Late onset hypogonadism

Introduction.  Controversy exists regarding testosterone replacement therapy (TRT) in men following radical prostatectomy (RP). Many clinicians are hesitant to offer patients TRT after an RP, out of concern that the increased androgen levels may promote tumor progression or recurrence from residual tumor. Recently, several small studies have demonstrated the use of TRT in men following an RP and have shown an improvement in serum testosterone levels with no increase in prostate-specific antigen (PSA) values.Aims.  The aim of this article is to assess changes in PSA and testosterone values in hypogonadal patients on TRT after RP and also to evaluate the impact of pathologic Gleason grade on ultimate PSA values.Methods.  All hypogonadal men who were treated with TRT by members of our department following RP were retrospectively reviewed. PSA values before RP, after RP, and after TRT were evaluated. Serum testosterone levels before and after TRT were also examined. Only patients with undetectable PSA values and negative surgical margins on pathologic specimen were offered TRT and included in the study.Main Outcome Measures.  Main outcome measures were changes in PSA and testosterone values after initiation of TRT.Results.  Fifty-seven men, ages 53–83 years (mean 64), were identified as having initiated TRT following RP. Men received TRT for an average of 36 months following RP (range 1–136 months). Patients were followed an average of 13 months after initiation of TRT (range 1–99 months). The mean testosterone values rose from 255 ng/dL before TRT to 459 ng/dL after TRT (P < 0.001). There was no increase in PSA values after initiation of TRT and thus no patient had a biochemical PSA recurrence.Conclusion.  TRT is effective in improving testosterone levels, without increasing PSA values, in hypogonadal men who have undergone RP. Khera M, Grober E, Najari B, Colen J, Mohamed O, Lamb D, and Lipshultz L. Testosterone replacement therapy following radical prostatectomy. J Sex Med **;**:**–**.

Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications were analyzed. Survival after the first decade was studied for 977 patients born since 1960 whereas survival since birth and complication appearance was studied for the 720 patients born after 1970. Better survival was demonstrated for patients born in more recent years (p&lt;0.00005) and for females (p=0.0003); 68% of the patients are alive at the age of 35 years. In the entire population 67% of the deaths were due to heart disease. There was a significant association between birth cohort and complication-free survival (p&lt;0.0005). The prevalence of complications was: heart failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes 6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were associated with a l...

The diagnosis of male hypogonadism requires the demonstration of a low serum testosterone (T) level. We examined serum T levels in pedigreed samples taken from 62 eugonadal and 60 hypogonadal males by four commonly used automated immunoassay instruments (Roche Elecsys, Bayer Centaur, Ortho Vitros ECi and DPC Immulite 2000) and two manual immunoassay methods (DPC-RIA, a coated tube commercial kit, and HUMC-RIA, a research laboratory assay) and compared results with measurements performed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Deming's regression analyses comparing each of the test results with LC-MSMS showed slopes that were between 0.881 and 1.217. The interclass correlation coefficients were between 0.92 and 0.97 for all methods. Compared with the serum T concentrations measured by LC-MSMS, the DPC Immulite results were biased toward lower values (mean difference, ؊90 ؎ 9 ng/dl) whereas the Bayer Centaur data were biased toward higher values (mean difference, ؉99 ؎ 11 ng/dl) over a wide range of serum T levels. At low serum T concentrations (<100 ng/dl or 3.47 nmol/liter), HUMC-RIA overestimated serum T, Ortho Vitros ECi underestimated the serum T concentration, whereas the other two methods (DPC-RIA and Roche Elecsys) showed differences in both directions compared with LC-MSMS. Over 60% of the samples (with T levels within the adult male range) measured by most automated and manual methods were within ؎ 20% of those reported by LC-MSMS. These immunoassays are capable of distinguishing eugonadal from hypogonadal males if adult male reference ranges have been established in each individual laboratory. The lack of precision and accuracy, together with bias of the immunoassay methods at low serum T concentrations, suggests that the current methods cannot be used to accurately measure T in females or serum from prepubertal subjects.

A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator-1. Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation. Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL 3 subfraction. The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended. © 2005 Elsevier Inc. All rights reserved. (Am J Cardiol 20052005;96[suppl]:67M-72M)

Iron overload in b-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P 5 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n 5 5) and hypoparathyroidism (n 5 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P 5 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.

Objective: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. Design: Case report. Setting: University-affiliated andrology practice within family practice clinic.

Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro-or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treat-ment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

Aim. Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testostosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio. Methods. Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed. Results. The mean age was 39 years, and the mean pretreatment testosterone and estrogen levels were 247.6 ± 39.8 ng/dL and 32.3 ± 10.9, respectively. By the first follow-up visit (4-6 weeks), the mean testosterone level rose to 610.0 ± 178.6 ng/dL ( P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 ( P < 0.001). There were no side effects reported by the patients. Conclusions. Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estadiol ratio in men with hypogonadism. This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway. Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, and Goluboff E. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med 2005;2:716-721.

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men.

THE development of sexual maturity and reproductive function in the male is dependent upon appropriate secretion of hormones that orchestrate the sophisticated relationship between the hypothalamus, pituitary, and testes -the hypothalamic-pituitary-gonadal (HPG) axis. A state of hypogonadism, i.e. inadequate testicular function, is manifested by deficiencies in secretion of androgens, with a wide range of effects on a number of physiological processes, including gametogenesis. Any dysfunction in the HPG axis can result in hypogonadotrophic hypogonadism, where a decrease in endocrine and/or gametogenic function of the testes results in retardation of puberty and reproductive insufficiency .

Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

Fluid homeostasis requires adequate water intake, regulated by an intact thirst mechanism and appropriate free water excretion by the kidneys, mediated by appropriate secretion of arginine vasopressin (AVP, also known as antidiuretic hormone). AVP exerts its antidiuretic action by binding to the X chromosome-encoded V2 vasopressin receptor (V2R), a G proteincoupled receptor on the basolateral membrane of renal collecting duct epithelial cells. After V2R activation, increased intracellular cyclic adenosine monophosphate mediates shuttling of the water channel aquaporin 2 to the apical membrane of collecting duct cells, resulting in increased water permeability and antidiuresis. Clinical disorders of water balance are common, and abnormalities in many steps involving AVP secretion and responsiveness have been described. This article focuses on the principal disorders of water balance, diabetes insipidus, and the syndrome of inappropriate antidiuretic hormone secretion.

Available online xxxx s u m m a r y Anabolic steroid-induced hypogonadism (ASIH) is the functional incompetence of the testes with subnormal or impaired production of testosterone and/or spermatozoa due to administration of androgens or anabolic steroids. Anabolic-androgenic steroid (AAS), both prescription and nonprescription, use is a cause of ASIH. Current AAS use includes prescribing for wasting associated conditions. Nonprescription AAS use is also believed to lead to AAS dependency or addiction. Together these two uses account for more than four million males taking AAS in one form or another for a limited duration. While both of these uses deal with the effects of AAS administration they do not account for the period after AAS cessation. The signs and symptoms of ASIH directly impact the observation of an increase in muscle mass and muscle strength from AAS administration and also reflect what is believed to demonstrate AAS dependency. More significantly, AAS prescribing after cessation adds the comorbid condition of hypogonadism to their already existing chronic illness. ASIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent ASIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use. This paper proposes a unified hypothesis that the net effects for anabolic steroid administration must necessarily include the period after their cessation or ASIH.

Objective: Obesity negatively affects human health. Limiting food intake, while producing some weight loss, results in reduction of lean body mass. Combined with moderate exercise it produces significant weight loss, maintains lean body mass and improves insulin sensitivity, but appears difficult to adhere to. Bariatric surgery is clinically effective for severely obese individuals compared with non-surgical interventions, but has limitations. Clinical and pre-clinical studies have implicated a role for testosterone (T) in the patho-physiology of obesity.

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.

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatme...

Testosterone replacement therapy has been applied to alleviate the various symptoms of late-onset hypogonadism (LOH) patients. Several routes are available for the administration of testosterone to LOH patients, and transdermal delivery is an attractive method above all. The aim of this article was to clarify the profile of serum total testosterone (TT) and free testosterone (FT) levels after application of testosterone ointment (Glowmin [GL], Daito Pharmaceutical Co. Ltd., Tokyo, Japan) and its clinical efficacy in LOH patients. Serum TT and FT levels were examined in healthy male volunteers and LOH patients after application of 3 mg of GL. Then, 50 LOH patients received 3 mg of GL twice daily on scrotal skin (6 mg/day) for 12 weeks. Subsequently, TT and FT levels immediately prior to GL application were compared with those at 1 hour after GL treatment. Furthermore, the clinical effects of GL in the aforementioned 50 LOH patients were estimated after 12 weeks of GL treatment. Hormonal effects of GL were evaluated by serum TT and FT levels. Aging males symptoms (AMS), international index of erectile function (IIEF-5), and MOS 36-item short form Healthy Survey (SF-36) questionnaire were used to assess the clinical efficacy of GL for LOH patients. Maximum TT and FT values, which were detected 1-2 hours after application of a 2-cm line of GL (3 mg of testosterone) to scrotal skin, were not elevated beyond physiological levels; subsequently, these levels returned to circadian rhythm after 4 hours in four healthy male volunteers. The highest TT and FT levels were also obtained after 1-2 hours in four LOH patients involving identical administration methods; moreover, these levels were maintained within a normal range for 6 hours. After 12 weeks of GL treatment in 50 LOH patients, TT and FT levels demonstrated the same satisfactory response as that of the initial GL administration without GL accumulation effects. GL accumulation after 1 week in healthy men and after 12 weeks in LOH patients was not observed. Furthermore, AMS score decreased markedly; IIEF-5 and four domains of the SF-36 score were elevated significantly following GL application. Severe adverse reactions were not observed. Accordingly, GL, which is a short-acting testosterone ointment eliciting physiological elevation of TT and FT, appears to be suitable for LOH treatment.

Erectile dysfunction (ED) is one of the earliest signs and markers of present or potential future endothelial dysfunction. One of the causes of ED can be low testosterone levels or hypogonadism. This article describes ways to identify and diagnose patients with ED or hypogonadism, and it offers a plan for treatment of these conditions. The mainstay first-line medical therapies for ED are phosphodiesterase-5 (PDE-5) inhibitors. For patients with symptomatic hypogonadism, testosterone replacement therapy is both safe and effective.

BACKGROUND: FSH-regulatory peptides participate with GnRH and sex steroids to regulate serum FSH concentrations. We hypothesized that day/night variations in FSH serum concentrations would be associated with diurnal variation in FSH-regulatory peptides. METHODS: Blood was obtained every 15 min for 24 h beginning at 08:00 h in eight girls [seven with variations in growth or puberty and one with idiopathic hypogonadotrophic hypogonadism (IHH)] and for 12 h beginning at 20:00 h in 12 additional girls with variant puberty, eight with gonadal dysgenesis or ovarian failure (GD/OF) and one with IHH. Samples across 3 h blocks were pooled for determination of LH, FSH, activin-A, inhibin-B and follistatin 288. RESULTS: LH and FSH concentrations increased from 23:00 to 08:00 h with respect to daytime concentrations in pubertal girls (P < 0.005) but only LH increased (P 5 0.002) in girls with GD/OF. In pubertal girls, inhibin-B declined during the day (P 5 0.019), reaching a nadir between 17:00 and 22:45 h just prior to the night-time increase in FSH. Follistatin concentrations exhibited diurnal variation (P 5 0.028), with the greatest concentrations occurring between 05:00 and 11:00 h. Activin-A concentrations declined coincident with the night-time increase in FSH in pubertal girls (P < 0.0001) but not in girls with GD/OF. CONCLUSIONS: The directionality of changes in FSH-regulatory proteins supports the notion that FSH-regulatory peptides may contribute to the night-time augmentation of circulating FSH during puberty in girls.

The hypothalamic-pituitary-gonadal (HPG) axis regulates the development, endocrine and reproductive function of the gonads throughout all phases of life. Male hypogonadism is defined an inadequate gonadal function, as manifested by deficiency in gametogenesis and/or secretion of gonadal hormones. In most cases, male hypogonadism is diagnosed through detailed history, physical examination and a few basic hormonal evaluations. In selected cases, however, additional tests are needed to define the aetiology and the extent of HPG axis dysfunction. These include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography, testicular biopsy and hormonal dynamic testing. The stimulation tests of the HPG are of particular importance in the differential diagnosis of congenital delayed puberty versus pre-pubertal hypogonadism in children. This review will focus on the methods, indications and limitations of endocrine testing in the characterisation and differential diagnosis of male hypogonadism at various ages. A practical hands-on guide on how to perform these tests is also provided.

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolicandrogenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed.

Introduction.  The general worldwide increase in metabolic syndrome (MS) among most populations may result in more individuals with sexual dysfunction.Aim.  To provide an update on clinical and experimental evidence regarding sexual dysfunction in patients with MS from both sexes and treatment modalities.Methods.  A comprehensive literature review was performed using MEDLINE with the MeSH terms and keywords for “metabolic syndrome,”“obesity,”“female sexual dysfunction,”“erectile dysfunction,”“androgen deficiency,”“weight loss,” and “bariatric surgery.”Main Outcome Measures.  To examine the data relating to sexual function in both men and women with MS, its relationship and the impact of treatment.Results.  The MS is strongly correlated with erectile dysfunction, hypogonadism (predictors of future development of MS), and female sexual dysfunction. Few studies have been addressed in the treatment of these dysfunctions in the special setting of MS, other than the observational effects on sexual function of individual risk factors correction. This can be a result of their understudied etiopathogeny. Nonsurgical weight loss has been shown to improve sexual function (with the mainstay on sedentarism prevention), whereas the efficacy of bariatric surgery in this respect, which has been suggested by some preliminary evidence, needs to be further confirmed by adequate clinical trials.Conclusion.  As the global incidence of MS increases, more individuals may experience sexual dysfunction and a systematic evaluation should be emphasized in this patient population, in order to identify those who are in need of intervention. Borges R, Temido P, Sousa L, Azinhais P, Conceição P, Pereira B, Leão R, Retroz E, Brandão Á, Cristo L, and Sobral F. Metabolic syndrome and sexual (dys)function. J Sex Med 2009;6:2958–2975.

Con el avance de la edad se ha observado una declinación progresiva de los andrógenos sanguíneos, los cuales desempeñan distintos papeles en el comportamiento sexual, metabolismo óseo, masa muscular y distribución de las grasas, estado de ánimo, bienestar y actividad intelectual. En el proceso de envejecimiento también ocurren cambios profundos en otras hormonas como la hormona del crecimiento, dehidroepiandrosterona (DHEA), melatonina, y en menor medida tiroxina y leptinas. Sin embargo, los términos de declinación androgénica en el hombre maduro (ADAM por las siglas en inglés de Androgen Deficiency of Aging Male), la declinación parcial androgénica (PADAM), o el más ampliamente conocido andropausia, se usan hoy en día como sinónimos de un mismo síndrome caracterizado por alteraciones de libido y de la erección, cambios en el humor y depresión, disminución de la fuerza muscular y del vello corporal, cambios en la piel, osteoporosis e incremento de la grasa visceral. Este trabajo muestra diferentes cuestionarios para el diagnóstico y seguimiento de andropausia. Cuando hay sospecha de hipogonadismo se recomienda la determinación de la testosterona biodisponible o de la testosterona libre con toma de la muestra entre las 8 y 11 AM. Distintas preparaciones se usan para la terapia hormonal sustitutiva, el undecanoato de testosterona no produce lesión hepática, con buenos niveles plasmáticos de testosterona. Se recomienda el manejo multidisciplinario.


Palabras clave: Andropausia, PADAM, terapia hormonal sustitutiva con testosterona, envejecimiento.

Introducción
La edad de la población mundial está aumentando
progresivamente1. La mejora en los
servicios sanitarios y de salud publica (vr.gr.:
Agua potable, vacunas, avance médico), y los
antibióticos, han incrementado la esperanza
de vida2, 3.
Según cifras de la Primera Conferencia
Regional Inter-Gubernamental sobre envejecimiento
de la Comisión Económica para
América Latina y el Caribe (CEPAL) se espera
que en 50 años, uno de cada 4 latinoamericanos
sea mayor de 60 años, lo que representa
184 millones de personas requiriendo
servicios especiales de salud, entre ellos el reemplazo
hormonal4,5.
La longevidad sin una adecuada medicina
preventiva causa una enorme cantidad de
adultos mayores incapacitados por las enfermedades
crónicas y degenerativas, muchas
Se discuten las manifestaciones clínicas y bioquímicas del Hipogonadismo
de Inicio Tardío (LOH), los efectos de la testosterona y otras hormonas
(hormona de crecimiento, tiroxina, leptinas, etc.), su relación con la hiperplasia
prostática y el cáncer de próstata (CaP), Osteoporosis, Síndrome Metabólico
y la Obesidad.
El uso de la testosterona mejora la calidad de vida de los hombres con
LOH, alejando los efectos de las enfermedades degenerativas y las incapacidades
relacionadas. El manejo del LOH es eminentemente multidisciplinario,
tomando como referencia la seguridad prostática y la consulta urológica
cuando se requiera, con un seguimiento por el medico de primer contacto, y
la participación activa de las especialidades afines. Se emiten recomendaciones
de diagnostico, tratamiento, monitoreo y prevención del LOH en el hombre
Latino Americano, que deben ser adaptadas a cada caso.
Palabras Clave: Andropausia, Menopausia Masculina, Hipogonadismo de
Inicio Tardío, Testosterona, Hombre Latino, Envejecimiento.

Obesity can be associated with biochemical evidence of isolated hypogonadotropic hypogonadism (IHH) in men. Prevalence and severity of IHH in obese men are not exactly known. To assess the prevalence of IHH in obese men. Cross-sectional study of 160 obese men, BMI &gt;30 kg/m2, who applied for medical or surgical treatment of obesity in a general teaching hospital. Main outcome measures: Total and calculated free testosterone (TT and FT) in relation to body mass index (BMI). Mean age of the study population was 43.3 +/- 0.8 years (mean +/- SEM), BMI ranged from 30.0 to 65.7 kg/m2. TT and FT levels were inversely related to BMI (-0.48, p&lt;0.0001). Total testosterone was subnormal in 57.5% and free testosterone in 35.6% of the subjects. The group of men with IHH was more obese, had higher Hba IC levels and had a 2.6 higher risk for cardiovascular disease. Decreased libido and erectile dysfunction were 7.1 and 6.7 times as common in IHH than in eugonadal obese men. Reduced T levels, ...

Until the 2000s Testosterone (T) Replacement Therapy (TRT) was not very satisfactory for male hypogonadic patients because the available T formulations were not able to reproduce the physiological pattern of T secretion in man. In fact, oral formulations (oral undecanoate T) showed very short half-life (<24 hours), requiring the administration of several daily doses, whereas the old injection products (T esters) were characterized by very long half-life (>7 days) because of their adipose tissue storage, requiring to be administered every 2-3 weeks but determining remarkable and quick fluctuations (in 2-3 weeks) of the testosteronemia with variations in a few days from over-physiological levels (> 2000 ng/dl) to very low levels (< 200 ng/dl). Nowadays, several compounds can attain the standards of suitability and effectiveness of TRT in hypogonadal men. Both transcutaneous (gel) T and long-acting injectable formulations are the most modern preparations that can satisfy the criteria of an ideal chronic replacement therapy. In fact, they keep the serum T levels in the physiological range imitating its circadian rhythm, leading to the development and/or the preservation of male sexual characteristics and, finally, positively influencing bone mass, skeletal muscle and adipose tissue distribution. In particular, the availability and use of long-acting injectable undecanoate T can really improve the patients' compliance as requested for a life-long treatment. However, definitive and conclusive evidence regarding the main end-points, such as the diminished recurrence of falls in elderly men, the decrease in fractures in osteoporotic subjects, the reduction in disabling conditions and the extension of life, have not been reached so far. Therefore, the aim of this review is to sum up the most important evidence that has been collected regarding TRT, highlighting in particular those concerning both transcutaneous and long-acting injectable T compounds.

Metabolic syndrome (MetS) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone replacement therapy (TRT) in MetS has not been completely clarified. Aim. To systematically analyse the relationship between androgen levels and MetS we performed a review and meta-analyses of available prospective and cross-sectional studies. In addition, a specific meta-analysis on the metabolic effects of TRT in available randomized clinical trials (RCTs) was also performed.

La declinación androgénica en el envejecimiento es el cambio hormonal más importante, pero se han descrito otras alteraciones en hormonas como la melatonina, tiroxina, leptina, factores y hormona de crecimiento. El hipogonadismo de inicio tardío o andropausia (ADAM, PADAM, PEDAM) es un síndrome caracterizado por manifestaciones clínicas fácilmente reconocibles como libido disminuido y alteraciones de la erección; cambios en el humor, disminución de la actividad intelectual, depresión y ansiedad; disminución en la fuerza y masa muscular; disminución del vello corporal y alteraciones de la piel; disminución de la densidad mineral ósea con osteoporosis; aumento en la grasa visceral. Para la determinación sérica de la testosterona la muestra debe ser tomada entre las 8:00 y 11:00 a.m. El reemplazo hormonal sólo debe iniciarse después de un diagnóstico clínico bioquímicamente confirmado, debe verificarse la ausencia de cáncer prostático. Existen múltiples preparaciones hormonales, los orales ofrecen niveles semejantes a los fisiológicos. Deberá tenerse cuidado en las contraindicaciones absolutas y relativas, y el seguimiento del paciente bajo tratamiento. En presencia de cuadros de osteoporosis, atrofia muscular, incremento del tejido graso, alteraciones de los lípidos séricos, trastornos del sueño, puede ser considerado el uso de dehidroepiandrosterona, hormona de crecimiento recombinante, melatonina o ambos, cuando esté indicado.


El manejo de la andropausia es multidisciplinario, sin embargo, en vista de la necesidad de seguridad prostática, es el urólogo el especialista idóneo para dirigir y coordinar a este equipo. El manejo de la andropausia debe incluir el ejercicio físico como parte esencial del tratamiento.


Palabras clave: Andropausia, ADAM, PADAM, PEDAM, envejecimiento, hipogonadismo, hombres.

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5 (PDE-5), which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men. (Asian J Androl 2008 Jan; 10: 36-43)