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

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.