Hormone Levels Altered After Long-Term Opioid Therapy

PALM SPRINGS, CA — Endocrine abnormalities may arise in patients following long-term opioid therapy, according to a study presented at the American Academy of Pain Medicine 2012 Annual Meeting.

Because little is known about opioid affects on the pituitary-adrenal-gonadal axis after a long period of treatment, Forest S. Tennant, MD, DrPH, of the Veract Intractable Pain Clinic, West Covina, CA, decided to conduct a study involving 10 men and 12 women with intractable pain. These patients were drawn from a rural California county clinic and had been maintained on opioids under the authority of the California Intractable Pain Act for ≥20 years.

Patients enrolled received an equivalent of 465–5,650mg morphine daily. No hormone replacement therapy was prescribed. During the study, each patient had an 8 a.m. fasting serum specimen taken that was tested for cortisol, pregnenolone, testosterone, estrogen, corticotropin (ACTH), and follicle stimulating hormone (FSH).

Two patients (9.1%) were normal on all six assays; 11 (50%) had only deficiencies, and five (22.7%) only elevations. Low testosterone was the most common abnormality and was present in 12 patients (54.5%), low FSH in six patients (30%), low cortisol and ACTH in two patients each (9.1%), and low pregnenolone and estrogen levels in one patient each (4.5%). High serum levels were found in patients as follows: cortisol in six patients (27.2%), pregnenolone in four (27.2%), ACTH in four (27.2%), and estrogen in one (4.5%).

Dr. Tennant concluded that low FSH and testosterone had major effects, and that the high levels of ACTH, estrogen, pregnenolone, and cortisol in some patients indicates that severe pain and its endocrine response may not be controlled by high-dose opioids.1 He added that patients with intractable pain must be routinely monitored with pituitary-adrenal-gonadal axis screening and clinically treated for deficient or excessive hormone levels.

1. Tennant F, Hermann L. Normalization of serum cortisol concentration with opioid treatment of severe chronic pain. Pain Med. 2002;3:132-134.