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PubMed1982

The effect of estrogen priming of hypogonadal women on the release of gonadotropins and prolactin in response to 2-hydroxyestradiol.

We have previously shown that the administration of a 2-hydroxyestradiol (20H-E2) infusion (250 microgram/h x 4 h) to hypogonadal women resulted in a selective increase in the levels of circulating prolactin (PRL) without changes in LH or FSH. The present study concerns the effect of estrogen priming of hypogonadal women on the release of gonadotropins and PRL in response to an identical 20H-E2 infusion. Estrogen priming consisted of a 5 day course of orally administered ethinyl estradiol at a daily dose of 300 micrograms. Significant (P less than 0.05) inhibition of LH release was observed within 1 h of the onset of the 20H-E2 infusion reaching a nadir (-25 +/- 2%) by 3.75 h. The circulating levels of FSH remained unaltered for the duration of the 8 h study. In contrast, significant (P less than 0.05) increments in the release of PRL could clearly be detected after a lag period of 1.5 h reaching a peak (+91 +/- 11%) by 4 h. These and previous findings demonstrate that the inhibitory influence of 20H-E2 on gonadotropin secretion is conditional upon prior estrogen priming while the ability of 20H-E2 to stimulate the release of PRL is not.

Aged↗

PubMed1991

Endometrial patterns during danazol and cyproterone acetate treatment for endometriosis: structural and ultrastructural study.

We studied the endometrial structure and ultrastructure in serial biopsies from 16 patients with endometriosis treated with danazol (n = 9) or the combination cyproterone acetate plus ethinyl estradiol (n = 7) for 6 months. Biopsies were performed before and at 3 and 6 months of treatment. The material obtained was studied by light (LM), scanning (SEM) and transmission electron microscopy (TEM). A morphometric analysis was performed evaluating three morphometric and three stereologic indices. The results indicate that danazol had a progestational effect on endometrial glands and stroma, associated with a marked hypotrophy of the mucosa. The cyproterone acetate/ethinyl estradiol combination induced progressive atrophy of the endometrium with an increase in the stromal component and a reduction of glandular tissue.

Adult↗

PubMedDate not supplied

Effect of later treatment with estrogen on reproductive tract lesions in neonatally estrogenized female mice.

Continuous ethinyl estradiol treatment following ovariectomy at day 38 of BALB/cfC3H mice treated neonatally with estradiol resulted in a more organized vaginal epithelium than that seen in the absence of postnatal estrogen, 30 days after treatment was initiated. Although the epithelium became increasingly disorganized in all neonatally estrogenized groups with age, the later estrogen treatment reduced the incidence and severity of vaginal epithelial lesions and the incidence of vaginal concretions. Uterine epithelial metaplasia was accelerated by the later estrogen treatment.

Animals↗

PubMed2001

Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

Adult↗

PubMed1991

Primary orchiectomy versus estrogen therapy in advanced prostatic cancer--a randomized study: results after 7 to 10 years of followup.

Of 163 new consecutively diagnosed cases of advanced (T3-4 M0 or T04M1) prostatic cancer 13 had contraindications for estrogen treatment, and the remainder were randomized to orchiectomy (76) or to estrogen treatment (74), consisting of 150 micrograms ethinyl estradiol daily and 80 mg. polyestradiol monthly. During the followup period of 7 to 10 years disease progression was noted in 27 patients (36%) treated with estrogen and 39 (51%) orchiectomized patients. The free of progression survival rate was significantly better (less than 0.05) among the estrogen treated patients but the over-all survival rates after orchiectomy and estrogen treatment were almost identical. A significantly higher frequency of cardiovascular side effects was noted in the estrogen group (23 cases) compared to the orchiectomy group (4 cases). Therefore, estrogen treatment in this form cannot be recommended for the palliative treatment of prostate cancer.

Aged↗

PubMed1988

Suitability of cyproterone acetate in the treatment of osteoporosis associated with athletic amenorrhea.

The effectiveness of the antiandrogenic agent cyproterone acetate (CA) in its contraceptive form (2 mg CA + 50 micrograms ethinyl estradiol) in the treatment of osteoporosis associated with athletic amenorrhea was studied in seven high-performance athletes. Four women with similar characteristics served as controls. Their mean age was 21.9 years +/- 3.9. Training was started at a mean age of 14.0 years +/- 2.0. The mean training intensity expressed as kilometers run per week was 35 +/- 15. Mineral density was primarily affected by the hypoestrogenic status of these athletes (= 22 pg/ml +/- 8.8 in the midluteal phase). All participants showed low serum progesterone (= 2.85 ng/ml +/- 2.10) and LH profiles (= 5.6 mlU/ml +/- 0.8) during the midluteal phase. Cyproterone acetate was administered for 8 months to treat the increased bone loss in seven women athletes. Vertebral density appeared to be increased with 9.5% +/- 2.45% (mean +/- SD) while cortical base mineral content measured at the radius was not significantly changed. Our results demonstrate that cyproterone acetate administered in combination with estrogens provides a suitable therapeutic agent in the management of osteoporosis due to a hypoestrogenic status. This treatment could substitute other contraceptive agents. Moreover, women with the most severe estrogen deficiency showed a more pronounced reaction to this therapy.

Adolescent↗

PubMed2006

Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol.

BACKGROUND: Steroid pre-treatments may be useful to program GnRH antagonist IVF/ICSI cycles. This prospective study assessed hormonal and ultrasound data collected during the free period after the discontinuation of three different pre-treatments to provide information on the optimal time interval required before starting stimulation. METHODS: Women were randomized to receive oral contraceptive pill (OCP) [ethinyl estradiol (E(2)) 30 microg + desogestrel 150 microg] (n = 21) or norethisterone 10 mg/day (n = 23) or 17-betaE(2) 4 mg/day (n = 25) or no pre-treatment (n = 24) for one cycle before IVF. Assessments were performed on post-treatment day (PD) 1, 3 and 5, or on spontaneous cycle day (CD) 1 and 3. RESULTS: After OCP and progestogen administration, FSH and LH concentrations shifted from strongly suppressed PD1 levels to PD5 values similar to those observed on CD1. Meanwhile, follicle sizes remained small up to PD5. In contrast, estrogen pre-treatment poorly reduced FSH levels on PD1 compared with OCP or progestogen. Consequently, follicle size was more heterogeneous. FSH rebound was maximal on PD3, whereas LH levels were slightly increased up to PD5. CONCLUSIONS: A 5-day free interval after OCP or progestogen offers the advantages of gonadotrophin recovery and homogeneous follicular cohort, whereas early FSH rebound occurring after estrogen pre-treatment argues for a short free period.

Adult↗

PubMed1978

Estrogen receptor in rat liver: translocation to the nucleus in vivo.

Following in vivo ethinyl estradiol (EE2) administration (100 microgram sc) to adult female rats, the estradiol-specific binding sites (ESBS) of liver cytosol were markedly reduced at 30 and 60 min. The reduction at 30 min was to one-quarter of that found in rats treated with vehicle alone. Coincident with this reduction, nuclear ESBS were increased. The ESBS of partially purified cytosol and of dense sucrose-purified nuclei were determined by gel filtration after incubations with tritiated estradiol using exchange assay conditions. An elevated temperature during the exchange assay incubations was necessary to demonstrate most of the ESBS in purified nuclei of EE2-treated rats and suggested that estrogens are attached at these sites. Following administration of 5 microgram EE2, the decrease in cytosol ESBS and the increase in nuclear ESBS were smaller. In contrast, 5 microgram EE2 was as effective as 100 microgram EE2 in substantially increasing the ESBS observed in uterine nuclear fractions. The low level of ESBS found in whole brain purified nuclei was unchanged by 100 microgram EE2 administration. The steroid specificity and proteolytic enzyme sensitivity of the purified nuclear ESBS of treated rats were similar to that of the partially purified cytosol ESBS of rats treated with vehicle alone. The data are consistent with the ESBS being estrogen receptor proteins which translocate from the liver cytosol to the nucleus after estrogen administration in vivo.

Animals↗

PubMed1978

Effect of chronic administration of estrogen, androgen, or both on serum levels of gonadotropins in adult men.

Ethinyl estradiol (50 micrograms/day) or fluoxymesterone (10 or 20 mg/day), chosen because each is orally active and because fluoxymesterone is probably not converted to an estrogen, were given alone and in combination to adult men over several weeks. Measurements were made of serum FSH, LH, testosterone, and estradiol. The estrogen given alone suppressed serum FSH while the androgen given alone did not; however, the androgen may have enhanced the suppressive effect of the estrogen on the serum FSH. Neither steroid alone changed the serum LH but both together suppressed it. The estrogen alone decreased the serum testosterone, an effect probably mediated by the concomitant fall in serum FSH and a resulting decrease in sensitivity to the constant level of LH; a direct effect of estrogen on the testis seems less likely. The doses of estrogen and androgen used probably had a biologic effect equal to or somewhat above that of endogenously produced estrogen and androgen and thus reflected the maximum physiological effects of the endogenous steroids. Thus, in the chronic physiological control of FSH and LH in adult men, these data indicate that (1) testosterone alone, as an androgen, has little effect on FSH or LH, (2) estradiol (or total estrogen) has a greater suppressive effect on FSH than on LH and by its effect on FSH may indirectly regulate the secretion of testosterone, and (3) testosterone and estradiol together may be involved in the regulation of both FSH and LH.

Adult↗

PubMed1998

Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females.

Plasma total homocysteine (tHcy) levels are higher in men vs. premenopausal women, but it is not known whether this difference is related to sex steroids. The effects of cross-sex hormone administration on plasma tHcy levels were therefore investigated. Plasma tHcy levels were measured at baseline and after 4 months of treatment in 17 male-to-female (M-->F) transsexuals treated with ethinyl estradiol (100 micrograms/day), in combination with the antiandrogen, cyproterone acetate (100 mg/day), and in 17 female-to-male (F-->M) transsexuals treated with testosterone esters (250 mg/2 weeks, im). In M-->F transsexuals, the plasma tHcy level decreased from geometric mean 8.2 mumol/L to 5.7 mumol/L (P < 0.001); and in F-->M transsexuals, it increased from 7.7 mumol/L to 9.0 mumol/L (P = 0.005). In M-->F transsexuals, changes in serum sex hormone-binding globulin levels correlated negatively, and changes in plasma creatinine and albumin levels correlated positively, with changes in plasma tHcy levels. In F-->M transsexuals, changes in serum 17 beta-estradiol levels correlated negatively, and changes in plasma creatinine levels correlated positively, with changes in plasma tHcy levels. We conclude that tHcy levels decrease after estrogen + antiandrogen administration to male (transsexual) subjects, and levels increase after androgen administration to female (transsexual) subjects. These changes may be both primary and secondary to the anabolic/catabolic effects, as reflected by changes of creatinine and albumin levels after cross-sex hormone administration.

Androgen Antagonists↗

PubMedDate not supplied

Comparison of transdermal and oral estrogen therapy in girls with Turner's syndrome.

Eight girls with Turner's syndrome were given low dose oral ethinyl estradiol or transdermal 17 beta-estradiol in order to compare the effect of the route of administration on selected markers of hepatic metabolism, and various hormonal concentrations. Oral estrogen was given at a dose of 100 ng/kg/day and transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day. The subjects received one form of estradiol for one month, and after a one month washout period, received the other form. Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal resulted in a significant decrease in LH. Oral estradiol, though not transdermal estradiol, increased serum high density lipoprotein, thyroxine binding protein and growth hormone binding protein. Urinary growth hormone excretion increased after both forms of therapy, while insulin-like growth factor-I and insulin-like growth factor binding protein-3 remained unchanged. Thus, in girls with Turner's syndrome, estrogen replacement by the transdermal route may have less deleterious effect on hepatic metabolism than oral estrogen.

Administration, Cutaneous↗

PubMed1980

Regulation of low density lipoprotein receptors by adrenocorticotropin in the adrenal gland of mice and rats in vivo.

Membranes prepared from the adrenal gland of mice and rats possess high affinity binding sites that recognize 125I-labeled human low density lipoprotein (LDL). These binding sites resemble the functional LDL receptors that mediate the uptake of LDL by cultured mouse and bovine adrenal cells. The number of LDL binding sites per mg of membrane protein increased 2- to 5-fold over 24 h when mice or rats were treated with adrenocorticotropin (ACTH). In rats, this increase was accompanied by a similar ACTH-induced increase in the adrenal uptake of intravenously administered 125I-LDL, suggesting that the LDL binding sites mediate the uptake of LDL by the adrenal in the intact animal. The number of LDL binding sites on adrenal membranes rose by 5-fold when animals were rendered lipoprotein-deficient, either by treatment of mice with 4-aminopyrazolopyrimidine or by treatment of rats with 17 alpha-ethinyl estradiol. This increase was prevented when endogenous ACTH secretion was blocked by administration of dexamethasone, suggesting that ACTH was required. The current experiments suggest that LDL receptors provide one source of cholesterol for the mouse and rat adrenal in vivo and that the number of LDL receptors of this organ is regulated by ACTH.

Adrenal Glands↗

PubMed1980

Estrogens and postoperative thrombosis evaluated by the radioactive iodine method.

Women who were to be operated upon for prolapse of the uterus were treated preoperatively with estrogens for atrophic vaginal mucosa and examined postoperatively by the 125I-fibrinogen uptake test and phlebography. Among 11 women who received 50 micrograms of ethinyl estradiol daily for three weeks, fibrin deposits were found in six. Of eight women receiving 200 micrograms daily for 12 days, such deposits developed in four. Corresponding figures for the control group were 18 of 157, p < 0.001. Estrogens, therefore, should not be given preoperatively, and those patients treated with preparations containing estrogens should have such therapy discontinued preoperatively.

Estradiol↗

PubMed1980

Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.

The pathogenesis of ovarian dysfunction in uremia was evaluated in 24 patients by measurements of plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone, prolactin, estradiol, and progesterone basally and after clomiphene, ethinyl estradiol, and bromocriptine. In the 17 premenopausal women, levels of plasma estradiol, progesterone, and FSH were comparable to those found in normal women during the follicular phase of the ovarian cycle; plasma luteinizing hormone was slightly elevated. In most patients, there was an absence of cyclicity. After clomiphene, plasma levels of luteinizing hormone, FSH, and estradiol rose; after ethinyl estradiol, plasma luteinizing hormone levels failed to increase. In seven postmenopausal patients, plasma estradiol was undetectable and gonadotropin levels were markedly elevated. Although plasma prolactin was generally elevated, suppression of prolactin with bromocriptine resulted in resumption of ovulation in only one patient; the other 2 remained amenorrheic. In uremic women, the continued secretion of estrogen, the rise of plasma levels of luteinizing hormone, FSH, and estradiol after clomiphene, and the elevated gonadotropin levels during menopause suggest that the negative estradiol feedback, the tonic gonadotropin secretion, and the pituitary ovarian axis were normal. The positive estradiol feedback associated with cyclic release of luteinizing hormone, however, was impaired as indicated by the prevalence of acyclicity and the failure of luteinizing hormone levels, to rise after ethinyl estradiol.

Adolescent↗

PubMed1989

Clinical experience with an ethinyl estradiol-desogestrel oral contraceptive.

Desogestrel (150 micrograms), a potent progestogen virtually devoid of androgenic activity, was used in combination with 30 micrograms ethinyl estradiol as an oral contraceptive preparation (Marvelon). 219 women completed a total of 4074 cycles, and the use-effectiveness was 0.58 Pearl Units. Serious side effects were not observed. The drug-related discontinuation index was 12.8% in six months.

Adult↗

PubMed1998

A randomized cross-over study on various hormonal parameters of two triphasic oral contraceptives.

The effect of two triphasic oral contraceptives (Triquilar [TRQ] and Trisiston [TRS]) containing ethinyl estradiol (EE) and levonorgestrel (LNG) on various hormonal parameters was investigated in 26 women during a cross-over study. TRS consisted of 0.03 mg EE + 0.05 mg LNG (six tablets), 0.04 mg EE + 0.075 mg LNG (six tablets), and 0.03 mg EE + 0.15 mg LNG (nine tablets), whereas TRQ was different in the second phase (five tablets) and third phase (10 tablets). Blood samples were taken on days 6, 11, 21, and 28 of the control and washout cycles and the third treatment cycle. Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins, free testosterone, and dehydroepiandosterone sulfate in a time-dependent manner, whereas estradiol and testosterone were already suppressed on day 6, indicating a direct suppressive effect on ovarian steroid synthesis. Prolactin, which rose sporadically in some women, was not significantly changed. In contrast, the levels of sex hormone binding globulin, corticosteroid binding globulin, and cortisol were significantly elevated by 100%. During the hormone-free interval of 7 days, all parameters returned at least partly to baseline. There was no significant difference between the effects of both formulations. The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis.

Adult↗

PubMed2004

Hormonal treatment of acne: review of current best evidence.

BACKGROUND: Recent controlled clinical trials have demonstrated the efficacy of various hormonal preparations, including oral contraceptives, in treatment of acne. OBJECTIVE: The goal of this article is to evaluate the best current evidence on the efficacy of hormonal treatment of acne. METHODS: English-language controlled clinical trials of systemic hormonal treatment of acne were sought by search of references of general dermatology texts, reviews on acne, drug product monographs, and computer-assisted search of MEDLINE, CINAHL, and COCHRANE databases between 1970 and 2003 using the key words hormonal, oral contraceptive, acne, spironolactone, cyproterone, flutamide, and therapy. For each agent, studies fulfilling the highest level of evidence were selected for further evaluation. RESULTS: The literature search recovered two placebo-controlled random controlled trials (RCTs) each of ethinyl estradiol 0.035 mg and norgestimate and ethinyl estradiol 20 microg and leonorgestrel 100 microg, three active-comparator RCTs of ethinyl estradiol 0.035 mg and cyproterone acetate 2 mg, one active comparator RCT of ethinyl estradiol 30 mug and drosperinone 3 mg, three small placebo-controlled RCTs of spironolactone, and one active-comparator RCT of flutamide. CONCLUSIONS: The efficacy of Tri-Cyclen and Alesse in acne is supported by high-quality RCTs (level A evidence). Evidence for the efficacy of Diane-35, spironolactone, and flutamide is derived from lower-quality RCTs (level B evidence). Results from a population-based epidemiological study suggests that Diane-35 is the most effective of these oral contraceptives in the treatment of acne (level B evidence; epidemiological study).

Acne Vulgaris↗

PubMed1973

Alteration of bile canalicular enzymes in cholestasis. A possible cause of bile secretory failure.

Bile secretory failure (cholestasis) may result from several possible mechanisms involved in bile secretion. We have examined the possibility that abnormalities in enzyme content, composition, and turnover of liver plasma membrane constituents are altered in cholestasis. Severe and mild cholestasis were produced by 5 days of bile duct ligation and ethinyl estradiol administration, respectively. Bile duct ligation but not ethinyl estradiol treatments was associated with elevations of the serum bilirubin level and 5'-nucleotidase activity. However, basal bile flow and bilirubin transport maximum (T(m)) were significantly reduced after ethinyl estradiol treatment. Liver plasma membrane fractions rich in canalicular membranes were prepared from groups of rats in each of three categories; normal, after bile duct ligation, or ethinyl estradiol administration, and their respective controls. Electron microscopy and enzyme marker studies demonstrated plasma membrane fractions free of significant contamination. Plasma membrane fractions prepared from mild as well as severe cholestasis had increased alkaline phosphatase activity, and reduced 5'-nucleotidase and Mg(2+)-ATPase activities. Co(2+)-CMPase activity was unchanged. Kinetic analysis of 5'-nucleotidase and Mg(2+)-ATPase activities in plasma membrane fractions demonstrated reduced V(maz) (but unaltered K(m)). Reducted V(maz) was unrelated to addition in vitro of di-or trihydroxy bile salts or ethinyl estradiol and, therefore, suggests that reduced activities in cholestasis are due to decreased enzyme content. Cholestasis was not associated with changes in the synthesis or degradation rate of pulse-labeled plasma membrane proteins or alterations in the major protein bands separated on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Plasma membrane cholesterol, phospholipid, and neutral sugar content was unaltered, but sialic acid content was significantly increased in both forms of cholestasis. Alterations in specific canalicular enzymes in two forms of cholestasis suggest that these changes may be involved in the pathogenesis of bile secretory failure, or may result from cholestasis.

Adenosine Triphosphatases↗