Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression

To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.     

The effect of smoking on serum progesterone, estradiol, and luteinizing hormone levels over a menstrual cycle in normal women

Since smoking has been shown to affect serum progesterone and estradiol levels in postmenopausal women, we evaluated the levels of these hormones and luteinizing hormone (LH) over an entire menstrual cycle (17 points) in eight healthy nonsmokers and eight healthy smokers. The total length of the cycle and the lengths of the follicular and luteal phases did not differ between the groups. There was no difference in estradiol, progesterone, or LH levels during the periovulatory and luteal phases. Follicular-phase serum progesterone, which had a level 37% higher in smokers, showed a plateau in both groups (28.3 +/- 5.7 ng/dl versus 20.7 +/- 5.7; P less than 0.0001). Follicular-phase serum estradiol showed a rising curve in both groups. The mean value in smokers was slightly higher than that in nonsmokers (107 pg/ml versus 95; P approximately 0.05); during the early part of the follicular phase, prior to the rapid preovulatory increase, the difference was greater (23%) and of higher statistical significance (80 pg/ml versus 65; P less than 0.001). The follicular-phase LH levels of smokers were skewed downward from the levels in nonsmokers, presumably by negative feedback from the elevated estradiol and progesterone levels; the difference was significant (P less than 0.001). The elevations of serum progesterone and estradiol in smokers probably represent activation of adrenocortical secretion by smoking. The greater and more clear-cut rise of progesterone than of estradiol is probably due to the fact that essentially all of the follicular-phase serum progesterone is secreted by the adrenal, while only part of the follicular-phase serum estradiol comes from the adrenal (via androstenedione and estrone).     

Patterns of estrogen and progesterone receptors in monkey endometrium during the normal menstrual cycle

Total concentrations of estradiol-17β (E₂) and progesterone (P) receptors (R) were measured in the endometrium of rhesus monkeys ($\text{Macaca mulatta}$) during the normal menstrual cycle. The endometrium was collected at abdominal fundal hysterotomy on days 8, 12, 15, 18 and 24 of the menstrual cycle. Visual inspection of the ovaries and measurement of E₂, P, follicle stimulating hormone (FSH) and luteinizing hormone (LH) provided assuredness of normal ovarian function. Exchange procedures were used in order to measure the total concentrations of E₂R and PR in nuclear and cytosol fractions. The pattern of estrogen receptor showed a slight increase in the cytosol and nuclear concentrations at the preovulatory interval. Later, the total E₂R concentration was decreased when P increased during the luteal phase. Cytosol PR synthesis was parallel to the serum E₂ increase during the late follicular phase. Secretion of P by the corpus luteum was accompanied by a rapid nuclear translocation and concomitant decrease in cytoplasmic PR. Thereafter the total PR concentration declined during the second half of the luteal phase. These findings in monkey endometrium are similar to those reported for human endometrium during the normal menstrual cycle and further establish the utility of these surrogate primates in investigations indicative of human endometrial function.     

Twenty-four-hour secretory patterns of cortisol,progesterone and estradiol in heifers during the follicular and luteal phases of the ovarian cycle

Daily variations of plasma cortisol, progesterone and estradiol concentrations were measured by radioimmunoassay in six different normally cycling heifers during estrus (day 1 of the cycle) and diestrus (days 12–15 of the cycle). Each animal was fitted with an indwelling jugular catheter, and blood was withdrawn at 30-min intervals over a 24-h period. Statistical evaluation of the hormonal profiles using time series analysis revealed that all three steroids are secreted episodically with secretory episodes varying in number, magnitude and timing among different heifers. After dividing the 24-h into three 8-h time periods (I, 09.00–17.00 h; II. 17.00–01.00h; III, 01.00–09.00 h) a prominent circadian rhythm was found for cortisol during estrus and diestrus. Diurnal periodicity similar to that of cortisol was noticed for plasma progesterone during estrus but not diestrus when a functional corpus luteum was present. Estradiol secretion during the follicular and luteal phase of the estrous cycle was characterized by intermittent sustained elevations lasting about 9–15 h and marked by a graded rise and fall of hormone levels unrelated to photoperiod.From our results obtained in cycling heifers we conclude the following: (1) Plasma cortisol exhibits a distinct circadian rhythm during estrus and diestrus which is highly correlated with the light–dark cycle. (2) Plasma progesterone during estrus demonstrates a diurnal pattern which is absent in diestrous heifers bearing a corpus luteum. (3) Plasma estradiol lacks circadian rhythmicity but shows a distinct pattern different from that of progesterone, indicating that both steroids are secreted independently and not controlled by a circadian pacemaker.     

Asymmetry and the menstrual cycle in women

Fluctuating asymmetry (FA) is small random deviations from perfect bilateral symmetry that are thought to accumulate during development. FA is therefore a measure of one component of fitness, that is, developmental stability. This work is not concerned with permanent between-individual differences in asymmetries but rather with temporary within-individual changes in asymmetry that are related to the menstrual cycle (cyclical asymmetry, CA). We present evidence from studies of non-sexually selected traits (ear and digit size) and a sexually selected trait (breast size) that, in characters made up wholly or in part of soft tissue, CA varies across the menstrual cycle in women. It is highest at the beginning and end of the cycle, when women are generally infertile, and low in mid-cycle, when fertility is highest. Furthermore in mid-cycle there is an indication of a transitory (24-hour) increase in CA followed by a substantial decrease, which may indicate ovulation. Temporal changes in CA could therefore be used by males to indicate a female's position in the cycle. We discuss these findings in relation to (1) our understanding of the evolution of human mating systems, (2) the practical implications of these data in the treatment of infertility and to facilitate contraception, and (3) their relevance to exercise and dieting as a means to minimize across-cycle increases in asymmetry.     

Level of estradiol and progesterone in blood serum during the menstrual cycle in woman with acute hepatitis b]

The study was aimed at the determination of blood serum levels of the ovarian hormones (estradiol and progesterone) in women during the first menstrual cycle occurring in the course of hospitalization because of the acute viral hepatitis of type B, and in the same women during the first menstrual cycle occurring in the course of early convalescence after leaving the hospital. The observed group consisted of 20 women of age between 18 and 35 years treated because of acute hepatitis without coexisting diseases including gynecological ailments. All the women had a regular 28-day menstrual cycle. Twenty healthy women served as a control group. The blood serum concentrations of estradiol and progesterone were determined in all the subjects on 6-th, 12-th, 14-th, 18-th and 22-nd day of the menstrual cycle by RIA method using the ready made reagent kits. A significant decrease in the mean value of estradiol was found in the group of sick women as compared to the control group and to the same group of women in the course of early convalescence. On the other hand the value obtained during the first menstrual cycle after discharge from the hospital did not differ from that observed in healthy women. Mean value of blood serum progesterone concentration was higher in sick women than those in the control group and in the same women during convalescence all the time except on the 22-nd day of the cycle. These values did not differ significantly when comparing the group of sick women during convalescence and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma estradiol, progesterone and LH level in the menstrual cycle of the adult female Japanese monkey during the mating season

Adult 15 female Japanese monkeys showing regular menstrual cycles were subjected to the daily blood sampling for the measurement of estradiol (E2), progesterone (P) and biological LH in the mating season. Monkeys were maintained under controlled conditions in a standardized environment. Of the 35 cycles observed, 18 (51.4%) were estimated as anovulatory cycles and 17 (48.6%) were ovulatory cycles. The anovulatory cycles were classified into three types according to the peak level of E2 (Type I: E2 less than 50 pg/ml 3 cycles, Type II: E2 less than 170 pg/ml 7 cycles, Type III: E2 greater than 170 pg/ml 8 cycles). The ovulatory cycles were classified into two Types according to the peak level of P (Type IV: P less than 5.0 ng/ml 5 cycles, Tyep V: P greater than 5.0 ng/ml 12 cycles). The menstrual cycle was 27.5 +/- 7.8 days. The differences between mid cycle LH surge and P level in Type IV and in Type V were statistically significant. It was revealed that female Japanese monkeys kept under controlled condition in the mating season showed high incidence of various types of anovulatory cycles and that the ovulatory cycles with low P elevation in the mid luteal phase showed low LH and P secretions on the mid cycle date.     

The distribution of oestrogen and progesterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle

The distribution of oestrogen and progresterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle was investigated by means of an immunocytochemical technique. A cyclic pattern of receptor distribution was observed. The highest concentration of hormone receptors was observed in the basal layer, in accordance with the idea that this layer is the source of endometrial regeneration.     

利用尿液中的雌二醇、孕酮含量监测雌性川金丝猴的月经周期和妊娠

During two consecutive mating seasons from August 2001 to December 2002, we observed the sexual behavior of Sichuan golden monkeys in the Chengdu Zoo and the Shanghai Wild Animal Park. We collected urine samples from females in the early morning. We also measured urinary estradiol and progesterone levels using radioimmunoassay. Based on the estradiol concentration during the menstrual cycle, we discovered that the length of the menstrual cycle was 286.33 1.67 days. The length of pregnancy was about 200 days. The level of estradiol after impregnation was significantly different with the level during the ,same period in the non-receptive part of the cycle. Thus we could diagnose early pregnancy in female Sichuan golden monkeys by checking their urinary estradiol level .     

Radioimmunoassay of plasma and salivary progesterone during the menstrual cycle

We have developed specific and sensitive radioimmunoassays for progesterone in saliva (SP4) easily applicable in routine practice to assess ovarian function. One of them uses [³H]progesterone, the other 3-CMO-[¹²⁵I]histamin as tracer. The reliability criteria of both techniques have been controlled and the results obtained with the two methods in 50 saliva samples are correlated well. Our clinical study has been chiefly done with [³H]progesterone. In the present study we reported the values obtained daily during the greatest part of the menstrual cycle in 14 normal cases and they are in agreement with previous reports. The use of [¹²⁵I]tracer, by increasing the sensitivity of the RIA and shortening the duration of the assay, improves the use of SP4 as a practical non-invasive sampling alternative for many clinical situations involving evaluation of the ovarian function.     

Determination of plasma progesterone using thin layer chromatography during pregnancy and normal menstrual cycle]

Plasma progesterone levels were measured during pregnancy and the normal human menstrual cycle by thin-layer densitometry of a specific fluorescence reaction for delta4-3-ketosteroids. 94 determinations were carried out from the 7th week of pregnancy until term. 84 plasma progesterone concentrations were estimated between day 16 and day 26 and other 10 during the preovulatory phase of the normal menstrual cycle.     

The effects of estrogen and progesterone on blood glutamate levels: evidence from changes of blood glutamate levels during the menstrual cycle in women

The gonadal steroids estrogen and progesterone have been shown to have neuroprotective properties against various neurodegenerative conditions. Excessive concentrations of glutamate have been found to exert neurotoxic properties. We hypothesize that estrogen and progesterone provide neuroprotection by the autoregulation of blood and brain glutamate levels. Venous blood samples (10 ml) were taken from 31 men and 45 women to determine blood glutamate, estrogen, progesterone, glucose, glutamate-pyruvate transaminase (GPT), and glutamate-oxaloacetate transaminase (GOT) levels, collected on Days 1, 7, 12, and 21 of the female participants' menstrual cycle. Blood glutamate concentrations were higher in men than in women at the start of menstruation (P < 0.05). Blood glutamate levels in women decreased significantly on Days 7 (P < 0.01), 12 (P < 0.001), and 21 (P < 0.001) in comparison with blood glutamate levels on Day 1. There was a significant decrease in blood glutamate levels on Days 12 (P < 0.001) and 21 (P < 0.001) in comparison with blood glutamate levels on Day 7. Furthermore, there was an increase in blood glutamate levels on Day 21 compared with Day 12 (P < 0.05). In women, there were elevated levels of estrogen on Days 7 (P < 0.05), 12, and 21 (P < 0.001), and elevated levels of progesterone on Days 12 and 21 (P < 0.001). There were no differences between men and women with respect to blood glucose concentrations. Concentrations of GOT (P < 0.05) and GPT (P < 0.001) were significantly higher in men than in women during the entire cycle. The results of this study demonstrate that blood glutamate levels are inversely correlated to levels of plasma estrogen and progesterone.     

Effects of testosterone, estradiol, aromatase inhibitor, gonadotropin and prolactin on the response of mouse testes to acute gonadotropin stimulation

These studies determined the local acute responsiveness of the testis to intratesticular administration of human chorionic gonadotropin (hCG) under basal, stimulated (systemic hCG pre-treated), hypogonadotropic (steroid pre-treatment) and hyperprolactinemic conditions in male mice. In addition, testicular testosterone (T) levels were determined after intratesticular administration of the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) or progesterone under basal or hCG-stimulated conditions. Intratesticular administration of 0.025, 0.25, 2.5 or 25 mIU hCG resulted in a dose-dependent (3- to 14-fold) increase in testicular T concentrations in hCG compared to vehicle-injected testes. Systemic (i.p.) pre-treatment with 5 IU hCG 24 h before prevented any further increases in the already elevated (10-fold basal) T levels after direct intratesticular hCG injection. Pretreatment with 250 micrograms testosterone propionate (TP) reduced basal testicular T concentrations, but resulted in increased responsiveness to intratesticular hCG administration. In contrast, estradiol benzoate (EB) pretreatment, which also reduced basal testicular T concentrations, did not affect the testicular responsiveness to hCG. Hyperprolactinemia reduced testicular responsiveness to intratesticular administration of 0.025, 0.25 or 2.5 mIU hCG, but basal levels of testicular T were elevated. One hour after intratesticular injections of an aromatase inhibitor, 4-OHA; (0.25 micrograms) testis, T levels were increased in males pre-treated with 5 IU hCG (i.p.) 24 h earlier. Higher doses of 4-OHA (2.5, 25 or 250 micrograms) resulted in significant, dose-related increases in basal testicular T levels which were attenuated by hCG-pre-treatment. Intratesticular administration of 20 micrograms progesterone increased testicular T concentrations 2.7-fold, but this effect was attenuated (1.5-fold) in hCG-pre-treated mice, suggesting that enzymatic lesions beyond progesterone may be involved in hCG-induced testicular desensitization. These results indicate that testicular responsiveness to hCG depends on the existing levels of gonadotropic stimulation. However, it is evident that estrogens and prolactin also influence the sensitivity of the testis to gonadotropin.     

Integration of the effects of estradiol and progesterone in the modulation of gonadotropin secretion

Estradiol secreted by the maturing follicle is the primary trigger for the surge of gonadotropins leading to ovulation. Progesterone has stimulatory or inhibitory actions on this estrogen-induced gonadotropin surge depending upon the time and dose of administration. The administration of progesterone to immature ovariectomized rats primed with a low dose of estradiol induced a well-defined LH surge and prolonged FSH release, a pattern similar to the proestrus surge of gonadotropins. A physiological role of progesterone is indicated in the normal ovulatory process because a single injection of the progesterone antagonist RU 486 on the day of proestrus in the adult cycling rat and on the day of the gonadotropin surge in the pregnant mare's serum gonadotropin stimulated immature rat resulted in an attenuated gonadotropin surge and reduced the number of ova per ovulating rat. Progesterone administration brought about a rapid LHRH release and an decrease in nuclear accumulation of estrogen receptors in the anterior pituitary but not the hypothalamus. The progesterone effect was demonstrated in vitro in the uterus and anterior pituitary and appears to be confined to occupied estradiol nuclear receptors. In in vivo experiments the progesterone effect on estradiol nuclear receptors appeared to be of approximately 2-h duration, which coincided with the time period of progesterone nuclear receptor accumulation after a single injection of progesterone. During the period of progesterone effects on nuclear estrogen receptors, the ability of estrogens to induce progesterone receptors was impaired. Based on the above results, a model is proposed for the stimulatory and inhibitory effects of progesterone on gonadotropin secretion.