Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.

The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.     

Inhibitory effect of progesterone in the postcastration gonadotrophin rise in women

This study was designed to investigate the effects of progesterone on the gonadotrophin rise after bilateral salpingo-oophorectomy (BSO). Twenty-eight regularly menstruating women underwent hysterectomy and BSO during the follicular phase of the menstrual cycle. They were divided into 5 groups depending on the treatment after BSO. Plasma LH and FSH were studied serially for 14 days after BSO and the patterns of LH and FSH rises were contrasted to those observed in the control group which received neither progesterone nor estrogen. LH and FSH levels in the group which were given low dose progesterone only, rose consistently after BSO and these patterns were similar to those seen in the control group. However, the addition of estrogen reduced gonadotrophin rises significantly more than estrogen did alone. Further, the luteal phase level of progesterone solely has a suppressive effect on the gonadotrophin rises after BSO. Our observations suggest that synergism of progesterone with estrogen may exist in suppressing gonadotrophin secretion in the normal luteal phase and should help in understanding why gonadotrophin levels in the luteal phase are lower than those in the follicular phase of the menstrual cycle.     

Sex hormones correlated with sex skin swelling and rectal temperature during the menstrual cycle of the pigtail macaque (Macaca nemestrina).

Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction.     

Plasma insulin and glucagon concentrations and biochemical variables in regularly menstruating females with ovulatory and anovulatory menstrual cycles.

Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations.     

Plasma gonadotrophin and ovarian steroid concentrations in women with menstrual cycles with a short luteal phase

Daily plasma concentrations of FSH, LH, oestradiol-17 beta and progesterone were compared for 12 cycles with a short luteal phase and 19 cycles with a luteal phase of normal length (i.e. cycles in which the luteal phase lasted 12 or more days). FSH and LH concentrations were suppressed in short luteal-phase cycles in the early follicular phase and the length of the follicular phase was prolonged (median duration, 14.5 days, range 13-21 days: compared with 12 days, range 9-17, in control cycles; P less than 0.025). Preovulatory oestradiol-17 beta values and the mid-cycle concentrations of FSH and LH were similar in both groups. Plasma progesterone values in the luteal phase were similar in both groups over the 2nd to 5th days inclusive after the midcycle LH peak but declined in the short luteal phases thereafter. In short luteal-phase cycles, menstruation occurred in the presence of higher levels of oestradiol-17 beta and progesterone than in cycles of normal length and the rise of gonadotrophin in the late luteal phase of the cycle was delayed. These findings suggest that in cycles with a short luteal phase there is a lack of synchrony between the ovarian and menstrual events.     

Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle.

Body temperature and sleep change in association with increased progesterone in the luteal phase of the menstrual cycle in young women. The mechanism by which progesterone raises body temperature is not known but may involve prostaglandins, inducing a thermoregulatory adjustment similar to that of fever. Prostaglandins also are involved in sleep regulation and potentially could mediate changes in sleep during the menstrual cycle. We investigated the possible role of central prostaglandins in mediating menstrual-associated 24-h temperature and sleep changes by inhibiting prostaglandin synthesis with a therapeutic dose of the centrally acting cyclooxygenase inhibitor acetaminophen in the luteal and follicular phases of the menstrual cycle in young women. Body temperature was raised, and nocturnal amplitude was blunted, in the luteal phase compared with the follicular phase. Acetaminophen had no effect on the body temperature profile in either menstrual cycle phase. Prostaglandins, therefore, are unlikely to mediate the upward shift of body temperature in the luteal phase. Sleep changed during the menstrual cycle: on the placebo night in the luteal phase the women had less rapid eye movement sleep and more slow-wave sleep than in the follicular phase. Acetaminophen did not alter sleep architecture or subjective sleep quality. Prostaglandin inhibition with acetaminophen, therefore, had no effect on the increase in body temperature or on sleep in the midluteal phase of the menstrual cycle in young women, making it unlikely that central prostaglandin synthesis underlies these luteal events.     

Subnormal follicular-phase serum progesterone levels and elevated follicular-phase serum estradiol levels in young women with insulin-dependent diabetes

In a search for possible hormonal reasons for the loss of protection from myocardial infarction seen in diabetic women, serum levels of estradiol, progesterone, and luteinizing hormone were compared throughout a menstrual cycle (17 points) in eight healthy nonsmoking women and five otherwise healthy nonsmoking insulin-dependent diabetic women. The total length of the menstrual cycle and the lengths of the follicular and luteal phases did not differ between the groups. During the periovulatory and luteal phases, there was no significant intergroup difference with respect to any of the three hormones. During the follicular phase, in both groups, there was a plateau in serum progesterone concentration, with the level approximately 42% lower in the diabetic group (12.0 +/- 6.6 ng/dl versus 20.7 +/- 5.7; P less than 0.0001). Follicular-phase serum estradiol showed a rising curve in both groups; day-by-day comparison (days -10 to -3 before the luteinizing hormone peak) showed consistently higher levels in the diabetic group (mean, 108 pg/ml versus 95 pg/ml; P less than 0.001). The follicular-phase serum estradiol to progesterone ratio was nearly twice as high in the diabetic group as in the normal group (8.9 versus 4.6), a difference that was highly significant. The finding of elevated serum estradiol and subnormal serum progesterone concentrations during the follicular phase is so far unique to women with insulin-dependent diabetes mellitus. The possibility that this pronounced abnormality in diabetic women may be related to coronary disease merits testing in suitable in vivo and in vitro models of atherogenesis.     

Effect of sex hormones on neuromuscular control patterns during landing.

The purpose of the study was to investigate the effects of sex hormones across menstrual cycle phases on lower extremity neuromuscular control patterns during the landing phase of a drop jump. A repeated-measures design was utilized to examine sex hormone effects in 26 recreationally active eumenorrheic women. Varus/valgus knee angle and EMG activity from six lower extremity muscles were recorded during three drop jumps from a 50 cm platform in each phase of the menstrual cycle. Blood assays verified sex hormone levels and cycle phase. The semitendinosus muscle exhibited onset delays (p0.006) relative to ground contact during the luteal phase, and demonstrated a significant (p0.05) difference between early and late follicular phases. Muscle timing differences between the gluteus maximus and semitendinosus were decreased (p0.05) in the luteal compared to early follicular phases. These results suggest a different co-contractive behavior between the gluteus maximus and semitendinosus, signifying a shift in neuromuscular control patterns. It appears that female recreational athletes utilize a different neuromuscular control pattern for performing a drop jump sequence when estrogen levels are high (luteal phase) compared to when they are low (early follicular phase).     

Estrogen receptor levels in the oviducts and endometria of cynomolgus macaques during the menstrual cycle

We sampled oviducts and endometria of 27 cynomolgus macaques during the menstrual cycle and measured the concentration of nuclear and cytoplasmic estrogen receptors in these tissues by exchange assay. We assessed the stage of the cycle by correlating serum estradiol (E2) and progesterone (P), as measured by radioimmunoassay, with the morphological condition of the ovaries, oviducts and endometrium of each animal. We have previously identified a series of oviductal stages that reflected the orderly sequence of cytological changes in the oviduct during the cycle, and we normalized receptor measurements to these stages. The amounts of nuclear and cytoplasmic estrogen receptor in both the oviduct and the endometrium were approximately twofold greater in the follicular phase than in the luteal phase. In the follicular phase, elevated receptor levels were associated with oviductal proliferation and differentiation, as well as with endometrial proliferation. During the luteal phase, lowered levels were correlated with atrophy and dedifferentiation in the oviduct, but with hypertrophy and progestational development in the endometrium. When the luteal phase of one cycle ends and the follicular phase of the next begins, it is a decline in serum P, not a rise in serum E2, that precedes the elevation in estrogen receptor level and the onset of proliferation in the oviduct and endometrium. Proliferation of the reproductive tract and elevations in nuclear estrogen receptor levels during the early follicular phase can therefore be viewed as consequences of the release of the system from antagonism by P.     

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.     

Menstrual Cycle Effects on Attitudes toward Romantic Kissing

Hormonal changes associated with the human menstrual cycle have been previously found to affect female mate preference, whereby women in the late follicular phase of their cycle (i.e., at higher risk of conception) prefer males displaying putative signals of underlying genetic fitness. Past research also suggests that romantic kissing is utilized in human mating contexts to assess potential mating partners. The current study examined whether women in their late follicular cycle phase place greater value on kissing at times when it might help serve mate assessment functions. Using an international online questionnaire, results showed that women in the follicular phase of their menstrual cycle felt that kissing was more important at initial stages of a relationship than women in the luteal phase of their cycle. Furthermore, it was found that estimated progesterone levels were a significant negative predictor for these ratings.     

Pathogen disgust,but not moral disgust,changes across the menstrual cycle

The Compensatory Prophylaxis Hypothesis (CPH) proposes that during periods of increased susceptibility to infections, e.g., during the luteal phase of the menstrual cycle when progesterone suppresses immune function, women should feel more disgust toward pathogen cues and behave prophylactically. We investigate differences in disgust sensitivity and contamination sensitivity during different phases of the menstrual cycle in regularly cycling, healthy 93 rural and urban Polish women using the within-subject design. Disgust sensitivity was measured during two different phases of a menstrual cycle: 1) the follicular phase (the 5th or 6th day of the cycle) and 2) the luteal phase (on the 5th day after a positive ovulatory test or on 20th day of a cycle if the result of the ovulatory test was not positive). In the luteal phase, women scored higher on the Pathogen Disgust of the Three-Domain Disgust Scale, the Contamination Obsessions and Washing Compulsions Subscale of Padua Inventory, and on ratings of photographs showing sources of potential infections than in the follicular phase. Moral Disgust of the Three-Domain Disgust Scale did not differ between cycle phases. Hence, results suggest that women feel more disgusted toward cues to pathogens during the luteal phase, when susceptibility to infection is greater. We suggest that it is necessary to incorporate ovulatory testing as well as to conduct repeated measurements of disgust sensitivity in future tests of the CPH. Moreover, we believe that understanding how the feeling of pathogen disgust varies across the menstrual cycle and in relation to progesterone levels could be useful in designing effective infectious diseases prevention strategies for women.     

Features of cardiovascular functioning during different phases of the menstrual cycle

The purpose of the present study was to determine whether there is a menstrual cycle effect on heart rate, blood pressure and heart rate variability. 10 healthy regularly cycling females (age 19-23 years) were studied during the follicular phase and luteal phase over two month. We found significant changes in heart rate, AMo and stress index during the menstrual cycle with a minimum in the follicular phase and maximum in the luteal phase. The HF and LF components decreased more during the luteal phase than during the follicular phase (p < 0.05), whereas a tendency for increase LF/HF was observed in the luteal phase. In the follicular phase SDNN, pNN50, Mo, MxDMn were significantly higher than in the luteal phase. Furthermore, the VIK was higher in the luteal phase compared to the follicular phase (p = 0.003). Blood pressure did not show any significant change during both these phases of the menstrual cycle. These findings indicate that sympathetic nervous activity in the luteal phase is greater than in the follicular phase, whereas parasympathetic nervous activity is predominant in the follicular phase. A difference of the balance of ovarian hormones may be responsible for these changes of autonomic functions during the menstrual cycle.     

Women's attractiveness judgments of self-resembling faces change across the menstrual cycle

Two lines of reasoning predict that women's preferences for people exhibiting cues to kinship will be lower in the follicular phase than in the luteal phase of the menstrual cycle. Women may avoid kinship cues during the follicular phase when they are most fertile due to the costs of inbreeding. Alternatively, women may seek kinship cues during the luteal phase as a byproduct of the benefits of associating with kin during pregnancy, which is also characterized by high progesterone. We find that preferences for facial resemblance, a putative kinship cue, follow this predicted pattern and are positively correlated with estimated progesterone levels based on cycle day. Neither estimated estrogen levels nor conception risk predicted preferences for self-resemblance, and the cyclic shift was stronger for preferences for female faces than male faces. These findings lead to the possibility that this cyclic change in preference for self-resemblance may be a byproduct of a hormonal mechanism for increasing affiliative behavior toward kin during pregnancy rather than a mechanism for preventing inbreeding during fertile periods.     

Characteristics and regulation of the ovarian cycle in vervet monkeys (Chlorocebus aethiops)

This study was designed to evaluate the timecourse of ovarian and pituitary endocrine events throughout the menstrual cycle in the vervet monkey, and whether circulating luteinizing hormone (LH) or the uterus regulates the functional lifespan of the vervet corpus luteum. Daily saphenous blood samples were collected from adult females (1) during spontaneous menstrual cycles (n = 7), and (2) during cycles in which a gonadotropin-releasing hormone antagonist (acyline) was administered for 3 days at midluteal phase (n = 3), and (3) for 30 days following recovery from hysterectomy (n = 4). Estradiol (E) and progesterone (P) levels were assayed using electrochemoluminescent assays. Gonadotropin levels were measured by radioimmunoassay using reagents developed for the assay of follicle-stimulating hormone and LH in macaques. Spontaneous cycles exhibited a midcycle E rise (476+/-49 pg/ml), engendering an LH surge, 12+/-1 days after onset of menses, followed by a luteal phase with peak P levels of 4.7+/-0.9 ng/ml. Histologic evaluation of the ovaries at late follicular phase or early luteal phase revealed the presence of a single, large Graafian follicle or developing corpus luteum, respectively. Acyline treatment caused a significant (P<0.05) decline in P levels (2.9+/-0.5 vs 0.5+/-0.3 ng/ml, 0 vs 48 h post-treatment) and premature menstruation compared with untreated controls (P<0.05). Hysterectomy had no apparent effect on the monthly pattern or levels of circulating E or P. Thus, the characteristics and regulation of the ovarian cycle in vervets appear similar to those in women and macaques, with cyclicity dependent on pituitary gonadotropin hormones and independent of a uterine luteolytic factor.     

Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women

AIM: The aim of this study was to investigate the effect of baclofen administration on growth hormone (GH) secretion during different phases of the menstrual cycle. METHODS: Twelve healthy women (33.6 +/- (SD) 2.8 years; range 23-40 years) with regular menstrual cycles were enrolled. The phases of the menstrual cycle were determined using transvaginal ultrasonography (TV-US) and detecting hormonal serum levels. Plasma GH levels were evaluated during the early follicular, periovulatory and luteal phases of the cycle before and after the baclofen challenge test. RESULTS: After acute baclofen administration, GH levels increased significantly (p < 0.001) compared to basal values during the periovulatory and luteal phases, while no significant variation was detected during the early follicular phase. In addition, plasma GH levels resulted significantly (p < 0.001) higher during the luteal phase than during the periovulatory phase. CONCLUSION: Acute baclofen administration induces a significant increase in plasma GH levels in healthy females during the periovulatory and luteal phases, but not during the early follicular phase. These data suggest a modulator role of plasma sex steroids levels on GH release induced by baclofen.     

Relation between levels of circulating ovarian steroids and pituitary gonadotropin content during the menstrual cycle of the rhesus monkey

Anterior pituitary glands were removed from 27 intact cycling rhesus monkeys sacrificed in the early (Day 2), mid (Days 6--9) and late (Days 11--12) follicular phase, and in the early and late luteal phase (3--5 and 10--15 days after the midcycle luteinizing hormone (LH) surge). Assignment of cycle stage was confirmed by the pattern of circulating steroid and gonadotropin levels seen in the blood samples taken daily throughout the cycle. The anterior pituitary glands were weighed, stored at -30 degrees C and assayed for LH and follicle-stimulating hormone (FSH) content by specific radioimmunoassays. Serum estradiol levels and pituitary LH and FSH contents rose simultaneously during the follicular phase. After the preovulatory gonadotropin surge, pituitary LH content was low and invariant. Pituitary FSH content reached a nadir in the early luteal phase and tended to rise in the late luteal phase. Multiple correlation analyses revealed that there is a positive correlation between rising levels of estradiol in the circulation and pituitary LH (p = 0.003) and FSH (p = 0.017) content, and that there is a significant negative correlation between circulating progesterone levels and pituitary FSH content (p = 0.002). Pituitary LH content is less strongly related to circulating progesterone levels. There was no significant difference in the wet weights of the anterior pituitary glands during the five phases of the menstrual cycle studied.     

Changes of common fragile sites on chromosomes according to the menstrual cycle

Summary The frequencies of chromosomal breaks and sister chromatid exchanges (SCE) are influenced by pregnancy, oral hormonal contraceptives and the menstrual cycle. The changes in the number and sites of spontaneous and aphidicolin-induced breaks on chromosomes from peripheral blood lymphocytes during the menstrual cycle were examined in 8 healthy women. Menstrual cycle was determined by menstruation and the quantity of serum estrogen, progesterone and luteinizing hormone. The number of spontaneous breaks at the follicular phase, the interval phase (which includes ovulation) and the luteal phase were 3.1 ± 1.1, 2.7 ± 2.3 and 3.9 ± 2.6 per 100 mitoses, respectively. The frequencies of aphidicolin-induced breaks in the same phases were 95.8 ± 23.3, 90.6 ± 14.3 and 122.7 ± 20.1 per 100 mitoses, respectively. The higher frequency at the luteal phase was statistically significant compared with the other phases. In the luteal phase, bands 2q32, 3q27, 6q26 and 16q23 had higher frequencies of breaks (P < 0.05); however, breaks at band 9q32 decreased significantly. SCE showed considerable variation, but with no statistical significance.     

Effects of the menstrual cycle phase on the blood lactate responses to exercise

The effects of menstrual cycle phase on the blood lactate response to exercise were examined in eumenorrheic women (n=9). Exercise tests were performed at the mid-follicular and mid-luteal points in the menstrual cycle (confirmed by basal body temperature records and hormone levels). Blood lactates were measured at rest and during the recovery from exercise. Resting lactates were not different between the exercise tests; however, recovery lactates were significantly (p < 0.05) lower in the luteal compared to the follicular phase. The mechanism for these differences is unclear, but may be related to an estrogen mediated increased lipid metabolism inducing a concurrent reduction in carbohydrate metabolism. The present findings question the use of blood lactate monitoring as a suitable technique to measure exercise intensity in eumenorrheic women.     

Changes in the density gradient distribution of erythrocytes during the menstrual cycle

Modifications in erythrocyte density distribution were evaluated, by means of centrifugation on Ficoll-Triosil discontinuous density gradient, in five healthy young women during menstrual cycle. Oestradiol and progesterone plasma levels were tested, showing normal and typically ovulatory-like variations during the cycle. Youngest cell populations showed always quantitative increases from the follicular to the ovulatory phase of the cycle, reverting to basal values in the luteal phase. Possible hormonal or haemorrhagic causes are discussed.