title: Enhanced hypothalamic-pituitary sensitivity to estrogen in premenopausal women with diminished ovarian reserve compared with older perimenopausal controls.
abstract: OBJECTIVE
  We have previously characterized the reproductive hormone profile in infertile women with diminished ovarian reserve (DOR) as being distinct from that seen in age-comparable healthy controls. Hypothesizing that DOR reflects accelerated reproductive aging, we herein compare urinary reproductive hormone dynamics between young women with DOR and a population of chronologically older perimenopausal controls.
  
  
  METHODS
  In this prospective observational study, urinary levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) and metabolites of estrogen (estrone conjugate) and progesterone were assessed in daily morning urine samples collected in a spontaneous menstrual cycle in 8 infertile premenopausal women with DOR and in 11 perimenopausal controls. Areas under the curves were calculated for the respective measured hormones, and comparisons were made using the Mann-Whitney U test.
  
  
  RESULTS
  Urinary estrone conjugate levels were significantly attenuated in premenopausal women with DOR compared with the older perimenopausal cohort. Despite the relatively lower estrogen, a significantly more pronounced luteinizing hormone surge was evident in the younger population. Early follicle-stimulating hormone was lower in women with DOR, but luteal urinary progesterone excretion was comparable in the two groups.
  
  
  CONCLUSIONS
  Our data suggest distinctions in functioning of the central (hypothalamic-pituitary) and peripheral (ovarian) components of the hypothalamic-pituitary-ovarian axis in premenopausal women with DOR compared with chronologically older perimenopausal controls. Increased hypothalamic-pituitary sensitivity to estrogen positive feedback is suggested in premenopausal women with DOR. Our observations identify DOR as a distinct entity in the paradigm of reproductive senescence.
authors.affiliation: University of Maryland Medical Center, Baltimore, MD, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Zhang
authors.forename: Gohar
authors.initials: G
authors.lastname: Zeitlian
authors.forename: Goli
authors.initials: G
authors.lastname: Adel
authors.forename: Nanette F
authors.initials: NF
authors.lastname: Santoro
authors.forename: Lubna
authors.initials: L
authors.lastname: Pal
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000652:urine; D004967:Estrogens / Q000652:urine; D005260:Female; D005640:Follicle Stimulating Hormone / Q000652:urine; D006065:Gonadotropins, Pituitary / Q000652:urine*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000652:urine; D008593:Menopause / Q000378:metabolism / Q000652:urine*; D008875:Middle Aged; D010053:Ovary / Q000378:metabolism*; D047648:Perimenopause / Q000652:urine; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D017697:Premenopause / Q000652:urine; D016649:Primary Ovarian Insufficiency / Q000378:metabolism / Q000652:urine*; D011374:Progesterone / Q000652:urine; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D004967:Estrogens; D006065:Gonadotropins, Pituitary; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone