Stress and the menstrual cycle: Short- and long-term response to a five-day endotoxin challenge during the luteal phase in the rhesus monkey

Previously, we reported that in the rhesus monkey a 5-day inflammatory-like stress during the early-mid follicular phase acutely stimulates the hypoth alamic-pituitary-adrenal. axis and exerts effects on the hypothalamic-pitui tary-gonadal axis, delays folliculogenesis and in some animals decreases lu teal function in the post-treatment cycle. Because the endocrine environmen t at the time of the stress may influence the response to the stress, we no w investigate the acute and long-term responses to a similar stress challen ge during the luteal phase of the menstrual cycle, at a time of progesteron e dominance. Nine monkeys with normal cycles were injected with endotoxin ( lipopolysaccharide; LPS, 150 mu g iv) twice a day for 5 days starting on da ys 4-8 after the LH peak. Blood samples were taken at hour 3 and hour 8 aft er each morning LPS injection to monitor the acute gonadotropin and cortiso l responses. To verify cyclicity, menses were checked every day, and daily Mood samples were taken for estradiol and progesterone measurement. Two con trol cycles, the LPS treatment cycle, and two post-treatment cycles were do cumented. Endotoxin activated the adrenal axis: mean (+/-SE) cortisol secre tion was significantly increased at hour 3 after the first morning LPS inje ction (74.1 +/- 4.9 vs. 24.1 +/- 1.8 mu g/dL in the control; P < 0.05) and remained elevated at hour 8. This response decreased progressively with tim e: on day 5 of LPS treatment, the cortisol level was still significantly hi gher than control at hour 3 (38.5 +/- 5.0 mu g/dL; P < 0.05) but had return ed to the control concentration by hour 8 (days 3-5 of LPS). Mean integrate d progesterone through the luteal phase of the LPS treatment cycle was sign ificantly decreased (33.5 +/- 3.3 ng/ml vs. 48.9 +/- 3.7 and 54.0 +/- 4.9 i n the two control cycles; P < 0.05), but luteal phase length remained uncha nged. When compared with control levels on the same day of the luteal phase , about one third of LH and FSH values were lower than one so below mean co ntrol levels. LPS administration had no effect on the two post-treatment cy cles, except that integrated luteal progesterone in 3 out of 9 monkeys was still reduced in post-treatment cycle 1. There were no differences in folli cular phase length and preovulatory estradiol peaks between control cycles and post-treatment cycles. When compared with our previous study, the resul ts illustrate specific responses to stress at different phases of the menst rual cycle and support the notion that a moderate short-term inflammatory-l ike stress episode has the potential to subtly alter critical aspects of cy clicity.