Hypoestrogenic inactive phases at the start of the menstrual cycle Changes with age and reproductive stage and relationship to follicular depletion.

Hypoestrogenic intervals at the beginning of the menstrual cycle in a population-based sample decrease and then increase in length with age, potentially reflecting both follicular depletion and hyperstimulation.

Rebecca J. Ferrell, Ph.D., M.D., Germán Rodriguez, Ph.D., Darryl Holman, Ph.D., Kathleen O’Connor, Ph.D., James W. Wood, Ph.D., Maxine Weinstein, Ph.D.

Volume 98, Issue 5, Pages 1246-1253.e3, November 2012


To investigate hypoestrogenic “inactive phases” (IP) in the follicular phase of the
menstrual cycle, with respect to age, reproductive stage, and follicular depletion.

Analysis of prospectively collected menstrual bleed and estrone-3-glucuronide data.

Center for Population and Health, Georgetown University.

White women (n = 88, aged 25–59 years, mean = 44.7 years) from the population-based Biodemographic Models of Reproductive Aging (BIMORA) project.


Main Outcome Measure(s):
IP durations by age and reproductive stage. Estimated follicular depletion rate based on IP durations.

Mean IP duration and variability decreased and then increased with age/reproductive stage. The proportion of very short (≤1-day) IP durations increased and then decreased with age/stage. Long IPs occurred most, but not exclusively, in the oldest age/latest stage. Follicular depletion rate estimates were a plausible 2-4% per year of age, but these models were a poor fit because IP durations did not consistently increase across ages/stages.

Follicular depletion models alone do not explain the observed pattern of IPs. Our data suggest that IPs reflect both follicular depletion and hyperstimulation in premenopausal and perimenopausal women. Knowledge of underlying IP patterns in the menstrual cycle could inform decisions about hormone sampling and contraception during the perimenopause.

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