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At least 37 records · Page 2Linked to original sources
PubMed1991

The endocrine effects of long-term treatment with mifepristone (RU 486).

Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.

Adrenocorticotropic Hormone↗
PubMed1976

[Preovulatory changes of steroidogenesis in isolated rabbit follicles (author's transl)].

In an attempt to investigate the effect of ovulating hormone on the steroidogenesis of mature follicles in the course of ovulation, transitory changes of steroidogenesis in isolated rabbit follicles have been studied at several intervals after injection of an ovulatory dose of human chorionic gonadotropin (hCG). Five to ten follicles of approximately 1-2 mm in diameter were isolated from ovaries of a mature rabbit (2.5-3.0 kg) under streomicroscope, before and at the 3rd, 6th, 9th and 12th hours after intravenous injection of of 100 IU/kg of hCG. Follicles were incubated with 100 muCi of acetate-1-14C in 2 ml of Krebs-Ringer bicarbonate buffer (pH 7.4) at 37 degrees C for 3 hours under 95% oxygen plus 5% carbon dioxide. Each incubation was terminated by quick freezing and stored forzen at -20 degrees C until eighty follicles had been collected for each time period before commencement of analysis. Incorporation of radioactive acetate into pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone., 20 alpha-dihydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol-17beta were analysed by the reverse dilution technique and identified in radiochemically pure form by recrystallization to constant specific activities. The steroidogenic activity of the follicles was evaluated by overall as well as fractionated incorporations. A peak in the overall incorporation of 14C- acetate into the ten steroids at the 3rd hour after hCG injection, followed by gradual decrease up to the 9th hour was observed. The incorporation decreased markedly to a minimum level at the 12th hour after hCG injection, which was below the level of preinjection control. Comparable quantitative fluctuations were found with the fractionated incorporation of 14C-acetate into the C21 and C18 steroids in the time sequence following hCG injection. However, the fractionated incorporation into C19 steroids reached to a maximum at the 6th hour after hCG injection. 5istribution patterns of incorporation among the individual steroids were varied at each interval of time. In the non-injected control, mature follicles synthesized predominantly estradiol-17beta, testosterone and androstenedione. Divergent steroids were formed from radioactive acetate at the 3rd hour after hCG injection. These included porgestogen, androgen and estrogen, but pregnenolone and 17hydroxyprogesterone were the two principal steroids produced. There was no essential difference in the steroidogenic patterns between the 6th and 9th hour, the major products being C21 and C19 steroids such as pregnenolone, 17hydroxyprogesterone, dehydroipiandrosterone and testosterone. The three androgens were the major steroids formed at the 12th hour after hCG injection. Thus the chages in the steroidogenic profile of the follicle was obvious in the course of ovulation. The basis of qualitative changes in follicular steroidogenesis during the process of ovulation have been discussed in connection with an accompanying effect of an ovulatory dose of hCG.

Acetates↗
PubMed1976

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↗
PubMed1977

The influence of combined cyproterone acetate-ethinyl oestradiol therapy on serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women.

Serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women suffering from either idiopathic hirsutism or the polycystic ovary syndrome were determined before and during treatment with cyproterone acetate combined with ethinyl oestradiol. During this treatment the hirsutism decreased markedly. In untreated hirsute women serum dehydroepiandrosterone levels do not differ from those in normal women and do not change during therapy; androstenedione levels are higher than normal and decrease markedly during treatment, and the testosterone levels are elevated compared to normals, with a considerable overlap, and show only a tendency to decrease. There is no correlation between dehydroepiandrosterone and androstenedione levels or between androstenedione and testosterone levels in the serum of untreated hirsute women. After 12-14 months of cyproterone acetate-ethinyl oestradiol therapy a linear correlation is found between dehydroepiandrosterone and androstenedione levels. This can be explained by the relatively higher contribution of the peripheral conversion of dehydroepiandrosterone to androstenedione to the occurrence of lower androstenedione levels. The linear correlation between androstenedione and testosterone after treatment, also found in normal women, indicates the restoration of the role of androstenedione as the major peripheral precursor of testosterone.

Adolescent↗
PubMed1977

Steroid sex hormones and prolactin in postmenopausal women with generalized mammary carcinoma during prolonged dexamethasone treatment.

The endocrine response to prolonged dexamethasone treatment was investigated in six postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly and became undetectable whereas significant concentrations of plasma dehydroepiandrosterone and androstenedione persisted throughout the study, even in two ovariectomized patients, indicating a certain degree of autonomy or a greater resistance of adrenal 'androgens' to the inhibition of ACTH secretion. Except in the ovariectomized patients, plasma testosterone did not fall significantly whereas the plasma oestrogens tended progressively towards undetectable concentrations. A similar response was found in six normal postmenopausal women although the disappearance of their oestrogens was relatively rapid. This indicates that much of the testosterone present after the menopause could still be produced by the ovaries whereas the ovarian production of oestrogens becomes negligible. The delayed disappearance of oestrogens in the patients with mammary carcinoma indicates that the persisting adrenal 'androgens' remained efficient precursors of oestrogen synthesis within the peripheral tissues and presumably within the mammary tumour itself. Plasma dihydrotestosterone behaved like the plasma oestrogens. Despite the fall in plasma oestrogens, plasma gonadotrophins did not increase further but plasma prolactin rose progressively. The persistance of steroid sex hormones and the rise of plasma prolactin might explain the poor response to dexamethasone treatment in mammary carcinoma.

Aged↗
PubMed1992

A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel.

The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Ciles) and levonorgestrel triphasic (Triphasi) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women treated through six menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values with values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in levels of high-density lipoprotein, which were favorably increased with norgestimate triphasic but reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as evidenced by low mean levels of estradiol in all on-therapy cycles; and both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptive agents. The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined oral contraceptive.

Adolescent↗
PubMed1976

Plasma steroid concentrations in conscious and anesthetized rabbits.

The ovarian steroids, estrogen, androgen, and progestin, were measured in the peripheral plasma of adult female rabbits that were either conscious or anesthetized with sodium pentobarbital (nembutal) or halothane. Concentrations of estrogen, androgens, and progestin were determined before and at 10 and 45 min after systemic injection of either buffer or LH. In the controls androgen levels were significantly different between animals anesthetized with nembutal and halothane. However, the greatest treatment effect was noted in plasma progestin concentrations which were significantly elevated in halothane-anesthetized animals in comparison to the conscious and nembutal-anesthetized animals. Following LH, the androgen and progestin levels were significantly elevated over basal levels. Most likely the treatment effect observed in the controls was still present but was overridden by the increased release of steroids following gonadotrophin stimulation. This study suggests that halothane, in contrast to nembutal, does significantly elevate peripheral progestin and androgen levels.

Androgens↗
PubMed1976

[Steroid receptors and hormonal receptivity. New pharmacological and therapeutic approaches applicable to the control of fertility].

The definition and main characteristics of the steroid hormone receptors are given. One may note a relationship between hormonal receptivity and the physiological changes in the concentration of the receptors in the target organs. The distribution of the various receptors is given in detail showing the existence of (a) different receptors for the same hormone in different target cells; (b) different receptors for different hormones in the same cells; (c) different receptors for the same hormone in the same cell. A new pharmacological approach is proposed based on differentiation of receptivities from which there results a dissociation of the therapeutic effects.

Drug Interactions↗
PubMed1975

[Comparison of chemical and radiochemical methods in determination of steroid hormones].

While in some cases steroids can be measured directly in serum or plasma by radioimmunoassay (RIA), in other cases, especially when analyses are carried out in urine, the samples must be processed before RIA can be performed. The operations involved in the preparation of urinary or blood extracts suitable for the RIA of steroid hormones are examined and compared in terms of practicability with the analytical procedures currently used for the chemical determination of the same steroids or their metabolites.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

[Steroidogenic function of the intra-arterial trophoblast in the rat. Ultrastructural, histoenzymologic and biochemical data].

The ultrastructural study of the intra-arterial trophoblast has revealed in the pregnant Rat a steroidogenic activity which has been confirmed by histoenzymologic observations (presence of delta 5-3 beta-HSDH and 17 beta-HSDH). At the 15th day postcoitum an in vitro investigation upon the metabolism of steroid hormone precursors suggests that the steroids (oestrogens, progestogens and androgens) secreted by the intra-arterial trophoblast have a local action upon the wall of the uterine placental arteries and are actively concerned with an important part upon the utero-placental hemodynamic as a whole.

Androstenedione↗
PubMed1976

Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure.

The association of excessive circulating androgens in blood and ovulatory failure in women is well documented in a variety of clinical conditions. The restoration of ovulatory function by wedge resection of the polycystic ovary, by the administration of glucocorticoids or removal of tumors of the adrenal or ovary--measures that also reduce the level of circulating androgens--is also well documented. In view of the many hypotheses of adrenal and ovarian abnormalities and disorders of the hypothalamic-pituitary axis in the human, resulting in hirsutism and ovulatory failure, a normal intact rat model was developed to study the effect of androgens on ovulation. The administration of a weak androgen, dehydroepiandrosterone (DHA), to immature rats resulted in a single precocious ovulation followed by ovulatory failure. The conversion of DHA to estrogens appeared to be the principle mechanism for the precocious ovulation. The steps appeared to be an elevation in blood estradiol, followed by the depletion of cytoplasmic estradiol receptors of the hypothalamus and pituitary and the gonadotropin surge leading to ovulation. These events appeared to be similar to those occuring in the adult cycling rat, in precocious puberty induced by the administration of pregnant mare serum gonadotropins and during the onset of natural puberty. The role of estrogens in inducing the precocious ovulation was further supported by the absence of precocious ovulation in animals in which the conversion of DHA to estrogens was blocked or by administering androgens that could not be converted to estrogens. In contrast, the subsequent ovulatory failure could not be explained entirely by the conversion of DHA to estrogens. There was a considerable time lag between the withdrawal of DHA treatment and the replenishment of pituitary and hypothalamic cytoplasmic estradiol receptors. Unlike those of the cycling animal, the receptors were not replenished when the levels of circulating estradiol in blood receded. The replenishment occurred only after the circulating levels of androstenedione, DNA and progesterone were reduced. Receptor replenishment in the hypothalamus and pituitary was followed by increases in the levels of circulating gonadotropins, particularly LH, with subsequent restoration of cyclic ovulatory function. The ovaries in the acyclic androgen-treated rat were responsive to gonadotropins. The pituitary responded to LH-RH administration, but the sensitivity was reduced. In the adult rat, ovulatory failure and the formation of polycystic ovaries took place with doses of DHA as low as 7.5 mg per kg of body weight. Attempts are being made to obtain further insights into the mechanism of androgen-induced ovulatory failure by studying the effect of androgens and progesterone on the steroid receptors and their function in the hypothalamus and the pituitary. Furthermore, a direct effect of DHA on the ovary, causing follicular atresia and cystic changes, is also being explored.

Animals↗
PubMed1977

Gonadal function following vasectomy in the rat.

Adult rats were studied at four, eight, and 12 months following vasectomy and sham-operation. The weights of the seminal vesicles, ventral prostate, pituitary, and kidneys were not significantly affected by vasectomy. Testicular endocrine function in vasectotomized rat was transiently stimulated as witnessed by elevation in testicular venous testosterone and androstenedione after four months. There then occurred signs of decline in gametogenic function and atrophy of the testis after 12 months whereas hormonogenesis appeared to remain at normal levels. There was no alteration in the morphology of the epididymis at any of the time intervals of study after vasectomy.

Animals↗
PubMedDate not supplied

The relevance of the pharmacologic properties of a progestational agent to its clinical effects as a combination oral contraceptive.

Levonorgestrel (LNg) is known for its marked progestational/contraceptive activity. As shown in animal experiments, however, high doses of LNg are required to elicit an androgenic response; in contrast, considerably lower doses of LNg are required for antiovulatory (contraceptive) action. Thus, a large dose separation exists between androgenic and contraceptive activity. When LNg is combined with an estrogen, as in the contraceptive formulations, the androgenic response is attenuated or negated. The results of recent clinical trials have demonstrated that the androgenic activity of LNg is not expressed at contraceptive doses, particularly when LNg is combined with ethinyl estradiol (EE), as in the low-dose monophasic/triphasic formulations (monophasic [Nordette]: 150 mcg LNg/30 mcg EE; triphasic [Triphasil/Trinordiol]: six days, 50 mcg LNg/30 mcg EE; five days, 75 mcg LNg/40 mcg EE; ten days, 125 mcg LNg/30 mcg EE). Clinical evidence from several trials confirms that sex hormone-binding globulin levels are increased, plasma androgen levels are decreased, and acne is markedly improved with the use of Triphasil and Nordette, suggesting a non-androgenic profile.

Acne Vulgaris↗
PubMedDate not supplied

Clinical evidence of the minimal androgenic activity of norgestimate.

The goal in improving the progestational component of oral contraceptives (OCs) is to enhance the selectivity of the progestin by achieving a high degree of contraceptive efficacy while decreasing undesirable side effects associated with existing progestational agents. The androgenic activity of current progestins results in changes in lipid metabolism, particularly decreased levels of high-density lipoprotein cholesterol (HDL), which have been associated with an increased risk of coronary heart disease (CHD). A progestin with high antiovulatory activity and minimal androgenicity would offer a clear therapeutic advantage in oral contraception. Norgestimate (NGM) is a new progestin with a unique profile of biological activity that has demonstrated a high level of selectivity in preclinical assays. The present studies were conducted to confirm clinically the low androgenic activity of NGM. Norgestimate (0.25 mg) in combination with 0.035 mg ethinyl estradiol (NGM 0.25/35) was compared with 0.30 mg norgestrel combined with 0.030 mg ethinyl estradiol (Lo/Ovral) in two multicenter clinical studies. In the first study (1,261 women), HDL levels were significantly increased from baseline levels in NGM 0.25/35 subjects but were significantly decreased in Lo/Ovral subjects. Increases in low-density lipoprotein cholesterol (LDL) levels were moderate in the NGM 0.25/35 group and pronounced in the Lo/Ovral group. A favorable lipid profile in NGM 0.25/35 subjects was also reflected in the LDL/HDL ratios, which were significantly lower in the NGM 0.25/35 subjects than in the Lo/Ovral subjects. Sex hormone binding globulin (SHBG) binds androgens, preventing clinical expression of androgenic activity. As a result, elevations in SHBG levels reduce bioactive (unbound) androgen levels and decrease the potential for androgenic side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗