Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.
Aromatase inhibitors (AIs), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms occur in approximately half of treated women and lead to treatment discontinuation in 20 to 30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AI-associated musculoskeletal symptoms. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (P = .006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In addition, there was no association with either measure of pain sensitivity and change in patient-reported pain with AI therapy. AI-associated musculoskeletal symptoms are not likely due to decreased pain threshold or impaired CPM prior to treatment initiation, or to effects of estrogen depletion on pain sensitivity.


CONCLUSIONS
This article presents our findings of the effect of estrogen deprivation on objective measures of pain sensitivity. In postmenopausal women, medication-induced estrogen depletion did not result in an identifiable change in pressure pain threshold or CPM. Impaired CPM may be associated with chemotherapy.
Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan. Electronic address: norahh@med.umich.edu.
N Lynn
NL
Henry
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
Anna
A
Conlon
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
Kelley M
KM
Kidwell
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
Kent
K
Griffith
Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
Jeffrey B
JB
Smerage
Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
Anne F
AF
Schott
Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
Daniel F
DF
Hayes
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, Michigan.
David A
DA
Williams
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, Michigan.
Daniel J
DJ
Clauw
Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, Michigan.
Steven E
SE
Harte
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D011312:Pressure; D011446:Prospective Studies; D016896:Treatment Outcome
D000700:Analgesics; D047072:Aromatase Inhibitors; D004967:Estrogens; D004958:Estradiol
Pain threshold; aromatase inhibitor; breast cancer; conditioned pain modulation; estrogen deprivation