Enhanced hypothalamic-pituitary sensitivity to estrogen in premenopausal women with diminished ovarian reserve compared with older perimenopausal controls

Menopause. 2011 Aug;18(8):880-5. doi: 10.1097/gme.0b013e31820cc564.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Biomarkers / urine
  • Estrogens / urine
  • Female
  • Follicle Stimulating Hormone / urine
  • Gonadotropins, Pituitary / urine*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism*
  • Luteinizing Hormone / urine
  • Menopause / metabolism
  • Menopause / urine*
  • Middle Aged
  • Ovary / metabolism*
  • Perimenopause / urine
  • Pituitary-Adrenal System / metabolism*
  • Premenopause / urine
  • Primary Ovarian Insufficiency / metabolism
  • Primary Ovarian Insufficiency / urine*
  • Progesterone / urine
  • Prospective Studies

Substances

  • Biomarkers
  • Estrogens
  • Gonadotropins, Pituitary
  • Progesterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone