Daily Fluctuations of Progesterone and Testosterone Are Associated With Fibromyalgia Pain Severity

Schertzinger, Meredith Marie; Wesson-Sides, K.; Parkitny, Luke; Younger, Jarred

doi:10.1016/j.jpain.2017.11.013

Cited by 64 publications

(39 citation statements)

References 48 publications

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“…It is important that these findings are replicated in women with chronic pain before starting to consider whether there may be any therapeutic benefit of inducing a high estradiol/high progesterone state. However, a recent study demonstrating a negative relationship between daily progesterone levels and pain ratings in women with fibromyalgia is in line with our findings ( 70 ).…”

Section: Discussionsupporting

confidence: 93%

“Luteal Analgesia”: Progesterone Dissociates Pain Intensity and Unpleasantness by Influencing Emotion Regulation Networks

et al. 2018

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Background: Pregnancy-induced analgesia is known to occur in association with the very high levels of estradiol and progesterone circulating during pregnancy. In women with natural ovulatory menstrual cycles, more modest rises in these hormones occur on a monthly basis. We therefore hypothesized that the high estradiol high progesterone state indicative of ovulation would be associated with a reduction in the pain experience.Methods: We used fMRI and a noxious thermal stimulus to explore the relationship between sex steroid hormones and the pain experience. Specifically, we assessed the relationship with stimulus-related activity in key regions of networks involved in emotion regulation, and functional connectivity between these regions.Results: We demonstrate that physiologically high progesterone levels are associated with a reduction in the affective component of the pain experience and a dissociation between pain intensity and unpleasantness. This dissociation is related to decreased functional connectivity between the inferior frontal gyrus and amygdala. Moreover, we have shown that in the pre-ovulatory state, the traditionally “male” sex hormone, testosterone, is the strongest hormonal regulator of pain-related activity and connectivity within the emotional regulation network. However, following ovulation the traditionally “female” sex hormones, estradiol and progesterone, appear to dominate.Conclusions: We propose that a phenomenon of “luteal analgesia” exists with potential reproductive advantages.

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Section: Discussionsupporting

confidence: 93%

“Luteal Analgesia”: Progesterone Dissociates Pain Intensity and Unpleasantness by Influencing Emotion Regulation Networks

et al. 2018

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“… 47 Estradiol may be pronociceptive, 48 whereas studies have generally shown that testosterone and progesterone may play a protective role in pain severity. 49 Another theoretical mechanism is that serotonin is a neurotransmitter involved in the modulation of pain and is found is significantly higher proportions in males. 21 , 50 However, to date, the biochemical role of sex hormones and neurotransmitters in hyperalgesia of FM appears to be limited, 51 and these explanations remain speculative with no definitive evidence.…”

Section: Discussionmentioning

confidence: 99%

Sex-Related Differences in Symptoms and Psychosocial Outcomes in Patients With Fibromyalgia: A Prospective Questionnaire Study

Jiang

D’Souza

et al. 2020

Mayo Clinic Proceedings: Innovations, Quality & Outcomes

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Objective To investigate sex-related differences in patients with fibromyalgia (FM) in terms of demographic characteristics and clinical features, including tender point count (TPC), mood disorders, sleep problems, FM symptom severity, fatigue, cognitive dysfunction, and quality of life (QOL). Patients and Methods We studied 668 consecutive patients with FM (606 women) from May 1, 2012, to November 30, 2013. Validated questionnaires assessed outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), sleep problems (Medical Outcomes Study Sleep Scale), FM symptom severity (Revised Fibromyalgia Impact Questionnaire), fatigue (Multidimensional Fatigue Inventory), cognitive dysfunction (Multiple Ability Self-report Questionnaire), and QOL (36-Item Short Form Health Survey). Nonparametric Mann-Whitney U and Pearson χ 2 tests were used to compare continuous and categorical outcome measures, respectively, between men and women. Linear regression models were performed for all continuous dependent variables, adjusting for age, body mass index, ethnicity, marital status, and highest education level completed. P <.05 was considered statistically significant. The Benjamini-Hochberg procedure was used to adjust for multiple comparisons. Results Multiple linear regression analysis revealed a significant association of female sex and greater TPC ( P <.001), lower overall FM symptom severity (lower overall Revised Fibromyalgia Impact Questionnaire score; P =.03), and higher QOL subscale score for vitality (36-Item Short Form Health Survey vitality subscale score; P =.02). After adjustment for multiple comparisons, only the association between female sex and greater TPC remained significant. There were no sex-related differences in demographic characteristics, depression, anxiety, sleep problems, FM symptom severity, cognitive dysfunction, and QOL. Conclusion A higher TPC may be associated with female sex in patients with FM. The assumption of other sex-based differences in the clinical presentation of FM was not supported in our study.

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“…There are clinical studies showing that testosterone replacement therapy reduces pain outcomes and improves the quality of life of patients with hypogonadism (Aloisi et al, 2011 ), thereby supporting the hypothesis that testosterone may have an anti-nociceptive role. However, some studies suggest that testosterone is necessary for a small nociceptive response (Thompson et al, 2008 ; Glaser et al, 2012 ; Schertzinger et al, 2017 ). According to these studies, low levels of testosterone are related to high discomfort, anxiety, and pain in response to noxious hot stimuli (Choi et al, 2017 ).…”

Section: Trpv1 Trpm8 and Testosteronementioning

confidence: 99%

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

Artero-Morales

González-Rodríguez

Ferrer-Montiel

2018

Front. Mol. Biosci.

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Chronic pain is one of the most debilitating human diseases and represents a social and economic burden for our society. Great efforts are being made to understand the molecular and cellular mechanisms underlying the pathophysiology of pain transduction. It is particularly noteworthy that some types of chronic pain, such as migraine, display a remarkable sex dimorphism, being up to three times more prevalent in women than in men. This gender prevalence in migraine appears to be related to sex differences arising from both gonadal and genetic factors. Indeed, the functionality of the somatosensory, immune, and endothelial systems seems modulated by sex hormones, as well as by X-linked genes differentially expressed during development. Here, we review the current data on the modulation of the somatosensory system functionality by gonadal hormones. Although this is still an area that requires intense investigation, there is evidence suggesting a direct regulation of nociceptor activity by sex hormones at the transcriptional, translational, and functional levels. Data are being accumulated on the effect of sex hormones on TRP channels such as TRPV1 that make pivotal contributions to nociceptor excitability and sensitization in migraine and other chronic pain syndromes. These data suggest that modulation of TRP channels' expression and/or activity by gonadal hormones provide novel pathways for drug intervention that may be useful for targeting the sex dimorphism observed in migraine.

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Daily Fluctuations of Progesterone and Testosterone Are Associated With Fibromyalgia Pain Severity

Abstract: Sex hormones fluctuate normally in women with fibromyalgia, but may still contribute to pain severity.

Cited by 64 publications

References 48 publications

“Luteal Analgesia”: Progesterone Dissociates Pain Intensity and Unpleasantness by Influencing Emotion Regulation Networks

“Luteal Analgesia”: Progesterone Dissociates Pain Intensity and Unpleasantness by Influencing Emotion Regulation Networks

Sex-Related Differences in Symptoms and Psychosocial Outcomes in Patients With Fibromyalgia: A Prospective Questionnaire Study

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

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