The endocrinology of perimenopause: need for a paradigm shift

Front Biosci (Schol Ed). 2011 Jan 1;3:474-86. doi: 10.2741/s166.


Perimenopause, rather than a time of declining estrogen, is characterized by three major hormonal changes that may begin in regularly menstruating women in their mid-thirties: erratically higher estradiol levels, decreased progesterone levels (in normally ovulatory, short luteal phase or anovulatory cycles), and disturbed ovarian-pituitary-hypothalamic feedback relationships. Recent data show that approximately a third of all perimenopausal cycles have a major surge in estradiol occurring de novo during the luteal phase. This phenomenon, named "luteal out of phase (LOOP)" event, may explain a large proportion of symptoms and signs for symptomatic perimenopausal women. Large urinary hormone data-sets from women studied yearly over a number of years in the Study of Women Across the Nation (SWAN) and in the Tremin data will eventually provide a more clear prospective understanding of within-woman hormonal changes. Predicting menopause proximity with FSH or Inhibin B levels is documented to be ineffective. Anti-Mullerian hormone levels may prove predictive. Finally, there is an urgent need to change perimenopause understandings, language and therapies used for midlife women's symptoms to reflect these hormonal changes.

Publication types

  • Review

MeSH terms

  • Adult
  • Estrogens / metabolism*
  • Female
  • Follicle Stimulating Hormone / metabolism*
  • Hot Flashes
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism*
  • Luteinizing Hormone / metabolism*
  • Ovulation / physiology*
  • Perimenopause / metabolism*
  • Perimenopause / physiology
  • Progesterone / metabolism*
  • Weight Gain


  • Estrogens
  • Progesterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone