The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 men

 Grant et al. Substance Abuse Treatment, Prevention, and Policy https://doi.org/10.1186/s13011-023-00573-8 RESEARCH Substance Abuse Treatment, Prevention, and Policy Open Access The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 men Bonnie Grant1, Joseph Kean2, Naim Vali3, John Campbell4, Lorraine Maden5, Prun Bijral3, Waljit S. Dhillo1, James McVeigh6, Richard Quinton7 and Channa N. Jayasena1* Abstract Background Anabolic–androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symp toms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objec tive evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. Methods An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they expe rienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. Results The majority of respondents were white, aged 18–30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respond ents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessa tion and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a con cern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. Conclusions Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and sui cidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. *Correspondence: Channa N. Jayasena c.jayasena@imperial.ac.uk Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Content courtesy of Springer Nature, terms of use apply. Rights reserved. Grant et al. Substance Abuse Treatment, Prevention, and Policy Page 2 of 8 This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use. Keywords Anabolic–androgenic steroids, Hypogonadism, Image and performance enhancing drugs, Post-cycle therapy, Testosterone, Withdrawal Introduction Anabolic–androgenic steroids (AAS) are synthetic drugs that mimic the effects of testosterone. They are misused to promote aesthetic body enhancement, energy and improved well-being. AAS use was previ ously confined to improving physical performance in professional sporting and bodybuilding communities, but the practice has risen substantially within the gen eral population [1–3]. Current best estimates predict that 2% of the U.K male population have used non medically prescribed androgens, although the true fig ure may be even higher [4, 5]. AAS use has been linked with an increased mortality and risks of cardiovascular disease, transmission of blood-borne viruses, infertility, and mental health disorders [6–9]. AAS use suppresses endogenous luteinising hormone (LH)-mediated testosterone production, which may per sist for many months to years after cessation [7, 10–12]. Men experiencing AAS-induced central hypogonadism may report physical and neuropsychiatric symptoms, including weakness, reduced libido, erectile dysfunc tion, depression, anxiety, and suicidality [10, 11, 13, 14]. Additionally, quality of life scores are found to be lower in men with all-cause hypogonadism, regardless of underly ing pathology [15]. Some men resume AAS use to avoid experiencing these symptoms and thus enter a potentially dangerous cycle of dependence [16, 17]. Men using AAS may use different strategies to avoid symptoms of hypogonadism. Some may take a “blast and cruise” approach whereby large doses of AAS are used (for instance in preparation for an event) followed by a longer period of continued lower dose AAS. An alterna tive is “cycling”, whereby men use AAS for 6–12 weeks “on-cycle” followed by a period “off-cycle” when they take post-cycle therapy (PCT) [2, 18]. PCT is a non medical term used to describe a varied group of self administered substances, either with the aim to limit the adverse effects of AAS use between AAS cycles or to accelerate recovery of endogenous hypothalamic pituitary–gonadal (HPG) axis function after permanent AAS cessation [3, 19, 20]. Various PCT regimes have been reported but typically involve the use of human chorionic gonadotrophin (hCG) in combination with selective oestrogen receptor modulators (SERM) and/or aromatase inhibitors (AI) [18, 19, 21, 22]. hCG directly stimulates testicular testosterone production within Leydig cells, while SERMs and AIs indirectly stimu late LH-mediated testosterone production and follicle stimulating hormone (FSH)-mediated maintenance of seminiferous tubule mass by reducing the oestrogenic negative feedback on the HPG axis. By restoring endog enous testosterone production quicker than would have otherwise occurred, men hope to minimise or avert the symptoms of AAS-induced hypogonadism and thus avoid some of the negative health effects of AAS use. The use of PCT to restore HPG function after AAS cessation is unproven with no randomised controlled trials to sup port this approach. T here is currently minimal evidence describing the effect of PCT on symptoms of AAS-induced hypog onadism. We conducted a survey of 470 men using AAS to investigate their experiences when ceasing AAS use; the effect of PCT on symptom relief and to establish whether they perceive a role for health service support. Methods An anonymous, self-administered, survey was completed between December 2021 and February 2023. Participants either currently or previously used AAS. The survey was distributed and completed online via Google Forms web page or paper versions which were subsequently entered onto Google Forms by the study team. Individuals were recruited through adverts on websites related to AAS use, snowball sampling, and via practitioners working within harm reduction clinics and / or alongside drug treatment services that provide support for individuals using AAS in the U.K [23]. This was a survey evaluation as part of patient and public involvement for a research grant proposal and, therefore, does not require research ethical approval. Participation in the survey was voluntary with partici pation implying informed consent. Information explain ing the purpose of the study and assurance that all responses would be kept confidential was stated at the beginning of the survey. Questions covered demographic details such as age, ethnic group, location and occupa tion as defined by the U.K. Office for National Statistics [24]. Participants were also asked symptoms experienced when using and stopping AAS and PCT. No identify ing data was collected. The survey consisted of up to 15 items of multiple-choice questions or Likert scales. Sev eral questions allowed the respondent to select multiple applicable responses (Additional file 1). Content courtesy of Springer Nature, terms of use apply. Rights reserved. Page 3 of 8 Grant et al. Substance Abuse Treatment, Prevention, and Policy Data analysis Completed questionnaires were submitted electronically to Google Forms and then tabulated using Microsoft Excel. Graphical techniques and analysis were performed using GraphPad Prism version 9. A total of 470 responses were received. Where appropriate, data are presented as median with interquartile range. Chi-squared tests were used to compare between groups larger than two. For all statistical testing, a p value of < 0.5 was considered significant. Results Demographics The survey was completed 470 times by differ ent individuals. 41.8% (n = 196) and 39.9% (n = 187) respondents were aged 18–30 years and 31–44 years respectively. The most common ethnicity was white (n = 298, 66.1%) and 62.2% (n = 291) lived in Yorkshire. Most respondents worked in skilled manual occupa tions (n = 129, 29.5%), followed by supervisory, clerical, and junior managerial (n = 80, 18.3%) and intermediate managerial roles (n = 72, 16.4%; Table 1). Adverse effects of anabolic–androgenic steroid use Most (n = 227, 51.7%) survey respondents reported no problems with the use of AAS. 35.3% (n = 155) reported increased aggression, 8.0% (n = 35) violence and 1.4% (n = 6) reported imprisonment that they associated with their AAS use. Respondents were able to report additional problems experienced with AAS use as a free text as “other”. Testicular atrophy, acne and mood swings were the most commonly reported additional problems (10.0%, 4.3% and 4.1% respec tively; Table 2). Anabolic–androgenic steroid cessation and post‑cycle therapy An attempt at AAS cessation was reported by 65.1% (n = 306) of all respondents. 95.1% of respondents who had attempted AAS cessation reported at least one symp tom upon AAS cessation. Low mood, tiredness, reduced sex drive and physical weakness was reported in over fifty percent of respondents who had attempted AAS cessation (72.9%, 58.5%, 57.0% and 56.0% respectively; Fig. 1A). Fourteen respondents (4.9%) reported no symp toms with AAS cessation. PCT use when stopping AAS was reported in 56.5% (n = 160) of respondents. Within our anonymous sur vey, PCT use was self-reported to reduce cravings to restart AAS by 60% (IQR 40—80), withdrawal symp toms by 60% (IQR 50 – 80) and suicidal thoughts by 50% (IQR 30 – 70; Fig. 1B). 58.1% (n = 273) respondents felt it was unlikely, or very unlikely they would stop AAS use in the next 5 years. The effects of stopping AAS on body composition or physical performance and the uncertain recovery of testosterone or fertility were reported as the biggest concerns in rela tion to stopping AAS (n = 268; 60.5% and n = 232; 52.4% respectively). Effectiveness and purity of PCT drugs were a concern for 41.1% (n = 182), while 24.8% and 24.2% were concerned about quality and access of NHS advice respec tively. 31.0% (n = 145) were interested, or very interested in participating in future trials of PCT. The majority of respondents (n = 206; 43.8%) felt that the community was the best place for NHS prescribed PCT, while only 10.0% (n = 47) preferred NHS specialist clinics (Table 3). Table 1 Demographics of survey respondents using anabolic androgenic steroids Age (Years) Respondents, n = 469 (%) 18–30 196 (41.8) 31–44 187 (39.9) 45–60 81 (17.5) 60 + 4 (0.9) Ethnicity Respondents, n = 470 (%) Asian or Asian British 100 (22.2) Black, African, Caribbean, or Black British 18 (4.0) Mixed or multiple ethnic groups 52 (11.5) Other 2 (0.4) White 298 (66.1) Location Respondents, n = 468 (%) England: East 4 (0.9) England: London and South-East 9 (1.0) England: Midlands 14 (3.0) England: North-East 17 (3.6) England: North-West 14 (3.0) England: South-West 43 (9.2) England: Yorkshire 291 (62.2) Scotland 57 (12.2) Wales 13 (2.8) Outside the UK 3 (0.6) Other 3 (0.6) Occupation Respondents, n = 438 (%) High-level managerial, administrative, or professional 30 (6.8) Intermediate managerial, administrative, or professional 72 (16.4) Supervisory, clerical, and junior manage rial, administrative, or professional 80 (18.3) Skilled manual work 129 (29.5) Semi and unskilled manual work 67 (15.3) Casual or lowest grade of work, unem ployed or pension 42 (9.6) Full-time student 18 (4.1) Content courtesy of Springer Nature, terms of use apply. Rights reserved. Grant et al. Substance Abuse Treatment, Prevention, and Policy Page 4 of 8 Table 2 Reported problems with anabolic–androgenic steroid use by survey respondents Problems reported with anabolic–androgenic steroid use Respondents, n = 439 (%) No problems Becoming more aggressive than usual Becoming violent Prison Other: Testicular atrophy Gynaecomastia Acne Mood swings Changes in hair growth Increased sex drive 227 (51.7) 155 (35.3) 35 (8.0) 6 (1.4) 44 (10.0) 10 (2.3) 19 (4.3) 18 (4.1) 15 (3.4) 9 (2.1) Association with age T he association between age groups and survey responses are shown in Additional file 2. Older men had significantly higher rates of attempted steroid cessation compared with younger men. Increasing age was associ ated with greater self-reporting low mood (p = 0.0001), problems sleeping (p = 0.0011) and headache (p = 0.0007) when stopping AAS use. Younger men were less likely to report problems with AAS use (p < 0.001) and had fewer worries about stopping AAS use (p < 0.0001). Younger men preferred PCT to be available online (p < 0.0001) whereas older men preferred from general practitioners (p = 0.0038). Discussion Anabolic–androgenic steroid use has risen within the general population, and many use PCT as an unproven practice to avoid or minimise the negative health effects associated with AAS use and cessation. There are cur rently no clinical guidelines for managing AAS-induced hypogonadism, and men often seek substances and advice from internet sources and peers, rarely health care professionals [2, 25, 26]. This study provides sev eral novel insights into experiences of AAS cessation and the role of PCT on symptoms. T he demographics within our study are broadly similar to previously reported [2, 3, 19]. Respondents were com monly aged 18–44 years old, white ethnicity, and work ing in skilled manual jobs. They were disproportionately from Yorkshire, the largest county in Northern Eng land. The majority of respondents reported no adverse effects with the use of AAS, contrasting with higher rates reported in other studies [3, 19, 20, 27]. This may be due to the limited response options given to our par ticipants, or a reluctance to divulge this information. A recent meta-analysis estimated that 73% of AAS found on Fig. 1 A Percentage (%) of respondents attempting anabolic–androgenic steroid cessation experiencing anabolic–androgenic steroid induced hypogonadal symptoms. Total n = 284 respondents. B Percentage (%) reported improvement in symptoms with respondents using post-cycle therapy. Data is shown for cravings/urge to restart anabolic–androgenic steroid use (n = 158), withdrawal symptoms (n = 105) and suicidal thoughts (n = 27). Data is presented as median, interquartile range, minimum and maximum. Scale is 10 – 100% with 100% being the maximum improvement Content courtesy of Springer Nature, terms of use apply. Rights reserved. Page 5 of 8 Grant et al. Substance Abuse Treatment, Prevention, and Policy the black market were counterfeit or of substandard qual ity; this may explain why half of our respondents did not report any adverse effects with AAS use [28]. The most reported symptoms upon cessation in our survey were low mood, reduced libido, tiredness, and physical weak ness have been reported previously [10, 11, 14]. Fifty-seven percent of respondents self-reported reduced libido when stopping AAS use. Two studies have reported improvements in erectile dysfunction (ED) symptoms with drugs commonly used as part of PCT. Firstly, men with a history of non-prescribed andro gen use were recruited to a single-centre cohort study to receive treatment with hCG and clomiphene versus observation, based on patient choice [29]. Following AAS cessation, there was no statistical significance between the two groups International Index of Erectile Function (IIEF) scores. In those who did not receive treatment, a statistically significant improvement in IIEF scores was not observed until 12 months after recruitment, whereas in the treatment group, scores improved from 6 months onward. A major limitations was that participants were given the choice of intervention or observation, and so the conclusions drawn may be due to placebo effect. Secondly, a cross-sectional observational study by Arm strong et al. assessed sexual function of 231 men cur rently, or previously using AAS with the abbreviated 5-item International Index of Erectile Function (IIEF-5) [30]. They reported higher IIEF-5 scores in those who concurrently used other substances, such as anti-oestro gens suggesting this may be a protective factor in main taining erectile function after AAS use. While these two studies show higher IIEF scores with hCG and SERM use, the lack of randomisation or placebo-control limits their conclusions. There are currently no studies that quantitatively evalu ate the effect of PCT on neuropsychiatric symptoms. In our anonymous survey, the use of self-administered PCT reduced self-reported craving symptoms and with drawal symptoms by 60% each and suicidal thoughts by 50%. Griffiths et al.’s thematic analysis reported increased mood disturbances upon AAS cessation with some reporting an improvement in symptoms with PCT [31]. Others however reported that the use of PCT worsened some psychiatric symptoms. Additionally, difficulty accessing PCT during the COVID-19 pandemic has been tentatively linked to worsening of mental health disor ders in men ceasing AAS use, however this was likely multicausal [32]. While some of the improved symp toms reported in the survey may be explained by placebo effect, there may be a role for PCT in managing symp toms of AAS-induced hypogonadism. While the majority of respondents felt it was unlikely or very unlikely they would stop AAS use in the next five years, this may be explained by worries around the effects of AAS cessation. Our findings showed the effect of AAS cessation on body composition or physical performance and recovery of testosterone levels or fertility was of con cern to respondents. These findings are corroborated by Griffiths et al. who reported participants awareness of the long term health consequences of AAS use, and PCT was a means used to maintain health or gains, of which fertil ity risk was a key concern [31]. Participants also reported challenges in obtaining PCT; in fact, accessing AAS was deemed much easier, which led some to prolong or indefinitely continue AAS use. Our findings found that 41.1% of respondents were concerned about the effec tiveness or purity of PCT. Most PCT is obtained illicitly through online sources or peers and so the verification of active hCG or SERM substances within these prod ucts often cannot be confirmed [28]. Piatkowski et al. also reported on concerns about the legitimacy of AAS Table 3 Anabolic–androgenic steroid cessation and post-cycle therapy Likelihood of stopping anabolic–andro genic steroids in next 5 years Respondents, n = 470 (%) 1 (Very unlikely) 135 (28.7) 2 138 (29.4) 3 96 (20.4) 4 48 (10.2) 5 (Very likely) 53 (11.3) Worries about stopping anabolic–andro genic steroids Respondents, n = 443 (%) Nothing 82 (18.5) Recovery of testosterone or fertility 232 (52.4) Effects on body composition or physical performance 268 (60.5) Access to NHS for advice 107 (24.2) Quality of NHS advice 110 (24.8) Effectiveness or purity of PCT 182 (41.1) Other 20 (4.5) Interest in participating in a research trial about post‑cycle therapy Respondents, n = 469 (%) 1 (Not at all interested) 156 (33.3) 2 76 (16.2) 3 92 (19.6) 4 42 (9.0) 5 (Very interested) 103 (22.0) Where would be best to access National Health Service (NHS) prescribed post cycle therapy? Respondents, n = 470 (%) Community e.g., harm prevention clinic or local pharmacy 206 (43.8) GP surgery 109 (23.2) NHS Specialist clinic e.g., endocrinology 47 (10.0) Online service 138 (29.4) Content courtesy of Springer Nature, terms of use apply. Rights reserved. Grant et al. Substance Abuse Treatment, Prevention, and Policy Page 6 of 8 or PCT substances used. The men interviewed felt that if the legitimacy of substances could be confirmed it would encourage safer practices and reduce potentially danger ous adverse effects [33]. The concerns highlighted in this study may be preventing cessation in many men and are therefore a target for cessation programmes. Importantly, there was an expression of interest in participating in a research trial about PCT by some of the respondents and engagement from within the community is vital for any future intervention studies. Around a quarter of respond ents to this survey were concerned about access to NHS advice or quality of NHS advice. Many physicians have attempted to manage a patient with AAS-induced hypo gonadism, but most do not feel confident in treating the condition [34]. Patients are often advised to wait until symptoms resolve, with many continuing to experience unresolved symptoms. Physicians are often rated poorly by men using AAS regarding their knowledge and exper tise when compared with coaches, bodybuilding websites and other men using AAS [3, 26]. In the U.K., men using AAS may seek support through community harm reduc tion clinics [23]. The availability, and trust, in this sup port network may explain why most respondents would prefer to access prescribed PCT in the community, rather than via specialist clinics or their general practitioner. T he drugs used as PCT are commonly used in the management of male hypogonadism, however there are no current controlled trials demonstrating their efficacy or safety in AAS-induced hypogonadism [35–37]. It is therefore premature to recommend its use to health care professionals. If PCT was objectively shown to help men with AAS-induced hypogonadism, engagement with healthcare professionals using interviews and focus groups to scope their attitudes would be important to translate PCT into practice. Despite the novel aspects identified in our study there are several limitations. 60% of respondents were from the Yorkshire area and our findings may reflect regional variations in practice, particularly around PCT use. It is unlikely this has significantly changed our conclusions however as the proportion of respondents using PCT in the non-Yorkshire area was similar to the whole group. As the survey was voluntary and with a focus on PCT, this exposes selection bias to those using PCT and, as it required respondents to recall their previous experi ences, it is necessarily subject to recall bias and uncer tainty. PCT describes a heterogeneous group of drugs and differing regimes are often used. A limitation of our study is that no information was collected about duration or specific drugs used as PCT, which may have helped identify specific patterns of usage associated with most experienced benefit. Details about prior history of AAS use, dosage and duration were not collected which may influence reported symptoms. This may have aided with interpretation of symptoms experienced by respondents to our survey. Finally, the self-reported improvement in symptoms may also be attributable to a placebo effect, and not a direct PCT effect. In summary, our study provides novel insights into the experience of AAS cessation and the perceived benefit of PCT on symptoms of AAS-induced hypogonadism. Respondents of our anonymous survey self-reported physical and neuropsychiatric symptoms of hypog onadism which improved with self-administered PCT use. The information from this study is critical for firstly planning future well-designed randomised controlled studies to compare the effectiveness of cessation versus hormonal treatment in managing AAS-induced hypog onadism. Once established, any successful treatment is likely to require an integrated approach engaging health care professionals and peer networks to address the endocrine and neuropsychiatric symptoms experienced by men motivated to stop AAS use long-term. Abbreviations AAS AI FSH hCG HPG IIEF IQR LH NHS PCT Anabolic–androgenic steroids Aromatase inhibitors Follicle-stimulating hormone Human chorionic gonadotrophin Hypothalamic-pituitary–gonadal International Index of Erectile Function Interquartile range Luteinising hormone National Health Service Post-cycle therapy SERM Selective oestrogen receptor modulators Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s13011-023-00573-8. Additional file 1: Complete survey administered to participants. Additional file 2: Supplemental Table 1: Survey responses by age group. Acknowledgements We would like to thank all organisations and individuals involved in distribut ing the survey and to all the respondents for their valuable contribution. Conflict of interests Logixx Pharma Ltd (CNJ). Authors’ contributions BG, JK, JM and CNJ conceptualised the study. BG, JK, NV, JC, LM, JM and CNJ collected data. BG and CNJ did data analysis. BG and CNJ drafted the manu script. JK, NV, JC, LM, PB, WSD, JM and RQ edited the manuscript. All authors approved the final submitted version. Funding The Section of Endocrinology and Investigative Medicine is funded by grants from the MRC, NIHR and is supported by the NIHR Biomedical Research Centre Funding Scheme and the NIHR/Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the Content courtesy of Springer Nature, terms of use apply. Rights reserved. Grant et al. Substance Abuse Treatment, Prevention, and Policy Page 7 of 8 NIHR or the Department of Health. The following authors are also funded as fol lows: NIHR Research Professorship (WSD), NIHR Post-Doctoral Fellowship (CNJ). Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate This was a survey evaluation as part of patient and public involvement for a research grant proposal and, therefore, does not require research ethical approval. Participation in the survey was voluntary with participation implying informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests. 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