However, these symptoms may be attributed to reasons for using opioid medications, such as underlying chronic pain or aging.1 Sexual side effects are not often reported by patients due to feelings of inadequacy, so direct inquiry by the physician is recommended. Careful questioning can establish the patient’s baseline levels of desire, arousal, and orgasmic function, in an effort to determine whether the symptoms of sexual dysfunction began with the use of opioids.2 Determining whether sexual dysfunction is a side effect of chronic opioid use may be easier for clinicians when it is reported as a new symptom after treatment initiation, noted investigators.2 The more specific symptoms of low testosterone, which patients may be hesitant to discuss, include erectile dysfunction, difficulty achieving an orgasm, lower intensity of orgasm, diminished ejaculatory volume
As many of the symptoms associated with OPIAD are nonspecific, it is essential to measure serum testosterone levels, particularly in the early morning hours, in order to diagnose the condition. The lower limit of total testosterone should range from 300 to 350 ng/dL, and studies indicate that approximately 50% of men on chronic opioid treatment have testosterone levels approximately 165 ng/dL compared with men not on the medication. When serum testosterone levels are found to be low, measurements should be repeated. Measuring the levels of other hormones (eg, hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and prolactin) can help determine the level of the lesion on the HPG axis as well as help determine whether hypogonadism is the result of another etiology. Some studies suggest that the rates of sexual dysfunction can be affected by comorbid depression and other psychological symptoms, but are contradicted by other studies.2
Modifying diet and lifestyle as well as reducing opioid doses or replacing opioids with nonsteroidal anti-inflammatory drugs or other non-narcotic painkillers are key for an effective treatment of OPIAD. However, because many patients require opioids to manage their pain, tapering or eliminating opioids may not be an option. As the incidence of OPIAD may be higher in individuals taking long- vs short-acting opioids, alternating these types of opioids or avoiding long-acting opioids may be preferable.
In patients who are persistently symptomatic and hypogonadal, androgen replacement therapy should be considered. Testosterone replacement therapy with transdermal gels, patches, or injections can provide varying degrees of symptom relief in men with hypogonadism. A study in which men who were taking opioids for chronic noncancer pain had hypogonadism indicated that treatment with 5 g transdermal testosterone gel was associated with improved sexual desire.1 Other studies in which men with OPIAD were treated with testosterone replacement therapy, found associated increases in testosterone levels and improvements in sexual function. Adverse events associated with testosterone replacement therapy include polycythemia, sleep apnea, reductions in high-density lipoprotein, azoospermia, gynecomastia, priapism, worsening of benign prostatic hyperplasia, and an increased risk for cardiovascular events. Men should be screened for osteoporosis (ie, measurements of bone mineral density and vitamin D levels) before initiating testosterone replacement therapy.3
“Fundamental management of OPIAD should be lifestyle therapies and tapering of opioids, with the goal of weaning off completely. There should be a low threshold for checking testosterone levels in opioid users, especially if they are receiving potent opioids and on high doses,” noted the investigators.3
1. Hsieh A, Digiorgio L, Fakunle M, Sadeghi-Nejad H. Management strategies in opioid abuse and sexual dysfunction: A review of opioid-induced androgen deficiency. Sex Med Rev. 2018;6(4):618-623.
2. Grover S, Mattoo SK, Pendharkar S, Kandappan V. Sexual dysfunction in patients with alcohol and opioid dependence. Indian J Psychol Med. 2014;36(4):355-65.
3. O’rourke TK, Wosnitzer MS. Opioid-induced androgen deficiency (OPIAD): prevalence, consequence, and efficacy of testosterone replacement. Curr Urol Rep. 2016;17(10):76.