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Estrogens in maternal plasma following intraamniotic injection of (3H)-dehydroepiandrosterone-sulfate in midpregnancy.

In 4 patients with normal pregnancies between the 18th and 20th week of gestation (3H7alpha)-dehydroepiandrosterone-sulfate ([H]-DHEA-S) was injected intraamniotically. Maternal venous blood was drawn before and at regular intervals for 240 minutes after DHEA-injection. Thereafter, legal abortion was performed by intraamniotic instillation of prostaglandine. The conjugated steroids were hydrolyzed enzymatically and the total steroids were isolated and identified. The following labelled metabolites were determined quantitatively: Estriol (e3, estradiol-17beta (E2-17beta), estrone(E1), 16alpha-hydroxy-estrone, (16alpha-OH-DHEA), ALPHA4-androstenedione (AD) and testosterone (T). The maximal increase of all estrogen fractions in matermal plasma occurred 120-180min after intraamniotic injection of the precursor. The most prominent rise of the C18-steroids could be shown for estriol. 60-70% of all metabolites were C16-hydroxylated.

Amnion↗

Plasma levels of medroxyprogesterone acetate (MPA), sex-hormone binding globulin, gonadal steroids, gonadotrophins and prolactin in women during long-term use of depo-MPA (Depo-Provera) as a contraceptive agent.

The aim of the study was to evaluate the functional state of the hypothalamo-pituitary-gonadal axis and to assess the concentrations of MPA in the peripheral blood during very long-term use of depo-medroxyprogesterone acetate (DMPA) as a contraceptive agent. The concentrations of MPA, sex-hormone binding globulin (SHBG) and the different pituitary and gonadal hormones in the peripheral blood were measured in nine 26-41 year old women. They had for 4.4-10.6 years (mean 8.9 years) been receiving DMPA im in a dose of 150 mg every 12th week as a contraceptive. Blood samples were obtained immediately before an injection of DMPA, 2 weeks later, and again immediately before the next injection. SHBG was measured by radio-electro-immunoassay; MPA, gonadal and pituitary hormones by RIA. The investigation showed that the oestradiol levels - even after very long-term use of DMPA - were still within the normal range for the early follicular phase. Gonadotrophins and prolactin were within the normal range for eumenorrhoeic women as well as the concentration of SHBG. MPA did not accumulate in the plasma. The changes in the plasma levels of oestradiol, MPA and SHBG after each injection disappeared within 12 weeks. The study appearts to warrant the conclusion that even up to 10 years' use of DMPA in a dose of 150 mg im every 12th week as a contraceptive agent, does not induce hormonal changes different from those seen after the very first injection.

Adult↗

Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.

Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.

Adrenocorticotropic Hormone↗

Plasma concentrations of oestrone, oestradiol, oestriol and progesterone during mechanical stretch-induced abortion at mid-trimester.

Plasma levels of unconjugated oestrone, oestradiol, oestriol and progesterone were serially studied in six uncomplicated patients in the mid-trimester of pregnancy before and during abortion induced by purely mechanical stretching of the uterus by laminaria and rubber balloon. Variability of these hormonal levels among patients was significant before the treatment. In four cases where the fetus was aborted alive, the plasma value of these hormones remained at a high level during the treatment with the exception of oestriol level in one case. In two early mid-trimester cases the fetus died during the treatment and plasma oestriol dropped significantly, while the level of the other hormones remained raised until fetal delivery. In these two cases the apparent onset of labour was noted before fetal death. It was concluded that the onset and progress of labour by mechanical stretching of the uterus is probably unrelated to the steroid hormones estimated in the present study.

Abortion, Induced↗

Hyperprolactinemia in cases of infertility and amenorrhea.

Of 17 patients with longstanding (3--15 years, mean 7.7 years) amenorrhea and hyperprolactinemia, 8 developed their amenorrhea after the use of oral contraceptives (Group I) and 9 became amenorrhoic spontaneously (Group II). There were no differences between the groups with respect to the basal serum levels of FSH, LH, low polar estrogens (estradiol-17 beta + estrone) and prolactin. Tomography revealed pituitary adenoma in four patients. One of these developed symptoms of her tumor during pregnancy; the symptoms disappeared after delivery. The other patients with tumors are checked twice a year and have not yet received any treatment. The patients with no detectable tumors were treated with bromocriptine starting with 1.25 X 3 daily. The peripheral serum levels of prolactin, FSH, LH, low polar estrogens and progesterone were determined once a week and if the prolactin levels remained high, the bromocriptine dose was increased. All these patients started to menstruate as soon as prolactin returned to normal levels (below 25 micrograms/l). All patients who wished to became pregnant, i.e. 6 patients. Three were delivered by cesarean section, one had a normal delivery and two are still pregnant. There was no difference between Group I and Group II in the dose required or in the duration of treatment before menstruation started. Three cases of galactorrhea were found.

Adult↗

Pharmacokinetic studies on low dose estradiol 17 beta administered orally to postmenopausal women.

Peripheral plasma from four postmenopausal women was analysed for estrone, estradiol, lutenizing hormone and follicle stimulating hormone during 24 hours following an oral intake of a single dose of 1.0 mg micronized estradiol, on the first day of therapy and after one month. A similar study was carried out with another four postmenopausal patients, who received 0.2 mg estradiol three times daily. The measurements were performed by radioimmunoassay (RIA). It is concluded that the plasma concentrations of estrone and estradiol are higher and those of FSH lower after one month of therapy than on the first treatment day, while plasma LH remains unchanged. Micronized estradiol is rapidly absorbed from the gastrointestinal tract and converted to estrone, and the plasma profiles of estrone during the day are more constant with a divided daily dose than with a single higher dose. The divided daily dose results in an equally good clinical effect even though the total administration of estradiol is lower.

Administration, Oral↗

Seminal estrone, estrone sulfate, and estradiol-17 beta levels in fertile and infertile males.

The seminal levels of estrone (E1), estrone sulphate (E1S), and estradiol-17 beta (E2) were measured simultaneously after a chromatographic step in the semen samples of 79 men, including fertile volunteers, vasectomized subjects, and patients with oligozoospermia and secretory azoospermia. E1S concentrations in seminal plasma were higher than in serum (with a semen/serum ratio of approximately 2). Seminal E1 and E1S levels in oligozoospermic subjects were significantly decreased compared to controls (p less than 0.02 and p less than 0.03, respectively). The seminal E1S concentration was significantly reduced in azoospermic patients (p less than 0.02) and to a greater extent in vasectomized subjects (p less than 0.001). As seminal E1S is likely to be mainly of testicular origin, the decreased seminal E1S levels in oligoazoospermia are an index of impaired testicular function.

Estradiol↗

Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor.

We have consistently found receptors for estradiol in both the cytosol and nuclear extracts of a rat endometrial cell line and in transplantable tumors derived from this cell line. The equilibrium dissociation constants (Kd) and the rate constants for the receptor-estradiol interaction in these cells and tumors did not differ significantly from those of the cytosol receptor in the rat uterus. A mean Kd of 3 x 10(-10) M with a rate of association (Ka) of 3 x 10(5) M-1sec-1 and a rate of dissociation (Kd) of 1.5 x 10(-5) sec-1 were obtained for nuclear and cytosol receptors for both tumors and cells. For uterine cytosol, a Kd of 8 x 10(-10) M, ka = 2.8 x 10(5) M-1sec-1 and kd = 1 x 10(-5) sec-1 were obtained. Although no differences were seen in equilibrium and kinetic parameters for estradiol-17beta binding between the nuclear and cytosol receptors of tumors and cells, an apparent difference in the relative affinities of nuclear and cytosol receptors for estrone was detected. This suggests that the binding site in nuclear receptors may have been modified. Implications of this observation with regard to receptor translocation and the mechanism of action of sex hormones are being considered.

Animals↗

Hormone levels and anogenital swelling of female chimpanzees as a function of estrogen dosage in a combined oral contraceptive.

A combined oral contraceptive consisting of ethinyl estradiol (EE2) in three dosages (50, 100, and 400 micrograms) and norethindrone (0.5 mg) was given to female chimpanzees to determine the effect on endogenous sex hormone levels and anogenital swelling. Serum levels of EE2 increased with increasing dosages of EE2, estradiol decreased, and luteinizing hormone, progesterone and testosterone were maintained at approximately midfollicular phase levels. Urinary levels of EE2 glucuronide increased with the increasing dosages of EE2, whereas estrone and pregnanediol glucuronide were essentially undetectable. The cyclic increase in female anogenital swelling was abolished when the norethindrone was combined with 50 micrograms of EE2 and relatively constant and low levels of swelling were recorded. Relatively constant but successively higher levels of swelling were recorded when the norethindrone was combined with the higher dosages of EE2. These effects of oral contraceptives on female genital tissues are relevant to our laboratory studies of sexual behavior in chimpanzees given oral contraceptives and could also have implications for women taking oral contraceptives.

Anal Canal↗

Estrogens and endometrial cancer: aspects of etiology and survival rate.

With a clinical study it could be demonstrated, that the frequency of diabetes hypertension, estrogen effect in the vaginal smear and proliferative changes of the endometrium was significantly higher in patients with endometrial cancer than in a control group (p less than or equal to 0.001). Obesity was also significantly more frequent (0.02 less than p less than 0.01). In vitro studies demonstrated a significantly higher aromatization of androstendione to estrone in adipose tissue of endometrial cancer patients (p less than 0.01), indicating etiologic correlations between endometrial cancer and extraglandular estrone production. An additional clinical study indicated a better 5-years-survival rate if parameters, indicating endogenous estrogen effect were present.

Adipose Tissue↗