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Biomedical subjects

E Diczfalusy

Publications and source records attributed to E Diczfalusy.

At least 91 records · Page 5Linked to original sources
PubMed1982

Pharmacokinetic and pharmacodynamic investigations with vaginal devices releasing levonorgestrel at a constant, near zero order rate.

The pharmacokinetic and pharmacodynamic effects of vaginal devices releasing levonorgestrel (L-NOG) at a constant rate (in vitro release: approximately 20 micrograms/day) were studied in a group of 20 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn two or three times (in the great majority of subjects, on Mondays, Wednesdays and Fridays) during a pretreatment (control) cycle, during 90 days of exposure and during the first week following the removal of the device, and the levels of L-NOG, estradiol and progesterone were analyzed by radioimmunoassay techniques. In 8 of these subjects, endometrial biopsies were also taken during days 23 to 25 of the control cycle, and then 6 and 10 weeks following the insertion of the devices. In addition, the initial absorption rate and removal half-life of L-NOG were assessed in 7 subjects using the devices for a period of 8 days only. Following insertion of the devices, the levels of L-NOG rose very rapidly, and reached the final "plateau" in some 30 minutes' time. This was followed by a limited period of "burst" with doubling the levels for a few hours, after which the levels remained stable and diminished very slowly in a linear fashion with an average decline of 23-26% during 90 days, corresponding to a daily decrease of 0.2 to 0.3 per cent. The removal half-life (first compartment) after 90 days of exposure in 19 subjects was 16.1 (13.7-18.6) hours. Sixty-nine treatment segments of 30 days were studied with frequent hormone assays; of these, 20 (or 29%) were anovulatory, 13 (19%) exhibited inadequate luteal function, and 32 (52%) had normal ovulatory-like cycles. All endometrial biopsies obtained during the pretreatment cycle were normal secretory; of the 16 biopsies obtained during treatment, 4 were suppressed, 2 proliferative, 6 secretory, and 4 could not be dated because of bleeding. An assessment of the bleeding profiles during exposure to L-NOG revealed almost a doubling of the number of days with bleeding and spotting (35% compared to 18% during the pretreatment cycle). However, significantly more frequent bleeding was found in the 20 anovulatory segments (37.3%) than in the 36 normal ovulatory-like ones (27.7%). It is concluded that differences in the frequency of bleeding and spotting with low-dose progestogens may reflect differences in the frequency of ovulation inhibition just as much as differences in the hormonal profiles of the compounds administered.

Adult↗
PubMed1982

Morphometric analysis of the human endometrium in relation to peripheral hormone levels.

Twelve indices were quantitated at three sites in 68 endometrial biopsies from 14 women in five cycles each in which daily plasma levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P) were measured. It was found that a single biopsy specimen is representative of the entire endometrium. Using classic dating, 59% of the biopsies were correct. The error rate increased with the distance from the LH surge. The morphometric indices revealed significant differences am ong all 48-hour secretory phase periods except days LH + 7 to LH + 10. The glandular diameter was positively correlated with proliferative phase E2 levels and with secretory phase P levels; the latter were negatively correlated with stromal mitoses. Basal vacuoles were negatively correlated with E2 and positively with P levels.

Adult↗
PubMed1982

Intratesticular and plasma steroid profiles in fertile and infertile men.

In 24 apparently healthy men who requested sterilization by vasectomy, we have measured the intratesticular and peripheral plasma levels of 9 unconjugated and 5 sulphoconjugated steroids. These steroid levels were then compared with those found in a group of 18 men, admitted to the hospital with complaints of infertility. With the exception of higher dihydrotestosterone levels in the infertile group, no differences were found between the two groups with regard to the peripheral plasma levels of the unconjugated or sulphoconjugated steroids studied. On the other hand, the intratesticular levels of cortisol, pregnenolone, androstenedione, dihydrotestosterone, pregnenolone sulphate and testosterone sulphate (but not those of testosterone) were significantly diminished in the infertile group. With the exception of dehydroepiandrosterone levels in the fertile group, and dehydroepiandrosterone sulphate and dihydrotestosterone sulphate in the infertile group, the intratesticular steroid levels were uncorrelated with the plasma levels. The data are interpreted as suggesting that a) male infertility may be associated with intratesticular alterations of steroid metabolism which are not reflected by the peripheral steroid levels; b) the plasma and intratesticular levels of testosterone are not sensitive enough indices for the endocrine evaluation of male infertility; c) the role of the sulphoconjugated forms of steroids in the maintenance of male fertility deserves further investigation.

Adult↗
PubMed1982

Improved in vitro bioassay of follitropin.

The FSH-dependent aromatase activity of Sertoli cell enriched cultures of testicular cells from immature rats was utilized as a sensitive and specific in vitro bioassay for FSH activity. The conversion of 19-hydroxyandrostenedione to estradiol was used as the end point of the assay. By the introduction of a phosphodiesterase inhibitor into the culture medium, the sensitivity was improved 5-10 times, so that 0.05 mIU of FSH showed a response significantly different from the blank. Other pituitary or placental hormones, such as hLH, hTSH and hCG exhibited less than 0.8% cross-reactivity, whereas hGH, hPRL, ACTH1-24, LH-RH, and prostaglandin E2 alpha did not show any cross-reaction at the doses tested.

Animals↗
PubMed1982

Gregory Pincus and steroidal contraception revisited.

The major milestone in physiology, chemistry and pharmacology which eventually resulted in the birth in steroidal contraception are discussed in the light of certain cultural, social and political changes, which have taken place over the past twenty years. The needs of some developing countries for a variety of improved, safe and inexpensive fertility regulating agents are considered against the background of the dramatically increased costs for the development of new fertility regulating drugs. It is suggested that an increased collaboration between the Pharmaceutical Industry and an International Public Sector Agency, such as the World Health Organization, might provide a suitable framework for the future development of new fertility regulating agents.

Animals↗
PubMed1981

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: II. A comparative assessment of the circadian variation in steroid and lutropin levels during the follicular, periovulatory and luteal phases.

In six normally menstruating women, ovarian and adrenal steroids and biologically active lutropin (LH) were measured in peripheral plasma samples collected every 3 h. during a period of 39 h. in the early follicular phase, periovulatory period or luteal phase of three consecutive cycles. The purpose of the study was to assess the influence of the phases of the cycle on the diurnal variation in the levels of different steroids and lutropin following the elimination of the between subject variation. Cortisol, 17-hydroxypregnenolone, dehydroepiandrosterone and androstenedione showed a marked circadian rhythm in all three phases of the cycle. No changes in the levels of cortisol, 17-hydroxypregnenolone and dehydroepiandrosterone with the phase of the cycle were observed when the "morning" samples were considered; however, when the "evening" samples were analyzed, the levels of these steroids were higher in the luteal phase than in the follicular phase. As a result of this increase, the amplitude of the circadian rhythm of these steroids considerably decreased in the luteal phase. The "morning" as well as the "evening" increase observed in the levels of androstenedione during the periovulatory period was not able to mask the circadian rhythm. A circadian rhythm in pregnenolone, 17-hydroxyprogesterone, testosterone, and dihydrotestosterone levels was detected only in certain phases of the cycle. All these steroids showed a circadian rhythm in the early follicular phase. The rhythm of pregnenolone and 17-hydroxyprogesterone was still present in the periovulatory period but was no longer detectable in the luteal phase, meanwhile that of testosterone and dihydrotestosterone was not demonstrable neither in the periovulatory period nor in the luteal phase. Compared to the levels of the follicular phase, an increase in pregnenolone and 17-hydroxyprogesterone levels was observed in the periovulatory period which was followed by a further rise in the luteal phase. This increase completely masked the circadian rhythm in the luteal phase. An inverse circadian rhythm in lutropin levels was detected during the luteal phase. The "morning" values were lower than those found during the "evening" period. No such changes were observed in the other phases of the cycle. In none of the phases studied did the levels of progesterone or estradiol show any circadian variation. The data indicate that a circadian rhythm in the peripheral levels of a given steroid mainly depends on the relative contributions of the ovaries and adrenals and that these contributions exhibit major differences at the various phases of the cycles. It is concluded that - in contradistinction to the situation in the human male - in normally menstruating women, the peripheral levels of steroids of predominantly gonadal origin do not exhibit a circadian rhythmicity.

Adrenal Glands↗
PubMed1981

Studies on ovarian and adrenal studies at different phases of the menstrual cycle. IV. The effect of dexamethasone suppression and subsequent ACTH stimulation at different phases of the menstrual cycle and following the administration of 150 mg of depot-medroxy-progesterone acetate (DMPA).

In an attempt to assess the effect of depot-medroxyprogesterone acetate (DMPA) on adrenal function, to peripheral levels of a variety of steroids were estimated after dexamethasone suppression and subsequent ACTH stimulation in 5 subjects. The steroid responses observed 16 and 54 days after a single injection of 150 mg of DMPA were compared with those obtained in the same women before DMPA treatment or with those found at different phases of the cycle in another group of 6 normally menstruating women. The levels of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione and dihydrotestosterone were significantly suppressed by dexamethasone and stimulated by ACTH in all phases of the cycle, and before and after DMPA administration. The extent of suppression or stimulation (expressed as a percentage) was different in case of different steroids, but was rather constant with regard to the same steroid. Hence, the functional capacity of the adrenal as reflected by the levels of these steroids. Dexamethasone administration did not exert any influence on the levels of progesterone and 17-hydroxyprogesterone during the different phases of the cycle; however, ACTH administration increased the levels of these two steroids in the follicular phase and also after DMPA treatment. The levels of estradiol and lutropin were not influenced by dexamethasone or ACTH at any of the occasions studied. It is concluded that the functional capacity of the adrenal cortex is constant during the various cycle phases and is not affected by the administration of a single dose of 150 mg of DMPA.

17-alpha-Hydroxypregnenolone↗
PubMed1981

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle. III. Steroid and lutropin levels before and after the administration of a single contraceptive dose of depot-medroxyprogesterone acetate (DMPA).

Ovarian and adrenal steroids and biologically active lutropin were measured in peripheral plasma samples obtained from 5 normally menstruating women. Plasma samples were collected every 3 h for a period of 39 hours in the periovulatory period of a pretreatment (control) cycle and then 16 and 54 days after a single i.m. injection of 150 mg of depot-medroxyprogesterone acetate (DMPA). Sixteen days after DMA administration, the levels of estradiol, progesterone, 17-hydroxyprogesterone, and lutropin were reduced to early follicular phase levels. No further decrease was found in 17-hydroxyprogesterone and lutropin levels; however an additional decrease occurred in the levels of estradiol and in the "morning" levels of progesterone 54 days after the administration of DMPA. Furthermore, the levels of pregnenolone, androstenedione, testosterone and dihydrotestosterone were significantly diminished in all samples collected after the administration of DMPA. Fifty-four days following the administration of DMPA, the levels of cortisol and 17-hydroxypregnenolone were significantly reduced. The administration of DMPA did not interfere with the circadian rhythm of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 17-hydroxyprogesterone, and androstenedione levels. A significant circadian rhythm was also found in testosterone (after 16 days) and lutropin (after 54 days) levels. No circadian variation was found in estradiol, progesterone and dihydrotestosterone levels.

Adrenal Glands↗
PubMed1981

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle. 1. Dynamic changes during the periovulatory period.

In order to assess the periovulatory interrelationships between the plasma levels of estradiol, estrone, 17-hydroxyprogesterone, progesterone, cortisol and biologically active lutropin (LH), peripheral blood samples withdrawn from 12 normally menstruating women at 07.00, 15.00 and 23.00 h. during seven days of the midcycle period were analyzed. The estradiol peak varied between 0.86 and 1.50 nmol/l; it preceded the LH peak in 11 subjects and occurred simultaneously with it in 1 case. Although the peak levels of estradiol were significantly higher than those associated with the LH peak, there was no significant difference between the estradiol levels at the LH peak and those found during the 32-hour period prior to the LH peak. Calculation of the estradiol to estrone ratios revealed the existence of two groups of subjects with significantly different ratios. In one group the estradiol levels were significantly lower and those of estrone significantly higher than in the other group. No difference was found between these two groups concerning the other hormonal indices measured. No significant variation was found in the estradiol, estrone and LH levels during the day; however, there was a significant overnight increase in their levels during 3 to 4 days preceding the day of the LH peak. A significant rise in 17-hydroxyprogesterone levels occurred 8 h. before the earliest rise in LH and progesterone levels; on the other hand, in none of the subjects did the first rise in progesterone levels precede the first significant elevation of LH levels.

Adrenal Glands↗
PubMed1981

A study of the short-time variation and interrelationship of plasma hormone levels reflecting pituitary, adrenocortical and testicular function in fertile men.

Using radioimmunoassay method, we have estimated the levels of cortisol (C), pregnenolone (delta 5P), 17-hydroxypregnenolone (17-OH-delta 5P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OH-P), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) in peripheral plasma samples collected at short-time (15 min) intervals from 10 fertile men, during two 4-h periods (06.00 to 10.00 and 18.00 to 22.00). In addition, the levels of biologically active luteinizing hormone (LH) were measured by an in vitro bioassay method in 9 of the subjects. The levels of all steroids studied exhibited diurnal variation with higher levels during the morning and lower levels during the evening period. The cortisol and the delta 5-steroid levels also exhibited individual short-term episodic spikes during the 2 periods. No short-term variation was observed in the levels of 17-OH-P, A, T and DHT. Statistically significant correlations were found between the levels of C and those of the delta 5-steroids and A in most of the subjects. No correlation was found between the above steroid levels and those of 17-OH-P, T and DHT. Also the LH levels exhibited episodic spikes of 60 to 90 min duration, but no diurnal variation. When the LH levels were related to those of T found in the same samples or in samples withdrawn 15 to 810 min afterwards, a significant positive correlation was found on repeated occasions in 5 of the 9 subjects. No systematic negative correlation was found when the T levels were related to those of LH in the same sequential fashion. Whereas the positive correlations found between LH and T levels in some of the subjects might suggest that physiological changes in peripheral LH levels are instrumental in regulating T-secretion, the rather consistent lack of significant negative correlation between T and LH levels seems to favour the view that the release of LH is not modulated by peripheral testosterone levels alone.

Adrenal Cortex Hormones↗