Male Central Hypogonadism Secondary to Exogenous Androgens

A Review of the Drugs and Protocols Highlighted by the Online Community of Users for Prevention and/or Mitigation of Adverse Effects

Stamatios Karavolos; Michael Reynolds; Nikoletta Panagiotopoulou; Kevin McEleny; Michael Scally; Richard Quinton

Disclosures

Clin Endocrinol. 2015;82(5):624-632. 

In This Article

Discussion

We analysed 20 websites offering advice on the use or selling ancillary medications to counteract the side effects of ASIH. We are not aware of any other study that has examined these online practices in the past. Our study illustrates the degree of information available on the Internet that extends beyond that covered in the current medical literature. We found that many sites conveyed controversial prodrug messages, often appearing to be based upon personal experience and nonrelevant available scientific literature. The authors of these websites sometimes accused the medical profession of biased motives.

The treatment of ASIH and subsequent subfertility remains inadequately studied, and many clinicians have limited experience with regard to managing men with ASIH. AAS users appear to be well aware of this and may thus tend to give less weighting to clinician recommendations than those of 'online expert users'.

hCG, SERMs and AIs are amongst the drugs commonly used to counteract the side effects of ASIH. Although some of these are certainly effective in the context of congenital (or pituitary lesion-related) hypogonadotrophic hypogonadism,[74] the extent to which data from medical treatments can be compared and extrapolated to ASIH is uncertain. This is because the pathophysiology of ASIH may be more complex, representing a combination of the endocrine disruption and direct testicular toxicity related to the supraphysiological doses or multiple drug combinations used by users.[75]

We recommend that, based on currently available evidence, if fertility is desired, the logical first-line management is to cease using AAS along with any other potentially 'culprit' agents (e.g. marijuana, opioids, methamphetamine, cocaine), with serial semen analysis. Studies of exogenous androgen–progestagen combinations examining their potential role in male contraception have shown that the typical probability of recovery of spermatogenesis to 20 million/ml was 67% within 6 months, 90% within 12 months, 96% within 16 months and 100% within 24 months,[76] so the timelines and outcomes for men with ASIH may not be dissimilar.

However, what if the period of biochemical recovery from ASIH is prolonged and associated with relationship-endangering features, and/or the partner's age militates against a prolonged watch-and-wait strategy in respect of fertility? A judgemental approach imputing patient 'fault' may not be hugely effective, whereas involvement of community-based addiction teams can be invaluable (e.g. http://goodhealth-manchester.nhs.uk/mphds/drugs/drugs-team.html).

If spontaneous reversal of hypogonadism does not occur with expectant management within a reasonable timeframe as discussed above, then use of hCG ± hMG, SERMs or AIs is potentially effective alternatives.[75] However, robust evidence on their effectiveness and safety is currently lacking, and there is no consensus on the actual regimes that are effective in treating ASIH or in shortening the recovery interval, which is highly variable between individual patients. More research is needed in this area in the form of therapeutic trials to assess the effectiveness of ASIH treatments. In the meantime, by ensuring that they are well-informed and have a good understanding of what supplements their patients use, clinicians will be more likely to retain the credibility and trust of AAH users, who will in turn be more open to engaging with lifestyle modification. We would also like to caution physicians against prescribing agents with significant resale value within the index community without first involving their local community drugs team.

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