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Hypothalamic-Pituitary-Adrenal Axis Responses in Women with Endometriosis-Related Chronic Pelvic Pain

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Abstract

Some chronic pain conditions and comorbidities suppress the hypothalamic-pituitary-adrenal (HPA) axis and response to dynamic testing. We measured HPA axis responses to corticotropin-releasing hormone (CRH) administration in relation to chronic pelvic pain and endometriosis. In a cross-sectional study of women (n = 54) with endometriosis-associated chronic pelvic pain (n = 22), chronic pelvic pain alone (n = 12), or healthy volunteers (n = 20), adrenocorticotropic-releasing hormone (ACTH) and cortisol levels were measured at 0, 15, 30, and 45 min after intravenous ovine CRH administration. ACTH and cortisol delta (peak-baseline) and area under the curve (AUC) were compared by study group and assessed for association with race and menstrual and non-menstrual pain severity. HPA axis responses did not differ among the racially diverse groups or in those with pain compared with healthy volunteers. However, when stratified by race, ACTH delta (129.9 ± 130.7 vs. 52.5 ± 66.0 pg/mL; p = 0.003), ACTH AUC (4813 ± 4707 vs. 2290 ± 2900 min*pg/mL; p = 0.013), and cortisol delta (26.3 ± 21.5 vs. 13.2 ± 9.7 μg/mL; p = 0.005) were significantly higher in black (n = 10) than predominately white (non-black) subjects (n = 44; 39/44 white). In analyses among primarily white (non-black) women, greater menstrual pain severity was associated with blunted ACTH delta (p = 0.015) and cortisol delta (p = 0.023), and greater non-menstrual pain severity with blunted cortisol delta (p = 0.017). Neuroendocrine abnormalities in women with chronic pelvic pain may differ by pain manifestations and may vary by race. The higher HPA axis response in black women merits investigation in pelvic pain studies stratified by race. In white (non-black) women experiencing pain, a blunted response was related to pain severity suggesting pain affects women independently of endometriosis lesions.

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Funding

This study was financially supported by the NIH Clinical Center and Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke, Clinical Trial Registration Number NCT00073801.

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Authors and Affiliations

  1. National Institutes of Health, 10 Center Drive, Bethesda, MD, USA

    Robin Ortiz

  2. Departments of Internal Medicine and Pediatrics, Johns Hopkins Hospital, 600 North Wolfe Street, Harvey Bldg. Rm 805, Baltimore, MD, USA

    Robin Ortiz

  3. Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 7-4647, 10 Center Dr., Bethesda, MD, 20892, USA

    Julie Anne L. Gemmill, Barbara Stegmann, Izabella Khachikyan, George Chrousos, James Segars & Pamela Stratton

  4. Department of Internal Medicine, Stony Brook University Medical Center, Health Sciences Tower, Stony Brook, NY, USA

    Julie Anne L. Gemmill

  5. Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Ninet Sinaii

  6. Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 7-4647, 10 Center Dr., Bethesda, MD, 20892, USA

    Pamela Stratton

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Correspondence to Pamela Stratton.

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Conflict of Interest

Dr. Stegmann worked for Merck for 3 years and owns Merck stock. Dr. Stratton is conducting a different NIH clinical trial on endometriosis and chronic pelvic pain, which is supported by Allergan through a clinical trial agreement and has received royalties from UpToDate for a section about acute pelvic pain. The remaining authors report no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (National Institutes of Health Clinical Center and the NICHD IRB (NCT00073801)) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Fig. 1

Adrenocorticotropic releasing hormone (ACTH) measures in women with endometriosis, chronic pelvic pain only, and healthy volunteers, by race. Subjects were women with chronic pelvic pain only (chronic pelvic pain and no endometriosis) (n = 12, black subjects n = 3), chronic pelvic pain and biopsy-proven endometriosis (n = 22, black subjects n = 3), and healthy volunteers (n = 20, black subjects = 4). Data are mean and standard errors; the only observed statistically significant difference among groups was for age-adjusted baseline ACTH in the non-black subjects (p = 0.020). (PPTX 66.9 kb)

Fig. 2

Cortisol measures in women with endometriosis, chronic pelvic pain only, and healthy volunteers, by race. Subjects were women with chronic pelvic pain only (chronic pelvic pain and no endometriosis) (n = 12, black subjects n = 3), chronic pelvic pain and biopsy-proven endometriosis (n = 22, black subjects n = 3), and healthy volunteers (n = 20, black subjects = 4). Data are mean and standard errors; no statistically significant differences in baseline, delta, or AUC cortisol values were observed among groups of either race. (PPTX 65.6 kb)

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Ortiz, R., Gemmill, J.A.L., Sinaii, N. et al. Hypothalamic-Pituitary-Adrenal Axis Responses in Women with Endometriosis-Related Chronic Pelvic Pain. Reprod. Sci. 27, 1839–1847 (2020). https://doi.org/10.1007/s43032-020-00201-x

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