Testing the boundaries : Self-medicated testosterone replacement and why it is practised / Mair Underwood, Katinka van de Ven, Matthew Dunn

• International Journal of Drug Policy 95 (2021) 103087 (September)
• DOI: 10.1016/j.drugpo.2020.103087

Abstract

Background

Testosterone is used therapeutically in medical settings. Non-prescribed testosterone use is typically illegal, described as ‘enhancement’ or ‘doping’, and considered a problem. However, research has found that some non-prescribed testosterone use may be therapeutic (i.e. self-medication). Little is known about testosterone self-medication. It has been noted among individuals who use image and performance enhancing drugs (IPEDs), but never systematically explored.

Approach

This paper describes the findings of a 4-year ethnographic study in online forums and social media groups frequented by people who use IPEDs. It focusses on 31 men who used enhancement doses of testosterone, but who described some of their testosterone use as ‘testosterone replacement therapy’ (TRT). In particular, it focuses on the 26 (84%) of these individuals who self-medicated TRT. Data was analysed thematically (using NVivo) in order to answer the question: ‘how and why is testosterone self-medicated?’. Using Bacchi's (2016) problematization approach to policy analysis, this paper also asks, ‘what happens to the ‘problem’ of non-prescribed testosterone use if such use is therapeutic?’.

Findings

Self-medicated TRT was found to be very similar to TRT as practised in medical contexts. Self-medication was often practised because of an inability to access testosterone through health practitioners (who were either reluctant or unable to prescribe). However, some individuals were found to prefer self-medication because of price, ease of access, reliability of supply, and because health practitioners were perceived as lacking expertise regarding testosterone use.

Conclusion

By documenting the therapeutic use of testosterone outside of medical settings, this paper calls into question previous conceptualisations of all illicit testosterone use as ‘abuse’, and the utility of the repair/enhancement dichotomy as a foundation for discussions of drug use. It suggests that in some cases the problem may not be non-prescribed testosterone use per se, but policies that prevent access to medical treatment.

Testing the validity and reliability of the doping willingness in sport scale / Nicholas Stanger, Lisa Whitaker, Susan H. Backhouse. - (Scandinavian Journal of Medicine & Science in Sports (2020) 16 April)

• doi:10.1111/sms.13683

Abstract

Although research investigating doping in sport is burgeoning, there is still a lack of proxy measures of doping behaviour that have undergone extensive psychometric testing. To address this issue, we modified a previously used measure of doping willingness in sport and tested aspects of validity and reliability across four studies. In Study 1, we provided support for the face and content validity of the items, and then found support for the factor structure of the scale in a sample of athletes (N = 205) using confirmatory factor analysis. In Study 2, we collected data from an independent sample of athletes (N = 236) to provide further evidence for the factor structure of the scale using confirmatory factor analysis as well as provided evidence for concurrent and discriminant validity. In Study 3, a further independent sample of athletes (N = 144) completed the scale and provided support for discriminant and predictive validity of the scale. In Study 4, we collected data from a further independent sample (N = 74) to provide support for the test‐retest reliability, and stability of items. Lastly, a confirmatory factor analysis was conducted on the samples across Studies 3 and 4, and the composite sample across all four studies which provided further support for the factor structure of the final 8‐item scale. Taken together, these findings provide psychometric support for the scale to be used to measure the willingness of athletes to use banned substances to help facilitate future research investigating doping in sport.

Testosterone and doping control / C. Saudan, N. Baume, N. Robinson, L. Avois, P. Mangin, M. Saugy. - (British Journal of Sports Medicine 40 (2006) Suppl. 1; p. i21-i24)

• PMID: 16799097
• PMCID: PMC2657495
• DOI: 10.1136/bjsm.2006.027482

Abstract

Background and objectives: Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone.

Methods: Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids.

Results: Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone.

Conclusions: Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.

Testosterone dose-response relationships in healthy young men / S. Bhasin, L. Woodhouse, R Casaburi, A.B. Singh, D. Bhasin, N. Berman, X. Chen, K.E. Yarasheski, L. Magliano, C. Dzekov, J. Dzekov, R. Bross, J. Phillips, I. Sinha-Hikim, R. Shen, T.W. Storer

• American journal of physiology. Endocrinology and metabolism 281 (2001) 6 (December), p. E1172-E1181
• PMID: 11701431
• DOI: 10.1152/ajpendo.2001.281.6.E1172

Abstract

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism : Pharmacodynamics and Pharmacokinetics / Ronald Wiehle, Glenn R. Cunningham, Nelly Pitteloud, Jenny Wike, Kuang Hsu, Gregory K. Fontenot, Michele Rosner, Andrew Dwyer, Joseph Podolski

• BJUI 112 (2013) 8 (December), p. 1188-1200
• PMID: 23875626
• PMCID: PMC4155868
• DOI: 10.1111/bju.12363

Abstract

Objectives: To determine the pharmacodynamic (PD) profile of serum total testosterone levels (TT) and luteinizing hormone (LH) in men with secondary hypogonadism following initial and chronic daily oral doses of enclomiphene citrate in comparison to transdermal testosterone. To determine the effects of daily oral doses of enclomiphene citrate (Androxal®) in comparison to transdermal testosterone on other hormones and markers in men with secondary hypogonadism.

Patients and methods: This was a randomized, single blind, two-center phase II study to evaluate three different doses of enclomiphene citrate (6.25mg, 12.5mg and 25 mg Androxal®), versus AndroGel®, a transdermal testosterone, on 24-hour LH and TT in otherwise normal healthy men with secondary hypogonadism. Forty-eight men were enrolled in the trial (ITT Population), but 4 men had T levels >350 ng/dL at baseline. Forty-four men completed the study per protocol (PP population). All subjects enrolled in this trial had serum TT in the low range (<350 ng/dL) and had low to normal LH (<12 IU/L) on at least two occasions. TT and LH levels were assessed each hour for 24 hours to examine the effects at each of three treatment doses of enclomiphene versus a standard dose (5 grams) of transdermal testosterone (AndroGel). In the initial profile TT and LH were determined in a naïve population following a single initial oral or transdermal treatment (Day 1). This was contrasted to that seen after six weeks of continuous daily oral or transdermal treatment (Day 42). The pharmacokinetics of enclomiphene was performed in a select subpopulation. Serum samples were obtained over the course of the study to determine levels of various hormones and lipids.

Results: After six weeks of continuous use, the mean ± SD concentration of TT at Day 42 C0hrTT, was 604 ± 160 ng/dL for men taking the highest of dose of enclomiphene citrate (enclomiphene, 25 mg daily) and 500 ± 278 ng in those men treated with transdermal testosterone. These values were higher than Day 1 values but not different from each other (p = 0.23, T-test). All three doses of enclomiphene increased C0hrTT, CavgTT, CmaxTT, CminTT and CrangeTT. Transdermal testosterone also raised TT, albeit with more variability, and with suppressed LH levels. The patterns of TT over 24 hour period following six weeks of dosing could be fit to a non-linear function with morning elevations, mid-day troughs, and rising night-time levels. Enclomiphene and transdermal testosterone increased levels of TT within two weeks, but they had opposite effects on FSH and LH Treatment with enclomiphene did not significantly affect levels of TSH, ACTH, cortisol, lipids, or bone markers. Both transdermal testosterone and enclomiphene citrate decreased IGF-1 levels (p<0.05) but suppression was greater in the enclomiphene citrate groups.

Conclusions: Enclomiphene citrate increased serum LH and TT; however, there was not a temporal association between the peak drug levels and the Cmax levels LH or TT. Enclomiphene citrate consistently increased serum TT into the normal range and increased LH and FSH above the normal range. The effects on LH and TT persisted for at least one week after stopping treatment.

Testosterone supplementation in older men restrains insulin-like growth factor's dose-dependent feedback inhibition of pulsatile growth hormone secretion / Johannes D. Veldhuis, Daniel M. Keenan, Joy N. Bailey, Adenborduin Adeniji, John M. Miles, Remberto Paulo, Mihaela Cosma, Cacia Soares-Welch

• Journal of Clinical Endocrinology & Metabolism 94 (2009) 1 (1 January), p. 246-254
• PMID: 18984660
• PMCID: PMC2630862
• DOI: 10.1210/jc.2008-1516

Abstract

Background: Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia.

Hypothesis: Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I.

Subjects: Twenty-four healthy men (ages, 50 to 75 yr; body mass index, 24 to 30 kg/m(2)) participated in the study.

Methods: We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m(2).

Analysis: Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted.

Results: Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P = 0.025), burst number (P = 0.005), interpulse variability (P = 0.032), and basal GH secretion (P = 0.009); and 3) increased secretory pattern regularity (P = 0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P = 0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I's inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity.

Conclusion: The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.

Testosterone supplementation therapy for older men : potential benefits and risks / David A. Gruenewald, Alvin M. Matsumoto. - (Journal of the American Geriatrics Society 51 (2003) 1 (January); p. 101-115)

• PMID: 12534854
• DOI: 10.1034/j.1601-5215.2002.51018.x

Abstract

Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded.

In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased.

Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials.

Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial / Fred Sattler, Shalender Bhasin, Jiaxiu He, Chih-Ping Chou, Carmen Castaneda-Sceppa, Kevin Yarasheski, Ellen Binder, E. Todd Schroeder, Miwa Kawakubo, Anqi Zhang, Ronenn Roubenoff, Stanley Azen. - (Journals of Gerontology: Series A 66A (2011) 1 (January); p. 122-129)

• PMID: 21059836
• PMCID: PMC3032430
• DOI: 10.1093/gerona/glq183

Abstract

Background: In the HORMA (Hormonal Regulators of Muscle and Metabolism in Aging) Trial, supplemental testosterone and recombinant human growth hormone (rhGH) enhanced lean body mass, appendicular skeletal muscle mass, muscle performance, and physical function, but there was substantial interindividual variability in outcomes.

Methods: One hundred and twelve men aged 65-90 years received testosterone gel (5 g/d vs 10 g/d via Leydig cell clamp) and rhGH (0 vs 3 vs 5 μg/kg/d) in a double-masked 2 × 3 factorial design for 16 weeks. Outcomes included lean tissue mass by dual energy x-ray absorptiometry, one-repetition maximum strength, Margaria stair power, and activity questionnaires. We used pathway analysis to determine the relationship between changes in hormone levels, muscle mass, strength, and function.

Results: Increases in total testosterone of 1046 ng/dL (95% confidence interval = 1040-1051) and 898 ng/dL (95% confidence interval = 892-904) were necessary to achieve median increases in lean body mass of 1.5 kg and appendicular skeletal muscle mass of 0.8 kg, respectively, which were required to significantly enhance one-repetition maximum strength (≥ 30%). Co-treatment with rhGH lowered the testosterone levels (quantified using liquid chromatography-tandem mass spectrometry) necessary to reach these lean mass thresholds. Changes in one-repetition maximum strength were associated with increases in stair climbing power (r = .26, p = .01). Pathway analysis supported the model that changes in testosterone and insulin-like growth factor 1 levels are related to changes in lean body mass needed to enhance muscle performance and physical function. Testosterone's effects on physical activity were mediated through a different pathway because testosterone directly affected Physical Activity Score of the Elderly.

Conclusions: To enhance muscle strength and physical function, threshold improvements in lean body mass and appendicular skeletal muscle mass are necessary and these can be achieved by targeting changes in testosterone levels. rhGH augments the effects of testosterone. To maximize functional improvements, the doses of anabolic hormones should be titrated to achieve target blood levels.

Testosterone, identity and the body : Exploring cultural definitions of disorder / Kyle J.D. Mulrooney, Rick Collins, Jack Darkes. - (International Journal of Drug Policy 95 (2021) September; 103366)

• PMID: 34412937
• DOI: 10.1016/j.drugpo.2021.103366

Abstract

Medically-sanctioned testosterone administration has seen increasingly widespread application in the treatment of gender dysphoria (GD). Yet, by comparison, this approach is not medically accepted for those who are experiencing muscle dysmorphia (MD), a specifier of body dysmorphic disorder (BDD), despite both conditions reflecting incongruences between self-perception, identity and phenotype, and both currently being classified as mental health disorders. Rather, by stark contrast, those with MD are largely treated with psychological intervention to accept themselves as they physically are and the illicit use of testosterone for muscle-related body perception purposes is generally subject to criminal justice enforcement actions. In this commentary, we examine attempts to distinguish between the use of testosterone for gender-affirming hormone therapy in the case of GD and for aesthetic (muscle enhancement) use in the case of MD, as well as explore the implications of this disparity. Moreover, we consider how such disparity in policy and practice may be understood, in part, as an example of a bias reflecting the selective pathologizing of anabolic-androgenic steroid (AAS) use, socio-cultural evolutions in gender identity and expression and, more broadly, the manner in which culture defines disorder and its appropriate response.

O credenciamento do laboratório antidopagem : ciência e política na luta contra o doping no esporte = The accreditation of the anti-doping laboratory : science and politics in the fight against doping in sport =  La acreditación del laboratorio antidopaje : ciencia y política en la lucha contra el dopaje en el deporte / Daniel Giordani Vasques, Ekain Zubizarreta Zuzuarregi, Marco Paulo Stigger

• Revista Brasileira de Ciências do Esporte 43 (202), e006321
• DOI: 10.1590/rbce.43.e006321

RESUMO

A pesquisa social sobre doping e a luta contra ele cresceu nos últimos anos, porém sua distribuição é desigual. O objetivo é descrever como os interesses da WADA e do governo brasileiro para ter o laboratório preparado para os Jogos de 2016 afetaram a luta antidopagem. Adotamos procedimentos etnográficos para analisar a suspensão, descredenciamento e recredenciamento do LBCD (2013-2015). Com ajuda da sociologia pragmática, visualizaram-se associações e interesses dos atores. Especificamente, retratou-se como a WADA conseguiu pressionar o governo por meio do descredenciamento de 2013 e, a partir das ações e associações do governo, como ela foi flexível para recredenciar um laboratório em condições inadequadas, a fim de mantê-lo atuante para os Jogos de 2016.

ABSTRACT

Social research on doping and anti-doping has grown in recent years. However, its distribution is uneven. The objective is to study how WADA and Brazilian government for having an operational laboratory affected anti-doping. We adopted an ethnographic approach to describe the processes of suspension, revocation and re-accreditation of LBCD (2013-2015). Using pragmatic sociology concepts, it is possible to identify actors’ associations and interests. Specifically, the paper will show that WADA managed to pressure the government through the 2013 revocation – forcing it to act and to associate with other actors − but it was then flexible to re-accredit a laboratory in inadequate conditions, in order to have it operational for 2016 Games.

RESUMEN

La investigación social sobre antidopaje ha crecido en los últimos años, sin embargo, la repartición es desigual. El objetivo es describir cómo los intereses de AMA y del gobierno brasileño de tener un laboratorio para los JJOO de 2016 afectaron la lucha antidopaje. Adoptamos métodos etnográficos para analizar los procesos de suspensión, desacreditación y reacreditación del LBCD (2013-2015). Es posible identificar las asociaciones e intereses de los actores. Específicamente, se relata cómo AMA logró presionar al gobierno con la desacreditación y que, tras las acciones y asociaciones posteriores del gobierno, cómo fue flexible a la hora de volver a acreditar el laboratorio en condiciones inadecuadas, a fin de mantener el laboratorio operativo para los Juegos.