Perceptual-motor performance during the menstrual cycle

Study I: Choice reaction times were measured in 12 normally menstruating women using a numerals-keys serial response task with three set sizes (two, four, and eight). Testing was carried out at four successive phases of the menstrual cycle corresponding with different states of neuroendocrine activity. They were, respectively: (i) 2nd day of flow; (ii) 4th day after cessation of flow (preovulation); (iii) 12th day after flow (postovulation); and (iv) 3rd day before next (estimated) flow. No consistent relationship between performance and phase of the cycle could be demonstrated. The only significant effect was an increase in reaction time with increasing set size. The study provides no support for the theory that variations in estrogen and progesterone levels may cause behaviorally relevant changes in central nervous system functioning. Study II: Four women suffering from premenstrual tension were examined thrice weekly on the same task for 4 consecutive weeks. Three hours prior to testing, a blood sample was drawn and assayed for estrogen, progesterone, and gonadotropin (LH). Performance on the serial choice response task bore no consistent relationship to blood levels of any of the three hormones. Performance before ovulation (as determined by peak LH level) did not differ significantly from that after ovulation. These results concur with those of Study I: there was no reliable relationship between hormonal status and performance.     

Variations in leucocyte count during menstrual cycle.

The neutrophil counts of seven women, three tkaing oral contraceptives and four nottaking them, showed cyclical variations during the menstrual cycle, most consistentlya fall in the neutrophil count at menstuation. The neutrophil count in women not taking oral contraceptives rose to a peak twice during each cycle. One womennot taking oral contraceptives was studied in detail over eight consecutive menstrualcycles. She showed two neutrophil peaks per cycle and a similiar variation in themonocyte count. The eosinophil count showed a reciprocal relation with the neutrophil count and the basophil count fell in mid-cycle. The changes in her neutrophil count seemed to follow changes in oestrogen level with a delay of one to two days. Oestrogen probably promotes release of neutrophils from the bone marrow rather than from the marginated pool.     

Changes in brain size during the menstrual cycle

Background

There is increasing evidence for hormone-dependent modification of function and behavior during the menstrual cycle, but little is known about associated short-term structural alterations of the brain. Preliminary studies suggest that a hormone-dependent decline in brain volume occurs in postmenopausal, or women receiving antiestrogens, long term. Advances in serial MR-volumetry have allowed for the accurate detection of small volume changes of the brain. Recently, activity-induced short-term structural plasticity of the brain was demonstrated, challenging the view that the brain is as rigid as formerly believed.

Methodology/Principal Findings

We used MR-volumetry to investigate short-term brain volume changes across the menstrual cycle in women or a parallel 4 week period in men, respectively. We found a significant grey matter volume peak and CSF loss at the time of ovulation in females. This volume peak did not correlate with estradiol or progesterone hormone levels. Men did not show any significant brain volume alterations.

Conclusions/Significance

These data give evidence of short-term hormone-dependent structural brain changes during the menstrual cycle, which need to be correlated with functional states and have to be considered in structure-associated functional brain research.     

Control of sweating during the human menstrual cycle

Thermoregulatory responses were studied in seven women during two separate experimental protocols in the follicular (F, days 4-7) phase and during the luteal (L, days 19-22) phase of the menstrual cycle. Continuous measurements of esophageal temperature (Tes), mean skin temperature (Tsk), oxygen uptake and forearm sweating (ms) were made during all experiments. Protocol I involved both passive heat exposure (3 h) and cycle exercise at approximately 80% VO2 peak during which the environmental chamber was controlled at Ta = 50.0 degrees C, rh = 14% (Pw = 1.7 kPa). In protocol II subjects were tested during thirty-five minutes of exercise at approximately 85% VO2 peak at Ta = 35 degrees C and rh = 25% (Pw = 1.4 kPa). The normal L increase in resting Tes (approximately 0.3 degrees C) occurred in all seven subjects. Tsk was higher during L than F in all experiments conducted at 50 degrees C. During exercise and passive heat exposure, the Tes threshold for sweating was higher in L, with no change in the thermosensitivity (slope) of ms to Tes between menstrual cycle phases. This rightward or upward shift in Tes threshold for initiation of sweating averaged 0.5 degrees C for all experiments. The data indicate the luteal phase modulation in the control of sweating in healthy women is also apparent during severe exercise and/or heat stress.     

Plasma alpha-melanocyte-stimulating hormone during the menstrual cycle in women

alpha-Melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) immunoreactivity (IR) was measured in the blood of 22 healthy women with normal ovulatory process in the early and late follicular (near to ovulation) phases and in the early luteal phase of the menstrual cycle. Plasma alpha-MSH IR ranged from undetectable values to 81.3 pg/ml, the highest levels being found in the late follicular phase (15.52 +/- 4.16 pg/ml). In contrast, plasma ACTH IR was always detectable (range: 18.5-63.2 pg/ml), but its concentration did not differ significantly between the 3 phases of the menstrual cycle. High-pressure liquid chromatography fractionation of Sep pak C18-purified alpha-MSH IR revealed in all 3 phases the presence of 3 major peaks of alpha-MSH IR, coeluting with desacetyl-alpha-MSH, alpha-MSH and diacetyl-alpha-MSH, respectively. The most abundant peak always coeluted with authentic desacetyl-alpha-MSH, and the ratio between this deacetylated and the other 2 acetylated forms was similar in the 2 follicular phases (1:1.25 and 1:1.16 in the early and late phase, respectively), but significantly different in the luteal phase (1:0.48). The fluctuations in plasma concentration of the above MSH-related peptides suggest that different rates of alpha-MSH acetylation and release take place in the pituitary gland depending on the phase of the menstrual cycle.     

Changes in plasma adrenomedullin levels during the menstrual cycle

We investigated whether the levels of adrenomedullin, a novel peptide produced by several tissues, including the pituitary gland, change during the ovarian cycle. We studied 13 healthy women with regular menstrual cycles. Plasma samples were collected at 7, 14, 21 and 28 days of the ovarian cycle and assayed for adrenomedullin 1-52 using a specific RIA. LH, FSH, 17beta-estradiol, and progesterone concentrations were also determined. The adrenomedullin profile during ovarian cycle was similar to that of LH; plasma adrenomedullin increased from 10.9 pg/ml at the 7th day to 15.1 pg/ml at the 14th, and decreased to 8.5 pg/ml in the subsequent menses. The changes in plasma adrenomedullin were related to changes in LH and 17beta-estradiol. The cause of the increase in adrenomedullin levels during the late follicular phase of the menstrual cycle is not clear. Since it has been demonstrated that adrenomedullin is involved in the regulation of hypothalamus-pituitary-adrenal gland and its secretion is regulated by sex hormones we speculate that adrenomedullin could also play a role in regulating the hypothalamus-pituitary-ovary feedback. Alternatively it may be involved in the regulation of fluid and electrolyte homeostasis during the menstrual cycle.     

CO2 sensitivity changes during the menstrual cycle

A study of the changes in CO2 sensitivity at rest was undertaken in 20 regularly menstruating females in an attempt to determine the influence of the menstrual cycle on this variable. A biphasic oral temperature graph was used to signify fertility and demarcate three phases of the cycle. A CO2-rebreathing test was conducted 3 times/wk for 6 wk to obtain CO2 sensitivity and CO2 threshold measures. An analysis of variance was used to compare the results collected in each phase of the cycle for each of the variables. A significant increase was found in the sensitivity to CO2 between the follicular and luteal phases, a significant decrease between the luteal and menstrual phases, and no significant difference between the follicular and menstrual phases. The change between follicular and luteal phases was attributed to the effect of progesterone, which is elevated during the luteal phase. No significant change was found in the CO2 threshold level.     

One-carbon metabolism during the menstrual cycle and pregnancy

Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B₁₂, vitamin B₆, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.     

Changes of markers of oxidative stress during menstrual cycle

The levels of urinary hydrogen peroxide and thiobarbituric acid reactive substances have been compared during the menstrual cycle of 12 regularly menstruating women. Higher level of both indices of oxidative stress (normalized with respect to creatinine content) were found in the luteal phase of the cycle. These results give further evidence for the usefulness of urinary hydrogen peroxide and thiobarbituric acid reactive substances as potential biomarkers of oxidative stress and for the antioxidant action of estrogens.     

Endometrial content of prostaglandin precursors during the menstrual cycle

Fractionated curettage was performed in 18 women with cervical intraepithelial neoplasia. Otherwise all appeared to be healthy. The histological examination showed 9 of them to have been sampled in the follicular phase and the other 9 in the luteal phase. Endometrial specimens were simultaneously taken for analysis of the fatty acid pattern of lecithin (PC) and phosphatidylethanolamine (PE) by means of gas-liquid chromatography (GLC). In the luteal phase we found increased concentrations of the total sum of essential fatty acids of the linoleic acid series both in PC and PE (p less than 0.01 in both cases). All the main fatty acid components within this series showed increased mean levels in the luteal phase but only arachidonic acid (20:4) in PE was significantly elevated (p less than 0.01). The total sum of the alpha-linolenic acid series was unaffected by the phase of menstrual cycle. These results seem to indicate that the endometrium accumulates prostaglandin precursors towards the time for menstruation.     

Hormone changes during the menstrual cycle of Chinese women

The concentrations of LH, FSH, prolactin, oestradiol and progesterone in serum were measured daily during the menstrual cycle of 100 normal Chinese women. The cyclic changes in LH, FSH, oestradiol and progesterone were typical of ovulatory cycles in women of other ethnic groups as reported in the literature. The geometric mean of the LH midcycle peak value was 51 X 64 i.u./l, the FSH mid-cycle peak value was 11 X 52 i.u./l, the preovulatory oestradiol peak was 1229 X 12 pmol/l, and the progesterone luteal maximum was 53 X 27 nmol/l. The cyclic changes of prolactin concentrations were irregular: the value at mid-cycle was significantly higher than that at the follicular or luteal phases. A correlation between the length of the cycle and mean concentrations of LH and oestradiol at different stages throughout the cycle was shown.     

Regulation of endometrial transglutaminase activity during the menstrual cycle

When human endometrial transglutaminase was measured a 10-fold higher activity was detected during the secretive phase. This change was not related to either differences in solubility of the enzyme or to selective contamination by plasma factor XIII and rather appears to depend on the expression of the tissue form of transglutaminase, suggesting that this enzyme is regulated in vivo by progesterone.