STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE

1977 ◽  
Vol 86 (3) ◽  
pp. 608-620 ◽  
Author(s):  
B.-M. Landgren ◽  
S. Campo ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT The variation of the plasma levels of 11 steroids and LH was investigated in 6 normally menstruating women during the peri-menstrual period. Blood was withdrawn continuously over a period of 42 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The changes in hormone levels were studied during 14 3-h sampling periods (42 h) which - with respect to the clock time - were identical in all subjects. Cortisol, 17-hydroxypregnenolone and dehydroepiandrosterone exhibited a marked circadian rhythm with the highest mean levels in the morning between 06.00 and 09.00 h and the lowest mean levels during the night between 21.00 and 03.00 h. The amplitude of the variation was high, the differences between the highest and lowest values being 200, 590 and 150%, respectively. Also the coincidence of individual peak values with the average peaks was high (mostly in 5 out of 6 cases). The correlation of cortisol levels with those of 17-hydroxypregnenolone and dehydroepiandrosterone was significant (r = 0.79 and 0.59, respectively; P < 0.001). The circadian variation of 17-hydroxyprogesterone, androstenedione and pregnenolone was also significant, but less pronounced, as indicated by lower amplitudes and larger spread of individual peaks around average peaks. The correlation of the levels of these steroids with those of cortisol was significant (r=0.47 P<0.001; r=0.44 P<0.001 and r=0.31: P<0.01, respectively). Progesterone, 20α-dihydroprogesterone, testosterone and oestradiol did not exhibit any circadian variation, but a steady decrease of levels. The levels of the first two steroids were significantly correlated (r = 0.81; P < 0.001). The dihydrotestosterone and LH levels did not show any significant changes during the entire study. If, however, only the second half of the sampling time was statistically analysed, a significant increase was found in the LH levels. During this time the LH levels were negatively correlated with the decreasing levels of progesterone and 20α-dihydroprogesterone (r=−0.59 and −0.66, respectively; P < 0.001). A comparison of the data with those of a previous study performed during the peri-ovulatory period suggests that the occurrence, intensity and regularity of the circadian rhythm varies according to different phases of the menstrual cycle. The data also suggest that 17-hydroxypregnenolone in plasma is an excellent indicator of adrenocortical activity.

1976 ◽  
Vol 82 (3) ◽  
pp. 600-616 ◽  
Author(s):  
A.-R. Aedo ◽  
B.-M. Landgren ◽  
Z. Cekan ◽  
E. Diczfalusy

ABSTRACT Plasma levels of 20α-dihydroprogesterone, 17-hydroxyprogesterone and 17-hydroxypregnenolone were assayed daily in 15 normally menstruating women during a complete menstrual cycle. In order to ascertain the normalcy of the cycles studied, LH, progesterone and oestradiol were also determined daily. The pattern of 20α-dihydroprogesterone was very similar to that of progesterone. The levels found during the proliferative phase (around 240 pg/ml) increased significantly on the day of the LH-surge and reached values of approximately 3.7 ng/ml at the peak period of luteal activity. The plasma levels of 17-hydroxyprogesterone in the proliferative phase were around 380 pg/ml. The first significant increase occurred one day before the LH-surge and was followed by a sharp peak (approximately 1.5 ng/ml) which coincided with the LH peak. A significant decrease occurred after this first peak, which reached a nadir two days after the LH-surge. This was followed by a second rise with a rather broad peak (about 1.8 ng/ml) around the 5th to 7th days after the LH-surge. The levels of 17-hydroxypregnenolone did not show any cyclic variation: from all figures a geometric mean value of 1.62 ng/ml was calculated with tolerance limits at 0.241 and 10.8 ng/ml. Individual day-to-day changes in steroid levels were assessed with regard to their potential for the early identification of the day of the LH-surge. A 17-hydroxyprogesterone value of 1.0 ng/ml, or more, was seen for the first time in the cycle on the day of the LH peak in 13 cycles and a progesterone + 17-hydroxyprogesterone level of at least 1.8 ng/ml in 14 of the 15 cycles studied. These data seem to warrant a study of the predictive value of progesterone and 17-hydroxyprogesterone assays in a much larger population.


1977 ◽  
Vol 84 (2) ◽  
pp. 320-332 ◽  
Author(s):  
A. R. Aedo ◽  
M. Nuñez ◽  
B.-M. Landgren ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT Circadian variations of the plasma levels of dehydroepiandrosterone, 17-hydroxypregnenolone, pregnenolone and testosterone were investigated by radioimmunoassay in 10 normally menstruating women during the periovulatory period. In seven of the subjects it was also possible to estimate androstenedione and dihydrotestosterone levels. Blood was withdrawn continuously over a period of 48 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The circadian rhythm was studied during 13 3-hour sampling periods (39 h) which were identical in all subjects. Dehydroepiandrosterone, 17-hydroxypregnenolone and pregnenolone showed a marked circadian rhythm with highest mean levels in the morning between 06.00 and 09.00 h and lowest mean levels during the night between 21.00 and 24.00 h. The peak levels of individual subjects coincided completely with the highest mean levels in the case of dehydroepiandrosterone, in 9 out of 10 cases with regard to 17-hydroxypregnenolone and in 8 of 10 cases as far as pregnenolone levels were concerned. The lowest individual levels were more dispersed around the means than were the individual peaks. The difference between the highest (morning hours: 06.00–09.00) and lowest (evening hours: 21.00–24.00) geometeric mean values was 404% for 17-hydroxypregnenolone, 163 % for dehydroepiandrosterone and 71 % for pregnenolone. The mean testosterone levels also exhibited an elevation between 06.00 and 09.00 h which was significant (P < 0.05). However, the individual peak values were scattered from 21.00 h of the first day to 18.00 h of the second day. The mean concentrations of androstenedione showed a significant increase between 06.00 and 18.00 h. The individual peaks were widely dispersed. Hence a uniform circadian rhythm correlated to the levels of the Δl5-steroids mentioned above could not be demonstrated in the case of testosterone and androstenedione. An analysis of variance indicated no significant differences between sampling periods as far as dihydrotestosterone levels were concerned. The extent and regularity of the circadian variation in the plasma levels of the Δl5-steroids studied makes it mandatory to standardize very carefully the exact time of blood withdrawal in any longitudinal study. In view of the sharp changes in the plasma levels during the morning hours, it is suggested that sampling during the afternoon period may provide more constant values.


1977 ◽  
Vol 84 (3) ◽  
pp. 620-632 ◽  
Author(s):  
B.-M. Landgren ◽  
A.-R. Aedo ◽  
M. Nuñez ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT By the use of a non-thrombogenic pump, blood was withdrawn continuously at a rate of 4.0 ml/h over a period of 48 h from 10 normally menstruating women during various phases of the peri-ovulatory period and the integrated levels of oestradiol, oestrone, 17-hydroxyprogesterone, progesterone, 20α-dihydroprogesterone and biologically active luteinizing hormone (LH) were estimated in 3-hourly plasma collections. The first significant change detected two days prior to the LH surge (day LH-2) in one subject studied during this period was a continuous parallel rise in oestradiol and oestrone levels, which occurred in the absence of any simultaneous change in LH and 17-hydroxyprogesterone levels. Marked fluctuations followed by a sudden drop in oestradiol levels were observed in another woman during the day preceding the LH peak (day LH-1). These changes were not associated with similar alterations in oestrone levels. The marked drop in oestradiol coincided with the beginning of a simultaneous major rise in LH and 17-hydroxyprogesterone levels followed some 6 to 9 h later by a small but significant increase in progesterone levels. The period of the LH surge (day LH) was studied in 3 women. This period was characterised by a constant decline in oestradiol levels in the presence of unchanged oestrone values. The decrease in oestradiol levels preceded the LH peak by at least 12 h. The LH peak was biphasic in all subjects; both the ascending and descending limbs of it were significantly correlated to similarly changing levels of 17-hydroxyprogesterone. The increase in these two hormones preceded that in progesterone levels, which occurred later, at the time of the steepest rise in LH levels. The findings of the subsequent day (day LH+1) were characterised in two subjects by a parallel decrease in plasma oestradiol, LH and 17-hydroxyprogesterone levels, until a plateau was reached. This plateau coincided with a new rise in progesterone and 20α-dihydroprogesterone levels. The hormonal profile observed two days following the LH surge (day LH + 2) in 3 women was similar to that of the preceding day, with the exception of a beginning new rise in 17-hydroxyprogesterone levels by the end of day LH + 2. This second rise in 17-hydroxyprogesterone paralleled that in progesterone and 20α-dihydroprogesterone levels and occurred in the presence of decreasing levels of LH. The data reported strongly suggest that different control mechanisms are involved in the regulation of ovarian steroid secretion during the various phases of the peri-ovulatory period.


1977 ◽  
Vol 86 (3) ◽  
pp. 621-633 ◽  
Author(s):  
M. Nuñez ◽  
A.-R. Aedo ◽  
B.-M. Landgren ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT The plasma levels of oestrone sulphate, oestradiol sulphate, oestrone and oestradiol were studied in samples collected daily from 8 normally menstruating women throughout a complete menstrual cycle. In order to ascertain the normality of the cycles studied, LH and progesterone were also determined daily. All compounds were measured by radioimmunoassay, the sulphates after solvolysis. For the determination of the sulphates a procedure was developed which fulfilled the recognized criteria of reliability. Both oestrone sulphate and oestradiol sulphate displayed a marked cyclic pattern, similar to and correlated with that of oestrone and oestradiol, i. e., all 4 oestrogens exhibited a marked mid-cycle peak and elevated levels during the luteal phase. The mean levels of the steroid moiety of oestrone sulphate were 10–15 times higher than those of oestrone, and 2–3 times higher than those of the 3 other oestrogens together. On the other hand, the mean levels of oestradiol sulphate were 1.2 to 4 times lower than those of oestradiol. The ratios of the levels of various pairs of oestrogens were calculated. All pairs showed a considerable change of ratios from the early follicular phase to mid-cycle. This demonstrates that the mutual metabolic equilibria of oestrogens are different in various phases of the cycle. Daily measurements of oestrone sulphate and oestradiol sulphate do not seem to provide a better index to predict the day of ovulation than the characteristic changes in progesterone and 17-hydroxyprogesterone levels.


1989 ◽  
Vol 120 (5) ◽  
pp. 649-654 ◽  
Author(s):  
D. Ghosh ◽  
Jayasree Sengupta

Abstract. To obtain an understanding of the sex steroid hormonal milieu during early gestation, the concentrations of estradiol-17β and progesterone were measured in endometria and reproductive tract luminal fluids collected during the post-ovulatory period (days 2 to 6) of conception, and of non-mated menstrual cycles of the rhesus monkey (Macaca mulatta). Estradiol content was found to be higher (P< 0.05) in endometria obtained from conception cycles; day-wise analysis revealed higher (P< 0.05) level of tissue estradiol concentration on day 6 of post-ovulation as compared with the normal menstrual cycle. Endometrial progesterone content remained, however, unaltered in both groups of monkeys and thus relatively lower (P< 0.05) endometrial progesterone to estradiol ratios were seen on days 4, 5 and 6 of gestation compared with normal menstrual cycle. There were no significant changes in the profiles and concentrations of estradiol and progesterone in luminal washings. The typical sex steroid hormonal milieu observed in the endometrium during the peri-implantation stage of gestation in conception cycle may be related to the endometrial differentiation towards implantation in the rhesus monkey.


1964 ◽  
Vol 47 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Reiner Svendsen ◽  
Børge Sorensen

ABSTRACT By a double isotope derivative technique, the content of »free« oestrone and 17β-oestradiol was determined in plasma from normally menstruating women. Through the cycle the concentration of the two hormones was found to range from 0.1–0.3 μg/l, substantially higher values being found only in the middle third of the cycle. Daily determinations around the time of ovulation in a few women showed a short-lasting increase up to 1 μg/l. This increase appears to precede ovulation, and the authors advance the idea that this increase is a contributory cause of ovulation.


1966 ◽  
Vol 52 (1) ◽  
pp. 130-148 ◽  
Author(s):  
P. Bauer-Sič

ABSTRACT For the determination of alcaline phosphatase of leucocytes (ALP) blood smears from 5 menstruating women, 2 pregnant women, 1 postmenopausal woman, and 3 men were examined daily during some cycles or for a period of several months. In contrast to the males and the postmenopausal woman, the women with a regular menstrual cycle show a significant increase in ALP starting approximately at the 15th day after the onset of the menstruation bleeding and lasting for 3–5 days. The maximum level corresponded to the time of ovulation. Furthermore there was a good correlation between the ALP-values with the known amounts of oestrogens excreted during a normal menstrual cycle. Therefore the cytochemical determination of ALP provides a rapid additional method for testing the ovarial function when carried out daily. When the single ALP determination is done, like in routine clinical analysis, consideration should be given to the day of the cycle when the sample was taken.


1978 ◽  
Vol 77 (3) ◽  
pp. 361-371 ◽  
Author(s):  
J. B. MAATHUIS ◽  
R. W. KELLY

The concentrations of prostaglandins F2α (PGF) and E2 (PGE) were measured by gas chromatography–mass spectrometry in endometrial tissue obtained from 45 normal women at various stages of the menstrual cycle. During the proliferative stages, the concentration of PGF in the endometrium was correlated with the concentration of oestradiol in the plasma. The concentration of PGF during the mid-secretory stage (mean, 2·047, range, 0·549–4·344 μg/g fresh endometrial tissue) was significantly higher than the concentrations during the late proliferative and late secretory stages. The endometrial concentration of PGE did not show a cyclic variation. The concentrations of PGF and PGE in samples of endometrium collected after the administration of clomiphene were significantly lower than the concentrations observed in endometrial tissue obtained from normally menstruating women in the mid-proliferative period. The administration of an oestrogen–progestogen pill resulted in higher endometrial concentrations of PGE than were measured in the mid-secretory phase. The concentrations of PGF and PGE in decidual tissue (conceptual age 3–10 weeks) were lower than those measured at any stage of the normal menstrual cycle. During the human menstrual cycle, high levels of oestradiol and progesterone are related to high endometrial levels of PGF but not PGE. The presence of a conceptus apparently blocks the effect of high concentrations of ovarian steroids on the synthesis or catabolism of prostaglandins.


1976 ◽  
Vol 81 (1) ◽  
pp. 133-149 ◽  
Author(s):  
R. Guerrero ◽  
T. Aso ◽  
P. F. Brenner ◽  
Z. Cekan ◽  
B.-M. Landgren ◽  
...  

ABSTRACT In an attempt to analyze the multiple changes and interactions in circulating steroid levels in the peri-ovulatory and peri-menstrual periods, the plasma levels of immunoreactive luteinizing hormone (LH), progesterone and unconjugated pregnenolone, dehydroepiandrosterone, testosterone, oestradiol and oestrone were assayed daily during a complete cycle in 17 normally menstruating women. In 14 of the 17 subjects studied androstenedione and unconjugated dihydrotestosterone were also estimated. The day of the LH-peak and the first day of menstruation, respectively, were used to synchronize the peri-ovulatory and peri-menstrual plasma levels of the various steroids. With the exception of dehydroepiandrosterone and dihydrotestosterone, the plasma levels of all steroids exhibited significant, but different changes during the cycle. Testosterone levels showed a slight but significant increase around the LH-peak, whereas the levels of pregnenolone and androstenedione were higher in the post-ovulatory than in the pre-ovulatory periods. The levels of oestradiol and oestrone, as well as the ratios of oestradiol to oestrone gradually increased from the low values observed in the early proliferative phase to pre-ovulatory peak values. The relationship between peaks of oestradiol and oestrone and that of LH exhibited great individual variation. The same was true for the individual oestradiol to oestrone ratios. The combination of several steroidal signals did not improve the predictive value of the analyses. However, an increase of individual progesterone values by at least 0.35 ng/ml from the day preceding the LH-peak to the day of the LH-peak was observed in 13 of the 17 subjects. It is suggested that for the early detection of the LH surge and prediction of the subsequent ovulation daily assays of plasma progesterone are of more value than the assay of the other steroids investigated.


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