By Thomas O’Connor, MD 2/26/16
It’s time to heal.
Anabolic Steroid Induced Hypogonadism (ASIH) AKA Acquired Shutdown of the Hypothalamic Pituitary/Testicular System
ASIH androgen deficiency has long been discussed in professional literature. It denotes the shutting down of the hypothalamic pituitary/testicular system (HPT) as a result of long term anabolic/androgenic steroid (AAS) use. The condition is evidenced by both clinical symptoms and somewhat less reliably by laboratory levels of testosterone, as the latter may be equivocal indicators, as will be discussed later. The acquired inability of the HPT to produce the body’s natural (endogenous) testosterone is the result of cyclical depletion of endogenous testosterone during long term self-dosing of supraphysiologic AAS- (synthetic testosterone). (Rahnema, 2014; Guillherme, 2011). The “dose(s) that are related to supraphysiologic states are widely debated and controversial. Such doses, which are required for anabolic affect (muscle building) are widely available on the Internet, without prescriptions, along with advice on how to use them for maximum effect. Such doses far exceed the recommended physiological dose that ethical physicians administer for hypogonadism and the long term health outcomes are unknown at this time. It is clear that men living on supraphysiologic doses of testosterone and other AAS often get sick.
AAS users desperately need physicians to help them address the many adverse health effects of AAS, during and following AAS use, and to relieve the suffering caused by AAS withdrawal as they strive for cessation.
Unique Physiopathology Pathophysiology of ASIH
In a systematic review of ASIH literature from 1965-2013, expert opinion and AAS user interviews, Rahnema et al (2013) reported on a number of studies which concluded that the use of AAS results in hypogonadatropic hypogonadism– anabolic steroid induced hypogonadism (ASIH). The authors identify the process in which heavy or long term AAS use shuts the hypothalamic-pituitary/testicular (HPT) down, causing the body to no longer be able to produce its own (endogenous) testosterone. When this occurs, users sometimes experience severe symptoms, primarily in mood and libido, either while cycling during use or when they attempt to end use. A number of other studies have also described the unique pathophysiology of ASIH and how this unique pathophysiology distinguishes hypogonadic AAS users from other substance abusers (Kanayama et al, 2009; Caraci, 2011) as well as from other hypogonadic populations. (Rahnema et al, 2014; Kelleher, 2004). A complex and global endocrine disruption takes place in AAS users as a result of long term use, stacking (use of several products simultaneously) and cycling (on and off AAS, typically over 12 weeks), and multiple high doses of ancillary drugs. The unique pharmacological milieu created in AAS users is such that, “…medical testosterone which is given at a fixed replacement dose may not be a good model to describe the pharmacodynamics in the AAS user.” (Rahnema et al, 2014, p.1274).
A number of experts have recommended management strategies including testosterone replacement therapy (TRT), human chorionic gonadatropin (hCG) and selective estrogen receptor modulators (SERMS) to restore the HPT axis and its ability to produce endogenous testosterone. (Talih, Fatal 86 Monroe/Cleveland Clinic,2007; Hochberg et al, 2003; Spratt, 2012; Pope 86 Brower, 2008; Rahnema et al, 2014). Because of the unique pathophysiology of AAS, with the added complication of AAS being variable and patient specific, Rahnema et al (2014) stress the importance of physicians, whom they had found to be largely uninformed about AAS, asking patients about their AAS use in order to provide appropriate treatment for AAS related conditions and to counsel about cessation.
Withdrawal Syndrome: Threat to Cessation
It is believed that 30% of AAS users have become dependent on these drugs. Brower, 2009). This has been described as a unique “dependence syndrome” of combined physiologic and psychologic etiology which subjects AAS users to long-term or permanent endocrine dysfunction when they are compelled by severe withdrawal symptoms—-or the fear of these– to continue AAS use. (Brower, 2009); Rahnema et al, 2014, p. 1273). Because of the potential severity of symptoms accompanying withdrawal, “cold turkey” cessation is not recommended. (Pope 86 Brower, 2008; Spratt, 2012; Tahil et al, ClevelandClinic, 2007; Hochberg, 2003). Abrupt cessation of AAS and waiting until natural testosterone levels return, unaided by medication, “leaves the body wide open to hormonal collapse”. (Turek, 2015). No physician should risk a patient’s health in this fashion. There is no guarantee, whether medically assisted or not, of when — or if — the HPT axis will recover. HPT axis recovery can take place in months, or can be quite prolonged, with ASIH persisting years after cessation. ASIH induced HPT can even be irreversible, depending in part on the damage done to the testes during AAS use. (Kanayama, et al, 2010; Jarow 86 Lipschultz, 1990; Kashin Kleban,1989; Pope 86 Brower, 2008; Medras & Tworowska, 2001; Borogowda et al, 2001) Persistence of hypogonadism even after drug cessation is “probably the result of long term adaptation to hormones which may involve relatively persistent changes in molecular switches”. (Hochberg, 2003). Failure to treat ASIH could result in permanent failed HPT axis. (Rahnema et al 2014). Fortunately, physicians do have options. Medications recommended to relieve withdrawal symptoms and assist HPT recovery have been found to be safe in physiologic doses. McLaren et al (2008) found that short-term (up to 5 years) TRT resulted in minimal pro static growth or development of lower urinary tract obstructive symptoms. Morgentaler (2010) has reported that the use of physiological dose of testosterone to restore the body to hormonal balance presents no significant medical risks: “While side effects of physiological dose testosterone can include some elevation of red blood count, with no reported stroke or other adverse effects; some minor swelling and some acne breakouts, these effects go away as soon as treatment is stopped”.
Brower (2009) has noted that treatments used with other substance abusers will be ineffective with AAS abusers, A number of experts have recommended a more rational, ethical and effective approach to alleviate suffering, to encourage cessation and to prevent relapse. A two-pronged approach is typically recommended: to ease withdrawal symptoms and to expedite patient from the hormonal excess state, a number of experts have recommended specific medications for substitution, or replacement therapies. Pope and Brower (2008) recommend endocrine pharmacotherapy, including injected testosterone esters, human chorionic gonadotropin (hCG) and anti-estrogens to restore functioning of the HPT axis in men whose withdrawal symptoms persist. Talih, et al, (2007), writing from the Cleveland Clinic, concluded that adverse effects of steroid abuse should be managed by discontinuing the drugs–by tapering if necessary with a substitution of enanthate (Andro-Estro).
Noted endocrinology experts Hochberg et al (2003), state, “(b)because AAS withdrawal is similar to corticosteroid withdrawal, rather than limiting treatment to medications for specific withdrawal symptoms, a more rational approach would be substitution therapy and tapering the dose (of testosterone), or use of chorionic gonadatropin (hCG) treatment… .with the understanding that withdrawal from androgen overdose is associated with hypogonadic hypogonadism which warrants replacement therapy until recovery of the HPG axis.” (Emphasis supplied). Rahnema et al (2014) recommend a 4 week tapered course of transdermal or injectable testosterone, with simultaneous SERMs and aromatase inhibitors for gynecomastia. These reviewers recommend monitoring response to treatment to inform continuing/cessation treatment with these medications.
Assessing Treatment Outcomes
There is broad consensus on medications required to assist in recovery of the HPT system in ASIH patients. There is also broad support for evaluating recovery of the HPT axis on the basis of symptom recovery and not solely on lablevels of testosterone. Zitzmann and Nieschlag (2000) have defined recovery of the HPT axis as return to sexual health: “restoration of libido, increase in sexual fantasies and the frequency of erections were considered signs of adequate therapy, while symptoms such as lethargy, inactivity and depressed mood indicated less than optimum therapy”.
A five year study by Kelleher et al,(2004) of the variability of testosterone thresholds in hypogonadal men receiving TRT provides objective evidence to support the “…common clinical practice of monitoring the adequacy of androgen replacement therapy by observing how well the presenting symptoms of androgen deficiency are rectified”. These authors found that while testosterone level threshold for androgen deficiency is consistent in an individual, this threshold differs “significantly and markedly” between individuals. Further, their research indicated that men with acquired hypogonadism, e.g. ASIH, have significantly lower threshold for symptoms.
The implication of these findings regarding the importance of symptoms as indicators of ideal testosterone levels– of adequate restoration of HPT axis in an individual patient– underscores the importance of using clinical judgment to guide treatment. Conners 85 Morgentaler (2013) state, “Since there is no serum testosterone value that reliably identifies men who will respond to treatment from those who will not, healthcare providers must exercise clinical judgment in making the diagnosis of TD (testosterone deficiency)”. (Emphasis supplied). Finkelstein et al (2013) recommend a continuum, rather than rigid threshold above which clinical measures are normal and below which adverse change occurs (p.1021). Clearly, diagnosis and recovery of androgen deficiency are not simple matters of recording “low” or “high” lab testosterone levels but are more reliably inferred from individual symptom report/response, both objective and subjective. “normal” result and falsely concludes that the problem lies elsewhere”.
As an expert physician in ASIH and dealing with men suffering with anabolic steroid use, I ask that you seek medical care from an expert physician who is experienced in ASIH.