Low Sex Hormone-Binding Globulin and Testosterone Levels in Association with Erectile Dysfunction among Human Immunodeficiency Virus-Infected Men Receiving Testosterone and Oxandrolone

Abstract

Introduction Men with acquired immunodeficiency syndrome (AIDS) wasting and hypogonadism are frequently treated with testosterone and oxandrolone, an orally administered anabolic–androgenic steroid hormone. We observed reductions in testosterone and sex hormone-binding globulin (SHBG) levels, in association with complaints of erectile dysfunction, after prolonged exposure to this therapeutic regimen. Aim First description of an association between long-term receipt of oxandrolone with erectile dysfunction, low SHBG and testosterone. Methods Case report of three human immunodeficiency virus-infected hypogonadal male patients receiving treatment for wasting syndrome and hypogonadism, and highly active antiretroviral therapy. All three patients received long-term oxandrolone in addition to testosterone replacement therapy. Results Testosterone and SHBG levels for patients 1, 2, and 3, respectively: total testosterone 183, 71, and 151 ng/dL (260–1,000 ng/dL); free testosterone (not done for patient 3) 58.3 and 26.9 pg/mL (50–210 pg/mL); SHBG 6, 9, and 6 nmol/L (7–50 nmol/L). No other hormonal abnormalities were detected. Following discontinuation of oxandrolone, levels of total testosterone rose, consistent with increase in SHBG. One patient received repeat SHBG assay documenting rise in SHBG level. Patient 2 reported return of libido and early morning erections several weeks after discontinuation of oxandrolone. Conclusions Patients had erectile dysfunction in association with low testosterone and SHBG, in spite of exogenous testosterone replacement. Discontinuation of oxandrolone led to the normalization or improvement of testosterone levels in all three patients with symptomatic improvement in one patient. First pass metabolism of orally administered oxandrolone may decrease hepatic synthesis of SHBG, allowing exogenously supplied testosterone to be excreted. Further work is necessary to elucidate the relationship.

Sexual Dysfunctions of HIV-Positive Men: Associated Factors, Pathophysiology Issues, and Clinical Management

“…In addition, testosterone replacement shows good results in improving the sexual dysfunction of most of hypogonadal HIV-infected individuals [44, 66–69]. The use of a topical testosterone gel [43] was shown to improve sexual function and also caused heightened erythropoiesis, weight gain, prevention of bone loss, increased energy, and improved mood [29].…”

Premature Decline of Serum Total Testosterone in HIV-Infected Men in the HAART-Era

“…The use of total serum T alone may have resulted in an underestimation of the prevalence of biochemical hypogonadism since calculated free serum T has been suggested as more appropriate in the context of HIV due to the possible rise in serum SHBG in these patients [17]. Changes of SHBG levels in the HIV context remain, however, controversial, since increases in SHBG with concomitant weight loss, [7], [17], [41], [42], decreases in SHBG [43], and no modifications of serum SHBG [13] have been described. Testing of serum total T has several advantages, in clinical practice, since it is widely available, accurate, unexpensive and reliable [44].…”

Wasting Disease, Chronic Immune Activation, and Inflammation in the HIV-Infected Patient

“…77 Oxandrolone is a 17α-methylated testosterone derivative for oral administration (Table 2). 75,78 Seventeen α-methylated testosterone analogs are subject to first pass hepatic metabolism and long-term use has been associated with hepatotoxicity. 78 Both groups (control and intervention) participated in a supervised resistance exercise program.…”

“…HIV-infected men who experienced a mean weight loss of 9% and received oxandrolone demonstrated significantly greater increases in lean body mass and strength when compared to patients in the control group. 75,79 Identification of a single androgen receptor gene (and protein) suggests that, at equivalent dosages, all testosterone formulations have essentially the same physiological effects. 78 Decreases in high density lipoprotein (HDL)-cholesterol and sex hormone-binding globulin have been documented in oxandrolone recipients.…”