Rituximab-it was the best of times, it was the worst of times

B cell depletion (BCD) has become established in the treatment of patients with rheumatoid arthritis (RA) vasculitis and systemic lupus erythematosus (SLE). However, although successfully confirmed to be useful in major large scale trials in RA and vasculitis, two SLE trials did not meet their endpoints. Given the widespread use of BCD in SLE it seems likely that it will continue to be used though better designed trials (which work) would help resolve on-going problems with regulatory and funding agencies.     

Sleep patterns related to menstrual cycle phase and premenstrual affective symptoms

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 rapid-eye-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.     

It was the best of times, it was the worst of times: a psychophysiologist's view of cognitive aging

This paper reviews research on age-related changes in working memory and attention control. This work is interpreted within a framework labeled "GOLDEN aging" (growing of lifelong differences explains normal aging), which is based on the idea that normal aging (as opposed to pathological aging) represents maturational processes causing progressive shifts in the distributions of mental abilities over the lifespan. As such, brain phenomena observed in normal aging are already apparent, under appropriate conditions, in younger adults. Among the phenomena that can be interpreted according to the GOLDEN aging framework are reductions in working memory capacity, impairments of inhibitory processes, increases in frontal lobe activation, and lack of suppression of responses as a function of repetition.     

Uterine contractility during the menstrual cycle

The non-pregnant uterus shows different patterns of contractility during the menstrual cycle. A renewed interest in uterine contractility has resulted from reports of non-invasive ultrasound (US) based studies. To clarify the changes in uterine contractility occurring throughout the menstrual cycle, we prospectively studied uterine contractions (UC) at six representative stages with US and intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results showed UC frequency could be measured by either US or IUP. UC amplitude and resting pressure tone could only be assessed by IUP. Conversely, direction of UC displacement could only be assessed by US. UC frequency increased at mid-cycle and decreased throughout the luteal phase suggesting oestradiol and progesterone exert positive and negative actions on uterine contractility, respectively. UC amplitude increased throughout the menstrual cycle to maximum values in the late luteal phase. Retrograde UC were most frequent at mid-cycle and convergent ('opposing') UC predominated during the luteal phase. While the former pattern ensures sperm transport, the latter may facilitate embryo implantation. In conclusion, UC changes throughout the menstrual cycle assessed by US and IUP emphasize the hormonal dependence of uterine contractility. Although UC patterns favouring sperm transport appear regulated by oestradiol, uterine quiescence and the dominance of convergent UC prevailing at the time of implantation are linked to progesterone. These data will serve to identify and treat possible dyskinetic changes in uterine contractility, particularly in women suffering from infertility, endometriosis, and dysmenorrhea.     

The relationship between exercise-induced oxidative stress and the menstrual cycle

The purpose of this study was to investigate the relationship between exercise-induced oxidative stress and the menstrual cycle in healthy sedentary woman. Eighteen women with regular menstrual cycles participated in this research. The subjects monitored their basal body temperature (BBT) and carried out a urinary ovulation test (twice) for 2 months prior to the study to determine their menstrual cycle. The subjects performed bicycle ergometer exercise (for 30 min at 60% O_2max) in each phase (menses, follicular and luteal phases) of the menstrual cycle. Serum estradiol and progesterone concentrations were determined from blood that was collected at rest. Serum thiobarbituric acid reactive substances (TBARS), total superoxide dismutase (T-SOD) and extracellular superoxide dismutase (EC-SOD) were determined as markers of oxidative stress in blood samples collected at rest and after exercise. TBARS was significantly lower after exercise [2.4 (0.5) nmol/ml] in the follicular phase, and T-SOD was significantly lower after exercise [3.2 (1.2) U/ml] in the luteal phase. EC-SOD did not show a significant change after exercise during each phase of the menstrual cycle. Furthermore, there was a negative correlation between estradiol and T-SOD (r=–0.46, P<0.05) and between estradiol and EC-SOD (r=–0.55, P<0.05) during the menses. All data are presented as the mean value and its standard deviation.The results of this study suggest that when the estradiol level is high in a menstrual cycle, free radicals produced as a consequence of exercise may be easily eliminated by sedentary women with normal menstrual cycles.     

The relationship between menstrual cycle phases and suicide attempts

OBJECTIVE: The validity of prior studies on the menstrual cycle and suicide attempts assumes that suicidal women accurately describe their cycles. The three objectives of this study were 1) to explore whether prior inconsistencies are due to the effects of sample selection and method of assessment of the menstrual cycle, 2) to assess the relationship between the menstrual cycle phase and suicide attempts, and 3) to establish the role of sexual hormones in suicide attempts. METHODS: The original sample included 134 women who came to the emergency room of a general hospital after a suicide attempt. One hundred eight female blood donors were recruited as control subjects. The menstrual cycle was divided into follicular, midcycle, and luteal phases using two clinical methods and serum hormonal assessment. Dividing the follicular phase into menstrual and nonmenstrual phases was also considered. RESULTS: Two of 11 previously used sampling methods produced a sample size similar to that of the hormonal assessment. kappa values between the two clinical and the endocrinological methods were low (0.40-0.50). The number of suicide attempts during the follicular phase (particularly during the menstrual phase) was significantly higher than expected. CONCLUSIONS: Despite the inability to control for other variables and limitations, the results of this study suggest that sample selection could introduce biases and that studies relating psychiatric symptomatology and menstrual cycle phases need to use hormonal determinations. New studies are needed to verify that suicide attempts are more frequent during the follicular phase (particularly during the menstrual phase).     

Isometric strength and endurance during the menstrual cycle

Seven healthy young women, 3 of whom had been taking oral contraceptives, were examined during the course of 2 menstrual cycles to assess their isometric strength, their endurance during a series of 5 fatiguing isometric contractions at a tension of 40% MVC, and their blood pressures and heart rates during those fatiguing contractions. Two sets of experiments were performed, one in which the subject's forearm temperature was allowed to vary as a function of T _A , and one with the muscle temperature stabilized by immersion of the forearm in water at 37 C. During exposure to ambient temperatures, isometric strength and both the heart rate and blood pressure responses at rest and at the end of a fatiguing, sustained isometric exercise, were not significantly different during any phase of the menstrual cycle in any subject. In contrast, the isometric endurance in the women not taking oral contraceptives varied sinusoidally in all 5 contractions with a peak endurance midway through the ovulatory phase and the lowest endurance mid-way through the luteal phase of the menstrual cycle. The isometric endurance of the women taking oral contraceptives did not vary during their menstrual cycle. After stabilization of the temperature of the muscles of the forearm in water at 37 C, the isometric endurance of the normal subjects showed a hyperbolic response with the maximal endurance at the beginning and end of their cycles, and the shortest endurance at mid-cycle. Here again, however, the isometric endurance of the women taking oral contraceptives did not vary after immersion of their forearms in the 37 C water.     

Bioelectrical impedance changes during the menstrual cycle

Numerous physiological factors that may influence estimates of body composition based on bioelectrical impedance analysis (BIA) have been recognized. The two studies to date investigating changes in bioelectrical impedance during the menstrual cycle have produced conflicting results. Male control subjects were included in this study in an attempt to discern variations in bioelectrical impedance associated with the menstrual cycle in women from those due to other physiological variables affecting both sexes. Body weight and bioelectrical impedance (tetrapolar Holtain Analyzer; 50 kHz, 800 μA) were measured two to five times per week for one menstrual cycle (21–34 days) on 42 women (6 taking an oral contraceptive, OC), aged 19.0–34.4 years, and for 22–32 days on 28 men (18.9–24.1 years). Body weight in the non-OC women decreased significantly between menses and the late follicular phase, and increased significantly between the late follicular phase and the premenstruum (paired t test, P < 0.05). These changes were not correlated with matching bioelectrical impedance changes (linear regression, P > 0.05). Bioelectrical impedance in the non-OC women, and body weight and bioelectrical impedance in the OC women and the men, did not differ significantly over the measurement period. Likewise, estimated lean body mass (LBM) and total body water (TBW) derived from BIA remained stable. The intraobserver test-retest reliability (S_meas) of bioelectrical impedance was 12.3 ohm (2.8% of mean bioelectrical impedance) which produced as much as a 10–12% error in estimating LBM and TBW. Measurement error was reduced to 4 ohm in a subgroup where electrode positions were marked with indelible ink. These results indicate that body composition assessments based on BIA measured at 50 kHz are not affected by the menstrual cycle. Am. J. Hum. Biol. 9:155–161, 1997. © 1997 Wiley-Liss, Inc.     

Follicle development during the normal menstrual cycle

An understanding of the factors which determine initiation of follicle growth, recruitment and dominant follicle selection may increase our understanding of the underlying process of ovarian aging. In this article, these aspects of the normal menstrual cycle are reviewed. The morphological and endocrinological development in the early follicle is described from the primordial follicle stage. The degree of follicle-stimulating hormone (FSH) dependency is discussed, as is the relationship of estradiol (E₂) production to follicle diameter. The principles governing mono-follicular selection are outlined, and the FSH `threshold' and `window' concepts are highlighted. Maximum FSH levels in the early follicular phase are shown to be variable between individuals. The relevance of this and the means by which individual sensitivity to FSH may be altered at the ovary in the context of ovarian aging are discussed.     

Cardiovascular functioning during the menstrual cycle.

Variations in cardiovascular functioning during the 'normal' menstrual cycle have been little researched. Resting-blood pressures, resting-heart rate, rate-pressure product (RPP) and a derived index of fitness (Schneider Index) were monitored throughout natural, hormonally defined menstrual cycles. Volunteers were 26 women (20-48 years) who had regular (25-35 days) cycles. Their blood pressures and heart rate (at rest and according to Schneider's protocol) were measured at the same time daily (Monday-Friday) for 5 weeks. Daily, early morning-urine samples were assayed for sex hormones enabling accurate definition of cycle phase for each woman. Resting systolic-blood pressure was significantly higher in the ovulatory phase (P < 0.05) than in the follicular or luteal phases, but resting-diastolic pressures did not differ significantly between phases. Resting-heart rate was significantly higher in both ovulatory (P < 0.01) and luteal (P < 0.01) phases than in the menstrual and follicular phases. The Schneider Index was higher during the follicular phase than during the ovulatory (P < 0.005) or luteal (P < 0.01) phases, the RPP was higher during the ovulatory phase than during the bleeding (P < 0.05) and follicular (P < 0.005) phases. These findings provide a pattern of menstrual cycle-related variation in cardiovascular functioning that can be related to established actions of the ovarian steroids.