One of every fourteen working women works a variable schedule that includes both day and night shifts. Rotating shift-work and night-work are associated with increased menstrual cycle abnormalities, decreased fertility and early miscarriage. It has been assumed that this association is caused by the stress associated with these schedules. There has been no attempt to isolate other contributing factors. It is known that the frequency of GnRH secretion is dynamically modulated across the menstrual cycle in normal women, that this modulation is critical for normal reproductive cycles, and that at specific times in the menstrual cycle, sleep is a profound regulator of the frequency of GnRH secretion. We hypothesize that the disruptions in sleep accompaning shift- and night-work schedules pay a key role in the associated reproductive abnormalities and there are specific times in the menstrual cycle at which the hormone regulation is particularly susceptible to this sleep disruption. These issues will be addressed in three specific aims.
Aim 1 will determine the effect of sleep disruption during the early follicular and mid-luteal phase on menstrual cycle dynamics.
Aims 2 and 3 will investigate the effects of sleep disruption at specific phases of the menstrual cycle, on the dynamics of pulsatile GnRH secretion.
In Aim 2, we will examine the early follicular phase changes in pulsatile LH secretion (as a marker of GnRH pulse generatory activity) with sleep disruption, and relate these changes to follicular phase length, follicle growth and FSH levels.
In Aim 3, we will examine the changes in pulsatile LH secretion in response to sleep disruption in the luteal phase, and relate these to changes in corpus luteum function and in the dynamics of the luteal-follicular transition. Cycle dynamics will be determined by daily menstrual logs, daily basal body temperature, daily urine gonadotropin and steroid levels, monthly urine ovulation kids, and monthly pelvic utrasonogrphay during a four-month protocol. These studies will provide the first systematic evaluation of the effect of sleep disruption on menstrual cycle dynamics, LH pulsatility and follicle development. Understanding physiologic mechanisms underlying the association of reproductive dysfunction with some work schedules will provide information for developing strategies, both at the personal and policy level, to minimize negative effects of work schedules on women's reproductive health.
| Klingman, Kara M; Marsh, Erica E; Klerman, Elizabeth B et al. (2011) Absence of circadian rhythms of gonadotropin secretion in women. J Clin Endocrinol Metab 96:1456-61 |
| Klerman, Elizabeth B (2005) Clinical aspects of human circadian rhythms. J Biol Rhythms 20:375-86 |
