Opioid-Induced Hypogonadism: Why and How
to Treat It
Authors: Aloisi Anna Maria 
Published: March 2021

Background: Gonadal hormones are critical factors in modulating the experience of pain, as
suggested by the several sex differences observed: women have a greater risk of many clinical
pain conditions, and postoperative and procedural pain may be more severe in them than in men.
A growing body of literature demonstrates the role of estrogen in the female pain experience,
whereas less attention has been given to testosterone and its functions.
Nevertheless, testosterone has an appreciable role in both women and men: adequate serum
levels are required in males and females for libido and sexuality; cellular growth; maintenance of
muscle mass and bone; healing; blood-brain barrier; and for central nervous system maintenance.
Pain therapy, and particularly opioid therapy, has been shown to affect testosterone plasma levels.
Thus, the chronic administration of pain killers, such as opioids, requires the physician to be aware
of both the consequences that can develop due to long-term testosterone impairment and the
available means to restore and maintain physiological testosterone levels.
Objective: The objective is to highlight to pain physicians that the endocrine changes occurring
during chronic pain therapy can participate in the body dysfunctions often present in chronic pain
patients and that there are possible hormone replacement methods that can be carried out in men
and women to improve their quality of life.
Study Design: A comprehensive review of the literature.
Methods: A comprehensive review of the literature relating to opioid-induced hypogonadism, as
well as other very common forms of hypogonadism, its endocrine effects, and possible therapeutic
actions. The literature was collected from electronic and other sources. The reviewed literature
included observational studies, case reports, systematic reviews, and guidelines.
Outcome Measures: Evaluation of the endocrine changes described in chronic pain therapy was
the primary outcome measure. The secondary outcome measures were functional improvement
and adverse effects of hormone replacement.
Results: The results of the survey clearly show that sex hormone determination is very rare in
pain centers. Given the complexity and widespread nature of pain therapy, there is a paucity of
qualitative and quantitative literature regarding its endocrine consequences. The available evidence
is weak for pain relief, but is consistent for many collateral effects, possibly deriving from pain
therapy, such as fatigue, depression, and neurodegenerative diseases.
Limitation: This is a narrative review without application of methodological quality assessment
criteria. Even so, there is a paucity of literature concerning both controlled and observational
literature for the endocrine effects of most analgesic drugs.
Conclusion: Testosterone replacement suffers from old prejudices about its utility and safety.
With this review we illustrate the available therapeutic choices able to maintain T concentration
into physiological ranges and reduce nociception with a final goal of improving patients’ quality
of life.
Key words: Pain, pain therapy, hypogonadism, adverse effects, morphine, HRT, testosterone