المؤلفون: Rodari G; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Federici S; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.; Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy., Todisco T; Endocrinology Unit, University-Hospital Pediatric Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Ubertini G; Endocrinology Unit, University-Hospital Pediatric Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Cattoni A; Pediatric Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.; Department of Medicine and Surgery, Milano-Bicocca University, Milan, Italy., Pagano M; Pediatric Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.; Department of Medicine and Surgery, Milano-Bicocca University, Milan, Italy., Giacchetti F; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Profka E; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Citterio V; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy., Messetti D; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy., Collini V; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy., Soranna D; Biostatistics Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy., Carbone E; Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy., Arosio M; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Mantovani G; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Persani L; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.; Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy., Cappa M; Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Bonomi M; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.; Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy., Giavoli C; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.; Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2023 Jun 07; Vol. 188 (6), pp. 467-476.

نوع المنشور: Multicenter Study; Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Progesterone*/therapeutic use , Hypogonadism*/drug therapy, Adult ; Female ; Humans ; Child ; Retrospective Studies ; Puberty/physiology ; Estradiol/therapeutic use

مستخلص: Objective: An evidence-based pubertal induction scheme in hypogonadal girls is still to be established. Interestingly, literature data report a suboptimal uterine longitudinal diameter (ULD) in >50% of treated hypogonadal women, negatively influencing their pregnancy outcomes. This study aims to investigate auxological and uterine outcomes of pubertal induction in girls in the light of underlying diagnosis and therapeutic schemes used.
Design: Retrospective analysis of longitudinal data from a multicentric registry.
Methods: Auxological, biochemical, and radiological data were collected at baseline and during follow-up in 95 hypogonadal girls (chronological age > 10.9 years, Tanner stage ≤ 2) treated with transdermal 17β-oestradiol patches for at least 1 year. Induction was started at a median dose of 0.14 mcg/kg/day with a 6-monthly increase and was considered completed for 49/95 patients who started progesterone with a concomitant oestrogen adult dose.
Results: At the end of induction, the achievement of the complete breast maturation was associated with a 17β-oestradiol dose at progesterone introduction. ULD showed a significant correlation with a 17β-oestradiol dosage. Final ULD was >65 mm in only 17/45 girls. At multiple regression analysis, pelvic irradiation represented the major determinant of reduced final ULD. After correction for uterine irradiation, ULD was associated with the 17β-oestradiol dose at progesterone introduction. Final ULD was not significantly different from the one assessed after progesterone introduction.
Conclusions: Our results provide evidence that progestins, hampering further changes in uterine volume and breast development, should be introduced only in the presence of a concomitant adequate 17β-oestradiol dose and an appropriate clinical response.
Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.
(© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

المؤلفون: Gashaw I; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Reif S; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Wiesinger H; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Kaiser A; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Zollmann FS; Pharma Consult, 12161 Berlin, Germany., Scheerans C; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Grevel J; Clinical Development, Bast GmbH, 69115 Heidelberg, Germany., Piraino P; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Seidel H; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Peters M; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Rottmann A; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Rohde B; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Arlt W; Medical Research Council London Institute of Medical Sciences, W12 0NN London, United Kingdom.; Department of Clinical Sciences, Faculty of Medicine, Imperial College London, W12 0NN London, United Kingdom., Hilpert J; Research and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2023 Jul 10; Vol. 188 (7), pp. 578-591.

نوع المنشور: Randomized Controlled Trial; Clinical Trial, Phase I; Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Aldo-Keto Reductase Family 1 Member C3*/antagonists & inhibitors , Aldo-Keto Reductase Family 1 Member C3*/metabolism , Androgens*/metabolism , Progesterone*, Female ; Humans ; Androsterone ; Dihydrotestosterone ; Hydroxyprostaglandin Dehydrogenases/metabolism ; Steroids

مستخلص: Objective: Aldo-keto reductase 1C3 (AKR1C3) has been postulated to be involved in androgen, progesterone, and estrogen metabolism. Aldo-keto reductase 1C3 inhibition has been proposed for treatment of endometriosis and polycystic ovary syndrome. Clinical biomarkers of target engagement, which can greatly facilitate drug development, have not yet been described for AKR1C3 inhibitors. Here, we analyzed pharmacodynamic data from a phase 1 study with a new selective AKR1C3 inhibitor, BAY1128688, to identify response biomarkers and assess effects on ovarian function.
Design: In a multiple-ascending-dose placebo-controlled study, 33 postmenopausal women received BAY1128688 (3, 30, or 90 mg once daily or 60 mg twice daily) or placebo for 14 days. Eighteen premenopausal women received 60 mg BAY1128688 once or twice daily for 28 days.
Methods: We measured 17 serum steroids by liquid chromatography-tandem mass spectrometry, alongside analysis of pharmacokinetics, menstrual cyclicity, and safety parameters.
Results: In both study populations, we observed substantial, dose-dependent increases in circulating concentrations of the inactive androgen metabolite androsterone and minor increases in circulating etiocholanolone and dihydrotestosterone concentrations. In premenopausal women, androsterone concentrations increased 2.95-fold on average (95% confidence interval: 0.35-3.55) during once- or twice-daily treatment. Note, no concomitant changes in serum 17β-estradiol and progesterone were observed, and menstrual cyclicity and ovarian function were not altered by the treatment.
Conclusions: Serum androsterone was identified as a robust response biomarker for AKR1C3 inhibitor treatment in women. Aldo-keto reductase 1C3 inhibitor administration for 4 weeks did not affect ovarian function.ClinicalTrials.gov Identifier: NCT02434640; EudraCT Number: 2014-005298-36.
(© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

المؤلفون: Thavaraputta S; Neuroendocrinology Unit, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.; Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Excellence Center in Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand., Ungprasert P; Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH 44195, United States., Witchel SF; Division of Pediatric Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States., Fazeli PK; Neuroendocrinology Unit, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2023 Sep 01; Vol. 189 (3), pp. S64-S73.

نوع المنشور: Meta-Analysis; Systematic Review; Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Anorexia Nervosa*, Humans ; Female ; Hydrocortisone ; Aldosterone ; Progesterone ; Dehydroepiandrosterone Sulfate

مستخلص: Objective: Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa.
Design/methods: We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model.
Results: We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa.
Conclusions: Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
Competing Interests: Conflict of interest: P.K.F. is a consultant for Regeneron and Xeris Pharmaceuticals.
(© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

المؤلفون: Magkos F; 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Fabbrini E; 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Patterson BW; 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Mittendorfer B; 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Klein S; 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2022 Jul 21; Vol. 187 (3), pp. 391-398. Date of Electronic Publication: 2022 Jul 21 (Print Publication: 2022).

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Estradiol* , Lipoproteins, VLDL*, Adipose Tissue/metabolism ; Adult ; Apolipoprotein B-100/metabolism ; Fatty Acids, Nonesterified ; Female ; Humans ; Kinetics ; Progesterone ; Triglycerides

مستخلص: Objective: Increased triglyceride (TG) and apolipoprotein B-100 (apoB-100) concentrations in plasma are important risk factors for cardiovascular disease in women. Administration of some estrogen preparations raises plasma TG and apoB-100 concentrations by increasing hepatic very low-density lipoprotein (VLDL) TG and apoB-100 secretion rates. However, the influence of physiological variation in endogenous estradiol on VLDL-TG and VLDL-apoB-100 metabolism and on free fatty acid (FFA) release into plasma (the major source of fatty acids for VLDL-TG production) is not known.
Design and Methods: We measured basal VLDL-TG, VLDL-apoB-100, and plasma FFA kinetics by using stable isotopically labeled tracers in 36 eumenorrheic, premenopausal women (age: 33 ± 2 years, BMI: 31 ± 1 kg/m2; mean ± s.e.m.) during the follicular phase of the menstrual cycle; participants were divided into two groups based on low (n = 18) or high (n = 18) plasma estradiol concentrations (defined as below or above the median value of 140 pmol/L in the whole group).
Results: Mean plasma estradiol concentration was >3-fold higher in the high-estradiol than in the low-estradiol group (299 ± 37 and 96 ± 7 pmol/L, P < 0.001); there was no difference in plasma progesterone concentrations between the two groups (P = 0.976). There were no significant differences in plasma FFA concentration, FFA rate of appearance in plasma, VLDL-TG and VLDL-apoB-100 concentrations, hepatic VLDL-TG and VLDL-apoB-100 secretion rates, VLDL-TG and VLDL-apoB-100 plasma clearance rates, and mean residence times (all P ≥ 0.45). No significant associations were found between plasma estradiol concentration and FFA, VLDL-TG, and VLDL-apoB-100 concentrations and kinetics (all P > 0.19).
Conclusions: Plasma estradiol concentration is not an important correlate of basal plasma FFA, VLDL-TG, and VLDL-apoB-100 kinetics in premenopausal women.

المؤلفون: McManus JM; Genitourinary Malignancies Research Center, Lerner Research Institute., Sabharwal N; Genitourinary Malignancies Research Center, Lerner Research Institute., Bazeley P; Center for Clinical Genomics, Genomics Medicine Institute., Sharifi N; Genitourinary Malignancies Research Center, Lerner Research Institute.; Department of Hematology and Oncology, Taussig Cancer Institute.; Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2022 May 12; Vol. 187 (1), pp. 1-14. Date of Electronic Publication: 2022 May 12.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Androgens*/biosynthesis , COVID-19*/epidemiology , COVID-19*/genetics, Aged ; Alleles ; Biological Specimen Banks ; Female ; Humans ; Male ; Multienzyme Complexes/genetics ; Progesterone Reductase ; Steroid Isomerases ; United Kingdom/epidemiology

مستخلص: Context: A sex discordance in COVID exists, with males disproportionately affected. Although sex steroids may play a role in this discordance, no definitive genetic data exist to support androgen-mediated immune suppression neither for viral susceptibility nor for adrenally produced androgens.
Objective: The common adrenal-permissive missense-encoding variant HSD3B1(1245C) that enables androgen synthesis from adrenal precursors and that has been linked to suppression of inflammation in severe asthma was investigated in COVID susceptibility and outcomes reported in the UK Biobank.
Methods: The UK Biobank is a long-term study with detailed medical information and health outcomes for over 500 000 genotyped individuals. We obtained COVID test results, inpatient hospital records, and death records and tested for associations between COVID susceptibility or outcomes and HSD3B1(1245A/C) genotype. Primary analyses were performed on the UK Biobank Caucasian cohort. The outcomes were identification as a COVID case among all subjects, COVID positivity among COVID-tested subjects, and mortality among subjects identified as COVID cases.
Results: Adrenal-permissive HSD3B1(1245C) genotype was associated with identification as a COVID case (odds ratio (OR): 1.11 per C allele, 95% CI: 1.04-1.18, P = 0.0013) and COVID-test positivity (OR: 1.09, 95% CI: 1.02-1.17, P = 0.011) in older (≥70 years of age) women. In women identified as COVID cases, there was a positive linear relationship between age and 1245C allele frequency (P < 0.0001). No associations were found between genotype and mortality or between genotype and circulating sex hormone levels.
Conclusion: Our study suggests that a common androgen synthesis variant regulates immune susceptibility to COVID infection in women, with increasingly strong effects as women age.

المؤلفون: Yoshida T; Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan., Matsumoto K; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan., Miyado M; Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan., Miyashiro Y; ASKA Pharma Medical, Kanagawa, Japan., Sago H; Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan., Horikawa R; Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan., Fukami M; Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2021 Oct 08; Vol. 185 (5), pp. K7-K11. Date of Electronic Publication: 2021 Oct 08.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Androgens/*analysis , Placenta/*chemistry , Testosterone/*analogs & derivatives , Testosterone/*analysis, Adult ; Dihydrotestosterone/analysis ; Female ; Humans ; Infant, Newborn ; Limit of Detection ; Male ; Pregnancy ; Progesterone/analysis ; Reproducibility of Results ; Steroids/analysis ; Tandem Mass Spectrometry

مستخلص: Introduction: The two major androgens in humans are testosterone (T) and dihydrotestosterone (DHT). DHT is produced via the classical, backdoor, and alternative steroidogenic pathways. In addition, recent studies have identified C11-oxy C19 steroids as novel human androgens. Although the placenta is known to be involved in steroid metabolism, androgen levels in full-term placentas have poorly been investigated.
Subjects and Methods: Ten placentas of healthy full-term neonates (five males and five females) were examined. We quantified progesterone, androstenedione (A4), T, allopregnanolone, androsterone, and estradiol, as well as four C11-oxy androgens (11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione (11KA4), and 11-ketotestosterone (11KT)), using liquid chromatography-tandem mass spectrometry.
Results: In all samples, levels of the ten steroids were above the detection limit. Progesterone was by far most abundant, while levels of T and androsterone were relatively low. Levels of 11KT and 11KA4 were higher than those of T and A4, respectively. There were no differences in steroid levels between male and female samples.
Discussion: This study demonstrates that full-term placentas contain several steroids in the classical, backdoor, and alternative pathways. Placentas are likely to function as the supplier of progesterone to other steroidogenic tissues. More importantly, we found that placentas comprise relatively large amounts of 11KA4 and 11KT, which may be produced through steroid transfer from the adrenal gland or from the maternal circulation. These results indicate that the placenta participates in a feto-maternal multi-organ network for androgen biosynthesis.

المؤلفون: Katsuki Y; Toxicology Laboratory, Mochida Pharmaceutical Co. Ltd, Fujieda, Shizuoka, Japan., Takano Y, Futamura Y, Shibutani Y, Aoki D, Udagawa Y, Nozawa S

المصدر: European journal of endocrinology [Eur J Endocrinol] 1998 Feb; Vol. 138 (2), pp. 216-26.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Print ISSN: 0804-4643 (Print) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Endometriosis/*drug therapy , Nandrolone/*analogs & derivatives , Progesterone Congeners/*therapeutic use, Animals ; Buserelin/therapeutic use ; Cell Division/drug effects ; Cyclic AMP/physiology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytotoxicity, Immunologic/drug effects ; Danazol/pharmacology ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Estradiol/pharmacology ; Female ; Immunity, Cellular/drug effects ; Interleukin-1/biosynthesis ; Killer Cells, Natural/immunology ; Macrophages, Peritoneal/metabolism ; Nandrolone/therapeutic use ; Progesterone/pharmacology ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley

مستخلص: Objective: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action.
Design: Experimental endometriosis induced by autotransplantation of endometrium in rats.
Methods: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication.
Results: Dienogest (0.1-1 mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 microg/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 microg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an antiproliferative effect on rat endometrial cells due to inhibition of protein kinase C activity plus a partial progestational effect.
Conclusions: Dienogest appears to be a potent agent with mechanisms of action different from those of danazol and GnRH agonists currently available for the treatment of endometriosis.

المؤلفون: Fiad TM; Department of Investigative Endocrinology St Vincent's Hospital, Dublin, Ireland., Cunningham SK, McKenna TJ

المصدر: European journal of endocrinology [Eur J Endocrinol] 1996 Sep; Vol. 135 (3), pp. 335-9.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Print ISSN: 0804-4643 (Print) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Androgens/*blood , Luteinizing Hormone/*blood , Polycystic Ovary Syndrome/*blood , Progesterone/*deficiency, Cohort Studies ; Female ; Gonadotropins/blood ; Hirsutism/etiology ; Humans ; Medroxyprogesterone Acetate/therapeutic use ; Polycystic Ovary Syndrome/drug therapy ; Progesterone Congeners/therapeutic use ; Prospective Studies ; Reference Values

مستخلص: The aetiology of polycystic ovary syndrome (PCOS) is unknown. It is uniquely characterized by oligomenorrhoea or amenorrhoea associated with normal or high oestrogen levels. This prospective clinical study was designed to examine the possible role of the lack of cyclical exposure to progesterone in the development of gonadotrophin and androgen abnormalities in PCOS. Gonadotrophin, androgen and oestrogen levels were measured in 15 PCOS patients and 10 normal subjects untreated and following treatment with the progestogen medroxyprogesterone acetate (MPA). When compared to control subjects, PCOS patients had significantly higher luteinizing hormone (LH) pulse height, pulse amplitude, integrated LH levels, LH response to gonadotrophin-releasing hormone (GnRH) and LH/FSH ratio; LH pulse frequency was similar in the two groups. In addition, the testosterone/sex hormone binding globulin ratio (T/SHBG), androstenedione and oestrone concentrations in the plasma were significantly higher in PCOS than in control subjects. When PCOS patients were treated with MPA for 5 days, there were significant decreases (p < 0.02-0.001) to values no longer different from normal: from 8.7 +/- 1.2 to 5.6 +/- 0.8 IU/l for integrated LH levels (untreated and MPA-treated PCOS); from 31.2 +/- 3.5 to 12.9 +/- 1.5 IU/l for LH response to GnRH; from 2.4 +/- 0.26 to 1.3 +/- 0.2 for LH/FSH ratio; and from 10.4 +/- 0.63 to 8.5 +/- 0.7 nmol/l for androstenedione. Significant decreases (p < 0.05-0.005) to values that still remained significantly higher than in normal subjects occurred for: LH pulse height, 11.05 +/- 1.3 to 6.88 +/- 0.79 IU/l (untreated and MPA-treated PCOS); LH pulse amplitude, 2.8 +/- 0.5 to 1.8 +/- 0.2 IU/l; total testosterone, 2.5 +/- 0.2 to 2.0 +/- 0.2 nmol/l; T/SHBG ratio, 14.1 +/- 1.7 to 11 +/- 1.5; and oestrone, 265 +/- 24 to 208 +/- 29 pmol/l. These results are consistent with the concept that ovulation failure and progesterone deficiency play a facilitatory role in the development of the hypothalamic-pituitary abnormality giving rise to disordered LH secretion in PCOS.

المؤلفون: Jiang J; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.; Medical Insurance Office, Liuzhou General Hospital, Liuzhou, Guangxi, People's Republic of China., Liu X; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Liu X; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Tian Z; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Zhang H; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Qian X; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Luo Z; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Wei D; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Jin S; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China., Wang C; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Mao Z; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2019 Dec; Vol. 181 (6), pp. 603-614.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Diabetes Mellitus, Type 2/*blood , Pregnenolone/*blood , Progesterone/*blood, Adult ; Case-Control Studies ; China/epidemiology ; Chromatography, Liquid ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Prediabetic State/blood ; Prediabetic State/epidemiology ; Rural Population/statistics & numerical data ; Tandem Mass Spectrometry

مستخلص: Objective: Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case-control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose-response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population.
Design: A case-control study.
Methods: A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone.
Results: Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99-3.55)) and T2DM (OR (95% CI): 6.41 (4.57-8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16-0.33)) and T2DM (OR (95% CI): 0.44 (0.31-0.62)). Additionally, the nonlinear dose-response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis.
Conclusions: Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose-response manner in Chinese rural population.

المؤلفون: Nguyen LS; Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, UNICO AP-HP.6 Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France.; Department of Cardiothoracic Surgery, Sorbonne Université, Institute of Cardiology, Pitie-Salpetriere University Hospital, ICAN, Paris, France., Rouas-Freiss N; Department of Research in Hemato-Immunology (SRHI), CEA, Saint-Louis Institute, UMR U976, Paris, France., Funck-Brentano C; Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, UNICO AP-HP.6 Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France., Leban M; Department of Endocrinology, Pitie-Salpetriere University Hospital, Sorbonne Universite, ICAN, Paris, France., Carosella ED; Department of Research in Hemato-Immunology (SRHI), CEA, Saint-Louis Institute, UMR U976, Paris, France., Touraine P; Department of Endocrinology, Pitie-Salpetriere University Hospital, Sorbonne Universite, ICAN, Paris, France.; Center for Rare Endocrine Disorders and center for Rare Gynecological Disorders, Paris, France., Varnous S; Department of Cardiothoracic Surgery, Sorbonne Université, Institute of Cardiology, Pitie-Salpetriere University Hospital, ICAN, Paris, France., Bachelot A; Department of Endocrinology, Pitie-Salpetriere University Hospital, Sorbonne Universite, ICAN, Paris, France., Salem JE; Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, UNICO AP-HP.6 Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France.; Department of Pharmacology and Medicine, Cardio-Oncology Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

المصدر: European journal of endocrinology [Eur J Endocrinol] 2019 Nov; Vol. 181 (5), pp. 481-488.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Adrenal Hyperplasia, Congenital/*metabolism , HLA-G Antigens/*blood , Hormones/*blood, Adrenal Cortex Hormones/therapeutic use ; Adrenal Hyperplasia, Congenital/drug therapy ; Adult ; Biomarkers/blood ; Cross-Sectional Studies ; Estradiol/therapeutic use ; Female ; Humans ; Male ; Mineralocorticoids/blood ; Progesterone/therapeutic use ; Renin/blood ; Young Adult

مستخلص: Background: HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency.
Methods: In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data.
Results: Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35-1.27) and -0.44 (-0.94, -0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04-0.41), P = 0.001) and estradiol (β = -0.22 (-0.57, -0.02), P < 0.001).
Conclusion: CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.