title: Assessment of serum HE4 levels throughout the normal menstrual cycle.
abstract: Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data.
  
  
  
  The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle.
  
  
  
  Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation.
  
  
  
  Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum.
  
  
  
  Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (<120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample.
authors.affiliation: Division of Gynecologic Oncology/Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY. Electronic address: Richard_Moore@URMC.Rochester.EDU.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moore
authors.affiliation: Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI.
authors.forename: Beth
authors.initials: B
authors.lastname: Plante
authors.affiliation: Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI.
authors.forename: Erin
authors.initials: E
authors.lastname: Hartnett
authors.affiliation: Division of Gynecologic Oncology/Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mitchel
authors.affiliation: Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Raker
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Wendy
authors.initials: W
authors.lastname: Vitek
authors.affiliation: Departments of Pathology and Laboratory Medicine and Obstetrics and Gynecology, Center for Biomarkers and Emerging Technologies, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Eklund
authors.affiliation: Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI; Departments of Pathology and Laboratory Medicine and Obstetrics and Gynecology, Center for Biomarkers and Emerging Technologies, Women and Infants Hospital, Alpert Medical School at Brown University, Providence RI.
authors.forename: Geralyn
authors.initials: G
authors.lastname: Lambert-Messerlian
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood; D010060:Ovulation / Q000097:blood; D011374:Progesterone / Q000097:blood; D011506:Proteins / Q000032:analysis*; D012016:Reference Values; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone
keywords: menstrual cycle; ovarian cancer; serum HE4