Opioid Use and Sexual Dysfunction

The Food and Drug Administration (FDA) recently issued a warning regarding severe safety issues associated with opioid pain medications.

Besides a few other issues that can occur, they reported that long term opioid use may be associated with decreased sex hormone levels (i.e., testosterone) and symptoms such as a decreased interest in sex, impotence, or infertility.

The data that the FDA based its conclusion on had limitations that make it difficult to determine whether the symptoms were caused by the opioids or other factors.

Sexual dysfunction is a common problem among people who experience chronic pain. 

One variable that may potentially be masking a link between sexual dysfunction and opioid use is depression.

Depression by itself is a risk factor for sexual dysfunction.

There are depressed people utilizing opioids and research indicates opioids may cause or exacerbate depression⁽¹⁾.

Highlights from this research demonstrate that:

• Opioid exposure is associated with over two-fold risk of depression recurrence.
• This association is independent of pain and other measured confounders.
• Prescription opioids may limit depression recovery or worsen residual symptoms.
• It may be sensible to conduct repeated depression screening during opioid therapy.

The medical community is still inconclusive as to whether depression, opiate use, or both reduce sexual function, or whether opiate use worsens both depression and sexual function.

In addition, smoking has strong associations with prescription opioid use and erectile dysfunction, making it difficult to ascertain which factor has the strongest influence over sexual function.

Before we dive into the available research in this area, let’s take a look at exactly what opioids are.  

Opioids are a class of powerful narcotic pain medicines used to treat moderate to severe pain that’s not responding well to other pain medicines.

They can help manage pain when other treatments and medicines are not able to provide enough pain relief, but they also have serious risks including misuse and abuse, addiction, overdose, and death.

Below is a list of generic and brand name opioids:

Recent evidence linking opioid use and sexual dysfunction

A 2018 study investigated the associations between chronic non-cancer pain, opioid use, lack of/low sexual desire, and dissatisfaction with sexual life. This was a quantitative study where 11,517 randomly selected individuals of the Danish population (18-74 years old without cancer) completed a self-administered questionnaire⁽²⁾.

Results showed that those who used opioids for longer than 6 months to manage chronic non-cancer pain experienced suppressed sexual desire.

A 2017 systematic review and meta-analysis evaluated whether opioid use was a risk factor for erectile dysfunction. This investigation included 8,829 mean (average age = 42 years) from 10 studies, 2,456 of whom received opioid management (duration of intervention = 4 months to 9.5 years)⁽³⁾.

Results indicted that the use of opioids was significantly associated with an increased risk of erectile dysfunction. 

The direction of causality between opioid use and risk of erectile dysfunction should be interpreted with caution because most studies utilized a cross-sectional design.

A 2013 study examined associations between use of medication for erectile dysfunction or testosterone replacement and use of opioid therapy, patient age, depression, and smoking status.

Results showed that daily opioid doses of 120 mg morphine-equivalent or more had greater use of medication for erectile dysfunction or testosterone replacement than patients without opioid use, even with adjustment for duration of opioid therapy⁽⁴⁾. The authors also identified age, comorbid medical conditions, and depression as having links to erectile dysfunction.

These results further corroborate the difficulty in isolating opioid use as a trigger for sexual dysfunction.

There isn’t too much research linking female sexual function and opioid use.  However, a fairly recent study reported decreased libido in 22 0f 32 female participants receiving opioid treatment⁽⁵⁾.

Mechanism of action

After taking an opioid, there is an impact on the endocrine system⁽⁶⁾ that can potentially cause hypogonadotropic hypogonadism and hypocorticism. Opioids may decrease sexual function by affecting the hypothalamic-pituitary-gonadal pathways, which control the production of sex hormones by secreting gonadotropin-releasing hormone from the hypothalamus.

Opioids inhibit gonadotropin-releasing hormone, leading to a decrement in the production of luteinizing hormone from the anterior pituitary gland.

This, in effect, inhibits the production of testosterone from the Leydig cells in the testes and theta cells in the ovary.

Consequently, many chronic non-cancer pain patients using opioids may experience endocrine dysfunction caused by opioid-induced inhibition of the hypothalamic–pituitary function⁽⁷⁾.

As a low level of testosterone has a significant impact on both genders’ sexual desire and infertility, sexual problems are most likely mediated by the reduced level of testosterone in opioid users⁽⁷⁾.  

In addition, low testosterone can cause depression which further exacerbates the sexual dysfunction issue.

Summary

Due to the nature of these observational studies, it’s not possible to ascertain whether opioid-induced hormone deficiency was causative of low sexual desire and dissatisfaction with sex life.

However, results or multiple studies are in agreement and have shown correlations between opioid use, hypogonadism, and sexual problems.

References:
1.    Scherrer, J.F., et al., Increased Risk of Depression Recurrence After Initiation of Prescription Opioids in Noncancer Pain Patients. J Pain, 2016. 17(4): p. 473-82.
2.    Hanne Birke, M., Ola Ekholm, MSc, Jette Højsted, MD, Per Sjøgren, MDSc, Geana Paula Kurita, PhD, Chronic Pain, Opioid Therapy, Sexual Desire, and Satisfaction in Sexual Life: A Population-Based Survey. Pain Medicine, 2019. 20(6): p. 1132–1140.
3.    Zhao, S., et al., Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med, 2017. 14(10): p. 1209-1219.
4.    Deyo, R.A., et al., Prescription opioids for back pain and use of medications for erectile dysfunction. Spine (Phila Pa 1976), 2013. 38(11): p. 909-15.
5.    Abs, R., et al., Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab, 2000. 85(6): p. 2215-22.
6.    Brennan, M.J., The effect of opioid therapy on endocrine function. Am J Med, 2013. 126(3 Suppl 1): p. S12-8.
7.    Gudin, J.A., A. Laitman, and S. Nalamachu, Opioid Related Endocrinopathy. Pain Med, 2015. 16 Suppl 1: p. S9-15.