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Biomedical subjects

E Diczfalusy

Publications and source records attributed to E Diczfalusy.

At least 55 records · Page 3Linked to original sources
PubMed1987

The interaction between sex hormone binding globulin and levonorgestrel released from Norplant, an implantable contraceptive.

Two-hundred-and-eighty Indonesian women were provided with Norplant, a levonorgestrel-releasing implant. At various time intervals, up to 5 years after Norplant insertion, levonorgestrel and sex hormone binding globulin (SHBG) were assayed in blood plasma. After an initial burst of approximately 7 nmol/l, the levels of levonorgestrel rapidly decreased during the first month. The decrease continued to a nadir (1.1 nmol/l) which was reached 10 months later. The decrease was followed by an increase to a broad peak of 1.5 nmol/l which was reached 2 years after insertion. Thereafter, a slow-decrease at a rate of approximately 18 pmol/month was seen. SHBG levels decreased significantly already 1 week after insertion. A nadir of levels (25 nmol/l) was reached 3 months later. The levels increased slowly again and remained constant (32 nmol/l) from about 15 months to 5 years. During the entire period of study highly significant correlations of levonorgestrel with SHBG were seen. In another group of 25 women the levels of levonorgestrel and SHBG were studied before and one week after insertion of Norplant. A significant correlation (r = 0.77) was found between the preinsertion levels of SHBG and postinsertion levels of levonorgestrel.

Adult↗
PubMed1987

Endometrial morphology and peripheral hormone levels in women with regular menstrual cycles.

Endometrial biopsies from 90 women with regular menstrual cycles and a hormonal profile compatible with normal luteal function were morphometrically assessed using 11 different indices and the results were plotted in 48-hour periods around the day of the luteinizing hormone (LH) surge (LH +/- 0). The endometrial dating reached its highest significance from days LH -3/-2 to days LH +7/+8, when the changes occurred with a high degree of regularity regardless of the length of the preovulatory and postovulatory phases. It is proposed therefore that the dating of the endometrium should be related to the LH surge rather than to the "ideal" 28-day cycle. The results also seem to suggest the existence of a regulatory mechanism for the synchronization of follicular maturation and midcycle endometrial development. Further study of the factors involved in this mechanism may result in a better understanding of certain forms of unexplained infertility.

Adult↗
PubMed1986

Pituitary, ovarian and endometrial effects of graded doses of medroxyprogesterone acetate administered on cycle days 7 to 10.

Eighteen apparently healthy women with normal menstrual cycles were studied during a control cycle and then during a treatment cycle, in which graded doses (2.5, 5.0 and 10 mg/day) of medroxyprogesterone acetate (MPA) were administered orally on cycle days 7 to 10. In both the control and the treatment cycle peripheral blood was drawn daily for the assay of luteinizing hormone (LH), estradiol (E2) and progesterone (PROG) and an endometrial biopsy was taken on cycle day 11. The lowest dose of MPA (2.5 mg X 4) did not influence the various cycle characteristics. Administration of higher doses (5.0 or 10 mg X 4) resulted in a lengthening of the duration of E2-peak (P less than 0.05), an increase in the area under the E2-peak (P less than 0.05), a decrease in the area under the PROG-curve (P less than 0.05) and a reduction in the height of the LH-peak (P less than 0.05). Furthermore, in 5 of these 12 subjects there was no ovulatory-like PROG-pattern during the cycle in which MPA was administered for 4 days. Morphometric analysis of the endometrial biopsy specimens revealed that the administration of MPA increased the diameter of endometrial glands (P less than 0.01) and the number of vacuolated glandular cells (P less than 0.001), decreased the number of glandular (P less than 0.01) and stromal (P less than 0.05) mitoses and reduced pseudostratification (P less than 0.001). There was no change in the number of endometrial glands and in glandular epithelial height. No leukocytic infiltration was observed. Dating of the biopsies indicated that all control biopsies were proliferative and all, but one (a suppressed proliferation including predecidual reaction), biopsies obtained after MPA administration were early secretory. The most conspicuous effect of MPA administration was a marked increase in subnuclear vacuolation, which could be demonstrated even at the lowest dose (P less than 0.01).

Adult↗
PubMed1986

The prediction and/or detection of ovulation by means of urinary steroid assays.

Twenty normally menstruating women volunteered for a study in which plasma samples were collected daily during an entire menstrual cycle. On the same days, samples of morning urine were also collected, as well as random samples of urine voided at the visit to the Outpatient Clinic. Progesterone (P), estradiol (E2) and lutropin (LH) were assayed in plasma, and pregnanediol-3-glucuronide (PdG), estrone-glucuronide (E1G), estriol-16-glucuronide (E3G), P, and E2 were measured in urine using radioimmunoassays. Progesterone in urine was assayed both with and without preceding chromatography. All urinary glucuronides and progesterone exhibited cyclic patterns similar to those of E2 or P in plasma. Seven-fold increases from early follicular to luteal phase values (for PdG and urinary P; the latter both with and without chromatography), or to peak levels (for E1G and E3G) were observed. The difference between the baseline and peak levels was less distinct (approximately 5-fold) for E2 in urine. The day-to-day coefficient of variation of early follicular phase values decreased from 40% to 25% by calculating the ratios of the glucuronides or P to creatinine (C). The peaks of estrogen glucuronides were delayed mostly by 1 day in comparison to the peaks of E2 in plasma. The urinary peaks of estrogens were in most cases more closely clustered around the day of the LH-peak when the measurements were corrected for C. For the determination of the first significant rise of steroid levels in a cycle, the calculation of a sustained rise (leading to a significant cumulative sum - CUSUM) was found superior when compared to other recommended indices, such as a 50% increase over the mean of 3 preceding values, or the increase over the baseline level plus 2 standard deviations. Sustained rises were calculated for all indices studied (including the ratio of urinary E1G to PdG). The ratio of E1G to C in morning urine gave consistently the most compact distribution of sustained rises. It is concluded that daily measurements of urinary PdG (or P) and E1G (or, possibly, E2) could substitute the serial assays of P and E2 in peripheral blood in the retrospective assessment of the ovarian functionn. The day-to-day variation can be significantly reduced, if results are expressed per concentration of C. For the prediction of ovulation or fertile period, the best index of urinary steroids appears to be the sustained rise in the ratio of E1G to C. However, this "best" method is still not good enough in terms of overall reliability and practicability.

Adult↗
PubMed1986

Pharmacokinetic studies with a vaginal delivery system releasing levonorgestrel at a near zero order rate for one year.

Vaginal rings releasing approximately 20 micrograms levonorgestrel per 24 hours were used continuously by ten women for a period of one year. Circulating plasma levels of levonorgestrel (L-NOG) were measured every second week. Steroid hormone binding globulin (SHBG) levels were measured in the first and last four blood samples drawn. A linear relationship between the logarithms of L-NOG concentrations and duration of use was found, indicating an exponential character of decrease in L-NOG levels during the study year. An average of 72% of the mean initial levels of L-NOG was found in the circulation after 6 months' and 52% after one year's use. The L-NOG levels decreased daily by 1.1 pmol/l (0.13%) on the average. The SHBG levels were not influenced by the long-term exposure to L-NOG. The initial SHBG levels were significantly correlated (r = 0.88; P less than 0.001) to the initial L-NOG levels. The rings were well tolerated. Only in two of the ten subjects did the average number of bleeding days per month increase from a pretreatment value of 4.5 days per month to 8.3 and 9.5 days per month, respectively.

Administration, Intravaginal↗
PubMed1986

Molecular composition of luteinizing hormone and follicle-stimulating hormone in commercial gonadotropin preparations.

The biologic (B) and immunologic (I) properties of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in three commercial urinary gonadotropin preparations and in the first international standard preparation of human urinary gonadotropins before and after fractionation by isoelectrofocusing (IEF). Significant differences were found in the IEF profiles of both bioactive and immunoreactive LH and FSH and in the B/I ratios of the preparations studied. The observed differences in the molecular composition of LH and FSH seem to be attributable to the purification procedures employed. The possible influence of these differences on the in vivo potencies, circulating half-lives, and clinical effects of gonadotropin preparations are discussed.

Biological Assay↗
PubMed1986

Menopause, developing countries and the 21st century.

According to the independent projections of the United Nations Population Division and of the World Bank, the global population (presently: 4.7 billion) will continue to grow until the year 2100 or 2150, when it is expected to stabilize at an approximate level of 11 billion. Ninety-five per cent of this future growth will occur in developing countries, with an increasing number and proportion of women aged 45 and over; their number will exceed 700 million before the turn of the century. The past decade, or two, witnessed a dramatic increase in life expectancy at birth, especially in developing country women, but little, if any, information is available about the menopause in those countries. An urgent task of high priority is therefore to establish on a country-to-country basis the age distribution and sociocultural significance of the menopause and of the prevalence of various menopausal disorders, which to a huge extent will determine the health- and social service needs of individual developing countries. Furthermore, a rapid progress must be made in the diagnosis, prevention and treatment of osteoporosis, atherosclerotic cardiovascular disease, musculoskeletal disorders and senility. It is suggested that the establishment of a Special Programme of Research by the World Health Organization on the problems of aging would significantly accelerate progress in this field.

Adolescent↗
PubMed1985

The interaction between sex hormone binding globulin and levonorgestrel released from vaginal rings in women.

The levels of levonorgestrel (L-NOG), progesterone and estradiol were measured in plasma samples of 17 normally menstruating women during a control cycle and during a subsequent period (90 days) with a L-NOG-releasing vaginal ring. During days 38-66 after the insertion of the vaginal ring the concentrations of sex hormone binding globulin binding sites (hereafter: SHBG levels) were also assayed. Significant correlations were found not only between the corresponding levels of SHBG and L-NOG during exposure to the latter compound (r = 0.44; P less than 0.05), but also between the levels of SHBG in the control cycle and the levels of L-NOG measured during exposure (r = 0.60; P less than 0.01). Furthermore, the decrease in SHBG levels during the vaginal administration of L-NOG was directly proportional to the levels of SHBG in the pretreatment cycle (r = 0.64; P less than 0.01). A significant relationship was found between the levels of L-NOG (and, hence - indirectly - the levels of SHBG) and the degree of suppression of ovarian function. Thus the levels of L-NOG were lower (P less than 0.01) in the subjects (n = 8) with an apparently normal or partially suppressed ovulatory-like pattern of progesterone than in those subjects (n = 9) in whom progesterone levels were completely suppressed.

Adult↗
PubMed1985

Pharmacokinetic and pharmacodynamic investigations with monthly injectable contraceptive preparations.

Eight normally menstruating women received Cycloprovera (25 mg medroxyprogesterone acetate with 5 mg estradiol cypionate) and seven other volunteers received HRP-102 (50 mg norethisterone enanthate with 5 mg estradiol valerate) injections at 30-day intervals for three consecutive months. The peripheral plasma levels of estradiol (E2), progesterone (PROG), medroxyprogesterone acetate (MPA) and norethisterone (NET) were measured in the luteal phase of a pretreatment cycle, during the third treatment month and during a subsequent recovery period of 60 days. Blood samples were drawn three times a week (Mondays, Wednesdays and Fridays) and endometrial biopsies were taken on day 20 to 26 of the pretreatment cycle, 20 to 24 days after the last injection and 20 to 24 days after the first normal menstrual-like bleeding during the recovery period. The (geometric) mean maximum level of MPA was 2.9 (2.4-3.7) nmol/1 and that of NET 10.1 (6.4-15.8) nmol/l. Thirty days after the last injection, the MPA level was 0.72 (0.46-1.1) nmol/l and that of NET 1.7 (1.2-2.3) nmol/l. The maximum level of exogenous E2 was 890 (700-1130) pmol/l after Cycloprovera and 1570 (870-2820) pmol/l after HRP-102 administration. Forty-nine and 41 days, respectively, after the last injection, a broad (endogenous) E2 peak was observed in all subjects, which was not followed by an ovulatory rise in PROG levels. The first ovulatory rise in PROG occurred between 71 and 90 days after the last Cycloprovera and 59 to 87 days after the last HRP-102 injection. One subject in each of the two groups failed to ovulate during the 90-day post injection period. Dating and morphometric analysis of the endometrial biopsy specimens obtained 20 to 24 days after the last injection revealed that the suppressive effect of Cycloprovera was stronger than that of HRP-102. Each injection of both formulations was followed by a bleeding-free period of approximately two weeks. The percentage of days with bleeding and spotting was 24% for Cycloprovera and 29% for HRP-102. It is concluded, that both monthly injectables inhibit follicle maturation for some 30 days and ovulation and corpus luteum formation for some 60 days, providing thus a considerable margin of safety in terms of the expected duration of contraceptive protection.

Adult↗
PubMed1985

A clinical pharmacological study of a new type of vaginal delivery system for levonorgestrel.

The pharmacokinetic and pharmacodynamic effects of a new type of levonorgestrel-releasing vaginal device (with an in vitro release rate of 25 micrograms/24 h) were studied in a group of 18 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were drawn three times weekly (Mondays, Wednesdays, Fridays) during a pretreatment (control) cycle and during the 90 days (3 segments) of exposure to levonorgestrel and the levels of levonorgestrel, progesterone and estradiol were analyzed. Blood samples were also drawn at frequent intervals during the first day and daily during the first week with the devices in situ. In addition, endometrial biopsy specimens were obtained during days 20-22 of the control cycle and then 6 and 10 weeks following the insertion of the devices for morphometric analysis and for the assay of progesterone and estradiol levels. Following insertion of the devices, plasma levels rapidly rose to 1 nmol/l in 12 hours; a plateau of approximately 1.6 nmol/l was reached in 3-4 days, after which the plasma levels declined in a linear fashion with a daily average rate of 7.4 pmol/l to 60% of the initial level in 90 days' time. Of the 54 treatment segments of 30 days, 68% were anovulatory and 24% showed normal, ovulatory-like estradiol and progesterone levels. A complete set of three biopsies were obtained from 15 of the 18 subjects. Of the biopsies obtained during exposure to levonorgestrel only one exhibited signs of atrophy, 80% showed suppressed or arrested proliferation, and 10% had a normal cyclic appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1985

Cyclic changes in human endometrial surface glycoproteins: a quantitative histochemical study.

We used histochemical methods specific for carbohydrates on accurately timed endometrial biopsies to examine changes in quantity or electronegativity of the endometrium's luminal glycocalyx through the menstrual cycle in normal fertile women. Electronegative glycocalyx was detectable light-microscopically throughout the menstrual cycle. On the third day after the luteinizing hormone peak, a significant increase (P = 0.005) in endometrial surface glycocalyx was evident along with the appearance, in endometrial glands, of material having the staining properties of acid mucus glycoprotein (MGP), which implies that after this material's production by the glands or by the surface epithelium, it becomes adsorbed onto the surface glycocalyx. This phenomenon was accompanied by an apparent decrease in glycocalyceal electronegativity as indicated by a shift from high iron diamine (pH 1.0) to alcian blue (pH 2.5) staining reactivity. Because the timing of the appearance of endometrial moderately acid MGP coincides with or precedes the time that the early fertilized embryo enters the endometrial cavity, a role for the MGP in embryo nutrition or in implantation is suggested.

Densitometry↗
PubMed1985

Radioimmunoassay of luteinizing hormone in the baboon (Papio hamadryas).

A heterologous radioimmunoassay (RIA) for luteinizing hormone (LH) consisting of a cynomolgus LH tracer and an antiserum raised against human chorionic gonadotropin (cynLH:anti-hCG) fulfilled the recognized criteria of reliability when applied to baboon (Papio hamadryas) plasma and pituitary extracts obtained in different endocrine conditions. This RIA is 5.5 times more sensitive than the ovine (oLH:anti-oLH) system, yields estimates of baboon LH (bLH) fairly close to those obtained by in vitro bioassay, and recognizes all bioactive molecular species of bLH present in male and female pituitary extracts. However, the system yields slightly but significantly lower estimates of bLH than the in vitro bioassay.

Animals↗
PubMed1985

Influence of gonadectomy on isoelectrofocusing profiles of pituitary gonadotropins in rhesus monkeys.

Isoelectrofocusing (IEF) profiles of bioactive and immunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were studied in saline extracts of pituitary glands from rhesus monkeys. No sex differences were found in the IEF profiles of FSH and LH in intact or gonadectomized animals. Gonadectomy in both sexes resulted in a marked increase in the formation of relatively more acidic molecular species of FSH and LH in parallel with the production of an unusual strongly alkaline FSH species.

Animals↗