[Frontiers in Bioscience S3, 474-486, January 1, 2011]

The endocrinology of perimenopause: need for a paradigm shift

Jerilynn C Prior, Christine L Hitchcock

Endocrinology and Metabolism, Department of Medicine, and Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, and Vancouver Coastal Health Research Institute, 2775 Laurel St, 4th floor, Vancouver, British Columbia, Canada V5Z 1M9


1. Abstract
2. Purpose, perspective and definitions
3.Ovarian changes of perimenopause
3.1. Estrogen changes-the paradox of perimenopause
3.2. Progesterone, ovulation and luteal phase changes in perimenopause
4. Hypothalamic-pituitary-ovarian feedback changes of perimenopause
4.1. Inhibin and control of perimenopausal follicle stimulating hormone (FSH)
4.2. Feedback loops, ovulation and the luteinizing hormone (LH) peak
5. Additional perimenopause hormonal changes in cortisol and catecholamines
6. Perimenopausal hormonal origins for common experience changes:
6.1. Heavy menstrual flow
6.2. Increased premenstrual symptoms
6.3. Weight gain
6.4. Night sweats/hot flushes
7. Perimenopausal hormonal changes and future health risks:
7.1. Cardiovascular disease
7.2. Breast and endometrial cancer
7.3. Osteoporosis and fracture risks
8. Summary and perspective
9. References


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.