[Outpatient clinic for users of anabolic androgenic; experiences and practical tools]. / De Anabolenpoli.

In the Netherlands, an estimated 20,000 men abuse illegal androgens. The confrontation with a patient who uses illegal substances can evoke questions and emotions. We advise not to moralize users of anabolic steroids, but to strive for harm reduction by starting a discussion about the pros and cons of androgen abuse, taking into account your assumptions and judgments about this subject. Underlying psychopathology should be recognized and treated if the user is open to it. We recommend against prescribing anabolic steroids without medical indication and not to perform health checks routinely while the patient continues using anabolic steroids as long as it is not established that this can prevent health damage. If the user reports with health problems, this should be used as a starting point to (re) open the conversation about the advantages and disadvantages of use. Harmful effects of use must be handled according to appropriate guidelines.

Disruption and recovery of testicular function during and after androgen abuse: the HAARLEM study.

STUDY QUESTION: What is the speed and extent by which endogenous testosterone production and spermatogenesis recover after androgen abuse? SUMMARY ANSWER: Testosterone concentrations normalized within 3 months after discontinuation of androgen abuse in most subjects but recovery of spermatogenesis took longer-approximately 1 year. WHAT IS KNOWN ALREADY: An estimated 4-6% of amateur strength athletes use androgens. Abuse of supraphysiological doses of androgens completely suppresses endogenous testosterone production and spermatogenesis. STUDY DESIGN, SIZE, DURATION: Prospective and observational cohort study in which 100 male amateur athletes participated for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects (≥18 years) were included if they had not used androgens for at least 3 months and intended to start an androgen cycle within 2 weeks. Clinic visits took place before (T0), at the end (T1), and 3 months after the end of the cycle (T2), and 1 year after start of the cycle (T3), and included a blood test for gonadotrophins and sex hormones, and semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE: During androgen abuse, 77% of subjects had a total sperm count (TSC) below 40 million. Three months after the end of the cycle (T2), total (-1.9 nmol/l, CI -12.2 to 8.33, P = 0.71) and free (-38.6 pmol/l, CI -476 to 399, P = 0.86) testosterone concentrations were not different compared to baseline, whereas mean TSC was 61.7 million (CI 33.7 to 90.0; P < 0.01) lower than baseline. At the end of follow-up (T3), there was no statistically significant difference for total (-0.82 nmol/l, CI -11.5 to 9.86, P = 0.88) and free (-25.8 pmol/l, CI -480 to 428, P = 0.91) testosterone compared to baseline, but there was for TSC (-29.7 million, CI -59.1 to -0.39, P = 0.05). In nine (11%) subjects, however, testosterone concentrations were below normal at the end of follow-up (T3), and 25 (34%) subjects still had a TSC below 40 million. LIMITATIONS, REASONS FOR CAUTION: The follow-up period (after the cycle) was relatively short, especially considering the long recovery time of spermatogenesis after discontinuation of androgens. WIDER IMPLICATIONS OF THE FINDINGS: Endogenous testosterone production and spermatogenesis recover following androgen abuse in the vast majority of users. Nevertheless, not all users achieve a normalized testicular function. This may especially be the case for athletes with a high past exposure to androgens. STUDY FUNDING/COMPETING INTEREST(S): There is no conflict of interest. The study was funded by the Spaarne Gasthuis academy. TRIAL REGISTRATION NUMBER: N/A.

Spontaneous haemorrhage of hepatic adenoma in a patient addicted to anabolic steroids.

This case report describes a patient with a nearly fatal spontaneous haemorrhage of a hepatic adenoma that occurred in association with anabolic androgenic steroid (AAS) use. The patient was addicted to AAS and had been using exceptionally high dosages as well as growth hormone. After cessation of AAS use, testosterone replacement therapy was started to prevent post-AAShypogonadism and consequent relapse.

Outpatient clinic for users of anabolic androgenic steroids: an overview.

BACKGROUND: Anabolic androgenic steroids (AAS) are used by approximately 20,000 amateur athletes in the Netherlands. AAS are harmful but data are lacking as to precisely how harmful they are. An outpatient clinic for past and current users of AAS was established in 2011 to acquire more knowledge about the health risks associated with AAS abuse. METHODS: All case files of the patients who visited the AAS clinic were reviewed retrospectively. RESULTS: 180 patients visited the AAS clinic between May 2011 and May 2016. Patients were strength athletes (99% male, mean age 34 years, range 19-61) who had started AAS use at a median age of 23 years (range 16-53). 95% used AAS in cycles (median of 4 cycles completed, median duration 10 weeks). Cycles consisted of a median of three different AAS, most commonly testosterone, nandrolone and trenbolone. Growth hormone was used by 34% in addition to AAS. Side effects occurred in 96% of patients, mainly acne (38%), gynaecomastia (34%) and agitation (27%) during cycles; decreased libido (34%) and erectile dysfunction (20%) afterwards. Medications regularly used by patients to self-treat side effects were aromatase inhibitors, clomiphene citrate, human choriogonadotropin, and tamoxifen. CONCLUSION: AAS abuse did not lead to critical health issues. However, the incidence of less severe side effects among AAS users appears high. Considering the large number of abusers in the community, AAS abuse poses an important public health problem. A prospective study with a systematic approach is required to provide more reliable data regarding health risks of AAS abuse.

Oestrogens are Not Related to Emotional Processing: a Study of Regional Brain Activity in Female-to-Male Transsexuals Under Gonadal Suppression.

Although the prevailing opinion is that emotional processes are influenced by sex hormones, the literature is still inconclusive. The aim of the current study was to examine the effects of gonadal suppression on brain activity during affective picture processing. Twenty-one female-to-male (FtM) transsexuals and 19 control women were recruited and underwent functional magnetic resonance imaging scanning while rating emotional pictures adapted from the International Affective Picture System. The gonadal hormone production of the FtMs was suppressed for 8 weeks, the control group did not receive any treatment before scanning. Under gonadal suppression, FtMs showed less brain activation in the superior temporal lobe compared with female controls during perception of positive affective pictures. Regression analysis showed that during processing of positive affective images, brain activity within the right superior temporal lobe was not correlated with levels of estradiol, luteinizing hormone, and follicle-stimulating hormone. In the absence of associations with hormonal levels, the difference in activation in the superior temporal lobe during positive emotional stimuli between FtMs and control women may be attributed to a priori differences between the 2 groups. Future studies should clarify if these differences are a result of atypical sexual differentiation of the brain in FtMs.

Feed-forward loops and diamond motifs lead to tunable transmission of information in the frequency domain.

Using a Gaussian model, we study the transmission of time-varying biochemical signals through feed-forward motifs and diamond motifs. To this end, we compute the frequency dependence of the gain, the noise, as well as their ratio, the gain-to-noise ratio, which measures how reliably a network transmits signals at different frequencies. We find that both coherent and incoherent feed-forward motifs can either act as low-pass or high-pass filters for information: The frequency dependence of the gain-to-noise ratio increases or decreases with increasing frequency, respectively. Our analysis of diamond motifs reveals that cooperative activation of the output component can increase the gain-to-noise ratio. This means that from the perspective of information transmission, it can be beneficial to split the input signal in two and recombine the two propagated signals at the output. Cooperative activation can be implemented via the formation of homo- or heteromultimers that then bind and activate the output component or via the binding of individual molecules of the intermediate species to the output component.

Elevated plasma creatinine due to creatine ethyl ester use.

Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure.

A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.

OBJECTIVE: Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. DESIGN: A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses. RESULTS: In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population. CONCLUSIONS: The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.

[Anabolic androgenic steroids in amateur sports in the Netherlands]. / Anabole androgene steroïden bij amateursporters in Nederland.

In the Netherlands an estimated 20,000 people use anabolic androgenic steroids (AAS). The use of AAS is particularly common in regular visitors to gyms and fitness centres. AAS are usually synthetic derivatives of testosterone with both an anabolic and an androgenic effect. AAS have many side effects like liver damage (oral use) or infections (intramuscular use), which can be explained partly by the androgenic effect and partly by the manner of use. Many of these side effects are only reported in case studies and have not been systematically investigated.

Mesoscopic statistical properties of multistep enzyme-mediated reactions.

Enzyme-mediated reactions may proceed through multiple intermediate conformational states before creating a final product molecule, and one often wishes to identify such intermediate structures from observations of the product creation. In this study, the authors address this problem by solving the chemical master equations for various enzymatic reactions. A perturbation theory analogous to that used in quantum mechanics allows the determination of the first (n) and the second (σ2) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V=d(n)/dt (or 'dose-response' curve) and the Fano factor F= σ2/(n) are both realistically measurable quantities, and whereas the mean flux can often appear the same for different reaction types, the Fano factor can be quite different. This suggests both qualitative and quantitative ways to discriminate between different reaction schemes, and the authors explore this possibility in the context of four sample multistep enzymatic reactions. Measuring both the mean flux and the Fano factor can not only discriminate between reaction types, but can also provide some detailed information about the internal, unobserved kinetic rates, and this can be done without measuring single-molecule transition events.

[Use of androgenic anabolic steroids before and during the Olympic Games: less but has not died out]. / Gebruik van androgene anabole steroïden voor en tijdens de Olympische Spelen: verminderd, maar niet verdwenen.

Androgenic anabolic steroids are compounds with a chemical structure and clinical effect very similar to those of the male hormone testosterone. Since their introduction these substances have been misused in an effort to improve athletic performance. Detection of misuse has long been inadequate. For this reason a state doping programme was developed by the government of the former German Democratic Republic (GDR). Systematic doping abuse ended with the collapse of the GDR and the introduction of out-of-competition surprise drug testing. The performance-enhancing effects of doping and the introduction of intensive doping surveillance are reflected in the decline in performance in several women's track and field events.

[Hormonal contraception in men]. / Hormonale anticonceptie bij de man.

Over the past few decades, female hormonal contraception has been seen to be very successful. However, this has still not resulted in a hormonal contraceptive for men. Certain injectable combinations ofandrogens and progestagens have been found to suppress spermatogenesis. All combinations that have been tested so far suffer from a relative lack of efficacy, a long lag time to achieve azoospermia, requiring the user to undergo one or more semen analyses, a moderate user friendliness, and concerns about the long-term safety and reversibility. It is not to be expected that male hormonal contraception will become a serious alternative to the already existing female equivalent during the coming 5 years.

Relationship between cortisol and physical performance in older persons.

OBJECTIVE: Hypercortisolism is associated with muscle weakness. This study examines the relationship between cortisol and physical performance in older persons. DESIGN/PATIENTS: The study was conducted within the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of healthy older persons in the Netherlands. Data from the second (1995/1996) and fourth (2001/2002) cycle were used pertaining to 1172 (65-88 years) and 884 (65-94 years) men and women, respectively. MEASUREMENTS: Physical performance was measured by adding up scores on the chair stands, tandem stand and walk test (range 0-12). In the second cycle serum total and calculated free cortisol were assessed; in the fourth cycle evening salivary cortisol was assessed. Regression analysis (stratified for sex, adjusted for age, body mass index, alcohol use, physical activity and region) was performed to examine the cross-sectional relationship between cortisol and physical performance. RESULTS: Women with higher calculated free cortisol scored less well on physical performance (b = -0.28 per SD higher cortisol, P = 0.016), which was mainly explained by poorer performance on the tandem stand (OR = 1.32 for a lower score per SD higher cortisol, P = 0.003). Men with higher salivary cortisol scored less well on physical performance (b = -0.90 in the highest vs. the lowest quartile, P = 0.008), which was mainly explained by poorer performance on the chair stands and walk test (OR = 1.88, P = 0.020 and OR = 1.81, P = 0.027, respectively, in the highest vs. the lowest quartile). CONCLUSION: Physical performance is negatively associated with high cortisol levels in older persons.

[Some new aspects of the Klinefelter syndrome]. / Enkele nieuwe aspecten van het klinefeltersyndroom.

Klinefelter syndrome (KS) is the most frequent form of male hypogonadism. Still, at least 50% ofcases are not diagnosed, partly because of the great variation in the clinical symptoms, partly because physicians are unfamiliar with KS. Timely treatment with testosterone can contribute to a more positive body image and, consequently, to a healthier psychosexual development in men with KS. Men with KS experience significantly more health problems and an increased risk ofa malignancy. New reproductive techniques no longer automatically mean that men with KS will remain infertile. Treatment with testosterone is in principle life-long to prevent osteoporosis and loss of muscle mass and strength.

['Hungry bone' syndrome, characterized by prolonged symptomatic hypocalcemia, as a complication of the treatment for hyperthyroidism]. / 'Hungry bone'-syndroom, gekenmerkt door langdurige symptomatische hypocalciëmie, als complicatie van behandeling wegens hyperthyreoïdie.

A 22-year-old woman presented with palpitations, agitation, heat intolerance and unintentional weight loss that had started several months before. Pharmacotherapy for hyperthyroidism was prescribed, but a year later thyroidectomy was performed in connection with a lack of treatment compliance. A few hours after the operation the patient developed a tingling sensation and muscle cramp, which were found to be due to severe hypocalcaemia. Although surgery was complicated by hypoparathyroidism, there was an unusually high need for calcium combined with a low calcium excretion in the urine. Such a high need for calcium due to the increased bone reconstruction induced by the hyperthyroidism is referred to as the hungry bone syndrome. One should be particularly alert to this complication in cases of severe, prolonged hyperthyroidism, certainly in the presence of existing or peroperatively induced damage to the parathyroids. In this patient, calcium suppletion led to normalisation of the serum calcium level two weeks postoperatively; she was discharged from the hospital in good condition after 3 weeks.

[Severe hypokalemia with paralysis in a patient with distal renal tubular acidosis as an initial expression of Sjögren's syndrome]. / Ernstige hypokaliëmie met paralyse bij een patiënte met een distale renale tubulaire acidose als eerste uiting van het syndroom van Sjögren.

In a 33-year-old woman with a recent flaccid paralysis of the arms and legs, laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidosis, thus establishing the diagnosis of distal renal tubular acidosis. The patient made a full recovery after potassium and alkali replacement. Further investigation revealed Sjögren's syndrome as the underlying cause.

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension.

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS)