[Show abstract][Hide abstract] ABSTRACT: Objective:
The role of testosterone (T) in regulating body composition is conflicting, thus our goal is to meta-analyze the effects of T supplementation (TS) on body composition and metabolic outcomes.
All randomized controlled trials (RCTs) comparing the effect of TS on different endpoints were considered.
Overall, 59 trials were included in the study enrolling 3029 and 2049 patients in TS and control groups, respectively. TS was associated with any significant modification of body weight, waist circumference and body mass index. Conversely, TS was associated with a significant reduction of fat and with an increase of lean mass as well as with a reduction of fasting glycaemia and insulin resistance. The effect on fasting glycaemia was even higher in younger individuals and in those with metabolic diseases. When only RCTs enrolling hypogonadal (total T<12 moles/L) subjects were considered, a reduction of total cholesterol as well as of triglyceride levels were also detected. Conversely, an improvement in HDL cholesterol levels as well as in both systolic and diastolic blood pressure was not observed.
Our data suggest that TS is able to improve body composition and glycometabolic profile particularly in younger subjects and in those with metabolic disturbances. Specifically designed studies are urgently needed to confirm this point.
Full-text · Article · Mar 2016 · European Journal of Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic-pituitary-gonadal (HPG) axis. In hypogonadotropic hypogonadism (HH), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in HH men is predictable by the origin of HH, indicating time of onset and severity of GnRH/gonadotropin deficiency. The data of 51 adult HH patients who had undergone one cycle of hCG/FSH treatment were reviewed. Five groups were established, according to the underlying HH origin. Therapeutic success by final bi-testicular volumes (BTVs) final sperm concentrations (SC) and conception rates were compared and related to baseline parameters, indicative of the degree of HPG-axis disruption. Overall, BTVs rose from 13 ± 15 to 27 ± 15 mL, spermatogenesis was induced in 98%, with mean SCs of 15 ± 30 mill/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses (BTV: 16.9 ± 10 mL; SC: 3.5 ± 5.6 mill/mL), followed by patients with congenital/infancy-acquired multiple pituitary hormone deficiencies (MPHD) and patients with HH+absent puberty (BTV: 21 ± 14/24 ± 9 mL; SC: 5.5 ± 6.5/ 14.5 ± 23.8 mill/mL). HH men with pubertal arrest and with post-pubertally acquired MPHD had the best results (BTV: 36 ± 14/38 ± 16 mL; SC: 25.4 ± 34.2/29.9 ± 50.5 mill/mL). Earlier conception after 20.3 ± 11.5 months (vs. 43.1 ± 43.8; p = 0.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post-pubertally acquired HH subgroups, compared to the three pre-pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline BTVs (pre- vs. post-pubertal HH: 5 ± 4 mL vs. 26 ± 16 mL; p < 0.0001) and higher baseline inhibinB levels (pre- vs. post-pubertal HH: 16.6 vs. 144.5 pg/mL; p = 0.0004). The cause of HH is a valuable predictor of outcome of gonadotropin replacement in adults.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Gender Dysphoria (GD) is characterized by the urge to live as member of the desired sex, different to natal sex. The goal of medical and surgical treatment is to improve the well-being and quality of life of transpeople [Meriggiola et al. 2015]. Sex re- assignment requires a multidisciplinary treat- ment [Hembree et al. 2009] including cross- sex hormone treatment (CHT) and sex-reas- signment surgery (SRS). For male-to-female patients, “devirilization” using cyproterone acetate followed by “feminization” using es- trogens combined with antiandrogens is usu- ally given [Gorin-Lazard et al. 2012]. There is no data about suspension of the hormones before surgery [Meriggiola et al. 2010]. Moreover, no controlled clinical trials of any feminizing hormone regimen have been con- ducted to evaluate safety or efficacy in pro- ducing physical transition [WPATH 2011]. The optimum steroid hormone treatment re- gime for transsexual subjects has not been es- tablished [van Kesteren et al. 1997].
Aim: To describe the influence of CHT itself and the influence of its different stopping points before SRS on the adrenal gland hor- mone profile we used mass spectrometry- based methods to compare 3 different treat- ment regimens in a multi-center study. Clinic A told the patients to stop CHT four to six weeks prior to SRS, in clinic B patients were told to discontinue treatment 2 weeks before and in clinic C patients were told not to stop at all.
Material and Methods Ethical committees of the Ärztekammer Westfalen-Lippe (no. 2012-555-f-S) and the Ärztekammer Hamburg (no. MC-131/13) approved this research. Written informed consent was received from each subject prior to study participation. Par- affin sections were deparaffinized, dehydrat- ed and PAS-stained according to published protocols [Brinkworth et al. 1995]. The spermatogenic state was evaluated with the Bergmann/Kliesch score [Bergmann/Kliesch 1998]. The adrenal-gland hormones were di- vided in three axes. 1st axis: progesterone, 17-desoxycorticosterone, corticosterone; 2nd axis: 17-hydroxyprogesterone, 11-desoxycor- tisol, 21-desoxycortisol, cortisol, cortisone; 3rd axis: 17-hydroxypregnenolone, DHEAS, androstendione, testosterone, DHT. They were measured by liquid-chromatography – tandem mass spectrometry.
￼Results: The first 15 subjects from each clin- ic were included (total 45 subjects). Accord- ing to the Bergman/Kliesch score, 5 showed complete spermatogenesis, 16 meiotic arrest, 15 spermatogenic arrest, 8 Sertoli-cell-only syndrome and one complete tubular atrophy.
1st axis: Mean 11-desoxycorticosterone lev- els of clinic B (*p < 0.05) were decreased be- low male and female reference levels. Lowest levels were observed in those patients with complete spermatogenesis. Interestingly, tes- ticular tissue with complete spermatogenesis showed the lowest levels in all three of them.
2nd axis: Mean 21-desoxycortisol was signifi- cantly higher in clinic C compared to clinic B (****p < 0.00001). Surprisingly, cortisone levels were significantly lower in clinic A (*p < 0.05) than in clinic C.
3rd axis: Mean androstendion of clinic A (mean: 84.42 ng/dl, SD: 64.07 ng/dl) was significant- ly higher than in clinic C (** p < 0.005). Mean DHEAS of clinic B was significantly lower comparing it to clinic A (**p < 0.005). Total testosterone was above the female ref- erence, but within the male ranges. Mean tes- tosterone of clinic A was within male ranges, mean testosterone of clinic B and clinic C was above the female and below the male limits. Testicular tissue with complete sper- matogenesis showed the highest testosterone levels.
Conclusion: In this first descriptive study ex- amining the adrenal gland hormone profile in GD patients undergoing SRS, we could show that CHT and its different stopping points were most effective on the sex-steroid and less effective on the mineralocorticoid axis. Our patient group in general didn‘t suffer from el- evated stress levels. Reduced stress levels were seen in clinic A. Best feminized blood serum levels on the day of SRS can – as exspected – only be achieved if CHT is not stopped.
[Show abstract][Hide abstract] ABSTRACT: Eine Elternschaft im späteren Lebensalter wird von vielen Menschen als vorteilhaft wahrgenommen, da die Lebensbedingungen in vielerlei Hinsicht häufig stabiler sind. Auch gibt es Männer, die eine zweite Familie gründen möchten. Damit sich die ältere Vaterschaft tatsächlich erfüllt, sind deren biologische Besonderheiten zu beachten.
[Show abstract][Hide abstract] ABSTRACT: Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this intervention may evolve as a novel approach to treatment of obesity in men with TD .
No preview · Article · Nov 2015 · Reviews in Endocrine and Metabolic Disorders
[Show abstract][Hide abstract] ABSTRACT: An international expert consensus conference regarding testosterone deficiency (TD) (also known as hypogonadism) and its treatment was held on 1 October 2015, in Prague, Czech Republic. The impetus for this meeting was to address several key scientific issues that have been misunderstood or distorted during the recent intense media attention to this topic. Eighteen experts from 11 countries participated, from the disciplines of urology, endocrinology, andrology, diabetology, and basic science research. The goal was to identify scientific concepts for which there was broad agreement. It was noted that recent public controversies regarding testosterone therapy have been anchored by two retrospective studies reporting increased cardiovascular (CV) risks. Both these studies contained major flaws, and are contradicted by a large body of evidence suggesting CV benefits with testosterone therapy. Other topics discussed included the negative impact of TD on male health; the questionable validity of restrictions on treatment based on age-specific cut-offs, presence of identified underlying conditions, or application of rigid biochemical thresholds; and the lack of evidence regarding prostate cancer risks. Final consensus statements (resolutions) are under development. It is hoped these will serve as a scientific foundation for further discussion, and will thereby reduce misinformation regarding TD and its treatment.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Cross-sex hormone treatment of gender dysphoria (GD) patients changing from male to female a prerequisite for sex reassignment. For initial physical adaptation, a combined treatment of anti-androgens and estrogens is used. Provided that patients fulfill specific criteria, sex reassignment surgery (SRS) presents the final step toward physical adaptation. However, systematic studies analyzing effects of hormone treatment regimens are lacking.
The aim of this study was to compare the effects of three different hormonal treatment strategies regarding endocrinological parameters and testicular histology.
Testicular tissues were obtained in a multicenter study from 108 patients on the day of SRS from three clinics following different treatment strategies. Patients either discontinued treatment 6 weeks (clinic A) or 2 weeks (clinic B) prior to SRS or not at all (clinic C). Testicular tissues, ethylenediaminetetraacetic acid blood and questionnaires were obtained on the day of SRS.
Main Outcome Measures:
Blood hormone and intratesticular testosterone (ITT) levels were measured. Testicular weight and histology were evaluated and the percentage of luteinizing hormone/choriogonadotropin receptor (LHCGR) positive cells was determined.
According to the questionnaires, patients showed desired phenotypical changes including breast growth (75%) and smooth skin (32%). While patients from clinics A and B presented with rather virilized hormonal levels, patients from clinic C showed generally feminized blood serum levels. Histological evaluation revealed highly heterogeneous results with about 24% of patients presenting with qualitatively normal spermatogenesis. In accordance with serum endocrine profile, ITT levels were lowest in clinic C and correlated with testosterone and free testosterone, but not with the spermatogenic state. The percentage of LHCGR-positive cells and ITT levels did not correlate.
Only patients that did not discontinue hormonal treatment showed feminized blood levels on the day of SRS. The ones who stopped re-virilized quickly. Interestingly, testicular histology was highly heterogeneous irrespective of the treatment strategy, a phenomenon that requires further investigation.
No preview · Article · Nov 2015 · Journal of Sexual Medicine
[Show abstract][Hide abstract] ABSTRACT: Hypogonadism (HG, testicular failure in men) has become a controversial and much misunderstood condition. Many men perceive testosterone as a panacea for the ills of ageing and "Low-T clinics" have sprung up to meet their demands, even though testosterone is often not the answer. In light of the unprecedented rise in testosterone prescriptions in recent years, particularly amongst middle-aged men, the US Food and Drug Administration (FDA) issued a Safety Communication in May 2015 intended to restrict the use of testosterone. This article is protected by copyright. All rights reserved.
No preview · Article · Sep 2015 · BJU International
[Show abstract][Hide abstract] ABSTRACT: Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings.
No preview · Article · Aug 2015 · Reviews in Endocrine and Metabolic Disorders
[Show abstract][Hide abstract] ABSTRACT: In pre-pubertal boys ≥ 14 years, the differentiation between constitutional delay of growth and puberty (CDGP) and hypogonadotropic hypogonadism (HH) is challenging, as current diagnostic tools have limitations in sensitivity and specificity. The aim of this study was to assess the usefulness of markers of gonadal activity, growth axis activation and adrenarche in differentiation between pre-pubertal CDGP and HH. This retrospective study was carried out between 2006 and 2015 in an academic out-patient referral centre. The clinical data of 94 boys, aged 13.9–23.2 years and referred for “pubertal delay” were reviewed. Definite diagnoses were established on initial work-up and clinical follow-up: 24 boys were diagnosed with HH, 22 boys with CDGP, pre-pubertal (PP CDGP) at referral and 28 boys with CDGP, early pubertal at referral (EP CDGP), the latter serving as control group. Twenty patients were excluded from evaluation because of previous sex steroid treatment or associated chronic disease. Inhibin B and AMH were measured in all (n = 74); INSL3, IGF1, IGFBP3 and DHEAS in a subset of patients (n = 45) in serum of first presentation. Inhibin B and AMH were higher in boys with PP CDGP than in boys with HH: inhibin B: 87.6 ± 42.5 vs. 19.8 ± 13.9 pg/mL; p < 0.001; AMH: 44.9 ± 27.1 vs. 15.4 ± 8.3 ng/mL; p < 0.001. Receiver operating characteristics (ROC) for the diagnosis of PPCDGP vs. HH (inhibin B ≥ 28.5 pg/mL): sensitivity: 95%, specificity: 75%; AUC: 0.955. In combination with an AMH cut-off ≥20 ng/mL the specificity increased to 83%. INSL3, IGF1, IGFBP3 and DHEAS levels were not different. In boys with EP CDGP, inhibin B and IGF1 levels were highest (138.7 ± 59.9 pg/mL/289.7 ± 117 ng/mL), whereas AMH levels were lowest (11.7 ± 9.1 ng/mL). Sertoli cell markers are helpful for establishing a prognosis, whether a boy with pubertal delay will enter puberty spontaneously, whereas Leydig cell, growth and adrenal markers are not.
[Show abstract][Hide abstract] ABSTRACT: IntroductionIn 2014, the International Society for Sexual Medicine (ISSM) convened a panel of experts to develop an evidence-based process of care for the diagnosis and management of testosterone deficiency (TD) in adult men. The panel considered the definition, epidemiology, etiology, physiologic effects, diagnosis, assessment and treatment of TD. It also considered the treatment of TD in special populations and commented on contemporary controversies about testosterone replacement therapy, cardiovascular risk and prostate cancer. AimThe aim was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of diagnosis and management of TD for clinicians without expertise in endocrinology, such as physicians in family medicine and general urology practice. MethodA comprehensive literature review was performed, followed by a structured, 3-day panel meeting and 6-month panel consultation process using electronic communication. The final guideline was compiled from reports by individual panel members on areas reflecting their special expertise, and then agreed by all through an iterative process. ResultsThis article contains the report of the ISSM TD Process of Care Committee. It offers a definition of TD and recommendations for assessment and treatment in different populations. Finally, best practice treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with TD. Conclusion
Development of a process of care is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to new insights into the pathophysiology of TD, as well as new, efficacious and safe treatments. We recommend that this process of care be reevaluated and updated by the ISSM in 4 years. Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, Bivalacqua TJ, Burnett AL, Buvat J, El Meliegy A, Hellstrom WJG, Jannini EA, Maggi M, McCullough A, Torres LO, and Zitzmann M. The International Society for Sexual Medicine's process of care for the assessment and management of testosterone deficiency in adult men. J Sex Med 2015;12:1660-1686.
Full-text · Article · Jun 2015 · Journal of Sexual Medicine
[Show abstract][Hide abstract] ABSTRACT: Testosterone substitution in male hypogonadism is a recognized tool to treat symptomatic patients. Various forms of this treatment exist including a long-acting intramuscular form using testosterone undecanoate given at approximately 3-monthly intervals. Safety aspects inherent to the intramuscular injection of a medication in an oily vehicle have to be recognized.
[Show abstract][Hide abstract] ABSTRACT: Introduction & Aim: According to standardized guidelines humans with GD receive cross-sex
hormone therapy (CSHT) for up to 2 years before SRS. In order to assess the effectiveness of CSHT
we evaluated changes of body constitution, testes and hormonal status in a multi-center study with
3 clinics advising different treatment strategies.
Material & Methods: Following written informed consent and ethical approval, 175 testicular tissues
from 114 patients were obtained from 3 German clinics. In clinic A CSHT was stopped 2 weeks
before SRS, in clinic B 4-6 weeks before and in clinic C not at all. Questionnaires were handed out
to patients about their CSHT. Hormone levels (LH, FSH, testosterone, estradiol, prolactin, free
testosterone, SHBG) were measured with standardized in-house assays and intratesticular
testosterone (ITT) levels with radioimmunoassay. Testicular tissues were histologically evaluated
for spermatogenic state and tubular diameter. Leydig cell ‘functionality’ was
immunohistochemically checked via LH-receptor stainings.
Results: Out of 83 subjects, 59 took a anti-androgens/estrogen combination. The 3 most prominent
changes of body constitution were breast growth, smooth skin, emotional instability. 20% of the
testicular tissues showed complete spermatogenesis, 28% meiotic arrest, 34% spermatogonial
arrest, 16% Sertoli-cell only and 2% tubular ghosts. The testicular mean weight decreased with the
drop of spermatogenic progress. Subjects from clinic B showed the highest LH, FSH, prolactin,
testosterone and free testosterone levels. Those from clinic C showed the highest SHBG, estradiol
and ITT-levels. Whilst percentages of tubules and interstitium increased, the percentage of lumen
dropped with the decrease of spermatogenic progress. The tubular diameter as well as the number
of LH-receptor positive cells decreased simultaneously.
Conclusion: A highly heterogeneous histological and endocrine picture was observed. Ongoing
CSHT provoked highly feminized endocrine parameters in clinic C when compared to the other
clinics. Hence we strongly recommend individually adapted CSHT, a close follow-up and hormonal
check-ups for GD patients before SRS.