Sleep Patterns Related to Menstrual Cycle Phase and Premenstrual Affective Symptoms

Transcription

1 Sleep 13(5): , Raven Press, Ltd., New York 1990 Association of Professional Sleep Societies Sleep Patterns Related to Menstrual Cycle Phase and Premenstrual Affective Symptoms Kathryn A. Lee, Joan F. Shaver, Elizabeth C. Giblin, and Nancy F. Woods Department of Physiological Nursing, University of Washington, Seattle, Washington, U.S.A. Summary: An ovulatory menstrual cycle is characterized by fluctuating levels of progesterone. Progesterone, a gonadal hormone known for its soporific and thermogenic effects, is present in negligible levels prior to ovulation and in high levels after ovulation. To describe and compare sleep patterns in relation to ovulatory cycles and premenstrual mood state, sleep was monitored in healthy women at two phases of the menstrual cycle. Results indicated that rapideye-movement (REM) latency was significantly shorter during the postovulatory (luteal) phase compared to the preovulatory (follicular) phase, but there was no significant difference in latency to sleep onset or the percentage of REM sleep. While there were no menstrual cycle phase differences in the percentages of various sleep stages, the women with negative affect symptoms during the premenstruum demonstrated significantly less delta sleep during both menstrual cycle phases in comparison with the asymptomatic subjects. Key Words: Women's sleep-progesterone-menstrual cycle-premenstrual symptoms. In both males and females, progesterone is secreted by the adrenal cortex and accounts for the low plasma concentrations of -1 mg/day. For females, however, luteinization of the granulosa cells in the ovary results in additional synthesis of high levels of progesterone during the ovulatory and postovulatory (luteal) phases of the menstrual cycle. As a result, the production rate of progesterone reaches 25 mg/day at its peak during the midluteal phase, and the level begins to decline at various rates during the premenstrual week (1). It is the thermogenic effect of this hormone that allows women to utilize basal body temperatures as an indicator of ovulation (2,3). The soporific effect of progesterone has been documented under various experimental conditions in animal models (4-7) and in various clinical situations with both males and females (8-10). Yet, little attention has been given to the effects of its monthly fluctuation in sleep studies involving women of child-bearing age (11). One purpose of this study was to compare sleep patterns during the follicular phase, when progesterone levels are negligible, with sleep patterns during the luteal phase, when progesterone Accepted for publication March Address correspondence and reprint requests to Dr. K. A. Lee at Department of Family Health Care Nursing, N4I1Y, University of California, San Francisco, San Francisco, CA , U.S.A. 403

2 404 K. A. LEE ET AL. levels and core body temperatures are significantly elevated. The second purpose of the study \-vas to describe hovi sleep patterns of women who experience premenstrual negative affect symptoms might differ from those who do not experience symptoms. METHODS A convenience sample, consisting of 17 healthy and presumably ovulating women between 25 and 35 years of age, volunteered to participate in a study of sleep and temperature rhythm patterns and were paid $75 upon completion. They had a history of regular, predictable menstrual cycles of between 25 and 35 days in length. With the exception of two subjects taking daily thyroid replacement, all subjects were free of medications during the study. Subjects had not been pregnant or lactating for a period of3 months prior to the study. Three additional subjects taking oral contraceptives, and thus anovulatory, were also monitored for the purpose of establishing the ovulatoryanovulatory menstrual cycle criteria using salivary progesterone (P sal) levels and mean rectal temperature (Tr) values. Alterations in the circadian rhythm for core temperature during the follicular and luteal phases of the menstrual cycle have been reported elsewhere for these subjects (12). After giving informed consent and receiving an orientation to the sleep laboratory, subjects began the study at either the follicular (days 3-10 after menses onset) or the luteal (3-12 days before onset of menses) phase of their cycle, whichever occurred at the first mutually available opportunity. Subjects were instructed to maintain their normal daily routine during each phase of the study. Daily diary recordings of meals, activity, and sleep were evaluated for compliance with instructions. Arriving ~ 1 h prior to their desired bedtime and awakening at their desired times, they spent 2 nights at each phase in the sleep laboratory. For each subject, lights-out time for the second menstrual phase occurred within 15 min of lights-out time for the first menstrual phase. Electroencephalogram, electrooculogram, and electromyogram were recorded continuously and scored in 30-s epochs according to standardized criteria (13). The sleep scorer remained blind to subjects' menstrual cycle phase until completion of the data analysis phase. A 10% random sampling for interrater reliability was consistently above 0.90 with another sleep researcher and another laboratory. Upon awakening each morning in the sleep laboratory, subjects were asked to produce a 3-ml sample of unstimulated saliva. Samples were frozen at - 20 C until completion of the study when one batch radioimmunoassay (RIA) was performed. A Coata-Count (Diagnostic Products) RIA kit, utilizing a solid-phase, no-extraction protocol with 125I-Iabeled progesterone to compete for antibody sites, was used to assay for P sal ' In a previous pilot study (K. A. Lee, unpublished data), saliva and serum samples for women during both follicular and luteal phases were significantly correlated (r = 0.92). Samples were analyzed in duplicate and mean P sal values for the 2 days at each menstrual cycle phase were used in further analyses. In conjunction with mean P sal values, the day of the menstrual cycle and Tr were also used to document follicular and ovulatory luteal phases. To quantify menstrual cycle negative affect symptomatology without biasing the results, subjects were asked to complete the Profile of Mood States (POMS) before sleep onset and upon awakening. Subjects assumed that changes in these evening and morning data would be used in a study of sleep's effect on daytime mood. Approximately 30 min prior to lights out, subjects completed the POMS, rating 65 adjectives

3 MENSTRUAL CYCLE SLEEP PATTERNS 405 according to how they felt "right now" on a scale of "not at all" (score of 0) to "extremely" (score of 4). The POMS contains six subscales: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion Bewilderment (14). A total evening POMS score was calculated for each subject at each phase by subtracting the Vigor-Activity score from the sum of the other five subscales. POMS subscale scores had internal consistency reliabilities ranging from 0.77 to 0.93, with the total POMS scores reaching a Cronbach alpha coefficient of 0.90 during the follicular phase and 0.81 during the luteal phase. In addition to the POMS, subjects completed a 7-day diary that contained space to rate both positive and negative symptoms as modified from the Woods Women's Health Diary (15). This diary included 22 negative affect symptoms rated on a scale of not present (score of 0) to extreme (score of 4). Like the POMS, the diary was completed within 30 min of bedtime and upon awakening. It was also completed on each of 7 days, during which time 2 nights included the sleep laboratory experience. A total negative affect score for 7 entire evenings was calculated for each subject. Based on the total 7-day diary scores during the follicular and luteal week or the evening total POMS scores during the follicular and luteal sleep laboratory experience, subjects were categorized as either premenstrually symptomatic or asymptomatic. The symptomatic subjects were defined as those with at least a 30% increase in total POMS or diary scores during their luteal phase in comparison with their own follicular phase. Analysis Subjects failing to meet ovulation criteria for significant menstrual cycle phase differences in P sal and Tr were eliminated from analyses related to changes in sleep patterns between the two phases of the menstrual cycle. The three subjects taking oral contraceptives, and thus anovulatory, had a cycle phase difference in P sal of < 100 pmol/l. Therefore, one criterion for ovulatory cycles was a P sal difference of > 150 pmol/l between cycle phases. Two subjects were eliminated because subsequent menses onset occurred 2 days earlier than predicted and they had <50 pmol/l difference in P sal. A third subject was eliminated because of a substantial change in ambient temperature in the sleep laboratory between her two menstrual cycle phases, resulting in mean Tr levels at extreme outlying levels. A fourth subject was eliminated after she reported an evening of dancing and alcohol consumption prior to coming into the sleep laboratory during one of the two menstrual cycle phases. The mean P sal values and circadian rhythm-adjusted mean (mesor) Tr values are presented in Table 1 for the 13 remaining subjects included in subsequent analyses of cycle phase differences in sleep patterns. Analyses for menstrual cycle phase comparisons consisted of Wilcoxon matchedpairs, signed-ranks tests for within-subject comparisons between follicular and luteal cycle phases. Mann-Whitney U analyses were performed for asymptomatic and symptomatic group comparisons. RESULTS Sleep pattern changes related to menstrual cycle phase The 13 subjects in the within-subject comparisons of sleep characteristics between menstrual cycle phases had total sleep times ranging from 308 to 482 min. The only significant finding (Wilcoxon Z = 1.99, p < 0.05) was a shorter REM latency during the

4 406 K. A. LEE ET AL. TABLE 1. Salivary progesterone (P sa ') levels and rhythm-adjusced mean rectal iemperaiures (T,) at two phases of the menstrual cycle (n = 13) Follicular Luteal P saj (pmoi/l) Mean ± SD ± ± a Median Range Tr Cc) Mean ± SD ± ± 0.141a Median Range a Significantly different from follicular phase: Wilcoxon Z = 3.18, p < luteal phase (93.5 ± 33.8 min) when compared to the follicular phase (109.8 ± 38.5 min). Rapid-eye-movement (REM) latency was defined as the number of minutes from stage 1 sleep onset to the first full minute of REM sleep. There were no significant menstrual cycle phase differences in total sleep time, sleep onset latency to stage 1 or stage 2, percentages of sleep period time (SPT) spent in various stages of REM and non-rem (NREM) sleep, or sleep efficiency (see Table 2). In the three women taking oral contraceptives and not experiencing ovulation or changes in core body temperature, REM latencies were short, falling into a narrow range of min, and varied by <5 min between the follicular and luteal phase. There were no other noticeable differences in sleep for these three women when compared to the group of ovulating women. Sleep patterns associated with premenstrual negative affect symptoms Ofthe 13 women, 6 were categorized as asymptomatic and 7 met the POMS or diary criteria for inclusion in the luteal phase symptomatic group. Table 3 contains the sleep variables for asymptomatic and symptomatic women during both the follicular and the luteal phases. When data were analyzed by group, there was a significant difference (p < 0.001) in the percentage of delta sleep (stages 3 and 4) between the asymptomatic and TABLE 2. Sleep pattern characteristics (mean ± SD) at two phases of the menstrual cycle (n = 13) Latency to Stage 1 (min) Stage 2 (min) REM (min) Time spent (% SPT) in Stage 0 Stage 1 Stage 2 Stage 3--4 REM Total sleep time (min) Sleep efficiency (% TST/TIB) Follicular 6.9 ± ± ± ± ± ± ± ± ± ± 0.5 Luteal 7.8 ± ± ± 33.8 a 5.7 ± ± ± ± ± ± ± 0.5 SPT, sleep period time; TST, total sleep time; TIB, time in bed. a Significantly different from follicular phase: Wilcoxon Z = 1.99, p < 0.05.

5 MENSTRUAL CYCLE SLEEP PATTERNS 407 TABLE 3. Sleep pattern characteristics (mean ± SD) during the two phases of the menstrual cycle for the asymptomatic and symptomatic group at both the follicular (F) and the luteal (L) menstrual cycle phases Menstrual cycle Asymptomatic Symptomatic phase (n = 6) (n = 7) Sleep onset latency (min) to Stage I F 7.9 ± ± 4.3 L 10.1 ± ± 3.5 a Stage 2 F 17.3 ± ± 4.8 L 14.8 ± ± 6.1 REM F ± ± 43.0 L 84.4 ± ± 43.2 Percentage of SPT in Stage 0 F 504 ± ± 2.7 L 4.3 ± ± 6.4 Stage I F 12.7 ± ± 3.8 L 9.9 ± ± 4.6 Stage 2 F 46.8 ± ± 4.6 b L 48.3 ± ± 9.1 Stage 3-4 F 15.6 ± ± 4.lc L 15.5 ± ± 2.5 c REM F 19.4 ± ± 4.9 L 22.0 ± ± 4.1 Total sleep time (min) F ± ± 56.8 L ± ± 51.5 Sleep efficiency index (% TSTffIB) F 94.5 ± ± 0.28 L 95.6 ± ± 0.67 SPT, sleep period time; TST, total sleep time; TIB, time in bed. Significantly different from asymptomatic group: amann-whitney U, p < 0.05; bmann-whitney U, p < 0.01; cmann-whitney U, p < symptomatic subjects at both the follicular and the luteal phases of their menstrual cycles. The asymptomatic group had a mean of 15.5 ± 5.1% delta sleep, while the symptomatic group had an average of only 4.4 ± 2.5% during the luteal phase. This finding was similar in the follicular phase. In addition to delta sleep differences, there was also a significant difference (p = 0.05) between the groups in sleep onset latency to the first full minute of stage 1. The latency for the asymptomatic group was 10.1 ± 4.0 min and the latency for the symptomatic group was 5 min shorter (5.9 ± 3.5 min) during the luteal phase. The same pattern was also evident during the follicular phase, although statistical significance was not reached. The symptomatic group also experienced an average of 7-10% more stage 2 sleep during both phases of the menstrual cycle. During the follicular phase, this difference was statistically significant (p < 0.01), whereas only a trend was revealed during the luteal phase (p = 0.18). DISCUSSION Little information exists in the literature with which to compare findings from this study. Williams et al. (16, p. 43) acknowledged the menstrual cycle's potential influence on sleep patterns by studying adult women only during their follicular phase. Follicular phase data from this current study closely resemble those reported by Williams and colleagues for sleep onset latency, REM latency, sleep efficiency, and the percentages

6 408 K. A. LEE ET AL. ofnrem sleep. However, they reported 25% REM sleep, only 0.5% stage 0, and only 4% stage 1 sleep. In a study of sleep-related breathing in 11 healthy women, Stahl and colleagues (17), in contrast to this study, reported only 13% REM sleep, more awake time, and a low sleep efficiency index without any demonstrable differences between the two menstrual cycle phases. These discrepancies may be explained by the lack of a night's adaptation to the sleep laboratory, the imposed limitation on their total sleep time due to awakening at 0530 h, or their extensive monitoring with equipment for assessing the respiratory parameters. While it is difficult to generalize from this small sample, findings suggest that sleep patterns, particularly altered REM latency, might indeed be affected by the phase of the menstrual cycle. The significantly shorter luteal phase REM latency for all ovulating subjects might be a function of progesterone's thermogenic effect. A relationship between REM latency and core body temperature has been established in both freerunning (18) and clinical (19) situations. In a previous report of circadian temperature rhythms for some of the women in this study (12), it was found that temperature rhythm amplitudes were dampened and mesors were elevated during the luteal phase when compared to the follicular phase. In these entrained subjects, however, no difference in temperature rhythm acrophases between the two menstrual cycle phases was apparent. Altered REM latency, in concert with the menstrual cycle change in temperature amplitude and no change in the temperature acrophase, adds further support for the circadian amplitude hypothesis (20). In this hypothesis, a dampened amplitude of the circadian rhythm is thought to be responsible for lowering the threshold for REM sleep at sleep onset. The finding of no menstrual cycle phase difference in REM sleep in this study supports earlier work by Ho (21) and Cluydts and Visser (22) but conflicts with an earlier report by Hartmann who concluded that "all seven women showed a tendency to have higher D-times [REM sleep] late in the cycle" (23, p. 413). Yet in comparing data from each menstrual cycle (23, p. 409), there was a great deal of variance in REM sleep. In one subject, for example, REM for the luteal phase ranged from 15.2% in the first cycle, to 25% in the third cycle and 32.5% in the fourth cycle. Furthermore, three of the seven subjects in Hartmann's study were psychiatric inpatients and one was anovulatory due to Enovid therapy. Overall, the 13 women in this study had amounts of stage 3--4 sleep comparable with that reported in the literature (16, p. 52). Yet when these women were categorized by premenstrual symptomatology, the symptomatic negative affect group had only about one-third as much stage 3--4 sleep as the asymptomatic group, regardless of menstrual cycle phase. Although the sample size is small, these findings support data from Cluydts and Visser (22) and suggest that women who experience premenstrual negative affect symptoms have significantly less deep sleep than would be expected for their age cohort, regardless of menstrual cycle phase. In comparison to the asymptomatic group, the symptomatic group also differed significantly in sleep onset latency during the luteal phase. While the mean difference was only 4 min and may not be of clinical relevance, falling asleep within 5 or 6 min is an indication that the symptomatic group may be more sleep deprived than the asymptomatic group, who took an average of 10 min to fall asleep. Until this study is replicated, sleep clinicians and researchers should be cautious in interpreting REM latency data from women when the phase of their menstrual cycle is

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