Impact of sex on pain and opioid analgesia: a review

Fullerton, Evan F; Doyle, Hillary; Murphy, Anne Z.

doi:10.1016/j.cobeha.2018.08.001

Cited by 48 publications

(50 citation statements)

References 95 publications

(98 reference statements)

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“…This can be a consequence of more attention being paid to pain reporting by men and more intense efforts to alleviate it. Older women have a lower risk of opioid misuse but may be more vulnerable to the adverse medical effects of opioids such as sedation, falls, constipation, respiratory depression, dysphoria, accidental overdose, and medication interactions ( 95 ). Women are at a greater risk of undertreatment of pain, although the use of both prescription and non-prescription analgesics is significantly higher among women than men ( 90 ).…”

Section: The Elements Of Pc Interventionsmentioning

confidence: 99%

Palliative Care for People Living With Heart Disease—Does Sex Make a Difference?

Sobański

Krajnik

Goodlin

2021

Front. Cardiovasc. Med.

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The distribution of individual heart disease differs among women and men and, parallel to this, among particular age groups. Women are usually affected by cardiovascular disease at an older age than men, and as the prevalence of comorbidities (like diabetes or chronic pain syndromes) grows with age, women suffer from a higher number of symptoms (such as pain and breathlessness) than men. Women live longer, and after a husband or partner's death, they suffer from a stronger sense of loneliness, are more dependent on institutionalized care and have more unaddressed needs than men. Heart failure (HF) is a common end-stage pathway of many cardiovascular diseases and causes substantial symptom burden and suffering despite optimal cardiologic treatment. Modern, personalized medicine makes every effort, including close cooperation between disciplines, to alleviate them as efficiently as possible. Palliative Care (PC) interventions include symptom management, psychosocial and spiritual support. In complex situations they are provided by a specialized multiprofessional team, but usually the application of PC principles by the healthcare team responsible for the person is sufficient. PC should be involved in usual care to improve the quality of life of patients and their relatives as soon as appropriate needs emerge. Even at less advanced stages of disease, PC is an additional layer of support added to disease modifying management, not only at the end-of-life. The relatively scarce data suggest sex-specific differences in symptom pathophysiology, distribution and the requisite management needed for their successful alleviation. This paper summarizes the sex-related differences in PC needs and in the wide range of interventions (from medical treatment to spiritual support) that can be considered to optimally address them.

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Section: The Elements Of Pc Interventionsmentioning

confidence: 99%

Palliative Care for People Living With Heart Disease—Does Sex Make a Difference?

Sobański

Krajnik

Goodlin

2021

Front. Cardiovasc. Med.

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“…This result was not detected in assessing an interaction or difference in the trends. Previous studies indicate that response to opioid medications differs in men and women, 27 and men and women are known to metabolize opioids differently. 28 In particular, higher CYP2D6 activity among extensive metabolizers has been observed in women compared to men, 29 suggesting that underlying biologic differences may contribute to differences in CYP2D6 activity.…”

Section: Discussionmentioning

confidence: 99%

<p>Sex Differences in Associations Between CYP2D6 Phenotypes and Response to Opioid Analgesics</p>

Lopes

Bielinski

Moyer³

et al. 2020

PGPM

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Background: Several small studies have previously investigated associations between the cytochrome P450 2D6 (CYP2D6) metabolism and response to opioids. We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use. We conducted additional analyses to determine whether our results were consistent among men and women. Methods: We used data from 2,877 participants in the RIGHT Protocol who were prescribed codeine and/or tramadol between 01/01/2005 and 12/31/2017 and who were not prescribed CYP2D6 inhibitors within 1 year prior to the opioid prescription. CYP2D6 phenotype categories were condensed into four groups: (1) Ultra-rapid and Rapid (n = 61), (2) Normal and Intermediate to Normal (n = 1,448), (3) Intermediate and Intermediate to Poor (n = 1,175), and (4) Poor metabolizer status (n = 193). Opioid-related outcomes included indications of poor pain control or adverse reactions related to medication use. We modeled the risk of each outcome using logistic regression, adjusting for age, sex, race, and ethnicity. Results: The results revealed a trend from poor to ultra-rapid and rapid CYP2D6 phenotypes in which the risk of adverse reactions incrementally increased and the risk of poor pain control incrementally decreased. This trend reached statistical significance among female (but not male) participants. Among normal and intermediate to normal metabolizers, a larger proportion of women experienced adverse reactions relative to men. Discussion: We replicated and extended the findings of previous research indicating associations between CYP2D6 phenotypes and response to opioids. In addition, the observed associations were stronger in women than in men. We recommend sex differences to be factored in future research investigating associations between pharmacogenomics and response to medications.

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“…Indeed, sex differences in morphine analgesia have been described in both humans and rodents. However, the results from human studies have often been contradictory (2, 22, 23). Alternatively, a vast majority of rodent studies have shown that morphine elicited weaker analgesia in females than in males (2).…”

Section: Discussionmentioning

confidence: 99%

“…However, the results from human studies have often been contradictory (2, 22, 23). Alternatively, a vast majority of rodent studies have shown that morphine elicited weaker analgesia in females than in males (2). Nevertheless, there are also discrepancies across rodent studies based on species, genotypes and paradigms used to assess the analgesic effects of morphine (24, 25).…”

Section: Discussionmentioning

confidence: 99%

“…Morphine analgesia, as well as the development of its side effects, is influenced by sex in mammals. In rodents, males show more potent analgesia than females with the same dose of morphine (for review, see (2)), whereas human studies have led to more conflicting results (3, 4). Several mechanisms, including hormonal, anatomical, cellular and metabolic disparities, have been proposed to explain these sex differences in animal models (2), although human behavioral discrepancies might also depend on other parameters, such as social context, patient history, strategies used to cope with pain and the presence of comorbidities (5).…”

Section: Introductionmentioning

confidence: 99%

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Central metabolism as a potential origin of sex differences in morphine analgesia but not in the induction of analgesic tolerance in mice

Gabel

Hovhannisyan

Andry

et al. 2020

Preprint

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In rodents, morphine analgesia is influenced by sex. However, conflicting results exist regarding the interaction between sex and morphine analgesic tolerance. Morphine is metabolized in the liver and brain into morphine-3-glucuronide (M3G). Sex differences in morphine metabolism and differential metabolic adaptations during tolerance development might explain the behavioral discrepancies. The present article investigates the differences in peripheral and central morphine metabolism after acute and chronic morphine treatment in male and female mice.The first experiment aimed to determine whether morphine analgesia and tolerance differ between male and female mice using the tail-immersion test. The second experiment evaluated morphine and M3G metabolic kinetics in the blood using LC-MS/MS. Morphine and M3G were also quantified in several central nervous system (CNS) regions after acute and chronic morphine treatment. Finally, the blood-brain barrier permeability of M3G was assessed in male and female mice.This study demonstrated that female mice showed weaker morphine analgesia. In addition, tolerance appeared earlier in females but the sex discrepancies observed seemed to be due to the initial differences in morphine analgesia rather than to sex-specific mechanisms involving metabolism. Additionally, compared to male mice, female mice showed higher levels of M3G in the blood and in several CNS regions, whereas lower levels of morphine were observed in these brain regions. These differences are attributable mainly to morphine central metabolism, which differed between males and females in pain-related brain regions, consistent with the weaker analgesic effect in females. However, the role of morphine metabolism in analgesic tolerance seems rather limited.

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Impact of sex on pain and opioid analgesia: a review

Cited by 48 publications

References 95 publications

Palliative Care for People Living With Heart Disease—Does Sex Make a Difference?

Palliative Care for People Living With Heart Disease—Does Sex Make a Difference?

<p>Sex Differences in Associations Between CYP2D6 Phenotypes and Response to Opioid Analgesics</p>

Central metabolism as a potential origin of sex differences in morphine analgesia but not in the induction of analgesic tolerance in mice

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