Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To summarize current evidence regarding testosterone treatment for women with low sexual desire. Materials and methods The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. Results Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. Conclusion Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8

Cambios histológicos del tracto genital y riesgo de malignidad, en hombres transgénero sometidos a tratamiento androgénico / Histological changes of the genital tract and risk of malignancy in transgender men undergoing androgenic treatment

RESUMEN Introducción y objetivos: La identidad de género es la vivencia interna e individual del género tal como cada persona la siente. En algunos casos, la adquisición de los caracteres sexuales secundarios del otro género es importante en el proceso de reasignación de género, siendo importante el tratamiento endocrinológico. La cuestión es si la administración prolongada de andrógenos es segura en los casos de pacientes transexuales mujer a hombre, ya que es poca la evidencia científica a largo plazo. El objetivo de este estudio es analizar las características clínicas de los pacientes trans de nuestra unidad, y los hallazgos anatomopatológicos de las piezas quirúrgicas de histerectomía y doble anexectomía, para ver la influencia de la androgenoterapia en los genitales internos femeninos. Métodos: Se trata de un estudio descriptivo donde se analizaron datos demográficos y clínicos de los pacientes remitidos para cirugía genital, así como se analizaron los resultados del estudio anatomopatológico de las piezas de histerectomía y anexectomía. Resultados: Se incluyeron 66 pacientes, de los que 59 se intervinieron. No se halló malignidad en ninguna de las piezas quirúrgicas, sí diversos hallazgos benignos como miomas, atrofia/proliferación endometrial, actividad folicular en ovarios u ovarios tipo síndrome de ovario poliquístico. Conclusiones: La exposición a andrógenos a largo plazo no parece producir cambios malignos en la histología uterina ni ovárica, sin embargo, a menudo lleva a cambios en la actividad y la arquitectura ovárica, apreciándose en la mayoría de los casos ovarios funcionales e incluso semejantes a los observados en mujeres con ovario poliquístico.

ABSTRACT Introduction and objectives: Gender identity is the internal and individual experience of the gender as each person feels it. In some cases, the acquisition of secondary sexual characteristics of the other gender is important in the process of gender reassignment, with endocrinological treatment being important. The question is whether prolonged administration of androgens is safe in cases of transsexual women to men, since there is little scientific evidence in the long term. The aim of this study is to analyze the clinical characteristics of trans patients in our unit, and the anatomopathological findings of the surgical pieces of hysterectomy and double adnexectomy, to see the influence of androgen therapy on the female internal genitalia. Methods: This is a descriptive study where demographic and clinical data of the patients referred for genital surgery were analyzed, as well as the results of the anatomopathological study of the hysterectomy and adnexectomy pieces were analyzed. Results: 66 patients were included, of which 59 were intervened. No malignancy was found in any of the surgical pieces, but several benign findings such as myomas, endometrial atrophy / proliferation, follicular activity in ovaries or ovaries like polycystic ovary syndrome. Conclusions: Long-term exposure to androgens does not seem to produce malignant changes in uterine or ovarian histology, however, it often leads to changes in ovarian activity and architecture, with functional ovaries being seen in most cases and even similar ones. those observed in women with polycystic ovary.

Hepatotoxicidad por esteroides anabólicos androgénicos, reporte de 2 casos en Uruguay / Hepatotoxicity induced by anabolic-androgenic steroids, 2 cases report in Uruguay / Hepatotoxicidade por anabolizantes esteróides androgênicos, relato de 2 casos no Uruguai

El consumo ilícito de esteroides anabólicos androgénicos con fines estéticos ha aumentado en los últimos años y, aunque raro, es causa de hepatotoxicidad. Los casos con daño hepatocelular son más frecuentes, pero los colestásicos son más graves y pueden asociarse a falla renal. Salvo por la suspensión del fármaco, la hepatotoxicidad por anabólicos no tiene tratamiento específico. Se describe y discuten las historias clínicas de dos hombres jóvenes, deportistas aficionados que consultaron por ictericia y presentaron colestasis e insuficiencia renal. El reporte de casos, en patologías poco frecuentes, resulta fundamental para difundir y ampliar la información que ayude al clínico a considerar con firmeza este diagnóstico, incluso ante la falta de reconocimiento inicial del consumo por parte del paciente.

Illicit consumption of anabolic-androgenic steroids for aesthetic purposes has increased in recent years. Hepatocellular damage is more frequent, but cholestasis is more dangerous and may be associated with renal failure. The clinical records of two young men, amateur athletes who consulted for jaundice in the last year and denied its consumption at the beginning, are described. Except for the drug interruption, hepatotoxicity by anabolics has no specific treatment. Usually presented as cholestatic liver disease and renal failure, case reports are fundamental to characterize its clinical-evolutionary presentation. This may also allow clinicians to firmly consider diagnosis even when the patient denies consumption.

O uso ilícito de esteróides androgênicos anabólicos para fins estéticos tem aumentado nos últimos anos e, apesar de raro, é causa de hepatotoxicidade. Casos com dano hepatocelular são mais freqüentes, mas colestesia é mais grave e pode estar associada à insuficiência renal. Com exceção da suspensão do medicamento, a hepatotoxicidade anabólica não possui tratamento específico. As histórias clínicas de dois homens jovens, atletas amadores que consultaram para icterícia e apresentaram colestase e insuficiência renal, são descritos e discutidos. O relato de casos, em patologias pouco freqüentes, é fundamental para disseminar e ampliar as informações que auxiliam o clínico a considerar com firmeza esse diagnóstico antes mesmo do não reconhecimento inicial do consumo pelo paciente.

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Androgênios e mama / Androgens and breast

O câncer de mama (BCA) é uma das neoplasias mais frequentes em mulheres de vários países, a exposição excessiva aos estrogênios é um dos principais fatores de risco. Os ovários são as principais fontes de produção estrogênica endógena; porém, na menopausa essa produção cessa e a síntese extragonadal, sobretudo nas células mesenquimais do tecido adiposo, passa a ser a principal fonte de produção estrogênica, pois essas células apresentam aromatase, enzima que converte androgênios em estrogênios. Apoiada por fortes evidências clínicas, a reposição androgênica tem sido recomendada para o alívio de sintomas decorrentes da síndrome da insuficiência androgênica feminina, tais como fadiga, alterações do humor e quadros de depressão; além disso, estudos experimentais têm sugerido a possibilidade de uma plausível proteção da reposição androgênica contra o BCA. Nesses estudos, em que atuou por meio de seus receptores, a testosterona apresentou efeitos antiproliferativos, pró­apoptóticos e inibiu a atividade dos receptores estrogênicos e do crescimento de tumores mamários; evidências clínicas também apoiam o papel protetor dos androgênios na mama. Entretanto, outros estudos indicam que esse papel protetor depende do nível de atividade da aromatase; assim, a testosterona pode exercer um efeito inibidor direto no crescimento tumoral ao ligar­se ao seu receptor, porém ter um efeito estimulador indireto através de sua conversão para estrogênios pela aromatase. A obesidade e a insulina, além de múltiplos outros fatores, alguns dos quais são fatores de risco independentes para BCA, podem resultar na superexpressão da aromatase e ter como resultado aumento na produção localizada de estrogênios, os quais são fatores estimulantes do BCA. Estudos sobre a administração de testosterona em mulheres são escassos e controversos e não existem estudos que forneçam dados em termos de segurança desse uso em longo prazo. Assim, nesta revisão pretendemos mostrar como os androgênios atuam na mama. Frente às evidências atuais, o uso de androgênios em mulheres com fatores de risco para câncer de mama não é recomendado.(AU)

Breast cancer (BCAA) is one of the most frequent malignancies in women in several countries, which excessive exposure to oestrogens is one of the main risk factors. The ovaries are the main source of endogenous estrogen production; however, at menopause this production sessate and extra­gonadal synthesis, especially in ectomesenchymal cells from adipose tissue, turns the main source of estrogen production, since these cells express aromatase, an enzyme that converts androgens to estrogens. Supported by strong clinical evidence androgen replacement has been recommended for the relief of symptoms caused by female syndrome of androgen insufficiency, such as fatigue, mood swings and depression; Furthermore, experimental studies have suggested the possibility of protection of androgen replacement against BCA. In these studies, acting through their receptors, testosterone showed antiproliferative, proapoptotic and inhibited the activity of estrogen receptors and growth of mammary tumors; Clinical evidence also support the protective role of androgens in the breast. However, studies indicate that this protective role depends on the level of aromatase activity; for instance, testosterone can exert a direct inhibitory effect on tumor growth by binding to its receptor, but have an indirect effect by stimulating its conversion to oestrogens by aromatase. Obesity and insulin, as well as multiple other factors, some of which are independent risk factors for BCA, may result in overexpression of aromatase, resulting in increased localized production of estrogens, which are inducible factors of BCA. Studies on the administration of testosterone in women are scarce and controversial, and there are no studies that provide data in terms of long­term use of safety. Thus, in this review we intend to show how androgens act in the breast. Given the current evidence, the use of androgens in women with risk factors for breast cancer is not recommended.(AU)

Morphometric study of the corpus cavernosum after anabolic androgenic steroid administration in pubertal and adult rats

PURPOSE: To evaluate the penile morphological modifications of pubertal and adult rats chronically treated with supra-physiological doses of anabolic androgenic steroids. METHODS: Forty-eight male Wistar rats were distributed into four groups: two control groups, 105- and 65-day-old (C105 and C65, respectively) injected with peanut oil (vehicle); and two treated groups, 105- and 65-day-old (T105 and T65, respectively) injected with nandrolone decanoate at a dose of 10 mg Kg-1 of body weight. The rats were injected once a week for eight weeks. The rats were then killed and their penises were processed for histomorphometric analyses. The mean of each parameter was statistically compared. RESULTS: A corpus cavernosum reduction of 12.5% and 10.9% was observed in the T105 and T65 groups, respectively, when compared with their respective control groups. The cavernosum smooth muscle surface density diminished by 5.6% and 12.9% in the T65 and T105 groups, respectively, when compared with their controls. In contrast, the sinusoidal space increased by 17% in the T105 group and decreased by 9.6% in the T65 group. CONCLUSION: The use of supra-physiological doses of AAS promotes structural changes in the rat penis, by altering the proportions of corpus cavernosum tissues, in both pubertal and adult treated animals. .

The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats

Purpose Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. Materials and Methods: We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). Results: The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared ...

Short term testosterone replacement therapy improves libido and body composition / Reposição de testosterona a curto prazo melhora libido e composição corporal

OBJECTIVE: To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement, and controls, during six months. METHODS: We assessed, through ADAM, AMS, IIEF-5 and SF-36 questionnaires, and through clinical and laboratorial examinations, 62 patients divided into three groups: 17 hypogonadal males (HR) used intramuscular testosterone every three weeks; 14 hypogonadal males (HV) and 31 non-hypogonadal males (CV) used oral vitamins daily. RESULTS: When compared to others, HR group obtained libido improvement assessed by ADAM 1 (p = 0.004), and borderline sexual potency improvement assessed by IIEF-5 (p = 0.053), besides a decrease in waist circumference after eight weeks (p = 0.018). The remaining parameters did not differ between the groups. PSA and hematocrit remained stable in those using testosterone. CONCLUSION: Six months of testosterone replacement improved sexuality and body composition, with prostatic and hematological safety.

OBJETIVO: Avaliar a eficácia e a segurança da reposição de testosterona em homens com hipogonadismo tardio comparados a hipogonádicos sem reposição e controles, durante seis meses. MÉTODOS: Mediante os questionários ADAM, AMS, IIEF-5 e SF-36, foram feitos exame clínico e laboratorial em 62 pacientes divididos em três grupos: 17 hipogonádicos (HR) usaram testosterona intramuscular a cada três semanas; 14 hipogonádicos (HV) e 31 não hipogonádicos (CV) usaram vitaminas via oral diariamente. RESULTADOS: Comparado aos demais, o grupo HR obteve melhora da libido avaliada pelo ADAM 1 (p = 0,004) e melhora limítrofe da potência sexual avaliada pelo IIEF-5 (p = 0.053), além de diminuição da cintura a partir da oitava semana (p = 0,018). Os demais parâmetros não foram diferentes entre os grupos. PSA e hematócrito se mantiveram estáveis nos que usaram testosterona. CONCLUSÃO: A reposição de testosterona durante seis meses melhorou a sexualidade e a composição corporal, com segurança prostática e hematológica.

Andropausa e reposição hormonal no envelhecimento masculino / Andropause and hormone replacement in aging male

Andropausa, ou deficiência androgênica do envelhecimento masculino (DAEM), descreve a entidade clínica definida como uma síndrome associada ao envelhecimento. É uma condição freqüente, mas subdiagnosticada. Os achados são semelhantes àqueles do processo de envelhecimento e incluem perda de energia, depressão, diminuição da libido, disfunção erétil, diminuição da massa e força muscular, osteopenia e osteoporose. Os autores revisam os achados associados com o hipogonadismo tardio, abordam o diagnóstico, as características clínicas e fisiopatológicas da diminuição hormonal, as indicações para reposição hormonal, com suas vantagens e desvantagens, assim como o seguimento destes pacientes.

Andropause or androgenic deficiency of the masculine aging (ADMA) describes a clinical entity which has been defined as a syndrome associated with advanced age. It is a frequent condition but under diagnosed. Symptoms and findings of testosterone deficiency are similar to those associated with aging and include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strenght, osteopenia and osteoporosis. This article reviews the findings associated with late hypogonadis, addresses the diagnosis, clinical and pathophysiological features of hormonal decline, the indications for hormone replacement with their disadvantages, as well as the monitoring of these patients.

Prevalência do uso de agentes anabólicos em praticantes de musculação de Porto Alegre / Prevalence of the use of anabolic agents among strength training apprentices in Porto Alegre, RS

Este estudo procura determinar, através de questionário realizado por entrevistadores, a prevalência do uso atual ou passado de esteróides anabólicos androgênicos (EAA), outros hormônios (OH), outros medicamentos (OM) e outras substâncias (suplementos alimentares e drogas ilícitas) em praticantes de musculação da cidade de Porto Alegre, entrevistando 288 indivíduos sorteados de uma amostra de 13 academias. A prevalência observada foi de 11,1 por cento (32/288) para EAA, 5,2 por cento (16/288) para OH e 4,2 por cento (12/288) para OM. Os EAA mais usados foram decanoato de nandrolona e estanozolol. Os OH foram gonadotrofina coriônica humana, triiodotironina e OM como lipostabil, diuréticos e medicamentos veterinários (ex.: Monovin E). Os efeitos colaterais mais freqüentes foram comportamentais (variação de humor, irritabilidade e agressividade) e endócrinos (acne e aumento/ diminuição da libido). Quando analisados os EAA juntamente aos OH na variável denominada "agentes hormonais" (AH), observamos diferença estatística (p< 0,05) entre os sexos, sendo o uso de AH mais prevalente em homens e entre os consumidores de suplementos alimentares. Comparar este estudo a outros é difícil, pois existe diferença no desenho epidemiológico. Entretanto, a alta prevalência observada sugere a necessidade de medidas preventivas, educativas e de cuidados na assistência desta população.

This study aimed to determine through a questionnaire applied to interviewers, the current or past use of anabolic androgenic steroids (AAS), as well as other hormones (OH), and other medicines (OM), food supplement and illicit drugs among strength training apprentices in the city of Porto Alegre, RS. We interviewed 288 subjects draw from a sample of 13 gyms. The prevalence of current and past use of AAS was about 11.1 percent (32/288), OH 5.2 percent (16/288) and OM 4.2 percent (12/288). The most used AAS were nandrolone and stanozolol; the OH were gonadotropin, triiodothyronine (T3) and OM, like lipostabil, diuretics and veterinary medicines (Monovin E). The most frequent side-effects were behavioral such as humor oscillation, irritability and hostility, and endocrine disturbances such as acne and increased or decreased libido. When analyzed together with other hormones in a variable named "hormonal agents" (AH), AAS presented a statistical difference (p< 0.05) among genders considering that the most frequent use of AH occurred among men and those who consume food supplements. The comparison of these findings to other national and international results is difficult due to the epidemiological design. Even if it is considered, the observed prevalence suggests that preventive attitudes as well as special care in the orientation and education of this population must be taken.

Nandrolone- induced myocardial infarction in a professional soccer player

Androgenic Anabolic Steroids [AAS] are often used by athletes for enhancing athletic performance but are strongly associated with detrimental cardiovascular effects including sudden cardiac death1. Herein, we present a 24 year-old professional soccer player who suffered acute myocardial infarction after nandrolone consumption

Ginecomastia (Estudio retrospectivo sobre 54 casos operados) / Gynecomastia: retrospective study of 54 cases surgically treated

Se realiza un estudio retrospectivo de 54 casos operados en el Hospital de Endocrinología y Metabolismo Dr. Arturo Oñativia de Salta. Entre los años 1987 y 2001 fueron intervenidas 63 ginecomastias que representan el 5,58 por ciento de los diagnósticos anátomo-patológicos y el 7,18 por ciento de los informes benignos. Sobre 54 pacientes con historias clínicas presentes se detallan aspectos epidemiológicos, formas de presentación, estudios practicados, diagnóstico causal, características anátomo-patológicas y se intenta cursar una guía para el estudio de la ginecomastia como así también para el tratamiento médico y quirúrgico. Por último se realiza determinación de receptores hormonales por inmunomarcación en 19 casos observando pisitividad nuclear epitelial para estrógenos en el 68,42 por ciento y de progesterona en el 47,36 por ciento.