Abstract
Introduction:
Anabolic–androgenic steroids (AASs) are commonly used by both professional and amateur athletes to improve strength, muscle mass, and physical appearance.
Aims:
Scientific data on the adverse effects of AASs are scarce and there is little place for the subject in medical curricula. This may lead to a lack of knowledge and distrusting attitudes of physicians toward AAS users. The aim of this case series is to illustrate how these issues may lead to diagnostic delay and to make a plea for better education on the topic.
Case Description:
We describe three patients who attended our outpatient AAS clinic with azoospermia, gynecomastia, and hypogonadism, respectively. After referral to the appropriate specialist, symptoms were wrongly appreciated, sometimes despite our medical recommendations, and patients did not receive the necessary additional investigations or treatment in a timely manner.
Discussion:
Diagnostic delay in the presented cases was the result of inexperience with the subject and unfamiliarity with health effects of AASs. Prejudice and stigmatization may lead to a tendency to wait, and a reluctance to help, (former) AAS users.
Conclusion:
All patients and substance abusers, including AAS users, should be treated equally, despite the cause of their illness. Diagnostic delay can be prevented with an unbiased attitude and improved education.
Introduction
Anabolic–androgenic steroids (AASs) are naturally occurring and sometimes synthetic hormones, such as testosterone, trenbolone, and nandrolone. Androgen or AAS abuse is defined as the use of androgens for nonmedical purposes, especially for improved muscular size, strength, and enhancing performance. 1 The abuse of AASs has spread from elite athletes to the general population, especially in Western culture, the Middle East, and South America, where it is used by amateur and professional athletes, as well as by men who want to improve general quality of life. 2 The overall global lifetime prevalence rate is estimated at 3.3% (men 6.4%, women 1.6%). 3 AASs are usually administered by intramuscular injections, with some compounds being suitable for oral administration, and they are commonly used in “cycles” of several months.
Health risks of AAS use are numerous and comprise endocrine (gynecomastia, testicular atrophy, decreased sperm count), cardiovascular (lipid profile changes, hypertension), psychological (addiction, aggression, depression after withdrawal), and neurotoxic effects.4–6 Evidence for these effects is derived from case reports and scientific data from human experimental studies are scarce, mainly due to ethical considerations. Numerous animal-based studies examining the adverse effects of androgens try to fill the knowledge gap. A recent review summarized the most relevant effects of androgen administration in animal models, such as an increase of inflammatory mediators. A promising new way to learn more about organ damage due to AAS abuse, such as liver toxicity, is through microRNA technologies. 7
Importantly, medical students are seldom taught about AASs and its associated health risks, and there is little place for this subject in specialization curricula such as general medical practice or endocrinology. This scarcity of knowledge results in an unawareness of AAS-induced health effects and possible prejudices among physicians and might prematurely—and wrongly—attribute certain symptoms to AAS use. Besides, strength athletes often do not disclose their abuse because of skepticism about their physicians' knowledge of AASs. This contributes to physicians being unable to treat AAS users properly. 8
The “Anabolenpoli” or outpatient AAS clinic was founded in 2011 in The Netherlands. 9 This clinic's main focus is to gain more insight into AAS use and its related health risks and to help previous abusers with possible AAS-related problems. The cases described in the current series are patients who attended this clinic and experienced diagnostic delay due to unfamiliarity of their physician with the topic. By describing the cases we aim to break the taboo of AAS abuse, encourage an unbiased attitude toward its (former) users, and raise awareness on the associated health issues.
Case Series
Patient A, a 25-year-old man, with an inability to achieve conception, visited our outpatient clinic. He had a history of 3 years of androgen abuse but had stopped the abuse 2 months ago. The patient history did not reveal cryptorchidism, genital infections (including mumps), surgical procedures, or pelvic trauma. Physical examination showed normal external genitalia, testicular volume, and vasa deferentia. Biochemical tests and endocrine markers were normal (Table 1). A semen analysis was performed, which showed azoospermia (pH 7.7). We started human chorionic gonadotropin (hCG; three times per week 1500 international unit [IU], subcutaneously) treatment.
Characteristics, Methods of Anabolic–Androgenic Steroids Use, and Laboratory Results of the Patients (Reference Range Between Brackets)
BMI, body mass index; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LH, luteinizing hormone; SERMs, selective estrogen receptor modulators; SHBG, sex hormone-binding globulin.
A 6-week follow-up semen analysis, >3 months after the patient had quit AAS use, still showed azoospermia. Postejaculatory urine examination excluded retrograde ejaculation. A scrotal ultrasonography showed homogeneous testes and normal epididymides. Genetic testing showed no Y-chromosome microdeletions. Our patient was referred to a urologist to exclude other causes and he was briefed that an association with AAS abuse was very unlikely at this point. The urologist, however, assigned the azoospermia to AAS abuse and advised to wait and repeat the semen analysis in 3 months.
Our patient did not agree with the advice and visited a private clinic in Germany for further examination, where an obstructive azoospermia was diagnosed, as well as type 1 globozoospermia. He underwent microdissection testicular sperm extraction, and in vitro fertilization with calcium ionophore treatment after intracytoplasmic sperm injection eventually led to a successful conception and pregnancy.
Patient B, a 30-year-old man, presented himself at our clinic with painful gynecomastia and galactorrhea that had been persisting for several months. He had a history of 3 years of AAS abuse, but the symptoms had remained despite quitting. Physical examination ruled out adipomastia/lipomastia. Endocrine tests are presented in Table 1. Notably, prolactin levels were normal. A focused breasts ultrasonography was performed, which showed enlarged glandular tissue (Tanner stadium 3) 10 with no indication of malignancy.
The patient was diagnosed with gynecomastia due to AAS abuse and we started a trial of tamoxifen (once daily 20 mg, oral). Cabergoline (once weekly 0.5 mg, oral) was prescribed to treat galactorrhea. After 6 weeks, the symptoms had remained unchanged. The dose of tamoxifen was increased (once daily 40 mg, oral) but to no avail. He was then referred to a plastic surgeon for surgical excision of the glandular tissue. We advised urgency due to severe symptoms, the persistent nature of the condition, and the ineffectiveness of hormonal therapy. The plastic surgeon unfortunately concluded that our patient had to cease AAS use for at least 1 year, before he would qualify for surgical excision.
In response to this conclusion, our patient opted for a second opinion and underwent a bilateral tissue excision elsewhere. At first, medical insurance would not cover the procedure because of a body mass index (BMI) >30 kg/m2, but after an appeal letter declaring that his high BMI was due to increased muscularity and not due to fat mass, the operation was reimbursed.
Patient C, a 58-year-old man with a history of 40 years of AAS use, visited our clinic. Two years before presentation, our patient had suffered a myocardial infarction and ceased his abuse immediately. He experienced extreme fatigue afterward. He discussed these symptoms with his general practitioner, cardiologist, and sports medicine physician, who contributed these symptoms to the cardiovascular event. None of them performed endocrinological tests and our patient felt not supported to cope with these symptoms. After presentation at our clinic, biochemical tests were performed (results given in Table 1).
We diagnosed our patient with chronic fatigue due to a persistent post-AAS-abuse hypogonadism. Owing to his history of cardiac disease, we determined replacement therapy was vital and started testosterone injections every 3 weeks (250 mg, intramuscular). After 6 weeks, his testosterone levels had increased and the majority of the symptoms were resolved.
Informed consent was obtained from the patients for the publication of this case series.
Discussion
In this case series, we describe three patients who experienced diagnostic delay due to one or more treating physicians who were unfamiliar with the health effects of AAS use.
Patient A was diagnosed with infertility due to androgen abuse at first. AASs exert a negative feedback on the hypothalamic–pituitary–gonadal axis, which leads to suppression of spermatogenesis. 11 The arrest of fertility during androgen use is well illustrated in male contraceptive studies, 12 but has also been documented in fairly large groups of AAS abusers.13,14 Interestingly, a prospective study in AAS users showed that one-third displayed azoospermia during the cycle and, of note, that recovery of some spermatogenesis is the rule within 3 months after androgens are discontinued. 15 In this particular case, however, azoospermia persisted after this period, despite hCG treatment that can be used to speed up recovery of spermatogenesis.
This should have triggered the involved urologist to consider another diagnosis—which we explicitly suggested—but the issue was nonetheless assigned to AAS use again and the patient was advised to await spontaneous recovery. The patient, who felt misunderstood, sought help abroad and turned out to have two fertility issues that were both unrelated to androgen abuse.
Our second Patient B presented with a chronic gynecomastia. Gynecomastia is defined as benign proliferation of the glandular tissue of the male breast and caused by an imbalance between estrogen and androgen activity. AASs induce gynecomastia because the administered testosterone is aromatized to estrogens. The incidence during androgen abuse is low and varies from 3% to 19%, depending on the androgen dose and the definition of gynecomastia.16,17 It is usually mild and tends to regress within a few months if the cycle is stopped, with only 1% going on to develop chronic persisting gynecomastia.
In the early stages of gynecomastia, medical intervention can be successful in achieving partial regression and relieving symptoms. The evidence regarding antiestrogens such as tamoxifen is limited, but they can be used to counter breast tissue proliferation and offer rapid pain relief. After ∼12 months, the glandular tissue is replaced by fibrosis and regression is rare. If patients experience considerable discomfort or psychological stress and persisting gynecomastia, surgery should be considered. 18
At the time of the evaluation by the plastic surgeon, our patient had stopped his androgen abuse for 5 months, and the gynecomastia had been present for over a year and was not responsive to tamoxifen. Despite the fact that the condition was very painful and spontaneous regression was highly unlikely, it was concluded that our patient had to wait for another half a year. This led to unwanted delay and as such our patient went to another clinic for a second opinion where he was operated within a few months.
Patient C was found to have severely symptomatic low levels of testosterone and was diagnosed with post-AAS-abuse hypogonadism. There is cumulating evidence from clinical studies that long-term or even permanent hypogonadism may follow AAS abuse.15,19,20 This appears to be associated with a long duration of cumulative androgen abuse,9,21 possibly due to prolonged suppression of gonadal function or AAS-induced Leydig cell toxicity. 22 A myocardial infarction had persuaded him to quit his androgen abuse. Of note, cardiovascular disease, including coronary atherosclerosis and heart failure, is probably the most important long-term hazard of AAS abuse.23,24
Despite his typical symptoms, and openness about his previous abuse, none of the consulted physicians had considered testosterone deficiency. A meta-analysis of Corona et al showed that low testosterone levels predicted overall and cardiovascular mortality. 25 Testosterone replacement improves markers of atherosclerosis and reduces cardiovascular risk factors. 26 Because hypogonadism was overlooked for 2 consecutive years, the patient had withheld an important therapy that worsened his already poor cardiovascular risk profile, he was less able to rehabilitate from his myocardial infarction, and had experienced a loss of quality of life in this period.
These three cases illustrate how diagnostic delay may result from the inexperience and unfamiliarity of physicians with health effects of AAS use. Even though the physicians consulted were the right experts for the medical problems at hand—urologist, plastic surgeon, and general practitioner, respectively—they wrongly interpreted the clinical situation and preferred not to act even when additional investigations or treatment were indicated. In the first 2 cases, the tendency to wait may have been the result of stigmatization, leading to a reluctance to help, also because the patient “had inflicted the medical issue upon himself.”
Factors initiating this stigmatization are lack of knowledge and experience, and attribution beliefs. Indeed, health care professionals reported a more negative reaction to androgen abusers than to healthy individuals or even cocaine users. 27 They show feelings of dissatisfaction, less motivation, and had diminished personal engagement. 28 It is not surprising that AAS users also show little trust in physicians' knowledge of AAS use. The attitudes of both physicians and AAS users can lead to baseless prejudices and result in doctors' as well as patients' delay.
Interestingly, AAS users give physicians high ratings on knowledge of cigarette smoking, alcohol, and use of other illicit drugs. For obvious reasons they are very knowledgeable about these substances that automatically leads to more trust and a better understanding between health care professionals and substance users. Both medically and ethically, AAS users with health problems should be treated in the same way as nonusers.
Their abuse should not disentitle them to proper medical treatment, just as smokers and alcoholics receive treatment in the face of ongoing addiction. When examining a patient with (a history of) AAS use, it is important to maintain an unprejudiced view, check the available literature and, if necessary, consult an AAS expert when symptoms might be related to AAS use as to establish the right course of treatment.
Conclusions
AAS abuse is still a taboo and most physicians know very little about its effects. We describe a case series that shows how this may lead to a fragile patient–doctor relationship in which medical issues caused by AASs are misinterpreted, and stigmatization and prejudice stand in the way of proper health care. It is no wonder abusers may feel reluctant to disclose their abuse to health care practitioners. This group of strength athletes, their foolhardy behavior notwithstanding, should be approached and treated no different than other patients using harmful—and more familiar—substances, such as cigarettes and alcohol. Future research should focus on developing methods to prevent diagnostic delay in these circumstances, for example, by improved education and enhancing medical curricula.
Footnotes
Authors' Contributions
M.A.J.R. and D.L.S. have drafted the article. W.d.R. revised it critically. All authors read and approved the final version of the article.
Author Disclosure Statement
The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the article.
Funding Information
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.