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Biomedical subjects

E Diczfalusy

Publications and source records attributed to E Diczfalusy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Reproductive health: towards a brighter future.

In 1972 the World Health Organization initiated the Special Programme of Research, Development and Research Training in Human Reproduction. Now cosponsored by the United Nations Development Programme, the United Nations Population Fund, the World Bank and WHO, the Programme has become the main instrument of research in reproductive health in the United Nations system. The progress that has been made, and the prospects for the future, are reviewed below.

Contraception↗
PubMed1991

Contraceptive prevalence, reproductive health and our common future.

The 1980s will go into history as a decade of lost opportunities to increase contraceptive prevalence and improve reproductive health worldwide. As the decade closes, 500 million couples still have no access to fertility regulation, there are 30-50 million induced abortions each year, 15 million infant and child deaths (30% of all deaths worldwide), an estimated 250 million new cases of sexually transmitted diseases and 60-80 million infertile couples. One of the major problems is that many policy makers are still unimpressed with the global demographic reality. World population was less than 300 million 1991 years ago. It took some 1500 years to double this number by the time of the voyages of Columbus to America. The first billion was reached at the beginning of the last century and the second in the lifetime of the author, in 1927. Then it took less than 50 years to double this number to 4 billion by 1976. Global population is 5.3 billion today. In view of such figures, it is understandable that, historically, it was this demographic concern that in the 1960s persuaded many governments to support family planning programmes. During the subsequent decades, it was gradually recognized by developing country governments that family planning lowers infant, child and maternal mortality and morbidity and reduces the number of illegal abortions and their health hazards. Today, 52 developing country governments support family planning programmes for the demographic rationale, but 65 for the reproductive health and human rights rationale. Where do we go from here? That will mainly depend on the number of years it will take to reach replacement level of fertility (around 2.1 children per couple) worldwide. If the level is reached in 2010 (the low projection of the United Nations), global population will stabilize by the end of the 21st century at 8 billion; if it is reached in 2035 (medium projection), population will stabilize around 10 billion; however, if it is reached only in 2065 (high projection), the global population in 2100 will consist of more than 14 billion people, with major consequences on every walk of life. To restrict the final population to 10 billion, contraceptive prevalence must increase from 51% to 58% of married women of reproductive age before the year 2000 and to 71% by 2020, implying an increase from the present 350 million users to 500 and 800 million, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Contraception↗
PubMed1990

Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in post-menopausal women.

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE1S, 2.5 mg/day) and oestradiol valerate (E2V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 micrograms/day) were compared in 8 post-menopausal women, using a randomized cross-over design. The end points measured in peripheral plasma included oestrone (E1), oestradiol (E2), oestriol (E3), oestrone sulphate (E1S), oestradiol sulphate (E2S) and oestriol sulphate (E3S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed. The plasma levels of E3 were invariably below the detection limit (220 pmol/l). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E3S) following PE1S administration than those recorded after E2V ingestion. The terminal half-lives of the circulating oestrogens measured after PE1S administration did not differ from those found after E2V administration. After 21 days of PE1S administration (in combination with LNG for the last 10 days), the maximum levels of all the oestrogens (except those of E2) were significantly higher than those seen after the first dose. No such difference was observed after E2V administration. There was no difference between the effects of the two treatment regimens with regard to the E1/E2 ratios, but the E1/E1S ratios were significantly lower after PE1S treatment than after E2V administration. It is concluded that, compared with an equivalent dose of PE1S, daily repeated oral administration of E2V yields consistently lower peripheral plasma levels of E2 and its principal metabolites. However, in contrast to PE1S therapy, prolonged administration of E2V does not result in an accumulation of the circulating oestrogens measured.

Administration, Oral↗
PubMed1990

Pituitary, ovarian and endometrial effects of 300 micrograms norethisterone and 30 micrograms levonorgestrel administered on cycle days 7 to 10.

The ovarian, endometrial and pituitary effects of 300 micrograms norethisterone (NET) and 30 micrograms levonorgestrel (L-NOG) administered orally on cycle days 7-10 were investigated in two groups of 10 women each, by daily analysis of plasma estradiol (E2), progesterone (PROG), immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) in a pretreatment control cycle and during NET or L-NOG administration. Endometrial biopsies were obtained for morphometric analysis on cycle day 11 in the control and treatment cycles. Treatment with 300 micrograms NET resulted in an increase in the area under the E2 peak (p less than 0.05), reduction in the number of subjects with normal progesterone profile (p less than 0.05) and a decrease in the area under the progesterone curve (p less than 0.05). The treatment suppressed the LH peak in 4 subjects and progesterone in 4 subjects. The follicular phase was prolonged in one subject. Norethisterone induced marked subnuclear vacuolation in the endometrium, while the glandular mitoses were decreased during NET treatment. Treatment with 30 micrograms L-NOG resulted in a decrease in subjects with normal progesterone profiles (p less than 0.05) and in the area under the progesterone curve (p less than 0.05). The treatment suppressed the LH peak in 3 subjects and progesterone in 4 women. The follicular phase was prolonged in one subject. L-NOG did not significantly increase the diameter of glands or induce subnuclear vacuolation in the endometrial glands.

Adult↗
PubMed1989

Effect of orally administered oestrogens on gonadotrophin levels in post-menopausal women.

The gonadotrophin-suppressing effect of 4 peroral oestrogen regimens (A: 2.5 mg piperazine oestrone sulphate; B: 1.25 mg piperazine oestrone sulphate + 5.0 mg oestriol; C: 2.0 mg oestradiol valerate; D: 10.0 mg oestriol; all administered daily) was studied in 7 post-menopausal women, in the absence, and then in the presence of daily oral doses of 250 micrograms of levonorgestrel. A randomized, complete cross-over design was used, and from each volunteer 80 blood samples were drawn during a period of 252 days for the assay of immunoreactive follicle stimulating hormone (FSH), luteinizing hormone (LH) and bioactive LH levels. All 4 formulations significantly diminished pretreatment gonadotrophin levels. Combination with levonorgestrel enhanced the suppressive effects. Subsequent placebo administration for a week restored gonadotrophin levels to those found previously during oestrogen administration, but not to pretreatment levels. Regimen D exhibited the relatively weakest and regimens A and B the strongest suppression, both in the absence and in the presence of levonorgestrel. Treatment with all oestrogen formulations decreased, and the addition of levonorgestrel increased the ratio of bioactive (B) to immunoreactive (I) LH. Seven days of placebo administration abolished the effect of levonorgestrel, but not that of the various oestrogens on the B/I ratios.

Administration, Oral↗
PubMed1989

Effect of orally administered oestrogens on circulating oestrogen profiles in post-menopausal women.

The effect of 4 peroral oestrogen regimens without and with levonorgestrel (LNG) supplementation (250 micrograms/day) was studied in 7 post-menopausal women. The regimens were: A: 2.5 mg piperazine oestrone sulphate/day; B: 1.25 mg piperazine oestrone sulphate + 5.0 mg oestriol/day; C: 2.0 mg oestradiol valerate/day and D: 10.0 mg oestriol/day. A randomized complete cross-over design was employed and systemic blood levels of progesterone (P), oestrone (E1), oestradiol (E2), oestriol (E3), oestrone sulphate (E1S), oestradiol sulphate (E2S) and oestriol sulphate (E3S) were analyzed. All subjects were consistently post-menopausal, as indicated by low P, E2, E1S and E3S and high FSH and LH levels. The pretreatment and post-treatment levels of E2 and E2S as well as those of E3 and E3S were invariably below detection limit (60 pmol/l and 220 pmol/l, respectively). Treatment with regimens A, B and C resulted in consistently detectable levels of E2, E2S and E3S, but not of E3, and in grossly elevated E1 and E1S levels. Treatment with regimen D gave rise to very high E3S levels. The oestrogen profiles produced by regimens A and C were almost identical, with the exception of higher E1 and lower E3S levels following the administration of regimen A. Combination with LNG did not modify the levels of unconjugated oestrogens, but in certain cases it seemed to diminish those of oestrogen sulphates. A comparison with the results of a preceding study (Aedo A-R et al., Effect of orally administered oestrogens on gonadotrophins levels in post-menopausal women. Maturitas 1989; 11:) reveals that the gonadotrophin-suppressing effect of all 4 regimens still persisted in the post-treatment period at a time when the levels of all oestrogens analyzed returned to those of the pretreatment period.

Administration, Oral↗
PubMed1989

The worldwide use of steroidal contraception.

Historically, concerns about rapidly growing populations and resources that could not support them persuaded governments of developing countries to initiate family planning programs. Between the early 1960s and the early 1980s, the number of governments supporting these programs increased from 7 to approximately 120. Today, 52 governments in developing countries provide support to family planning programs because of the demographic rationale, and 65 governments do so because of human rights and health considerations: The effective use of family planning significantly diminishes infant, child, and maternal mortality and morbidity. Forty-five percent of married women of reproductive age worldwide are practicing contraception today; however, 69% do so in East Asia and only 11% in Africa. Female sterilization and use of intrauterine devices are the most popular methods in developing countries, and oral contraceptives and condoms, in developed countries. Of the 400 million women of reproductive age, 140 million (35%) are relying on family planning methods requiring male cooperation and less than 60 million (15%) are using oral contraceptives. More than half of these oral contraceptive users live in four countries: the United States, Brazil, France, and the Federal Republic of Germany. On the other hand, the percentage of currently married women, aged 15 to 19 years, who have never used any form of contraception is as high as 85% to 90% in Bangladesh, Sudan, and Pakistan. In many developing countries, there is a statistically significant correlation between women's use of contraception and years of education. Other important factors influencing contraceptive prevalence include the established or perceived side effects of currently available methods, the status of women, the political climate, and a number of behavioral and social determinants.

Adolescent↗
PubMed1988

Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes.

In a randomized, cross-over study endometrial and vaginal response to transdermal 17 beta-oestradiol (TTS-oestradiol 50 micrograms) and two forms of oral oestrogen replacement therapy (conjugated oestrogens 1.25 mg and oestradiol valerate 2 mg) were studied in 13 peri-menopausal and post-menopausal women. Five (5) of the women exhibited periodic ovarian function as evidenced by peripheral oestradiol and progesterone levels and were considered to be peri-menopausal. In the post-menopausal group of 8 women the bleeding pattern was more regular than among the peri-menopausal women. In the case of the post-menopausal group the number of days on which spotting and bleeding occurred was significantly lower during the administration of TTS-oestradiol than during treatment with conjugated oestrogens. This finding was paralleled by a significantly higher karyopyknotic index in the vaginal epithelium and significantly increased deoxyribonucleic acid (DNA) synthesis in the endometrial cells during treatment with equine oestrogens. No significant difference was seen in these indices when the effect of TTS-oestradiol was compared with that of oestradiol valerate. The study results in the post-menopausal group suggested a relationship between the intensity of the oestrogen treatment and not only the proliferation and maturation of the oestrogen target-organ cells but also the number of days on which bleeding occurred. It was concluded that a clear distinction needs to be made between peri-menopausal and post-menopausal women. In the present study the irregular ovarian activity among the peri-menopausal subjects precluded an unbiased assessment of the exogenous oestrogens. It is also likely that exogenous oestrogens exert a cumulative action with oestrogen secreted endogenously, interfere with the physiological events at the target organ level and induce uncontrollable endometrial bleeding. The complete cessation of ovarian activity may therefore have to be established before exogenous oestrogens are administered to climacteric patients.

Administration, Cutaneous↗
PubMed1988

Clinical-pharmacological studies on human menopausal gonadotrophin.

Using a randomized, cross-over design, the clinical, pharmacokinetic and pharmacodynamic properties of commercially available gonadotrophin preparations were studied. Following i.v. administration of 150 IU of follicle-stimulating hormone (FSH) in the form of Humegon, Pergonal and Metrodin, the maximum concentrations (CMax) were 27.5, 24.1 and 26.5 IU/l, respectively which were reached after 15.4, 16.9 and 16.9 min (TMax), respectively. The half lives (t1/2) were 1.6, 2.3 and 2.0 h, respectively (fast compartment) and 11, 10 and 7.3 h, respectively (slow compartment). The t1/2 of luteinizing hormone (LH) could only be estimated in a surgically hypophysectomized patient: the fast compartment was 1.2 and 1.3 h after the administration of Humegon and Pergonal, respectively and the slow compartment was 3.3 h in both cases. Marked individual differences of the same type were found in plasma FSH profiles, ovarian images and peripheral oestradiol levels after the administration of both preparations (150 IU daily for 8 days) and the approximate t1/2 of FSH exceeded 40 h. It is concluded that the pharmacokinetic and pharmacodynamic properties of the preparations studied are similar, if not identical, and that there are marked individual differences in patient responsiveness, which are unrelated to the preparation administered.

Biological Assay↗
PubMed1988

Plasma clearance in the rat of the LH bioactivity of two human LH standards of differing molecular composition.

The LH biological potency of the International Reference Preparation (IRP) of Human Pituitary LH for Immunoassay (IRP 68/40) relative to that of the 2nd IRP of Human Pituitary FSH and LH for Bioassay (IRP 78/549) is markedly greater when estimated by in-vitro interstitial cell testosterone production (TICT) bioassay than by in-vivo bioassay, and by the 4-h ovarian ascorbate depletion (OAAD) assay than by the 4-day seminal vesicle weight gain assay. Other preparations of human LH which, like IRP 68/40, were highly purified, showed a similar spectrum of bioactivity in these assay systems and also contained a higher proportion of more basic LH isoforms than are found in crude pituitary extracts such as IRP 78/549. In an attempt to explain these differences, a comparison was made of the plasma survival in rats of the LH bioactivity (by TICT assay) of these two preparations. Contrary to expectation, their relative plasma clearance rates over a 4-h period did not account for their differing bioactivities. The plasma half-life of the LH bioactivity (with 95% confidence limits) was estimated to be 42.4 (35.3-49.5) min for IRP 68/40 and 41.3 (31.5-51.0) min for IRP 78/549. Furthermore the time-course of action in vivo of IRP 78/549 did not appear to be more prolonged than that of IRP 68/40. Thus their plasma testosterone responses during the course of these 4-h plasma clearance studies were similar, and estimates of the LH potency of IRP 68/40 relative to that of IRP 78/549 were no greater by 2-h than by 4-h OAAD assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗