title: Sequential classification of endocrine stages during reproductive aging in women: the FREEDOM study.
abstract: OBJECTIVE
  Reproductive aging involves complex endocrine changes affecting women's fertility, health, and well-being; however, understanding of the specific changes involved is limited by the lack of detailed quantitative studies. We undertook a thorough study with the aim of characterizing the different endocrine stages involved in female reproductive aging.
  
  
  METHODS
  FREEDOM is a cohort study designed to determine the endocrine changes during reproductive aging in women. Here, we ascertained the different endocrine patterns in a representative population and developed a staging system. In this study, 112 women aged 30 to 58 years collected daily urine samples over a 6- to 18-month period and recorded their menstrual periods. A total of 36,786 samples were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone, estrone 3-glucuronide, and pregnanediol 3-glucuronide.
  
  
  RESULTS
  A classification of five sequential endocrine stages of reproductive aging was developed: stage 1, regular menstrual cycles with mean initial (day 1-5) FSH less than 5 IU/L; stage 2, regular cycles with FSH greater than 5 IU/L; stage 3, menstrual irregularity (with the appearance of "delayed-response cycles"); stage 4, acyclical ovarian activity with no evidence of ovulation and luteinization; and stage 5, ovarian quiescence and persistently raised gonadotropins. Distinct hormonal characteristics during the follicular and luteal phase were noted at each stage.
  
  
  CONCLUSIONS
  This classification provides a detailed insight into the endocrinology of reproductive aging in women that could be useful for both clinical guidance and personal health care.
authors.affiliation: Unipath Limited, Priory Business Park, Bedford, United Kingdom. fernando.miro@unipath.com
authors.forename: Fernando
authors.initials: F
authors.lastname: Miro
authors.forename: Susan W
authors.initials: SW
authors.lastname: Parker
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Aspinall
authors.forename: John
authors.initials: J
authors.lastname: Coley
authors.forename: Paul W
authors.initials: PW
authors.lastname: Perry
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Ellis
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D000465:Algorithms; D015331:Cohort Studies; D004970:Estrone / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D005640:Follicle Stimulating Hormone / Q000652:urine; D006801:Humans; D007986:Luteinizing Hormone / Q000652:urine; D008597:Menstrual Cycle / Q000523:psychology*; D008875:Middle Aged; D010053:Ovary / Q000378:metabolism / Q000502:physiology*; D047648:Perimenopause / Q000502:physiology* / Q000652:urine; D011276:Pregnanediol / Q000031:analogs & derivatives / Q000652:urine
chemical_list: C022270:pregnanediol-3 alpha-glucuronide; C015856:estrone-3-glucuronide; D004970:Estrone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011276:Pregnanediol