Androgenic Anabolic Steroid Use and Severe Hypothalamic-Pituitary Dysfunction: a Case Study
letes seen with typical presentation of anabolic steroid use. In order to regain normal hypothalamic-pituitary function, supraphysiological doses of 200 mg LH-RH should be considered when the physiological challenge test with LH-RH (50 mg) fails to show an acceptable response.
Introduction
mone and follicle stimulating hormone [3, 7]. Although full spontaneous recovery of these disturbances has been reported, there are indications that complete recovery may take years in longterm users [2, 6]. We describe a patient who developed persistent hypogonadism due to the use of mixtures of AAS, which did not recover spontaneously after AAS cessation, and the successful recovery of pituitary-testicular axis after priming with LH-releasing hormone (LHRH).
The use of androgenic anabolic steroids (AAS) has been linked to the occurrence of premature cardiovascular events in healthy strength athletes [5]. Furthermore, its use not only among strength athletes but among adolescents in general appears to be related with the use of other psychotropic drugs, alcohol and tabacco and is often secondarily related with strength-sport involvement [4, 9]. Finally, it has been suggested that anabolicandrogenic steroids act as a gateway to opioid dependence [1].
Key words Hypogonadism ´ high dose LHRH-treatment ´ body building ´ drug abuse
Case description A growing number of users take AAS for periods ranging from 8 to 16 weeks several times a year and often take the more serious health threats for granted. Self-administration of AAS may result in much higher doses than therapeutically recommended, with possibly more severe side effects, and more profound effects on endocrine function. For instance, in men, AAS administration disturbs, through the negative feedback loop of the hypothalamic-pituitary gonadal axis, the production of luteinising hor-
1
A previously fit 37-year-old caucasian male semi-professional bodybuilder was seen by us at the exercise endocrinology unit with a chief complaint of gynaecomasty and severe acne associated with headaches and weight gain. He had no other history of severe medical problems. He smoked no tobacco and drank no alcoholic beverages. Sexual function and desire were greatly diminished. There was no family history of endocrine abnormal-
Affiliation Department of Movement Sciences , Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University, Maastricht, the Netherlands 2 Department of Endocrinology, University Hospital Maastricht, Maastricht, the Netherlands Correspondence Dr. E. van Breda ´ Dept. Movement Sciences ´ Maastricht University, ´ P. O. Box 616 ´ 6200 MD Maastricht ´ Netherland ´ Phone: +31 43 3881318 ´ Fax: +31 43 3670972 ´ E-Mail:
[email protected] Accepted after revision: September 10, 2002 Bibliography Int J Sports Med 2003; 24: 195±196 Georg Thieme Verlag Stuttgart ´ New York ´ ISSN 0172-4622
Physiology & Biochemistry
The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often overlooked in severe cases. Although this latter central side-effect usually recovers spontaneously when AAS intake is discontinued, the present case shows that spontaneous recovery does not always take place. We suggest that hypothalamic-pituitary dysfunction should always be considered in the differential diagnosis in ath-
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E. van Breda1 H. A. Keizer1 H. Kuipers1 B. H. R. Wolffenbuttel2
On physical examination the patient appeared very muscular and trained. Blood pressure and pulse rate were normal. Examination of heart, lungs and abdomen were otherwise unremarkable. There were acne-like lesions on the torso. Genital examination revealed testicular atrophy (testes were very small, volume 2 ml, and weak).
Physiology & Biochemistry
Blood count and chemistry were normal. Endocrinological investigations showed luteinizing hormone (LH) (< 0.5 IU/L) and follicle stimulating hormone (FSH) (< 0.5 IU/L) levels to be below the detection limit. Plasma testosterone (T) was critically low (4.5 nmol/L). Serum Thyrotropin (TSH) (2.9 nmol/L), Thyroxine (T4) (19.9 nmol/L) and cortisol (547 nmol/L) were all within the normal range. In view of the probable diagnosis of severe hypogonadotropic hypogonadism a hypothalamic test was performed with 50 g LHRH. This test resulted in an inadequate stimulation of LH release from the hypothalamus (0.5 IU/L and 14.8 IU/L, for baseline and 2 hour value respectively). Despite testicular atrophy, semen analysis revealed a normal count (77 10 6 spermatozoa/ml) and mild morphology derangements (between 45 and 56 %).
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Since this situation had persisted for months after AAS withdrawal, it was decided to treat the patient with a high dose of LHRH injections on 3 consecutive days in order to restore the normal pituitary-testicular axis interplay. The patient received 3 injections on consecutive days with 200 g LHRH. Two hour values on 3 consecutive days were: LH (7.9; 4.1 and 6.2 IU/L) FSH (2.4, 1.8 and 2.3 nmol/L) and T (9.0, 13.3 and 11.1 nmol/L ) and were within the normal range. The patient reported to the out patient clinic three times in the next 12 months. On all three occasions plasma T levels remained within the normal range (11.2, 17.7 and 12.9 nmol/L) indicating a normal hypothalamicgonadotropic function.
Discussion This case clearly shows that AAS not only produces the obvious peripheral side effects such as gynaecomasty, acne, headaches, aggressiveness, and anxiety but also the more imperative central
side effect of hypothalamic-pituitary dysfunction. The case described above with a non-responsive pituitary LH release to clinical doses of LHRH [8] should alert physicians to a more thorough regimen of LH-RH therapy. We suggest that a thorough medical check-up of patients using AAS should focus more on a central endocrine dysfunction rather than to the obvious peripheral side effects. We therefore suggest that hypothalamic-pituitary dysfunction should always be considered during the differential diagnosis in athletes seen with typical presentation of anabolic steroid abuse. In order to regain normal hypothalamic-pituitary function, supraphysiological doses of 200 g LH-RH should be considered when the physiological challenge test with LH-RH (50 g) fails to show an acceptable response. In conclusion, we would like to suggest that supraphysiological doses of LH-RH should be considered when a) there are clear symptoms of gynaecomasty and acne, b) there are critically low T and LH values and c) when there are no signs of improvement during a standard physiological LH-RH challenge test (50 g).
References 1
Arvery D, Pope HG. Anabolic-androgenic steroids as a gateway to opioid dependence. New Engl J Med 2000; 342: 1532 2 Gill GV. Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin. Postgrad Med J 1998; 74: 45 ± 46 3 Hickson RC, Ball KL, Falduto MT. Adverse effects of anabolic steroids. Med Toxicol Adverse Drug Exp 1989; 4: 254 ± 271 4 Kindlundh AM, Isacson DG, Berglund L, Nyberg F. Factors associated with adolescent use of doping agents: anabolic-androgenic steroids. Addiction 1999; 94: 543 ± 553 5 Madea B, Grellner W. Long-term cardiovascular effects of anabolic steroids. Lancet 1998; 352: 33 6 Martikainen H, Alen M, Rahkila P, Vihko R. Testicular responsiveness to human chorionic gonadotrophin during transient hypogonadotrophic hypogonadism induced by androgenic/anabolic steroids in power athletes. J Steroid Biochem 1986; 25: 109 ± 112 7 Matsumoto AM. Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle stimulation hormone, and sperm production. J Clin Endocrinol Metbab 1990; 70: 282 ± 287 8 Mori T, Murakami Y, Nishiki M, Kato Y. Clinical course of long term treatment with intermittent subcutaneous injection of LHRH in combination with GH replacement in a male patient with hypothalamic hypogonadism due to disruption of the pituitary stalk. Endocr J 1998; 45(suppl): S155 ± S158 9 Wichstrom L, Pedersen W. Use of anabolic-androgenic steroids in adolescence: winning, looking good or being bad? J Stud Alcohol 2001; 62: 5 ± 13
Breda E van et al. Treatment of Persistent Hypogonadism ¼ Int J Sports Med 2003; 24: 195 ± 196
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ities. Anabolic regimens consisted of two periods of 18 weeks a year with mixtures of methylandrostenediol, stanozolol, mesterolone, metenolone enanthate, trenbolone acetate nandrolone laurate and drostanolone propionate as the main anabolic components.
