocele treatment. Both approaches have some advantages and disadvantages. This review summarizes the effect of varicoceles on total plasma testosterone level and addresses whether varicocele repair is effective to improve testosterone levels in hypogonadal men with varicoceles. Experience from large clinical studies in the literature suggests that varicocele repair may increase serum testosterone level in men with varicoceles and testosterone deficiency. Varicocele repair could be offered to men with clinically palpable varicocele and hypogonadism. As the treatment method, microsurgical varicocele repair could be preferred to provide the best improvement. Another advantage of varicocele repair for hypogonadism, instead of exogenous testosterone treatment, is its ability to preserve the fertility status in men who may desire a child in the future. However, further studies are required to clarify varicocel-related Leydig cell dysfunction and to advise hypogonadal patients about the sufficient effectiveness of varicocele repair.

PD26-10 TREATMENT OF HYPOGONADAL MEN WITH ORAL TESTOSTERONE UNDECANOATE (TU) IMPROVES PSYCHO-SEXUAL, WELL-BEING AND BODY COMPOSITION PARAMETERS

INTRODUCTION AND OBJECTIVE: A new, first-in-class oral testosterone (T) replacement therapy product [T-undecanoate (TU) capsules] was recently approved by FDA to treat appropriate hypogonadal men. Two clinical trials were conducted to evaluate, in part, the impact of oral TU therapy on important secondary efficacy endpoints: a) Psycho-sexual and/or general health/well-being (Trial I and II) and; b) Body composition (Trial II). METHODS: Hypogonadal men (AM serum T ≤ 300 ng/dL) age 18 to 65 (Trial I) or 75 years old (Trial II) were randomized into open-label, active-comparator (T-gel/solution) trials. Subjects received: Trial 1: Either oral TU (n=166) or a topical T solution (Axiron®; n=55) for 4-6 mos.; or Trial II: Oral TU (n=162) or T-gel (AndroGel® 1%; n=163) for 12 mos. The starting oral TU dose (with food) was 237 mg TU, BID in Trial I and 316 mg TU, BID in Trial II; up to 2 dose-titration opportunities were available to achieve eugonadal T concentrations (Cavg; assayed by LC-MS/MS). In Trial I, Psycho-sexual Daily Questionnaires (PDQ) were completed by study subjects for 7 days at baseline and prior to final clinic visit (Day 105-180). In Trial II, the SF-36 well-being questionnaire was completed on Days 0, 30, 90, 180, 270 and 365 and PDQs were completed for 7 days prior to clinic visits on these same days. Body composition was assessed by DEXA scan on Days 0, 180 and 365. Safety was monitored by physical exam and standard clinical laboratory tests. RESULTS: Serum T Cavg in response to oral TU was 489 ± 155 ng/dL (mean ± SD) (Trial I) and 628 ± 342 ng/dL (Trial II); 84% of subjects in each trial achieved T Cavg in the eugonadal range. Mean changes from baseline for SF-36 well-being parameters increased significantly in both oral TU and topical T groups. Psycho-sexual questionnaire results also demonstrated statistically significant improvement (p<0.0001) in each parameter at Day 30 and all time points thereafter. At Day 365, oral TU was associated with a statistically significant reduction in fat mass [-2.4 ± 3.6 (SD) kg] and increase in lean mass (+3.2 ± 2.7 kg). Oral TU also significantly increased mean BMD over baseline in hip [+0.01 ± 0.04 (SD) g/cm2] and spine (+0.01 ± 0.02 g/ cm2]. Oral TU exhibited a safety profile consistent with other available T-replacement products -- including the potential to increase blood pressure in some men. CONCLUSIONS: Treatment of hypogonadal men with oral TU yielded circulating T Cavg concentrations in the mid-eugonadal range and significantly improved psycho-sexual, general well-being and body composition parameters. Source of Funding: Clarus Therapeutics, Inc.

Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism

Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.

Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.

ABSTRACTPurpose The 2018 American Urological Association guidelines on the Evaluation and Management of Testosterone Deficiency recommended that 300 ng/dL be used as the threshold for prescribing testosterone replacement therapy (TRT). However, it is not uncommon for men to present with signs and symptoms of testosterone deficiency, despite having testosterone levels greater than 300 ng/dL. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. We sought to evaluate serum testosterone response and duration of therapy of hCG monotherapy for men with symptoms of hypogonadism, but total testosterone levels > 300 ng/dL.Materials and Methods We performed a multi-institutional retrospective case series of men receiving hCG monotherapy for symptomatic hypogonadism. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy. Descriptive analysis was performed and Mann Whitney U Test was utilized for statistical analysis.Results Of the 20 men included in the study, treatment indications included low libido (45%), lack of energy (50%), and erectile dysfunction (45%). Mean testosterone improved by 49.9% from a baseline of 362 ng/dL (SD 158) to 519.8 ng/dL (SD 265.6), (p=0.006). Median duration of therapy was 8 months (SD 5 months). Fifty percent of patients reported symptom improvement.Conclusions Treatment of hypogonadal symptoms with hCG for men who have a baseline testosterone level > 300 ng/dL appears to be safe and efficacious with no adverse events.

233 Human Chorionic Gonadotropin (hCG) Monotherapy for the Treatment of Symptoms of Hypogonadism in Men with Total Testosterone > 300 ng/Dl

Recent testosterone deficiency guidelines from the American Urological Association suggest that total testosterone < 300ng/dL be used as threshold for prescribing testosterone therapy. Treatment for men with total testosterone > 300ng/dL along with symptoms include selective estrogen receptor modulators or human Chorionic Gonadotropin (hCG) as well as a combination of these medications. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. To evaluate serum testosterone response and duration of therapy for men treated with hCG monotherapy for symptomatic hypogonadism. We performed a retrospective chart review of men who were receiving hCG. A total of 37 patients met inclusion criteria of being treated with hCG monotherapy (1500 IU SQ weekly) for symptoms of hypogonadism and a total serum testosterone level > 300 ng/dL. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy.

Clomiphene Citrate for the Treatment of Hypogonadism.

Clomiphene citrate (CC) is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men since the 1970s. It acts centrally to increase secretion of luteinizing hormone and follicle-stimulating hormone, thereby increasing testosterone production and serum levels. Unlike testosterone replacement therapy, CC does not suppress the hypothalamic-pituitary-gonadal axis, preserving intratesticular testosterone production and spermatogenesis. This is especially useful in treating hypogonadal men who are interested in fertility. To review the literature regarding the use of CC in the setting of hypogonadism. A review of the relevant literature through September 2018 was performed via PubMed. The data regarding the efficacy and safety of CC when used in the setting of hypogonadism is summarized. Although results are mixed, many studies show CC reduces symptoms in hypogonadal men. Studies have also shown improvement in erectile function and bone mineral density, as well as a reduction in body mass index. There have been few studies investigating fertility rates in hypogonadal men treated with CC, but a metaanalysis of these shows significant improvement in fertility rates. Several studies show improvement in semen parameters. Few studies have investigated adverse effects of the drug. Reports include headache, dizziness, gynecomastia, and exacerbation of psychiatric illnesses. Despite these reports, CC is generally considered to be safe and well tolerated. CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, etal. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.

Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta-analysis of randomized controlled trials.

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2 =28%; p=0.02) and -27.94 (95% CI: -52.33 to -3.54; I2 =76%; p=0.02).Subgroup analyses revealed that the heterogeneity (I2 =76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2 =45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD=2.79; 95% CI: 0.73 to 4.86; I2 =0%; p=0.008), but there was no improvement in developed countries (MD=1.02; 95% CI: -4.55 to 6.60; I2 =91%; p=0.72). However, LDL-C levels were not improved consistently.Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.

Treatment of Hypogonadism: Current and Future Therapies.

The treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits of androgens whilst minimizing unwanted side effects.

A summary of the controversy surrounding off-label medications in men's health.

While there are common and accepted practices in men’s health, barriers exist to treatment of these disorders with Food and Drug Administration (FDA) approved medications. In male factor infertility, these barriers include studies that are often underpowered for desired outcomes. This has led to the use of medications previously examined in females in an off-label fashion for treatment of male infertility. Issues surrounding the treatment of hypogonadism in men are more complex, becoming increasingly so in the last few years. Drug companies have developed compounds for treatment of hypogonadism for particular subgroups of men. However, the indicated groups for these medications are narrow leading to these medications being regularly used for an indication the FDA considers to be part of “normal aging”. This work will examine the controversy surrounding the use of off-label medications in men’s health and how factors like pharma advertising, FDA regulation and difficulties in creating adequate studies has affected the current paradigm.

PD34-03 THE INCIDENCE AND TREATMENT OF HYPOGONADISM IN PATIENTS WITH TESTICULAR CANCER

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I1 Apr 2016PD34-03 THE INCIDENCE AND TREATMENT OF HYPOGONADISM IN PATIENTS WITH TESTICULAR CANCER Jamal Nabhani, Diana Jin, and Siamak Daneshmand Jamal NabhaniJamal Nabhani More articles by this author , Diana JinDiana Jin More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.988AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Though the diagnosis of testicular cancer (TC) has been associated with hypogonadism, the mechanistic and clinical interrelation remains unclear. The fraction of men with TC who are on androgen replacement therapy (ART) has not been previously quantified. We investigate the pattern of diagnosis and treatment of hypogonadism in men with TC. METHODS Using Humana administrative claims data from 2007-2013, men with and without a diagnosis of TC were identified. Testosterone laboratory and prescription data were analyzed between the cohorts and by decade of life in order to adjust for differences in the rates of hypogonadism with age. RESULTS 2,647 men with and 6,337,475 without TC were identified, yielding a rate of 4.2 cases of TC per 100,000 men, peaking at 11.6 per 100,000 men in the fourth decade of life. 428 men with testis cancer (16.2%) had a serum testosterone checked. The odds ratio (OR) of having a serum testosterone level measured in patients with TC was 4.5 95% CI [4.0,5.0]. This increased with age, peaking with an 8.2 fold increase in the ninth decade of life. 211 of the 428 men with TC who had a serum testosterone measured (8.0% of all men with testis cancer) were found to have a low serum testosterone. The OR of having a low testosterone was 4.0 95% CI [3.5,4.6] in men with TC compared to controls, peaking at 6.1 in the eighth decade of life. The diagnosis of low serum testosterone predated TC diagnosis by > 30 days in 144 men (5.4% of all TC cases). In terms of ART 225 men (8.5%) with TC were prescribed testosterone. The OR of receiving a prescription was 4.5 95% CI [4.2,5.5] times higher than in men without TC and disproportionately high in younger men, with an 8.1 fold increase in the third decade of life. CONCLUSIONS Men with a diagnosis of TC are four times more likely to have a serum testosterone checked, be diagnosed with hypogonadism, and receive ART. Serum testosterone is measured and more frequently found to be low in elderly patients with a history of TC compared to age-matched controls. Additionally, hypogonadism often predates the diagnosis of testis cancer. Finally, despite higher detection in elderly patients, ART is prescribed more often to young men with TC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e839-e840 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jamal Nabhani More articles by this author Diana Jin More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...