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The Androgen Society is an international, multidisciplinary medical organization committed to advancing research and education in the field of testosterone deficiency and testosterone therapy (TTh). This position paper is written in response to results of the TRAVERSE study, published in June 2023, which reported no increased risk of major adverse cardiovascular events (MACE) in men who received TTh compared with placebo.

Male-to-female (MtF) transgender individuals are at risk for prostate cancer, although guidelines for screening and management in this population are not well established. We describe a series of 9 MtF transgender patients who underwent prostate tissue sampling and highlight histopathologic features and challenges related to pathologic interpretation of prostate tissue in this patient population. Seven of 9 total patients were diagnosed with prostate cancer and all had elevated prostate-specific antigen at the time of diagnosis. Three of the 7 patients diagnosed with prostate cancer had received different types of hormone therapy for gender affirmation before the diagnosis of prostate cancer, and in all 3 of these patients, there was histologic evidence of hormone therapy effect in both benign prostate tissue and/or the adenocarcinoma. The 2 patients with benign prostate tissue underwent transurethral resection for lower urinary tract symptoms and were previously on hormone therapy for gender affirmation. Both of these specimens showed diffuse glandular atrophy and basal cell hyperplasia, indicative of hormone therapy effect on benign prostatic tissue. In the patients diagnosed with prostate cancer, a spectrum of grades was observed, ranging from Grade Group 1 to Grade Group 5. Four patients underwent radical prostatectomy, with 2 cases showing extraprostatic extension and Grade Group 5 prostatic adenocarcinoma, and 2 showing Grade Group 2 prostatic adenocarcinoma. Three of the 4 patients who underwent radical prostatectomy had received gender-affirming hormone therapy before surgery, and all 3 of these specimens showed hormone therapy effect in non-neoplastic prostate tissue and focal hormone therapy effect in prostatic adenocarcinoma. The presence of areas of viable carcinoma without hormone therapy effect enabled the assignment of a Gleason score and Grade Group in these 3 cases. Hormone therapy administered for gender identity affirmation induces histopathologic changes to both benign prostate tissue (nonkeratinizing squamous metaplasia, diffuse atrophy, basal cell hyperplasia, and stromal dominance with decreased numbers of glands) and prostatic adenocarcinoma (nuclear pyknosis, atrophy, cytoplasmic vacuolization, and architectural patterns that would qualify for Gleason 4 and 5 in the absence of hormone therapy effect) that have been traditionally seen in cis-male prostate cancer patients receiving hormone therapy. In the absence of hormone therapy, the morphology of prostatic adenocarcinoma in transgender patients shows classic morphologic features similar to those seen in cis-male patients not on hormone therapy. Prostate cancer with hormone therapy effect may not only be histologically quite subtle and may be overlooked if not suspected, but also should not be assigned a Gleason score because the Gleason score would substantially overstate its biologic potential. Therefore, similar to cis-male patients who have received androgen deprivation therapy for prostate cancer, transgender patients on hormone therapy for gender affirmation may be at risk for both underrecognition and over-grading of prostate cancer, particularly if the pathologist is not aware of the clinical history.

Hypogonadism is a common clinical condition affecting men, with older men having an increased incidence. Clinicians (endocrinologists and urologists) who may be involved in providing testosterone therapy should be familiar with the effects of testosterone on the prostate. Before initiating testosterone therapy, physicians and patients should partake in shared decision-making, including pretreatment testing, risks and benefits of testosterone therapy relating to benign prostatic hyperplasia and lower urinary tract symptoms, a discussion on prostate cancer in those who have not been diagnosed with malignancy, and a thorough discussion with patients who may have a previous diagnosis of prostate cancer.

Based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, the number of individuals eligible for statin therapy to reduce atherosclerotic cardiovascular disease risk has greatly expanded. Statins inhibit cholesterol biosynthesis, which can impair gonadal steroidogenesis. We evaluated the effect of statins on endogenous sex hormones in a large epidemiological study.

In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up.

To address widespread concerns regarding the medical condition of testosterone (T) deficiency (TD) (male hypogonadism) and its treatment with T therapy, an international expert consensus conference was convened in Prague, Czech Republic, on October 1, 2015. Experts included a broad range of medical specialties including urology, endocrinology, diabetology, internal medicine, and basic science research. A representative from the European Medicines Agency participated in a nonvoting capacity. Nine resolutions were debated, with unanimous approval: (1) TD is a well-established, clinically significant medical condition that negatively affects male sexuality, reproduction, general health, and quality of life; (2) symptoms and signs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology; (3) TD is a global public health concern; (4) T therapy for men with TD is effective, rational, and evidence based; (5) there is no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not; (6) there is no scientific basis for any age-specific recommendations against the use of T therapy in men; (7) the evidence does not support increased risks of cardiovascular events with T therapy; (8) the evidence does not support increased risk of prostate cancer with T therapy; and (9) the evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. These resolutions may be considered points of agreement by a broad range of experts based on the best available scientific evidence.

Most human immunodeficiency virus (HIV) infections among women occur early in reproductive life, which highlights the importance of understanding the impact of HIV on reproductive functions, and also the potential implications of reproductive function and aging on the course of HIV disease. Ovarian function is a crucial component of reproductive biology in women, but standard assessment methods are of limited applicability to women with chronic diseases such as HIV. Pregnancy can now be achieved without transmission of HIV to sexual partner or newborn, but complications of pregnancy may be more common in women infected with HIV than uninfected women.

To examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.

Gynecomastia is caused by drugs in 10 – 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

Background: Hypogonadism is manifest in all age groups, and a growing elderly population is requiring treatment for testosterone deficiency, presenting new safety challenges, as many of these individuals present with comorbidities and significant risk profiles. Objective: To discuss testosterone replacement modalities, their advantages and disadvantages, and provide a discussion of safety issues. Methods: We reviewed the literature regarding testosterone replacement therapy and have provided a summary of our most outstanding findings. Conclusion: Potential benefits of testosterone replacement therapy include increased lean body mass, heightened libido, increased bone density and elevation of mood. Some disadvantages are clearly defined, while others require further investigation. Patient and physician must cooperate to agree on an individual patient's most appropriate and tolerable route of administration.

Vitamin D has been recognized for more than a century as essential for the normal development and mineralization of a healthy skeleton. More extensive roles for vitamin D were suggested by the discovery of the vitamin D receptor (VDR) in tissues that are not involved in calcium and phosphate metabolism. VDR has been discovered in most tissues and cells in the body and is able to elicit a wide variety of biologic responses. These observations have been the impetus for a reevaluation of the physiologic and pharmacologic actions of vitamin D. Here, we review the role of vitamin D in regulation of the immune system and its possible role in the prevention and treatment of cancer and immune-mediated diseases.

Male hypogonadism is a common endocrine problem that affects men of all ages. Recently, there has been a surge in testosterone use among middle-aged and older men who in the past may have been considered to have borderline or even normal testosterone levels. This increasing use of testosterone therapy among men has paralleled the increasing improvements in the development of treatments for male hypogonadism that have been made over the past few decades. Current therapies using transdermal formulations and long-acting injectables such as testosterone undecanoate are quickly replacing the old injectable testosterone esters. In recent years, pharmaceutical sales and prescription data have readily shown a shift in the testosterone marketplace towards greater use of slightly more expensive treatments such as transdermal therapies, which are easier to administer and yield more physiological levels of testosterone. On the horizon are several new compounds in development, such as selective androgen receptor modulators (SARMS), 7α-methyl-19-nortestosterone, aromatase inhibitors, clomifene, dihydrotestosterone and human chorionic gonadotropin. Compounds such as SARMs are designed to selectively target androgen receptors in specific tissues (such as bone and muscles), in the hope of dispersing some of the side effects experienced on the prostate, which are presently associated with therapy of exogenous testosterone.

Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen‐deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long‐term ADT on fasting glucose levels, insulin levels, and insulin resistance.To evaluate the long‐term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross‐sectional study at a university‐based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age‐matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non‐ADT group), and 18 age‐matched controls (the control group). None of the men had a known history of diabetes mellitus.The mean age was similar in all 3 groups (P = 0.33). Serum total testosterone levels (P < 0.0001) and free testosterone levels (P < 0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P = 0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0 ± 7.43 mg/dL in the ADT group compared with 103.0 ± 7.42 mg/dL in the non‐ADT group (P = 0.01) and 99.0 ± 7.58 mg/dL in the control group (P < 0.01). 2) Insulin levels were 45.0 ± 7.25 uU/mL in the ADT group compared with 24.0 ± 7.24 uU/mL in the non‐ADT group (P = 0.05) and 19.0 ± 7.39 uU/mL in the control group (P = 0.02). 3) Leptin levels were 25.0 ± 2.57 ng/mL in the ADT group compared with 12.0 ± 2.56 ng/mL in the non‐ADT group (P < 0.01) and 6.0 ± 2.62 ng/mL in the control group (P < 0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR) = 17.0 ± 2.78 in the ADT group compared with HOMAIR = 6.0 ± 2.77 in the non‐ADT group (P < 0.01) and HOMAIR = 5.0 ± 2.83 in the control group (P = 0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR.The current data suggested that men with PCa who are receiving long‐term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation. Cancer 2006. © 2005 American Cancer Society.

Over the last six decades, tremendous strides have been made in the development of safe, efficacious and ‘patient-friendly’ modalities of testosterone replacement therapy in men. The most recent forms of androgen replacement that are in widespread use include testosterone patch and gel. These preparations are convenient in their use and deliver a physiological amount of testosterone. Although these transdermal preparations are gaining popularity, many hypogonadal men still receive treatment with intramuscular esters. Testosterone enanthate remains the most commonly prescribed ester. Although testosterone esters are efficacious in terms of improving bone and muscle mass, they possess unfavourable pharmacokinetics that result in fluctuations in the mood, energy and sexual function of patients. Furthermore, these esters need to be injected every 2 – 4 weeks. Hence, there has been a need to develop long-acting esters that can be administered infrequently and deliver a physiological amount of testosterone without major fluctuations. Recently, injectable testosterone undecanoate (Nebido®) has become available in Europe and will soon be marketed in south America, Asia and Australia. In this paper, the structure, pharmacokinetics, efficacy and side-effect profile of testosterone undecanoate will be reviewed and also compared with other existing testosterone esters.

SUMMARYObjective:To evaluate the efficacy of high and moderate doses of simvastatin (80 and 40 mg), for raising high density lipoprotein-cholesterol (HDL-C), improving HDL sub-fractions, and affecting other parameters, including high sensitivity C-reactive protein (hs-CRP), in patients with type 2 diabetes mellitus (DM) and low HDL-C.Research design and methods:This double-blind, placebo-controlled, randomized, 3-period, complete block, 6-week crossover study examined the efficacy of simvastatin in adult men and women (N 151) with stable type 2 DM (HbA1C< 9), low density lipoprotein-cholesterol (LDL-C) > 100 mg/dL (2.6 mmol/L), HDL-C < 40 mg/dL (< 1 mmol/L), and fasting triglyceride level > 150 (> 1.7 mmol/L) and < 700 mg/dL (< 7.9 mmol/L). This study included adult men (71) and women (29) of various races (89 white, 6 black, 1 Asian, 3 other) enrolled from 29 practice-based sites in the United States.Main outcome measures:Percentage change in HDL-C from baseline at the end of each 6-week treatment interval.Results:Both simvastatin 80 and 40 mg significantly increased total HDL-C from baseline (mean increases of 8 ± 1 [SE] and 5 ± 1, respectively; p< 0.001) compared with placebo, and significantly reduced plasma concentrations of LDL-C ( p< 0.001), triglycerides ( p< 0.001), apolipoprotein B ( p< 0.001), and hs-CRP ( p≤ 0.012). Compared with simvastatin 40 mg, the 80 mg dose provided additional efficacy. Simvastatin 80 mg also significantly ( p< 0.001) increased HDL2from baseline (14 ± 3[SE]) and placebo phases (10 ± 3). An exploratory analysis showed 87 (simvastatin 80 mg) and 82 (simvastatin 40 mg) of patients reached the NCEP ATP III treatment goals for LDL-C compared with 14 on placebo.Conclusions:Both simvastatin 80 and 40 mg raise HDL-C and improve other measures associated with elevated coronary risk in patients with type 2 DM and low HDL-C.

Purpose The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities.Methods This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings.Results And Conclusions The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency. Less well appreciated is the varied expressivity of 47,XXY Klinefelter syndrome, in particular neurological/cognitive perturbations like language and behavioral problems. Effective therapies are available. Reproductive technologies allow 47,XXY men to sire offspring through intracytoplasmic sperm injection (ICSI); however, genetic counseling is complex and success is low. Behavioral and expressive language difficulties are amenable to treatment by androgen therapy and psychological help. Early treatment may be imperative for optimal outcome.

Purpose The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities.

In the 35 years since the active compound of marijuana Δ9‐tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic‐pituitary‐adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long‐term consequences of marijuana use in humans on endocrine systems remain unclear.

Objectives:To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women. Methods:Participants were tested with a randomized, double-blind design on the Identical Pictures, Cube Comparisons, Building Memory and Shape Memory tasks before and after 4 months of hormone treatment. Results:Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task, whereas those receiving estrogen alone showed a decrease in performance. Conclusions:These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women.

In view of the role of both the de novo biosynthesis and receptor-mediated uptake of cholesterol for normal steroidogenesis, we evaluated whether extending the therapeutic dose of the hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, to 80 mg/d would affect adrenal and gonadal steroid synthesis in men with hypercholesterolemia. To evaluate this question, we enrolled men into a multicenter randomized, placebo-controlled study lasting 12 weeks. Men with serum low-density lipoprotein cholesterol (LDL-C) more than 145 mg/dL after 6 weeks of a lipid-lowering diet were randomized to 80 mg simvastatin or placebo. Half of the subjects were asked to undergo a 6-hour infusion of corticotropin (ACTH) to evaluate cortisol synthesis, and the entire cohort received a human chorionic gonadotropin (hCG) stimulation test to assess gonadal hormone secretion using pooled serum samples taken 15 minutes apart. A total of 81 men (age, 45 ± 11 years; 93% Caucasian) with baseline serum LDL-C of 197 mg/dL (placebo, n = 39) and 184 mg/dL (simvastatin 80 mg, n = 42) completed the study. After 12 weeks, serum LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) in the simvastatin group changed by −43%, −25%, and 8%, respectively (all P< .001). The basal cortisol level and the peak serum cortisol and area under the curve response to the 6-hour ACTH infusion were comparable between the two treatment groups at baseline and after 12 weeks. The pooled total testosterone level at baseline was 541 and 513 ng/dL in the placebo and simvastatin-treated groups, respectively, which declined to 536 ± 20.5 ng/dL (−1.5%) and 474 ± 30.4 ng/dL (−13.6%, P= .09) after treatment (mean ± SD). The pooled free testosterone declined by 6.3% in the simvastatin group, versus a 4.9% increase in the placebo group (P= .588), while pooled bioavailable testosterone declined 10.2% in the simvastatin group and increased 1.4% in the placebo group (P= 035). There were no changes in serum gonadotropin levels or sex hormone-binding globulin (SHBG). After administration of hCG, there were no differences in the peak total pooled testosterone level before or after 12 weeks of treatment. Simvastatin 80 mg was well tolerated compared with placebo. In conclusion, basal and stimulated cortisol production was unaffected by the use of simvastatin 80 mg versus placebo. As reported with other statins and cholestyramine, there were small declines in the simvastatin-treated group for pooled total, free, and bioavailable testosterone after 12 weeks, although there was no compensatory increase in serum follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels.

To determine the efficacy of the lung as an alternative route of delivery for insulin in controlling glucose below diabetic levels (11.2 mmol/L) 2 h after the ingestion of a meal in patients with type 2 diabetes mellitus.

Recently approved methods for testosterone delivery have provided increased options for men who require hormonal replacement therapy. Intramuscular administration of testosterone has classically been associated with early, high serum peaks in hormone followed by a gradual decline over the dosing interval. Transdermal patches are now available as an alternative. Testoderm® is applied to the scrotum; Androderm® is applied to nonscro-tal skin. Using either system, the majority of patients can achieve normal serum testosterone levels with a circadian variation and normal estradiol levels. Serum luteinizing hormone levels generally decrease but not to suppressed levels. Testoderm® use leads to an increase in plasma dihydrotestosterone. Clinical response in mood, energy level, and sexual function are improved with both systems and are generally comparable with intramuscular injection of testosterone. There are no clinically significant changes in laboratory parameters, including prostatic specific antigen, and prostate size did not increase to above normal. Skin reactions, however, are common and may require some patients to discontinue therapy. Patients with inadequate scrotal size may not have satisfactory results with Testoderm®. Patches are more costly than IM injections but do not require frequent office visits. Both the transscrotal and transdermal testosterone delivery systems offer a good alternative treatment for hypogonadal men who do not desire fertility during the treatment period.

Amiodarone, an antiarrhythmic drug approved for use in patients who survive cardiac arrest, has been associated with infiltration of or inflammatory changes in various tissues. To date thyroid dysfunction has been the only endocrine disturbance noted. In an initial group of seven amiodarone-treated men undergoing evaluation for sexual dysfunction, an elevation in serum gonadotropin concentration was detected, suggesting testicular dysfunction.

The authors studied 15 patients at risk for central adrenocortical insufficiency to evaluate the role of naloxone in establishing the integrity of the hypothalamic–pituitary–adrenal axis. Each patient was admitted to the General Clinical Research Center for 2days. Naloxone, 125μg/kg body weight, was administered intravenously, and plasma adrenocorticotropic hormone (ACTH) and Cortisol concentrations were measured at −15, 0, 30, 45, 60, 90, and 120minutes. Metyrapone, 30mg/kg body weight, was administered orally at 11PM on the second day of hospitalization. Plasma ACTH, Cortisol, and 11-deoxycortisol concentrations were measured at 8AM pre- and postmetyrapone. The results of the metyrapone test were used to distinguish patients who had central adrenal insufficiency from those who were normal. In 11 patients who had a normal metyrapone test, the plasma ACTH level increased from 6±1 pmol/L at baseline to 11±2 pmol/L 30minutes after naloxone administration. The plasma Cortisol increased from 191±21nmol/L at baseline to 379±47nmol/L 45minutes after naloxone administration. In four patients with central adrenal insufficiency, the plasma ACTH and Cortisol concentrations did not increase after naloxone administration. Reliance solely on the individual ACTH and Cortisol responses to naloxone would have permitted a correct decision regarding glucocorticoid replacement therapy in 14 (93%) of 15 patients. Naloxone stimulation testing may have a role in the clinical evaluation of patients with suspected central adrenocortical insufficiency.

Objective: To attempt to determine clinical or hormonal characteristics that could help distinguish benign idiopathic low testosterone (ILT) from pituitary tumor. Methods: On retrospective review of medical records of patients encountered by Johns Hopkins endocrine staff between 1985 and July 1995, 64 patients who fulfilled our enrollment criteria--27 men with ILT and 37 patients with imaging-proven pituitary tumor--were identified. Men 21 years of age or older needed to have had serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels measured before hormonal replacement therapy or pituitary tumor extirpation (or both) and a high-quality imaging scan (computed tomography or magnetic resonance imaging) done and interpreted by the Johns Hopkins radiology staff. Results: In comparison with men who had ILT, men with pituitary tumors had similar serum testosterone levels and significantly higher serum levels of LH, FSH, and prolactin. In addition, significantly more men with pituitary tumors had visual field abnormalities, headaches, and symptoms of hypothyroidism in comparison with the men with ILT. In contrast, the group with ILT complained significantly more of impotence, erectile dysfunction, and depression than did the group with pituitary tumors. The age at initial assessment was comparable in both study groups. Conclusion: Although age at initial manifestation did not predict the presence of pituitary tumor, the group of men with tumors were more likely than those with ILT to have serum testosterone levels <150 ng/dL, higher serum gonadotropin and prolactin levels, and visual field abnormalities and less likely to have sexual dysfunction. Therefore, on the basis of our data, we recommend that men with these findings should be referred for a magnetic resonance image to exclude the presence of a tumor.

Objective: To report the efficacy and safety of a permeation-enhanced nonscrotal testosterone transdermal (TTD) system for the treatment of Klinefelter's syndrome. Methods: Fifteen male patients with Klinefelter's syndrome, including 12 patients who received previous intramuscular (IM) treatment with testosterone esters, were part of the study population from three phase III clinical studies; 13 completed the studies. Patients applied two TTD systems nightly for 6 months or more. Nocturnal erections were assessed by RigiScan monitoring; sexual function was evaluated by using the Watts and Davidson questionnaires. Hypogonadal symptoms were determined by direct patient questioning. Results: Mean morning serum testosterone levels increased to within normal range in all 13 patients (from 5.9 &#45 3.2 nmol/L at hypogonadal baseline to 22.3 &#45 5.6 nmol/L at 6 months). Luteinizing hormone levels decreased to within normal range in six patients and showed clinically significant decreases in four of the other seven patients (from 25 &#45 12 IU/L at hypogonadal baseline to 17 &#45 11 IU/L at 6 months). Nocturnal erections improved significantly during TTD system therapy in comparison with the hypogonadal state. Patient self-reported measures of sexual functioning were comparable to those during prior IM testosterone treatment and better than during the hypogonadal state. Hypogonadal symptoms decreased during TTD therapy in comparison with hypogonadal baseline. No clinically significant changes were noted in prostate volume, prostate-specific antigen, or lipid values. Three patients experienced anxiety or depression during TTD treatment, requiring discontinuation of therapy in one case and use of antidepressants in the other two. Conclusion: The testosterone patches were generally well tolerated in all patients. The nonscrotal TTD system for testosterone replacement is a safe and effective treatment for patients with Klinefelter's syndrome.

Though the exact physiology and pathology of lipoprotein (a) [Lp(a)] remains unknown, it has been demonstrated that increased serum Lp(a) levels are correlated with an increased risk of atherosclerotic vascular disease. The effects of lipid-lowering drugs on Lp(a) levels is unclear because of inconsistencies between study designs. This study analyzes the effects of the commonly used lipid-lowering drugs pravastatin (PRAV), lovastatin (LOV), and cholestyramine (CHOL) on serum Lp(a) and other serum lipid levels in a parallel study design. Hyperlipidemic men (n=32) were enrolled from three centers and treated for 48 weeks in a multicenter clinical trial using PRAV, LOV, CHOL, or a placebo (for the first 16 weeks only). Baseline serum low-density lipoproteins (LDL-C), high-density lipoproteins (HDL-C), and triglycerides were 199±38, 40±9, and 160±70 mg/dl, respectively. At the end of 48 weeks, serum plasma LDL-C declined in patients randomized to PRAV, LOV, and CHOL, respectively, by 31%, 29%, and 23% (all p<0.001); HDL increased by 4%, 11%, and 11% (all p<0.001); and TG changed by -16%, -28%, and + 43% (all p<0.001). Subjects in PRAV and LOV changed Lp(a) by 9% and 3%, respectively. Although there was an initial Lp(a) decline in the first 8 weeks of CHOL therapy (p<0.05, ANOVA), this returned to baseline after 48 weeks. In this parallel study design PRAV, LOV, and CHOL are effective LDL-lowering medications with minimal effects on plasma Lp(a).

PurposeThe influence of radical prostatectomy on the hypothalamic pituitary axis has not been well studied. It is also unclear how alterations in serum androgen levels that result from surgical removal of the prostate might influence the recovery of libido and sexual function following radical prostatectomy. We determined the influence of radical prostatectomy on the hypothalamic pituitary testicular axis of 63 men with clinically localized prostate cancer treated only with radical prostatectomy.Materials and MethodsA total of 63 healthy men 43 to 67 years old were enrolled in this prospective study. Phlebotomy was performed immediately before and 1 year following radical retropubic prostatectomy. Sera were stored frozen and analyzed as a group at the end of the study. We measured serum testosterone, percent free testosterone, dihydrotestosterone (DHT), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin and prolactin.ResultsFollowing radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone, estradiol, LH and FSH (p <0.0001), and statistically significant decrease in serum DHT (p <0.0001). No difference was noted in serum sex hormone binding globulin or prolactin levels. There was no statistically significant correlation between any serum hormone and sample storage time, patient age or prostate volume that could limit potential bias in study design. Serum hormone changes did not correlate with pathological stage or histological grade for this group of patients.ConclusionsRadical prostatectomy influences the hypothalamic pituitary axis by increasing serum testosterone, percent free testosterone, estradiol, LH and FSH while decreasing serum DHT levels. These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion. Further investigation is warranted to identify this substance or substances.