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Persistent primary hypogonadism associated with anabolic steroid abuse
CASE REPORT Persistent primary hypogonadism associated with anabolic steroid abuse Kusuma Boregowda, M.R.C.P.,a Lisa Joels, F.R.C.O.G.,b Jeffrey W. Stephens, F.R.C.P.,a and David E. Price, F.R.C.P.a a
Department of Diabetes and Endocrinology, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, and Department of Obstetrics and Gynaecology, Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, Wales, United Kingdom
b
Objective: To report a case of primary gonadal failure due to the chronic abuse of anabolic steroids used for bodybuilding. Design: Case report. Setting: Department of Diabetes and Endocrinology, Morriston Hospital, Swansea, Wales, United Kingdom. Patient(s): A 40-year-old man. Intervention(s): None. Main Outcome Measure(s): Clinical symptoms, levels of serum T, FSH, and LH. Result(s): Primary gonadal failure resulting from anabolic steroid use. Conclusion(s): We describe a case of initially secondary gonadal failure resulting from anabolic steroid use with subsequent primary gonadal failure and infertility. This case adds to the current literature and illustrates that the side effects of anabolic steroids can be prolonged and irreversible. (Fertil Steril 2011;96:e7–8. 2011 by American Society for Reproductive Medicine.) Key Words: Anabolic steroids, primary gonadal failure, secondary gonadal failure, androgens
In the 1930s anabolic steroids were developed as a therapy for hypogonadism. Treatment with these agents in supraphysiological doses is associated with increased muscle size and strength (1), and as a result this has led to abuse by competitive athletes and bodybuilders to improve physical appearance and performance (2, 3). Anabolic steroids are now readily available through Internet sites (4). Previous case reports describe reversible hypogonadism, infertility, and testicular atrophy associated with prolonged use of anabolic steroids (2, 5–8). Rarely, reports of persistent hypogonadism associated with anabolic steroid abuse have been described, and of interest, these cases are typically associated with endocrine abnormalities consistent with secondary hypogonadism (4, 9). We report a 40year-old man with persistent primary hypogonadism and infertility associated with previous anabolic steroids abuse.
CASE REPORT A 40-year-old man was referred by his primary care physician to the local endocrine clinic with erectile dysfunction and infertility over the preceding 6 years. He and his partner had undergone infertility investigations. Two of his former partners had conceived in the past. Over 10 years he administered nandrolone, T, and growth horReceived February 11, 2011; revised April 1, 2011; accepted April 4, 2011; published online May 14, 2011. K.B. has nothing to disclose. L.J. has nothing to disclose. J.W.S. has nothing to disclose. D.E.P. has nothing to disclose. Reprint requests: Kusuma Boregowda, M.R.C.P., Morriston Hospital, Department of Diabetes and Endocrinology, Heol Maes Eglwys, Morriston, Swansea, Wales SA6 6NL, United Kingdom (E-mail: kusuma. [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2011.04.029
mone to promote muscle growth and bodybuilding. He reported he had stopped taking anabolic steroids 2 years before seeking medical help. He complained of low libido and erectile dysfunction since stopping anabolic steroid use. Examination showed him to have a muscular physical appearance and normal secondary sexual characters apart from bilateral testicular atrophy (volume, 3 mL). Endocrine investigations are shown in the Table 1. As can be seen, he has clear evidence of secondary gonadal failure 12 months after discontinuing the anabolic steroids, with low serum levels of LH, FSH, and T of 0.2 U/L (normal range, 1.7–8.6 U/L), 0.52 U/L (1.5–12.4 U/L), and 1.6 nmol/L (8.0–40.0 nmol/L), respectively. Prolactin was within normal limits. He also had azoospermia, with a sperm count of 0/mL (normal range, 80–400 mU/L). These results are consistent with suppression of the hypothalamic–pituitary– gonadal axis by exogenous anabolic steroids. Thirty months after discontinuing anabolic steroids he had evidence of primary gonadal failure (Table 1). There was an increase in LH and FSH to supranormal levels, suggestive of recovery of hypothalamic–pituitary axis, which was associated with a modest but low sperm count (100,000/mL) and T (9.6 nmol/L) in keeping with primary gonadal failure. Clinically he continued to have a muscular physique with reduced testicular volume. His erectile function improved with a phosphodiesterase-5 inhibitor.
DISCUSSION Anabolic steroids cause secondary hypogonadism by suppressing the hypothalamic–pituitary axis. A reduction in gonadotropin secretion causes atrophy of the testis as well as decrease of sperm cell
Fertility and Sterility Vol. 96, No. 1, July 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
e7
TABLE 1 Pituitary and gonadal function after discontinuing anabolic steroids. Duration after stopping anabolic steroids (mo)
T (nmol/L)
FSH (U/L)
LH (U/L)
Prolactin (mU/L)
Sperm count (per mL)
1.6 6.4 9.6 7.2
0.52 9.5 15 16
0.2 16 22 29
384 407 149
0
12 18 30 36
100,000
Boregowda. Hypogonadism and anabolic steroids. Fertil Steril 2011.
production. Gonadal function usually returns within 12–14 weeks but can take several months. Prolonged hypogonadism lasting more than 1 year has been reported (5, 6). Cases of persistent secondary hypogonadism caused by anabolic steroids have been reported previously, but there are no reports of persistent primary hypogonadism. Our subject initially had secondary hypogonadism due to prolonged use of anabolic steroids. It is possible that he did mislead us and was taking anabolic steroids at presentation. This would be supported by the observation that he had a muscular physique with low levels of FSH, LH, and T. However, there is no reason to doubt him because he and his partner were keen to achieve fertility and he seemed truthful in relation to his previous anabolic steroid abuse. The hypothalamic–pituitary axis showed recovery 18 months after discontinuation of the anabolic steroids, but testicular function only showed partial recovery, with persistent primary hypogonadism. This may be the result of persistent testicular atrophy, which would be consistent with the reduced testicular volume. The treatment options are therefore limited. If the treatment goal was to improve libido and sexual function, then physiological T replacement
would be appropriate. Treatment of the oligospermia would be difficult: successful reversal of persistent secondary hypogonadism after anabolic steroid abuse with hCG is occasionally successful (8). However, this was a case of infertility due to primary testicular failure, and it is unlikely that hCG therapy in a man with testicular atrophy and elevated gonadotropins would reverse oligospermia. Therefore, the management plan was to wait and see whether there was any spontaneous improvement in testicular function and treat the erectile dysfunction with phosphodiesterase-5 inhibitor. Many men who abuse anabolic steroids are aware of the risk of testicular atrophy. Many also take illegally acquired hCG to try and prevent this happening. Anecdotally this seems to be effective at preventing the loss of testicular volume, but it is unknown whether this prevents subsequent hypogonadism and infertility. This is a difficult area to study because the drugs are illegal and patients are often secretive. In summary, we describe a case of initially secondary gonadal failure resulting from anabolic steroid use with subsequent primary gonadal failure and infertility. This case adds to the current literature and illustrates that the side effects of anabolic steroids can be prolonged and irreversible.
REFERENCES 1. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1–7. 2. Bagatell CJ, Bremner WJ. Androgens in men—uses and abuse. N Engl J Med 1996;334:707–15. 3. Perry PJ, Andersen KH, Yates WR. Illicit anabolic steroid use in athletes: a case series analysis. Am J Sports Med 1990;18:422–8.
e8
Boregowda et al.
4. Pirola I, Cappelli C, Delbarba A, Scalvini T, Agosti B, Assanelli D, et al. Anabolic steroids purchased on the Internet as a cause of prolonged hypogonadotropic hypogonadism. Fertil Steril 2010;94:2331.e1–3. 5. Jarow JP, Lipshultz LI. Hypogonadotropic hypogonadism. Am J Sports Med 1990;18:429–31. 6. Boyadjiev NP, Georgieva KN, Massaldjieva RI, Gueorguiev SI. Reversible hypogonadism and azoospermia as a result of anabolic-androgenic steroid use in a bodybuilder with personality disorder. A case report. J Sports Med Phys Fitness 2000;40: 271–4.
Hypogonadism and anabolic steroids
7. Takayanagi A, Kobayashi K, Hashimoto K, Kato R, Masumori N, Itoh N, et al. [Case of androgenic anabolic steroid abuse caused hypogonadotropic hypogonadism]. Nippon Hinyokika Gakkai Zasshi 2008;99: 729–32. 8. Menon DK. Successful treatment of anabolic steroidinduced azoospermia with human chorionic gonadotropin and human menopausal gonadotropin. Fertil Steril 2003;79(Suppl 3):1659–61. 9. Van Breda E, Keizer HA, Kuipers H, Wolffenbuttel BH. Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study. Int J Sports Med 2003;24:195–6.
Vol. 96, No. 1, July 2011
Department of Diabetes and Endocrinology, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, and Department of Obstetrics and Gynaecology, Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, Wales, United Kingdom
b
Objective: To report a case of primary gonadal failure due to the chronic abuse of anabolic steroids used for bodybuilding. Design: Case report. Setting: Department of Diabetes and Endocrinology, Morriston Hospital, Swansea, Wales, United Kingdom. Patient(s): A 40-year-old man. Intervention(s): None. Main Outcome Measure(s): Clinical symptoms, levels of serum T, FSH, and LH. Result(s): Primary gonadal failure resulting from anabolic steroid use. Conclusion(s): We describe a case of initially secondary gonadal failure resulting from anabolic steroid use with subsequent primary gonadal failure and infertility. This case adds to the current literature and illustrates that the side effects of anabolic steroids can be prolonged and irreversible. (Fertil Steril 2011;96:e7–8. 2011 by American Society for Reproductive Medicine.) Key Words: Anabolic steroids, primary gonadal failure, secondary gonadal failure, androgens
In the 1930s anabolic steroids were developed as a therapy for hypogonadism. Treatment with these agents in supraphysiological doses is associated with increased muscle size and strength (1), and as a result this has led to abuse by competitive athletes and bodybuilders to improve physical appearance and performance (2, 3). Anabolic steroids are now readily available through Internet sites (4). Previous case reports describe reversible hypogonadism, infertility, and testicular atrophy associated with prolonged use of anabolic steroids (2, 5–8). Rarely, reports of persistent hypogonadism associated with anabolic steroid abuse have been described, and of interest, these cases are typically associated with endocrine abnormalities consistent with secondary hypogonadism (4, 9). We report a 40year-old man with persistent primary hypogonadism and infertility associated with previous anabolic steroids abuse.
CASE REPORT A 40-year-old man was referred by his primary care physician to the local endocrine clinic with erectile dysfunction and infertility over the preceding 6 years. He and his partner had undergone infertility investigations. Two of his former partners had conceived in the past. Over 10 years he administered nandrolone, T, and growth horReceived February 11, 2011; revised April 1, 2011; accepted April 4, 2011; published online May 14, 2011. K.B. has nothing to disclose. L.J. has nothing to disclose. J.W.S. has nothing to disclose. D.E.P. has nothing to disclose. Reprint requests: Kusuma Boregowda, M.R.C.P., Morriston Hospital, Department of Diabetes and Endocrinology, Heol Maes Eglwys, Morriston, Swansea, Wales SA6 6NL, United Kingdom (E-mail: kusuma. [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2011.04.029
mone to promote muscle growth and bodybuilding. He reported he had stopped taking anabolic steroids 2 years before seeking medical help. He complained of low libido and erectile dysfunction since stopping anabolic steroid use. Examination showed him to have a muscular physical appearance and normal secondary sexual characters apart from bilateral testicular atrophy (volume, 3 mL). Endocrine investigations are shown in the Table 1. As can be seen, he has clear evidence of secondary gonadal failure 12 months after discontinuing the anabolic steroids, with low serum levels of LH, FSH, and T of 0.2 U/L (normal range, 1.7–8.6 U/L), 0.52 U/L (1.5–12.4 U/L), and 1.6 nmol/L (8.0–40.0 nmol/L), respectively. Prolactin was within normal limits. He also had azoospermia, with a sperm count of 0/mL (normal range, 80–400 mU/L). These results are consistent with suppression of the hypothalamic–pituitary– gonadal axis by exogenous anabolic steroids. Thirty months after discontinuing anabolic steroids he had evidence of primary gonadal failure (Table 1). There was an increase in LH and FSH to supranormal levels, suggestive of recovery of hypothalamic–pituitary axis, which was associated with a modest but low sperm count (100,000/mL) and T (9.6 nmol/L) in keeping with primary gonadal failure. Clinically he continued to have a muscular physique with reduced testicular volume. His erectile function improved with a phosphodiesterase-5 inhibitor.
DISCUSSION Anabolic steroids cause secondary hypogonadism by suppressing the hypothalamic–pituitary axis. A reduction in gonadotropin secretion causes atrophy of the testis as well as decrease of sperm cell
Fertility and Sterility Vol. 96, No. 1, July 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
e7
TABLE 1 Pituitary and gonadal function after discontinuing anabolic steroids. Duration after stopping anabolic steroids (mo)
T (nmol/L)
FSH (U/L)
LH (U/L)
Prolactin (mU/L)
Sperm count (per mL)
1.6 6.4 9.6 7.2
0.52 9.5 15 16
0.2 16 22 29
384 407 149
0
12 18 30 36
100,000
Boregowda. Hypogonadism and anabolic steroids. Fertil Steril 2011.
production. Gonadal function usually returns within 12–14 weeks but can take several months. Prolonged hypogonadism lasting more than 1 year has been reported (5, 6). Cases of persistent secondary hypogonadism caused by anabolic steroids have been reported previously, but there are no reports of persistent primary hypogonadism. Our subject initially had secondary hypogonadism due to prolonged use of anabolic steroids. It is possible that he did mislead us and was taking anabolic steroids at presentation. This would be supported by the observation that he had a muscular physique with low levels of FSH, LH, and T. However, there is no reason to doubt him because he and his partner were keen to achieve fertility and he seemed truthful in relation to his previous anabolic steroid abuse. The hypothalamic–pituitary axis showed recovery 18 months after discontinuation of the anabolic steroids, but testicular function only showed partial recovery, with persistent primary hypogonadism. This may be the result of persistent testicular atrophy, which would be consistent with the reduced testicular volume. The treatment options are therefore limited. If the treatment goal was to improve libido and sexual function, then physiological T replacement
would be appropriate. Treatment of the oligospermia would be difficult: successful reversal of persistent secondary hypogonadism after anabolic steroid abuse with hCG is occasionally successful (8). However, this was a case of infertility due to primary testicular failure, and it is unlikely that hCG therapy in a man with testicular atrophy and elevated gonadotropins would reverse oligospermia. Therefore, the management plan was to wait and see whether there was any spontaneous improvement in testicular function and treat the erectile dysfunction with phosphodiesterase-5 inhibitor. Many men who abuse anabolic steroids are aware of the risk of testicular atrophy. Many also take illegally acquired hCG to try and prevent this happening. Anecdotally this seems to be effective at preventing the loss of testicular volume, but it is unknown whether this prevents subsequent hypogonadism and infertility. This is a difficult area to study because the drugs are illegal and patients are often secretive. In summary, we describe a case of initially secondary gonadal failure resulting from anabolic steroid use with subsequent primary gonadal failure and infertility. This case adds to the current literature and illustrates that the side effects of anabolic steroids can be prolonged and irreversible.
REFERENCES 1. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1–7. 2. Bagatell CJ, Bremner WJ. Androgens in men—uses and abuse. N Engl J Med 1996;334:707–15. 3. Perry PJ, Andersen KH, Yates WR. Illicit anabolic steroid use in athletes: a case series analysis. Am J Sports Med 1990;18:422–8.
e8
Boregowda et al.
4. Pirola I, Cappelli C, Delbarba A, Scalvini T, Agosti B, Assanelli D, et al. Anabolic steroids purchased on the Internet as a cause of prolonged hypogonadotropic hypogonadism. Fertil Steril 2010;94:2331.e1–3. 5. Jarow JP, Lipshultz LI. Hypogonadotropic hypogonadism. Am J Sports Med 1990;18:429–31. 6. Boyadjiev NP, Georgieva KN, Massaldjieva RI, Gueorguiev SI. Reversible hypogonadism and azoospermia as a result of anabolic-androgenic steroid use in a bodybuilder with personality disorder. A case report. J Sports Med Phys Fitness 2000;40: 271–4.
Hypogonadism and anabolic steroids
7. Takayanagi A, Kobayashi K, Hashimoto K, Kato R, Masumori N, Itoh N, et al. [Case of androgenic anabolic steroid abuse caused hypogonadotropic hypogonadism]. Nippon Hinyokika Gakkai Zasshi 2008;99: 729–32. 8. Menon DK. Successful treatment of anabolic steroidinduced azoospermia with human chorionic gonadotropin and human menopausal gonadotropin. Fertil Steril 2003;79(Suppl 3):1659–61. 9. Van Breda E, Keizer HA, Kuipers H, Wolffenbuttel BH. Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study. Int J Sports Med 2003;24:195–6.
Vol. 96, No. 1, July 2011