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

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 previously confined to improving physical performance in professional sporting and bodybuilding communities, but the practice has risen substantially within the general population [1‐3]. Current best estimates predict that 2% of the U.K male population have used non-medically prescribed androgens, although the true figure 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 persist 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 dysfunction, 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 underlying 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 alternative 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 stimulate 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 endogenous 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 support this approach.

There is currently minimal evidence describing the effect of PCT on symptoms of AAS-induced hypogonadism. 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.

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 webpage 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 participation implying informed consent. Information explaining 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 occupation 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 identifying data was collected. The survey consisted of up to 15 items of multiple-choice questions or Likert scales. Several questions allowed the respondent to select multiple applicable responses (Additional file 1).

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 currently 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 several novel insights into experiences of AAS cessation and the role of PCT on symptoms.

The demographics within our study are broadly similar to previously reported [2, 3, 19]. Respondents were commonly aged 18–44 years old, white ethnicity, and working in skilled manual jobs. They were disproportionately from Yorkshire, the largest county in Northern England. 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 participants, or a reluctance to divulge this information. A recent meta-analysis estimated that 73% of AAS found on the black market were counterfeit or of substandard quality; 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 weakness 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 androgen 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 Armstrong et al. assessed sexual function of 231 men currently, 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-oestrogens suggesting this may be a protective factor in maintaining 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 evaluate the effect of PCT on neuropsychiatric symptoms. In our anonymous survey, the use of self-administered PCT reduced self-reported craving symptoms and withdrawal 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 disorders in men ceasing AAS use, however this was likely multicausal [32]. While some of the improved symptoms reported in the survey may be explained by placebo effect, there may be a role for PCT in managing symptoms 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 concern 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 fertility 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 effectiveness 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 products often cannot be confirmed [28]. Piatkowski et al. also reported on concerns about the legitimacy of AAS 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 dangerous 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 respondents 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 hypogonadism, 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 expertise 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 reduction clinics [23]. The availability, and trust, in this support network may explain why most respondents would prefer to access prescribed PCT in the community, rather than via specialist clinics or their general practitioner.

The 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 healthcare 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 experiences, it is necessarily subject to recall bias and uncertainty. 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 hypogonadism 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 hypogonadism. Once established, any successful treatment is likely to require an integrated approach engaging healthcare professionals and peer networks to address the endocrine and neuropsychiatric symptoms experienced by men motivated to stop AAS use long-term.