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Cytoplasmic receptors for 17 beta-estradiol, 5 alpha-dihydrotestosterone and progesterone in normal and abnormal human uterine tissues.

Determinations of specific cytoplasmic receptors for 17 beta-estradiol (E), 5 alpha-dihydrotestosterone (DHT) and progesterone (P) in normal and abnormal endometrium are reported. The standardization of methodology with particular emphasis on specificity trials is outlined. Receptors were present in all but one case, a moderately differentiated endometrial adenocarcinoma. Generally speaking, steroid and peptide hormone plasma content in patients with malignant conditions were at the lower limit values of normal, except for follicle-stimulating hormone which had values significantly higher than normal. The question of E competition with DHT in binding DHT-receptor and the therapeutic implications of P-receptor estimation are discussed.

Adult↗

[Oral contraceptives in prophylaxis of acute exacerbations of intermittent porphyria (author's transl)].

Out of 14 women with acute intermittent porphyria seven were treated for an average of five years with ovulation inhibitors. In another two cases a bilateral surgical oophorectomy and a radiotherapeutic castration were performed. Five untreated women formed the control group. In contrast to the control group there were no further acute exacerbations in the group treated with oral contraceptives. The two patients with oophorectomy and irradiation castration died following multiple acute exacerbations. In four of the women treated with oral contraceptives the development of persistent, and in some cases severe, arterial hypertension was observed. The pathogenesis cannot be explained.

Acute Disease↗

A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology.

Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.

Adult↗

Prolonged biphasic response of plasma testosterone to single intramuscular injections of human chorionic gonadotropin.

The response of plasma testosterone to varying doses of hCG (0--6000 IU) given as a single im injection has been evaluated in normal men. After an initial rise at 2 h, the levels of testosterone demonstrated a secondary rise, reaching a peak 48 h after the im injection. The magnitude of the response varied directly with the dose of hCG used, and at the highest dose (6000 IU) testosterone levels were still elevated 6 days after administration. Plasma estradiol levels showed a dose-dependent rise, with peak levels being attained 24 h after hCG. The prolonged response of plasma testosterone to a single injection of hCG should prompt a reevaluation of diagnostic and therapeutic regimens using this agent.

Adult↗

Effects of hormone deprivation and 2-methoxyestradiol combination therapy on hormone-dependent prostate cancer in vivo.

2-Methoxyestradiol (2-ME) has potent antiproliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgen-dependent and independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay and measuring microvessel density (MVD) in excised tumors. Animals harboring hormone-dependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, and 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis and a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo and combination therapy resulted in a significant increase in efficacy compared to no treatment controls and trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

2-Methoxyestradiol↗

[A case of Leydig cell tumor of the testis].

Leydig cell tumors represent about 3% of all testicular neoplasms. Actually no specific pathologic criteria has really distinguished the benign from the malignant tumors which represent about 11% of the cases. The presence of metastases is the only unequivocal criteria of malignancy. Authors present a rare Leydigoma case with gynecomastia. Clinical, diagnostical and most of all therapeutical aspects are discussed reconfirming the role of the orchifuniculectomy in T1 N0 M0 stage.

Adult↗

Estrogenic absorption through the skin: an experimental study.

Our results show in an unquestionable way that both the steroid (ethinylestradiol) and non-steroid (Ralone) estrogens studied by us were absorbed percutaneously by the rat. They also demonstrate that both estrogens affected target organs in a quite similar way being proportionally dependent upon the 1-to-1,000 ratio existing between them, as established on the basis of a known activity parameter. When one of the two estrogens is given for therapeutical purposes its systemic effects are of a dose-related type.

Animals↗

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release.

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

Animals↗

Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone.

Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed. This study examines the specific effects of estradiol and progesterone on neutrophil apoptosis and function in healthy adult men and women. We also examined the contribution of these hormones to the persistence and resolution of an inflammatory response. Spontaneous apoptosis was significantly decreased in women compared with men. Physiologic doses of estradiol and progesterone caused a further delay in spontaneous apoptosis in both men and women but did not diminish Fas antibody-induced apoptosis. The delay in apoptosis was mediated at the level of the mitochondria with decreased release of cytochrome c, which may alter caspase cleavage and activity. There were no associated alterations in neutrophil CD11b, but production of reactive oxygen intermediates (ROIs) in women was increased. Thus, female sex hormones mediate delayed neutrophil apoptosis in both sexes and enhance female intracellular production of ROIs. Modulating hormonal responses may be an effective therapeutic tool in combating inflammatory diseases.

Adult↗

[Combined therapy with bromocriptine, clomiphene and gonadotropin for polycystic ovary syndrome patients failing to respond to clomiphene alone].

The purpose of this study is to investigate the ovulatory effect of the combined therapy with bromocriptine (Brc), clomiphene (Cl) and HMG. We investigated 25 patients with polycystic ovary syndrome (PCOS) who had anovulatory normoprolactinemia and failed to respond to Cl therapy alone. The results were as follows: 1) The ovulation rate with Method I(Brc/Cl) was 64.0% (16/25) in 25 cases, and 59.8% in 122 cycles. 2) Resting levels of serum dehydroepiandrosterone sulfate in the effective group with Method I were significantly lower than those in the non-effective group. 3) With Method I, serum prolactin (PRL), LH and testosterone were significantly decreased, while estradiol and progesterone concentrations were significantly increased in the effective group. However, there were no significant changes in the hormone levels except PRL in the non-effective group. 4) Out of the 9 nonrespondent Method I cases, 5 additional cases ovulated with both Method II(Brc/Cl+ a small dose of HMG) and Method III(Brc/Cl+ an increased dose of HMG-HCG). The total ovulatory rate was 84.0% (21/25) in 25 cases and 59.4% (85/143) in 143 cycles. 5) The total pregnancy rate was 43.8% (7/16). Six cases were normal pregnancies, one case was a twin pregnancy and there was no case of abortion. Our results suggested that the combined therapy with Brc, Cl and HMG had almost the same therapeutic effect as the HMG-HCG therapy in severe cases of PCOS.

Adolescent↗

Effect of electro-acupuncture on ovarian expression of alpha (1)- and beta (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries.

BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. METHODS: In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of alpha1a-, alpha1b-, alpha1d-, and beta2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). RESULTS: It was found that EV injection results in significantly higher mRNA expression of ovarian alpha1b- and alpha1d-AR in PCO rats compared to control rats. The p75NTR and beta2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of beta2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of alpha1a-, alpha1b- and alpha1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for alpha1b-AR. CONCLUSION: The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.

Animals↗

[Experimental study on preventive and therapeutic effect of bushen huoxue recipe on autoimmune premature ovarian failure model].

OBJECTIVE: To investigate the mechanisms of Bushen Huoxue Recipe (BSHXR), a Chinese herbal medicinal preparation for tonifying Kidney and invigorating blood circulation, to prevent and treat autoimmune premature ovarian failure (POF) model. METHODS: Female 8-10 weeks old BAL B/c mice were immunized by intracutaneously injecting porcine ovum zona pellucida (ZP), isolated by immuno-chromatography, in multiple points of two hind footpads to establish the POF model and treated with BSHXR started from early stage of immunization (prevented group) or after 3 times of injection (treated group). Changes in vaginal smears, serum estradiol (E2), antibody titer against ZP, response of splenic lymphocyte to ZP stimulation of different concentrations, and numbers of ovarian follicles and corpus luteum were analyzed. RESULTS: Serum E2 level in the prevented and treated mice was all higher than that in the non-treated immunized model mice (the control group), P < 0.01 and P < 0.05 respectively. But the anti-ZP titer lowered significantly after BSHXR administration, as compared with that in the control group. Level of antibodies in the treated group was lower than that of the control, and it was also lower in the prevented group than that in the control. The histo-morphological examination showed that the developing follicles and corpus luteum after BSHXR medication in both prevented and treated group increased significantly as compared with that of the control group (P < 0.05 and P < 0.01 respectively). Splenic lymphocyte in the immunized model showed a higher antigen-specific proliferation reaction than that in non-immunized animal, and the reaction was ameliorated by BSHXR medication. CONCLUSION: BSHXR could recover part of the ovarian function in POF mice mainly through inhibiting specific immune injury to revive the remnant follicles in ovary. The preventive effect of BSHXR was superior to the therapeutic effect of it.

Animals↗

Estrogen activates protein kinase C in neurons: role in neuroprotection.

It has been previously demonstrated that estrogen can protect neurons from a variety of insults, including beta-amyloid (Abeta). Recent studies have shown that estrogen can rapidly modulate intracellular signaling pathways involved in cell survival. In particular, estrogen activates protein kinase C (PKC) in a variety of cell types. This enzyme plays a key role in many cellular events, including regulation of apoptosis. In this study, we show that 17beta-estradiol (E2) rapidly increases PKC activity in primary cultures of rat cerebrocortical neurons. A 1 h pre-treatment with E2 or phorbol-12-myristate-13-acetate (PMA), a potent activator of PKC, protects neurons against Abeta toxicity. Protection afforded by both PMA and E2 is blocked by pharmacological inhibitors of PKC. Further, depletion of PKC levels resulting from prolonged PMA exposure prevents subsequent E2 or PMA protection. Our results indicate that E2 activates PKC in neurons, and that PKC activation is an important step in estrogen protection against Abeta. These data provide new understanding into the mechanism(s) underlying estrogen neuroprotection, an action with therapeutic relevance to Alzheimer's disease and other age-related neurodegenerative disorders.

Amyloid beta-Peptides↗

[Cyclic ethinyl estradiol and medroxyprogesterone in climacteric women. Their clinicAL efficacy and patterns of uterine bleeding].

The study evaluated the clinical efficacy substitutive hormonotherapy regime in a group of 40 postmenopausal, women with moderate to severe symptomatology and negative progesterone challenge test. Each cycle consisted in the administration of 15 micrograms of ethinyl estradiol during 21 days, plus 10 mg medroxyprogesterone acetate (MPA) the last 10 days. Each patient received four cycles of therapy with 10 days of interval between them. The global clinical response was evaluated as favorable (excellent and good responses) in 97.5% of the patients. All the patients showed an improvement of the vaginal trophism (colpocytology). The great majority of the women experimented cyclical bleeding as consequence of the treatment. The post-therapeutic bleeding (Withdrawal) was the predominant bleeding pattern. This fact suggests that the 10 mg of MPA added daily during 10 days could allow a suitable opposition to the estrogenic proliferative effect inducing an adequate secretory response and the subsequent endometrial desquamation.

Climacteric↗

Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study.

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.

Adult↗