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Biomedical subjects

M L Swahn

Publications and source records attributed to M L Swahn.

50 records · Page 3Linked to original sources
PubMed1989

The effect of tamoxifen on the function and lifespan of the corpus luteum and on subsequent ovarian function.

The aim of the present study was to investigate the effects of tamoxifen on pituitary and luteal function and on the bleeding pattern when administered continuously in the secretory phase. The study included 16 women with regular menstrual cycles followed during one control, one treatment and one follow-up cycle. Each volunteer received 20 mg tamoxifen twice daily from cycle day 18 to menstruation in the treatment cycle. The luteal phase was slightly, but significantly prolonged during treatment, and FSH, progesterone, 17-hydroxyprogesterone, 20 alpha- dihydro progesterone, estrone, estrone sulphate and estradiol significantly elevated in comparison with corresponding data during the control cycle. The results indicate that estrogen may be of some importance for the regulation of the life span of the corpus luteum in the human. The significantly elevated levels of pregnanediol glucuronide and estrone glucuronide during the follow-up cycle are most likely a result of either a direct effect of remaining circulating tamoxifen levels on the ovary, or mediated through the increased release of FSH. If estrogens are of importance for the process of implantation, which has recently been suggested in sub-human primates, also in the human remains unclear. Studies on the effect of anti-estrogens on the endometrium during the secretory phase of the cycle are ongoing.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Termination of early pregnancy with RU 486 (mifepristone) in combination with a prostaglandin analogue (sulprostone).

The antiprogestin RU 486 (mifepristone) has been shown to induce abortion when administered in early pregnancy, but the rate of incomplete abortion is high, around 40%. As blockage of the progesterone receptor increases the myometrial sensitivity to prostaglandins, a combination of RU 486 and a prostaglandin E2-analogue was tested for termination of pregnancy. One hundred and sixteen women, with a gestational length of less than 49 days from the first day of the last menstrual period, were treated with a daily dose of 50 or 100 mg RU 486 for 3 to 6 days, complemented with an intramuscular dose of 0.25 mg sulprostone (16-phenoxy-PGE2-sulfonylamide) on the last day of RU 486 treatment. The results confirmed that a reduction of treatment duration to 3 days is just as effective for inducing abortion (91% complete abortion) as a 4-6-day treatment regimen (95% complete abortion). Six patients had an incomplete abortion and in one the pregnancy continued unaffected. Side effects included intense uterine pain after the prostaglandin administration (16%), vomiting associated with the antiprogestin intake (9%) and after the prostaglandin administration (9%). One woman needed emergency curettage due to heavy bleeding. Six percent of the treated patients had a decrease in hemoglobin exceeding 20 g/l during the first week but no patient needed blood transfusion. No serious side effects were recorded.

Abortifacient Agents↗
PubMed1988

Development of a vaginal gel containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 for cervical dilatation and pregnancy termination.

A stable hydrophilic gel for vaginal administration containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2) was developed and its clinical usefulness for preoperative cervical dilatation and for termination of first and second trimester pregnancy evaluated in 521 pregnant patients admitted to the hospital for therapeutic abortion. Following vaginal administration of 3 mg of 9-methylene PGE2 gel a peak plasma level of between 3.5 and 10 ng/ml was found 3 to 6 hours following treatment. The "bioavailability" of the drug was in the order of 25-30%. 9-methylene PGE2 was found to be equally effective as 1 mg Cervagem for preoperative cervical dilatation. With a pretreatment period of 3 hours side effects were rare with both compounds. If the pretreatment period was extended to 12 hours the degree of cervical dilatation, but also the frequency of side effects increased significantly. Repeated administration of 9-methylene PGE2 was found to be effective (96% complete abortion) in terminating very early pregnancy provided the total dose was 10 mg or more. During second trimester the minimum effective dose was 4.5 mg of the compound repeated every fourth hour. The results of the present study have shown that with the new gel formulation the amount of 9-methylene PGE2 needed to terminate first and second trimester pregnancy was approximately ten times less in comparison with the previously used lipid base suppositories. The treatment was also associated with a low frequency of side effects.

16,16-Dimethylprostaglandin E2↗
PubMed1988

The effect of RU486 administered during the proliferative and secretory phase of the cycle on the bleeding pattern, hormonal parameters and the endometrium.

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P2-G), oestrone glucuronide (E1-G), oestradiol (E2), progesterone (P4), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin.

The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16-phenoxy-PGE2 methyl sulfonylamide (16-phenoxy-PGE2) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE2 was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE2 caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE2 on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible.

Abortion, Therapeutic↗
PubMed1987

Role of prostaglandins in human reproduction: recent advances.

Our knowledge of the importance of PGs for the physiological regulation of male and female reproductive organs is rapidly increasing. In this presentation two examples have been described in detail. Data are accumulating indicating that PGs in semen are of major importance for sperm motility and the functional capacity of sperms. Recording of intrauterine pressure in early pregnant patients has shown that treatment with an antiprogestin depriving the myometrium from progesterone influence, will induce regular uterine contractions. The data support the hypothesis that the uterine activity is regulated by the balance between PGF2 alpha and progesterone.

Female↗
PubMed1986

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women.

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

Abortifacient Agents↗
PubMed1985

Progesterone receptor blockage. Effect on uterine contractility and early pregnancy.

RU 486 is an antiprogestin which acts at the receptor level. In the present study the effect of this compound on uterine contractility and sensitivity during early pregnancy was evaluated in 10 patients. Five patients in the 6th to 7th week of pregnancy received 25 mg RU 486 twice daily for four days. On the fourth day of treatment, uterine contractility was recorded. The remaining five early pregnant patients were untreated and served as control. Withdrawal of progesterone locally by RU 486 treatment resulted in the development of a regular uterine activity which was in sharp contrast to the low level contractility pattern found in the untreated control patients. Also the sensitivity to prostaglandin increased following RU 486 treatment. The efficacy of a sequential therapy of RU 486 and the PGE analogue 16-phenoxy-tetranor-PGE2 methyl sulfonylamide for termination of early pregnancy was also studied. Thirty-four early pregnant women (duration of amenorrhea for up to 49 days) admitted to the hospital for termination of their pregnancy volunteered for the study. The patients received 25 mg RU 486 twice or four times daily for four days. In the morning of the fourth day of RU 486 treatment, a small dose (0.25 mg) of the PGE analogue was given as a single intramuscular injection. The combined treatment resulted in complete abortion in 32 patients (94%). One patient experienced an incomplete abortion and in one patient the pregnancy continued unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents, Nonsteroidal↗
PubMed1984

Termination of very early pregnancy by RU 486--an antiprogestational compound.

RU 486, a new antiprogestational compound, was given to 37 women seeking termination of pregnancy and with amenorrhea of 42 days or less. One patient was found at the second follow-up visit to have an extrauterine pregnancy. The patients received either 25 mg, 50 mg or 100 mg RU 486 twice daily for four days. All patients attended three follow-up visits, one, two and five to six weeks after the start of therapy. The start, duration and amount of bleeding as well as plasma progesterone, beta-hCG and cortisol concentrations were determined for each treatment day and at the follow-up visits. All patients but three started to bleed during treatment. Frequency of complete abortion was 61% (22 out of 36 patients). In only three patients was the pregnancy unaffected by treatment. The clinical efficacy of the treatment was not dose-dependent. Most of the patients experienced only minor side effects in terms of mild uterine pain, nausea and vomiting. However, two patients suffered from heavy bleeding requiring blood transfusion and curettage. In the patients with complete abortion, beta-hCG values decreased significantly but not until the first follow-up visit. The plasma progesterone also decreased. The decrease appeared earlier with the higher daily dose of RU 486. Cortisol concentrations increased during treatment with all 3 dosage regimens but the levels remained within the normal range. It is concluded that treatment with RU 486 may provide a novel therapy for "menstrual regulation" but the efficacy of the treatment needs to be improved to compete with alternatives such as vacuum aspiration.

Abortifacient Agents↗
PubMed1984

Diurnal variation of uterine contractility.

The diurnal uterine activity in four normal women in the secretory phase of their menstrual cycles and one woman suffering from dysmenorrhea were studied in relation to concomitant hormone levels in blood (progesterone, hGH, prolactin, cortisol, vasopressin, and 15-keto-13,14-dihydro-PGF2 alpha). In the four normal women uterine activity decreased after midnight, unrelated to circulating levels of 15-keto-13,14-dihydro-PGF2 alpha. But during a dysmenorrheic episode the uterine hypercontractility pattern correlated well with levels of the PGF2 alpha-metabolite, indicating a role of endogenous-produced PGF2 alpha in this condition. The results demonstrate a diurnal rhythm, possibly related to the wake-sleep cycle. No simple associations were seen between vasopressin, cortisol, prolactin, hGH, the PGF2 alpha-metabolite, and uterine activity.

Circadian Rhythm↗
PubMed1983

The effect of intravenous and intrauterine administration of prostacyclin on non-pregnant uterine contractility in vivo.

Intravenous administration of prostacyclin at a dose of 10 ng/min/kg bodyweight for 10 minutes did not have any effect on non-pregnant human contractility in three subjects. Higher doses were not given due to side effects. Intrauterine administration of PGI2 at doses of 0.3-0.6 micrograms resulted in a gradual stimulation of the myometrial activity. Whether this response is a secondary effect of the vasodilation caused by PGI2 or a direct effect on the myometrium could not be established in these experiments.

Epoprostenol↗
PubMed1983

The possible roles of prostaglandins and related compounds in endometrial bleeding. A mini-review.

This mini-review summarizes some aspects of hemostatic defects, with particular reference to endometrial bleeding, both the normal menstruation and some bleeding disorders of the uterus. Two cell types are of particularly great interest in the hemostatic mechanism, viz. the platelet and the vascular endothelial cell. We will therefore start with a brief survey of the roles of platelets and vascular endothelium in hemostasis, and the underlying biochemical events will be discussed, particularly the participation of the arachidonate metabolites: the prostaglandins, the thromboxanes and the leukotrienes. This section is then followed by a brief description of some histological findings in the menstruating endometrium; the normal as well as the pathologically bleeding tissue. The possible roles of arachidonate metabolites in these events will be discussed. Several clinical studies have been published, in which various attempts have been made to treat excessive endometrial bleeding with inhibitors of prostaglandin biosynthesis. The findings in these studies are described. The relevance of this approach and its possible effects on other areas of arachidonic acid metabolism will be discussed. Finally, some studies will be summarized in which various attempts have been made to quantitate and endometrial prostaglandins in different physiological and pathological conditions.

Animals↗
PubMed1982

Profiles of prostaglandin metabolites in the human circulation. Identification of late-appearing, long-lived products.

The pattern of metabolites appearing in the circulation after intravenous injection of [9 beta-3H]prostaglandin F2 alpha was investigated in the human. Analysis of profiles of products was performed by two-dimensional TLC and autoradiography. Identification of labeled metabolites was accomplished by comparing their chromatographic behaviour with reference compounds in several chromatographic systems. After injection of [9 beta-3H]prostaglandin F2 alpha the initially formed metabolite was 15-keto-13,14-dihydroprostaglandin F2 alpha. However, this compound only dominated the spectrum of metabolites during the first few minutes, and several more polar products soon appeared. About 20 min after the injection the most prominent metabolite was 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprostane-1,16-dioic acid, which remained the dominating plasma compound and was also the major metabolite in urine. Several other highly oxidized products were also identified in plasma. Also these metabolites appeared later and remained longer in the circulation than the initially formed 15-ketodihydro metabolite. Our findings suggested that the more degraded metabolites might serve as more reliable plasma parameters for monitoring prostaglandin production than the traditional parameter, 15-ketodihydroprostaglandin F2 alpha. This hypothesis was supported by radioimmunoassay of metabolite levels in plasma appearing after either exogenous (intravenous administration) or endogenous prostaglandin F2 alpha (late human pregnancy and parturition). In all cases studied, the tetranor metabolites remained elevated in the circulation for several hours, in contrast to their precursor, 15-ketodihydroprostaglandin F2 alpha, which disappeared rapidly.

Autoradiography↗