Review Question - QID 216525

This semi-professional athlete with sudden, marked muscular development, acne, and needle markings is most likely abusing androgens to improve his athletic performance. Androgen abuse is reflected in the hypothalamic-pituitary-gonadal (HPG) axis as decreased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), decreased sperm count, and increased estrogen.

The production of endogenous testosterone takes place in the testes and is regulated by the HPG axis. The hypothalamus secretes GnRH, which stimulates the anterior pituitary. The anterior pituitary then secretes LH and FSH, which in turn stimulate the testes to produce testosterone. The HPG axis is regulated by feedback inhibition and is often affected by exogenous administration of any of its component hormones. Exogenous testosterone administration, which is often used for improving athletic performance and building muscle mass, results in the suppression of the entire HPG axis. Testosterone acts directly on the hypothalamus to decrease the production of GnRH and on the anterior pituitary to decrease FSH and LH. Because of this suppression, long-term use of androgens often results in testicular atrophy and decreased sperm count. Additionally, excess testosterone can be peripherally aromatized to estrogen, leading to unwanted side effects such as gynecomastia. Notably, while testosterone can be aromatized to estrogen, certain synthetic androgens have modified chemical structures making aromatization impossible; in those cases, increased estrogen and gynecomastia are not seen.

Basaria provides a detailed discussion on the short- and long-term consequences of androgen abuse. The suppressed HPG axis can take months to resume normal activity after cessation of steroid use, resulting in low libido, erectile dysfunction, and infertility. Other non-endocrine effects of androgen abuse include cardiac hypertrophy, increased risk of tendon rupture, transaminitis, and psychiatric symptoms including increased aggression.

Figure A presents potential results of an investigation of the HPA axis and sperm count.

Incorrect Answers:
Answer 2: Decreased GnRH, decreased FSH, decreased LH, decreased estrogen, and decreased sperm count are inconsistent with this patient's presentation. Although suppression of the HPG axis due to exogenous testosterone use would cause a decrease in GnRH, FSH, LH, and sperm count, it would be likely to increase, rather than decrease, estrogen due to increased aromatization. This leads to gynecomastia, a common finding in patients using exogenous testosterone.

Answer 3: Increased GnRH, increased FSH, decreased LH, increased estrogen, and increased sperm count is inconsistent with exogenous testosterone administration. In the case of testosterone abuse, hypothalamic secretion of GnRH is suppressed, leading to decreased levels of GnRH and diminished downstream activity of the axis (decreased FSH, LH, and sperm count). Although estrogen is also 'downstream' on the axis, levels may be increased due to increased aromatization of testosterone.

Answer 4: Increased levels of GnRH, FSH, and LH combined with decreased estrogen and decreased sperm count is incorrect. Increased GnRH, FSH, and LH are more consistent with an over-active, rather than suppressed, HPG axis. Even if that were the case, however, the sperm count would not be decreased as in this answer choice, making this set of test results unlikely in a clinical scenario.

Answer 5: Decreased levels of GnRH, decreased FSH, increased LH, increased estrogen, and decreased sperm count would be unlikely for this patient. Since this man is taking testosterone, his entire HPG axis is likely suppressed due to feedback inhibition, causing a decrease in all downstream hormones including LH. The increased LH level in this set of results, therefore, rules this answer choice out.

Bullet Summary:
Exogenously administered testosterone suppresses the hypothalamic-pituitary-gonadal axis, leading to decreased levels of GnRH, FSH, and LH as well as testicular atrophy and increased levels of estrogen.