title: Impact of cancer therapies on ovarian reserve.
abstract: OBJECTIVE
  To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age.
  
  
  METHODS
  Cross-sectional analysis of data from a prospective cohort study.
  
  
  METHODS
  University medical center.
  
  
  METHODS
  Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years).
  
  
  METHODS
  None.
  
  
  METHODS
  Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression.
  
  
  RESULTS
  In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls.
  
  
  CONCLUSIONS
  Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.
authors.affiliation: Department of Obstetrics/Gynecology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. cgracia@obgyn.upenn.edu
authors.forename: Clarisa R
authors.initials: CR
authors.lastname: Gracia
authors.forename: Mary D
authors.initials: MD
authors.lastname: Sammel
authors.forename: Ellen
authors.initials: E
authors.lastname: Freeman
authors.forename: Maureen
authors.initials: M
authors.lastname: Prewitt
authors.forename: Claire
authors.initials: C
authors.lastname: Carlson
authors.forename: Anushree
authors.initials: A
authors.lastname: Ray
authors.forename: Ashley
authors.initials: A
authors.lastname: Vance
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D054304:Anti-Mullerian Hormone / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007247:Infertility, Female / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging; D007265:Inhibins / Q000097:blood; D008593:Menopause / Q000187:drug effects; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010053:Ovary / Q000187:drug effects*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging; D011446:Prospective Studies; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C422364:inhibin B; D004958:Estradiol; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone