Hormonal contraception without estrogens

The long-term clinical effects of ethinyl estradiol and the impact on environmental safety of the alkylated estrogen components used in combined contraceptive pills remain the subject of debate. The development of improved methods for the use of progestogen-only contraception would represent a viable and desirable option. Several progestogen compounds are not alkylated, and these can be delivered through a variety of routes. Some of the progestogen-only methods are well established in clinical use. Estimates for both perfect and typical effectiveness are less than one pregnancy per 100 woman-years with oral, injectable, implantable and intrauterine methods. In practice, with the oral progestogen-only method, perfect and typical effectiveness range from three to five pregnancies per 100 woman-years. The main side effect with all progestogen-only methods is unpredictable vaginal bleeding during the first months of use, and this may lead to discontinuation. Nevertheless, continuation of use is more frequent if patients are well informed of this side effect before treatment begins. No cardiovascular- and cancer-related side effects have been proven.     

Anti-Müllerian hormone concentrations in maternal serum during pregnancy

BACKGROUND: In females, anti-Müllerian hormone (AMH) is expressed only by the ovary. AMH is secreted by the granulosa cells of ovarian follicles and appears to regulate early follicle development. AMH is detected in serum from women of reproductive age and its levels vary slightly with the menstrual cycle, reaching the peak value in the late follicular phase. This study investigated serum AMH levels throughout gestation and after delivery in healthy pregnant women. METHODS: This cross-sectional study recruited pregnant women and healthy non-pregnant women, 84 in total. AMH, FSH and E2 were measured in the follicular phase, in the three trimesters of pregnancy and in early puerperium. RESULTS: Estradiol and FSH levels followed the expected patterns during gestation. During the follicular phase of the menstrual cycle AMH levels were 1.9 +/- 0.5 ng/ml. In the three trimesters of pregnancy and in early puerperium AMH levels were: 2.1 +/- 0.56, 2.4 +/- 0.64, 1.95 +/- 0.6 and 2.05 +/- 0.55 ng/ml respectively. No significant modifications were found in AMH levels during pregnancy and in the early puerperium. CONCLUSIONS: This study has obtained information on AMH and on the possible relationship with FSH. We hypothesize that the profile of the new marker of ovarian activity AMH may indicate that initial non-cyclic ovarian follicular activity during pregnancy is not abolished. Moreover FSH, does not seem to play a direct role on AMH synthesis and secretion.     

Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 μg/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 ± 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.     

激素性股骨头坏死血管新生相关基因的鉴定及其靶向中药成分筛选验证

目的 基于生物信息学分析筛选激素性股骨头坏死（steroid induced osteonecrosis of femoral head,SONFH）中涉及血管生成相关的基因,进一步探讨其作用机制并筛选靶向中药活性成分。方法 通过Perl语言和R软件处理GEO数据,获得SONFH的关键差异基因,使用David工具进行基因本体（gene ontology,GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）分析。然后使用STRING平台和Cytoscape软件分析蛋白互作关系,用MCODE和CytoHubba插件识别重要基因簇模块和核心基因,并进一步验证。使用CTD数据库搜索靶向核心基因的中药活性成分并用autodock vina软件进行分子对接,以及探索核心基因与SONFH的相互作用。利用激素诱导人股骨头骨微血管内皮细胞（bone microvascular endothelial cells,BMECs）,通过CCK-8、细胞划痕实验和Transwell实验观察白藜芦醇对细胞增殖及迁移的影响,通过Western ...     

The effect of ketoconazole and transdermal estradiol on serum sex steroid hormones levels

Summary In this randomized, open-label trial, 24 subjects were studied. There were 12 subjects with essential hypertension and 12 normotensive controls who received, after an initial control period, 48 h of treatment with a transdermal estradiol patch or ketoconazole tablets every 8 h for six doses, or in combination. LHRH (100 g) and ACTH (250 g) were given at 48 h of each treatment. Each treatment was one week apart.In both normotensive and hypertensive men ketoconazole reduced adrenal and gonadal androgens, raised 11-deoxycortisol and 17 -hydroxyprogesterone levels; blunted the rise of cortisol to ACTH and had no effect on the response of LH to LHRH. Transdermal estradiol raised serum estradiol levels, blunted the time to peak plasma concentration of LH to LHRH and produced a normal response to ACTH. Although baseline level of total and free testosterone and DHEA-S were lower in hypertensive men, the response of the pituitary (LH) to LHRH and adrenal axis with ACTH were similar in both normotensive and hypertensive men. Blood pressure was unaffacted by any of the treatment interventions in either normotensive or hypertensive men.Although ketoconazole or transdermal estradiol reduce androgens, there was no evidence that this reduction in androgens was involved with the short term regulation of blood pressure in hypertensive men.     

Mechanism of Ethanol-Enhanced Estradiol Permeation Across Human Skin in Vivo

The influence of ethanol on the permeation of 17-estradiol (estradiol) across viable human skin in vivo was investigated with the human skin sandwich flap model. Maintaining continuous delivery of a constant concentration of the solute in phosphate-buffered saline, pH 7.4 (PBS), or mixtures of ethanol in PBS to the skin surface revealed that steady-state flux of estradiol was achieved within 30–60 min and maintained throughout 4 hr. The 10-fold decrease in in vivo flux and permeability coefficient (K _p) of tracer estradiol solutions in ethanol or ethanol solutions compared with PBS vehicle reflected the 10-fold difference in the apparent partition coefficients (K _m) of estradiol from the respective vehicles into isolated human stratum corneum. Neither the stratum corneum thickness nor the diffusion coefficient of estradiol was significantly different among the vehicles tested. In vivo flux of estradiol in ethanol or ethanol solutions across viable human skin was increased with saturated solutions of estradiol. Further, in vivo flux of estradiol from vehicles such as PBS, ethanol, and ethanol mixtures, which minimally alter the rate-limiting barrier, can be successfully predicted with knowledge of only two physicochemical parameters, the estradiol concentration in the vehicle and the K _m of estradiol from the vehicle into isolated human stratum corneum.     

Study on Relevance of Endothelin to Abnormal Uterine Bleeding Associated with Long-Term Subdermal Implants Use

Objective To investigate the relationship between estradiol, progesterone and endothelin (ET) and abnormal uterine bleeding after using sub-dermal contraceptive implant Materials & methods A prospective self-control clinical trial was conducted in 29 women in the self-control group. Blood samples were obtained on four occasions across the different phases of menstrual cycle before and after using implant. A blood sample was taken for a single determination in another 59 women in the already-use implant group. Plasma of estradiol, progesterone and endothelin were determined by using radioimmunoassays (RIA) in both groups.Results The level of estradiol and progesterone had no significant differences in women before and after using implant in self-control group. The level of estradiol,progesterone had no differences between women with normal and abnormal menstrual cycle in both groups. The levels of plasma endothelin (ET) in women with abnormal bleeding pattern were higher than women with normal bleeding pattern, but difference was not significant. Women with abnormal bleeding pattern had significantly higher ET level than that in women with normal bleeding pattern before using implants,especially in early-proliferative phase and mid-proliferative phase. the level of plasma endothelin was significantly higher in women with disturbed bleeding pattern than that in normal women in the already-use group.Conclusion High serum concentrations of ET are likely to be correlated with abnormal uterine bleeding in long-term subdermal contraceptive implants users.     

妊娠期雌二醇和催乳素与瘦素的关系

目的 研究妊娠期间性激素与瘦素水平之间的关系。方法 在180例不同孕周的妇女中,按孕周分为＜20周组,20－23周组,≥28周组,采用酶联免疫吸附法测定其外周血血清雌二醇（E2）和催乳素（PRL）,放射免疫法测定血清瘦素水平,分析这些激素之间的相互关系。结果 E2和PRL均随妊娠进展而逐步升高（P＜0．0001）,组间均有显著差异（P＜0．05）。各组瘦素水平均高于非妊娠组,但组间差异无显著性。瘦素水平与孕妇体重及体重指数显著相关（P0．01）,与PRL也呈相关（P＜0．05）,而与E2无明显相关。结论 PRL水平与妊娠期瘦素水平升高有一定关系。     

Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells

Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 M estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-xL or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.     

Effects of estradiol on concentrations of gonadotropin-releasing hormone receptor messenger ribonucleic acid following removal of progesterone

To test the hypothesis that low levels of estradiol are sufficient to increase concentrations of GnRH receptor mRNA in the absence of progesterone, ewes were ovariectomized and immediately treated with estradiol implants for 12 h to achieve circulating concentrations of estradiol typical of the early (n=5) or late (n=4) follicular phase. Five additional ewes underwent lutectomy, and control ewes were untreated. Treatment of ewes with 1/2 or 1 estradiol implant increased concentrations of estradiol in serum to 3.0 ± 0.8 pg/ml or 6.3 ± 0.3 pg/ml, respectively, and concentrations of estradiol in lutectomized ewes (2.4 ± 0.5 pg/ml) were intermediate. Ovariectomy did not alter concentrations of GnRH receptor mRNA or numbers of GnRH receptors. Treatment of ewes with 1 estradiol implant increased concentrations of GnRH receptor mRNA and numbers of GnRH receptors. In ewes treated with 1/2 estradiol implant, concentrations of GnRH receptor mRNA were intermediate between controls and ewes treated with 1 estradiol implant, and numbers of GnRH receptors were greater than controls. Lutectomy increased concentrations of GnRH receptor mRNA but did not affect numbers of GnRH receptors. We conclude that estradiol stimulates expression of the GnRH receptor gene and numbers of GnRH receptors in the absence of progesterone. However, effects of estradiol on expression of the GnRH receptor gene were clearly evident only when concentrations of estradiol were elevated to levels typical of the late follicular phase.