DOCSLIB.ORG

Safety of Vaginal Estrogens: a Systematic Review Supplemental

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Safety of Vaginal Estrogens: a Systematic Review Supplemental Safety of Vaginal Estrogens: A Systematic Review Supplemental Tables Page # Supplemental Table 1. National Library of Medicine’s DAILYMED Repository 2 Search Results Supplemental Table 2. Contraindications to vaginal estrogens approved by the U.S. 3 Food and Drug Administration Supplemental Table 3. Excluded articles and reasons for exclusion 4 Supplemental Table 4. Study design characteristics of clinical trials of vaginal 30 estrogen in postmenopausal women Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and 45 manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women Supplemental Table 6. Endometrial biopsy results in clinical trials of vaginal estrogen 52 in postmenopausal women Supplemental Table 7a. Summary of Heterogeneity of Level 1 Studies with 55 Endometrial Biopsy Outcomes Supplemental Table 7b. Summary of Heterogeneity of Level 2 Studies with 55 Endometrial Biopsy Outcomes Supplemental Table 7c. Summary of Heterogeneity of Level 1 Studies with 56 Endometrial Thickness Outcomes Supplemental Table 7d. Summary of Heterogeneity of Level 2 Studies with 57 Endometrial Thickness Outcomes Bibliography 58 1 Supplemental Table 1. National Library of Medicine’s DAILYMED Repository Search Resultsa Retrieved result for non-injectable preparation of Vaginal route confirmed after estrogen alone (without other hormones) review of label Alora estradiol transdermal system patch No Climara estradiol patch No Divigel estradiol gel No Dotti estradiol patch extended release No Elestrin estradiol gel No Estra-50 estradiol pellet, implantable No Estrace estradiol cream 0.01% Yes Estrace estradiol tablet No Estraderm estradiol patch No Estradiol cream 0.01% Yes Estradiol film, extended release No Estradiol insert, 10mcg estradiol per insert Yes Estradiol patch No Estradiol tablet No Estradiol transdermal system estradiol patch No Estradiol vaginal cream 0.01% Yes Estradiol vaginal inserts estradiol tablet film-coated, 10mcg Yes estradiol Estring estradiol ring 2 mg releasing 7.5 mcg/d Yes Estrogel estradiol gel No Evamist estradiol spray No Femring estradiol acetate ring Yes Imvexxy estradiol insert 10mcg estradiol per insert Yes Menostar estradiol patch No Minivelle estradiol film No Premarin conjugated estrogens tablet No Premarin vaginal conjugated estrogens cream Yes Vagifem estradiol insert, film-coated, 10mcg or 25 mcg Yes estradiol per insert Vivelle dot estradiol patch No Yuvafem estradiol tablet 10mcg estradiol per tablet Yes a Note: To ensure that the list of estrogen preparations used as search terms was inclusive of all U.S. FDA-approved vaginal estrogen preparations, we performed a search of the U.S. National Library of Medicine’s DAILYMED webpage (https://dailymed.nlm.nih.gov/dailymed/index.cfm) “estrogen” drug class on 3/8/2019. The search revealed vaginal estrogens in the form of estradiol cream, estradiol insert (also known as estradiol vaginal tablet), estradiol ring, and conjugated equine estrogens cream. 2 Supplemental Table 2. Contraindications to vaginal estrogens approved by the U.S. Food and Drug Administration Preparation Contraindications Vaginal conjugated estrogens • Undiagnosed abnormal genital bleeding, cream, estradiol cream, vaginal • known, suspected, or history of breast cancer estradiol insert (tablet) • known or suspected estrogen-dependent neoplasia • active deep vein thrombosis, pulmonary embolism, or a history of these conditions • active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions • known liver dysfunction or disease • known protein C, protein S, or antithrombin deficiency or other known thrombophilic a disorders b • known or suspected pregnancy a known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders is not listed as a contraindication of the estradiol vaginal ring (Estring) b Known or suspected pregnancy is not listed as a contraindication of Imvexxy vaginal estradiol insert. 3 Supplemental Table 3. Excluded Articles and Reasons for Exclusion Ref. Author, year Reason for Reason for exclusion after full-text # exclusion after search title/abstract search 1 1972 Eur J Cancer Not VE 2 1989 Contraception Special pop 3 1991 Fertil Steril Not VE 4 1993 Int J Fertil Menopausal Not VE Stud 5 Abate 1999 Clin Exp Obstet Not VE Gynecol 6 Abdalla 1992 Contraception Special pop 7 Abdel-Aleem 2005 Not VE Contraception 8 Abdelbary 2015 Urology Excluded after full- No AE text search 9 Abdullah 2005 J Coll Not VE Physicians Surg Pak 10 Abraham 2014 Maturitas Not VE 11 Achiron 1995 Fertil Steril Not VE 12 Adler 2005 Gynecol Obstet Not VE Invest 13 Affinito 1998 Ultrasound Not VE Obstet Gynecol 14 Agarwal 2016 J Obstet Special pop Gynaecol 15 Aguirre 2010 Gynecol Not VE Endocrinol 16 Ahlstrom 1990 Gynecol Obstet Not FDA app prep Invest 17 AinMelk 1996 Fertil Steril Not VE 18 Akrivis 2003 Clin Exp Obstet I Gynecol 19 Al-Azzawi 2003 Climacteric Hi dose VE 20 Al-Azzawi 2005 Menopause Excluded after full- Not VE Alone text search 21 Albert 2002 Obstet Gynecol Not VE 22 Albertazzi 1999 Obstet Gynecol Not VE 23 Algorta 2017 Eur J Contracept Special pop Reprod Health Care 24 Al-Saqi 2015 Post Reprod Not VE Health 25 Alvarez 1996 Contraception Not VE 26 Alvarez-Sanchez 1992 Special pop Contraception 27 Anderson 2003 JAMA Not VE 28 Andersson 2000 Maturitas Not VE 4 29 Andreen 2003 Eur J Endocrinol Not VE 30 Andreen 2005 Not VE Psychoneuroendocrinology 31 Apperloo 2006 J Sex Med Not VE 32 Apter 1990 Contraception Special 33 Apter 2016 Contraception Not VE 34 Archer 2017 Menopause I 35 Archer 2001 Fertil Steril Not VE 36 Archer 2007 J Clin Not VE Endocrinol Metab 37 Archer 2018 J Womens Excluded after full- Not FDA app prep Health (Larchmt) text search 38 Archer 2012 Menopause Not VE 39 Archer 2014 Menopause Not VE 40 Archer 2016 Contraception Special 41 Artini 1995 J Endocrinol Special Invest 42 Artymuk 2010 Int J Gynaecol Special Obstet 43 Ata 2010 J Reprod Med Special 44 Atmaca 2005 Tohoku J Exp Med Not VE Alone 45 Aylward 1974 Curr Med Res Not VE Opin 46 Aylward 1978 Postgrad Med J Not VE 47 Ayton 1996 Br J Obstet I Gynaecol 48 Bachmann 2010 Climacteric Not VE 49 Bachmann 2009 Menopause I 50 Bachmann 2011 Menopause Not VE 51 Bachmann 2008 Obstet Gynecol I 52 Bachmann 2010 Menopause Not VE 53 Bachmann 2009 Menopause Not VE 54 Back 1987 Contraception Special 55 Baerug 1998 Climacteric Not VE 56 Bahamondes 1995 Hum Reprod Not VE 57 Bahamondes 2000 Not VE Contraception 58 Bai 2007 Maturitas Not VE 59 Baird 1995 J Clin Endocrinol Not VE Metab 60 Baird 1996 J Clin Epidemiol Not VE 61 Baker 1995 J Assist Reprod Not VE Genet 62 Baker 1998 J Clin Endocrinol Not VE Metab 63 Balasch 1982 Fertil Steril Not VE 5 64 Balk 2002 J Soc Gynecol Not VE Investig 65 Ballagh 1994 Contraception Special 66 Ballagh 1994 Contraception Special 67 Baracat 2001 Clin Exp Obstet Not VE Gynecol 68 Barbosa 2009 Gynecol Not VE Endocrinol 69 Barentsen 1997 Eur J Obstet I Gynecol Reprod Biol 70 Barnabei 2005 Obstet Gynecol Not VE 71 Barnabei 2002 Obstet Gynecol Not VE 72 Barton 2018 Support Care Not VE Cance 73 Barton 2018 Support Care Not VE Cance 74 Bassol 2005 Maturitas Not VE 75 Basson 2003 BJOG Not VE 76 Bateson 2009 Menopause Excluded after full- No AE text search 77 Battaglia 2009 J Sex Med Not VE 78 Baysoy 2006 Reprod Biomed Not VE Online 79 Beardsworth 1999 Br J Obstet Not VE Gynaecol 80 Beaton 1967 Br J Clin Pract Not VE 81 Behilovic 1987 Contraception Not VE 82 Behre 2001 J Int Med Res Not VE 83 Bellantoni 1991 J Gerontol Not VE 84 Bellina 1983 Lasers Surg Med Not VE 85 Belsey 1988 Contraception Special 86 Ben-Chetrit 1996 Fertil Steril Not VE 87 Ben-Chetrit 2005 Isr Med Assoc Not FDA app prep J 88 Benjamin 1971 J Reprod Med Not VE 89 Benson 1996 Am J Obstet Not VE Gynecol 90 Berger 1979 Contraception Not VE 91 Berning 2000 Maturitas Not VE 92 Bhamra 2011 Menopause Not FDA app prep 93 Bishop 1992 Cancer Chemother Not VE Pharmacol 94 Bishun 1977 J Surg Oncol Not VE 95 Bjarnadottir 2002 Am J Obstet Special Gynecol 96 Blakely 2004 Clin Cancer Res Not VE 97 Bolaji 1996 Gynecol Endocrinol Not VE 6 98 Bolognese 2009 J Clin Not VE Endocrinol Metab 99 Bonneterre 2001 Cancer Not VE 100 Bonneterre 2000 J Clin Oncol Not VE 101 Boon 2003 Maturitas Not VE 102 Botsis 1997 Maturitas I 103 Bottiglione 1995 Maturitas Not FDA app prep 104 Bouchard 2015 Climacteric Not VE 105 Bouchard 2016 Horm Mol Biol Not VE Clin Investig 106 Brache 2007 Contraception Not VE 107 Brache 2000 Contraception Not VE 108 Brache 2001 Contraception Not VE 109 Breast International Group 2005 Not VE N Engl J Med 110 Brenner 1988 Obstet Gynecol Not Original 111 Brezina 2012 Reprod Biol Special Endocrinol 112 Brinsmead 1989 J In Vitro Fert Special Embryo Transf 113 Bronstein 1967 Int J Fertil Not VE 114 Brown 2001 Obstet Gynecol Not VE 115 Bruce 2004 Climacteric Not VE 116 Bruhat 2001 Maturitas Not VE 117 Bruni 2008 Eur J Obstet Not VE Gynecol Reprod Biol 118 Brunner 2010 Menopause Not VE 119 Bruyniks 2016 Climacteric Not VE 120 Brys 2009 Sao Paulo Med J Not FDA app prep 121 Brzyski 1992 Am J Obstet Not VE Gynecol 122 Buckler 2003 BJOG Hi Dose VE 123 Burch 1995 Br J Obstet Not VE Gynaecol 124 Buzdar 2001 J Clin Oncol Not VE 125 Bygdeman 1996 Maturitas Not FDA app prep 126 Cagnacci 1992 Life Sci Not VE 127 Cagnacci 1999 Maturitas Not FDA app prep 128 Campbell 1977 Clin Obstet Not VE Gynaecol 129 Cano 2012 Menopause Not FDA app prep 130 Cano 1999 Fertil Steril Not VE 131 Carmignani 2010 Maturitas Not VE 132 Carmignani 2015 Menopause
Load more

Recommended publications
  • Androgen Excess in Breast Cancer Development: Implications for Prevention and Treatment
    26 2 Endocrine-Related G Secreto et al. Androgen excess in breast 26:2 R81–R94 Cancer cancer development REVIEW Androgen excess in breast cancer development: implications for prevention and treatment Giorgio Secreto1, Alessandro Girombelli2 and Vittorio Krogh1 1Epidemiology and Prevention Unit, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milano, Italy 2Anesthesia and Critical Care Medicine, ASST – Grande Ospedale Metropolitano Niguarda, Milano, Italy Correspondence should be addressed to G Secreto: [email protected] Abstract The aim of this review is to highlight the pivotal role of androgen excess in the Key Words development of breast cancer. Available evidence suggests that testosterone f breast cancer controls breast epithelial growth through a balanced interaction between its two f ER-positive active metabolites: cell proliferation is promoted by estradiol while it is inhibited by f ER-negative dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal f androgen/estrogen balance hyperplasia) results in an increased estrogen production and cell proliferation that f androgen excess are no longer counterbalanced by dihydrotestosterone. This shift in the androgen/ f testosterone estrogen balance partakes in the genesis of ER-positive tumors. The mammary gland f estradiol is a modified apocrine gland, a fact rarely considered in breast carcinogenesis. When f dihydrotestosterone stimulated by androgens, apocrine cells synthesize epidermal growth factor (EGF) that triggers the ErbB family receptors. These include the EGF receptor and the human epithelial growth factor 2, both well known for stimulating cellular proliferation. As a result, an excessive production of androgens is capable of directly stimulating growth in apocrine and apocrine-like tumors, a subset of ER-negative/AR-positive tumors.
    [Show full text]
  • Androgens Utilization Management Criteria
    ANDROGENS UTILIZATION MANAGEMENT CRITERIA DRUG CLASS: Androgens Generic (Brand) NAMES: • Fluoxymesterone (Androxy®) • Methyltestosterone (Android®, Methitest®, Testred®) • Testosterone, topical A. Androderm®, Androgel® - Preferred topical testosterone ® ® ® ™ B. Testim , Fortesta , Axiron , Bio-T-Gel • Testosterone, buccal (Striant®) • Testosterone cypionate (e.g., Depo-Testosterone®) • Testosterone enanthate (e.g., Delatestryl®) FDA-APPROVED INDICATIONS: Replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired): Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchidectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. Hypogonadotropic hypogonadism (congenital or acquired): Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. Delayed puberty: To stimulate puberty in carefully selected males with clearly delayed puberty. Metastatic mammary cancer in women: Used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are 1 to 5 years postmenopausal COVERAGE AUTHORIZATION CRITERIA for the androgen products listed above: 1. Being used for ONE of the following: a. Males for the treatment of hypogonadism (low testosterone): i. patient has symptoms of androgen deficiency AND ii. has a baseline (pre-treatment) morning serum total testosterone level of less than or equal to 300 ng/dL or a serum total testosterone level that is below the testing laboratory’s lower limit of the normal range OR iii. baseline morning serum free testosterone level, measured by the equilibrium dialysis method, of less than or equal to 50 pg/ml or a free serum testosterone level that is below the testing laboratory’s lower limit of the normal range, OR b.
    [Show full text]
  • Phase II Study of Hormone Therapy with Tamoxifen in Patients with Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET)
    Phase II study of hormone therapy with tamoxifen in patients with well differentiated neuroendocrine tumors and hormone receptor positive expression (HORMONET) Time of researchers and respective Departments: Rachel Riechelmann (Main Investigador)1, Milton Barros 1, Marcos Camandaroba1,2, Virgilio Souza1,2, Celso Abdon Mello1, Paula Nicole3, Eduardo Nóbrega4, Ludmilla Chinen5, Marina De Brot6, Héber Salvador7. Departaments: 1- Clinical Oncology; 2- postgraduate student; 3- Radiology; 4- Nuclear Medicine; 5-International Research Center (CIPE); 6-Pathologic anatomy; 7- Abdomen Surgery AC Camargo Cancer Center - Brazil Registration Number on Institutional Research Ethics Committee: 2626/18 March,06,2019 Introduction Neuroendocrine tumors (NET) are rare neoplasms, but with increasing incidence and prevalence in the last decades. Although they may manifest in the most diverse tissues, the vast majority of cases will affect organs of the digestive tract and lung. At diagnosis, more than half of the cases present metastatic disease, and among patients with localized disease, up to one-third will have recurrence of the disease. Unfortunately, the minority of patients with metastatic disease are eligible for curative intent.1 Although there are many types of NET, they are often studied together as a group because their cells share common histological findings, have special secretory granules, and the ability to secrete bioactive amines and polypeptide hormones. Approximately 25 percent of the tumors present functional hormonal syndromes (situation of great morbidity for these patients), being the carcinoid syndrome, the most common one. From the molecular point of view, these neoplasias are largely dependent on the activation of the mTOR pathway and neoangiogenesis.2 Another striking feature of neuroendocrine cells is the expression of cell surface hormone receptors whose activation or blockade may exert an important regulatory function.
    [Show full text]
  • CASODEX (Bicalutamide)
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Gynecomastia and breast pain have been reported during treatment with These highlights do not include all the information needed to use CASODEX 150 mg when used as a single agent. (5.3) CASODEX® safely and effectively. See full prescribing information for • CASODEX is used in combination with an LHRH agonist. LHRH CASODEX. agonists have been shown to cause a reduction in glucose tolerance in CASODEX® (bicalutamide) tablet, for oral use males. Consideration should be given to monitoring blood glucose in Initial U.S. Approval: 1995 patients receiving CASODEX in combination with LHRH agonists. (5.4) -------------------------- RECENT MAJOR CHANGES -------------------------- • Monitoring Prostate Specific Antigen (PSA) is recommended. Evaluate Warnings and Precautions (5.2) 10/2017 for clinical progression if PSA increases. (5.5) --------------------------- INDICATIONS AND USAGE -------------------------- ------------------------------ ADVERSE REACTIONS ----------------------------- • CASODEX 50 mg is an androgen receptor inhibitor indicated for use in Adverse reactions that occurred in more than 10% of patients receiving combination therapy with a luteinizing hormone-releasing hormone CASODEX plus an LHRH-A were: hot flashes, pain (including general, back, (LHRH) analog for the treatment of Stage D2 metastatic carcinoma of pelvic and abdominal), asthenia, constipation, infection, nausea, peripheral the prostate. (1) edema, dyspnea, diarrhea, hematuria, nocturia, and anemia. (6.1) • CASODEX 150 mg daily is not approved for use alone or with other treatments. (1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca Pharmaceuticals LP at 1-800-236-9933 or FDA at 1-800-FDA-1088 or ---------------------- DOSAGE AND ADMINISTRATION ---------------------- www.fda.gov/medwatch The recommended dose for CASODEX therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening).
    [Show full text]
  • Study Protocol and Statistical Analysis Plan
    Confidential Clinical study protocol number: J1228 Page 1 Version Date: May 7, 2018 IRB study Number: NA_00067315 A Trial of maintenance Rituximab with mTor inhibition after High-dose Consolidative Therapy in CD20+, B-cell Lymphomas, Gray Zone Lymphoma, and Hodgkin’s Lymphoma Principal Investigator: Douglas E. Gladstone, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 1650 Orleans Street, CRBI-287 Baltimore, MD 21287 Phone: 410-955-8781 Fax: 410-614-1005 Email: [email protected] IRB Protocol Number: NA_00067315 Study Number: J1228 IND Number: EXEMPT Novartis Protocol Number: CRAD001NUS157T Version: May 7, 2018 Co-Investigators: Jonathan Powell 1650 Orleans Street, CRBI-443 Phone: 410-502-7887 Fax: 443-287-4653 Email: [email protected] Richard Jones 1650 Orleans Street, CRBI-244 Phone: 410-955-2006 Fax: 410-614-7279 Email: [email protected] Confidential Clinical study protocol number: J1228 Page 2 Version Date: May 7, 2018 IRB study Number: NA_00067315 Satish Shanbhag Johns Hopkins Bayview Medical Center 301 Building, Suite 4500 4940 Eastern Ave Phone: 410-550-4061 Fax: 410-550-5445 Email: [email protected] Statisticians: Gary Rosner Phone: 410-955-4884 Email: [email protected] Marianna Zahurak Phone: 410-955-4219 Email: [email protected] Confidential Clinical study protocol number: J1228 Page 3 Version Date: May 7, 2018 IRB study Number: NA_00067315 Table of contents Table of contents ......................................................................................................................... 3 List of abbreviations
    [Show full text]
  • Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis
    ORIGINAL ARTICLE Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis Ana E. Espinosa De Ycaza, Robert A. Rizza, K. Sreekumaran Nair, and Michael D. Jensen Division of Endocrinology, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905 Downloaded from https://academic.oup.com/jcem/article/101/4/1719/2804555 by guest on 24 September 2021 Context: Dehydroepiandrosterone (DHEA) and T hormones are advertised as antiaging, antiobe- sity products. However, the evidence that these hormones have beneficial effects on adipose tissue metabolism is limited. Objective: The objective of the study was to determine the effect of DHEA and T supplementation on systemic lipolysis during a mixed-meal tolerance test (MMTT) and an iv glucose tolerance test (IVGTT). Design: This was a 2-year randomized, double-blind, placebo-controlled trial. Setting: The study was conducted at a general clinical research center. Participants: Sixty elderly women with low DHEA concentrations and 92 elderly men with low DHEA and bioavailable T concentrations participated in the study. Interventions: Elderly women received 50 mg DHEA (n ϭ 30) or placebo (n ϭ 30). Elderly men received 75 mg DHEA (n ϭ 30),5mgT(nϭ 30), or placebo (n ϭ 32). Main Outcome Measures: In vivo measures of systemic lipolysis (palmitate rate of appearance) during a MMTT or IVGTT. Results: At baseline there was no difference in insulin suppression of lipolysis measured during MMTT and IVGTT between the treatment groups and placebo. For both sexes, a univariate analysis showed no difference in changes in systemic lipolysis during the MMTT or IVGTT in the DHEA group and T group when compared with placebo.
    [Show full text]
  • Estradiol Acetate Vaginal Ring) Rx Only
    NDA 21-367/S-002 Page 3 PRESCRIBING INFORMATION Femring® (estradiol acetate vaginal ring) Rx Only ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. (See WARNINGS, Malignant neoplasms, Endometrial cancer.) CARDIOVASCULAR AND OTHER RISKS Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. (See WARNINGS, Cardiovascular disorders and Dementia.) The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL PHARMACOLOGY, Clinical Studies and WARNINGS, Cardiovascular disorders and Malignant neoplasms, Breast cancer.) The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens
    [Show full text]
  • Reproductive DHEA-S
    Reproductive DHEA-S Analyte Information - 1 - DHEA-S Introduction DHEA-S, DHEA sulfate or dehydroepiandrosterone sulfate, it is a metabolite of dehydroepiandrosterone (DHEA) resulting from the addition of a sulfate group. It is the sulfate form of aromatic C19 steroid with 10,13-dimethyl, 3-hydroxy group and 17-ketone. Its chemical name is 3β-hydroxy-5-androsten-17-one sulfate, its summary formula is C19H28O5S and its molecular weight (Mr) is 368.5 Da. The structural formula of DHEA-S is shown in (Fig.1). Fig.1: Structural formula of DHEA-S Other names used for DHEA-S include: Dehydroisoandrosterone sulfate, (3beta)-3- (sulfooxy), androst-5-en-17-one, 3beta-hydroxy-androst-5-en-17-one hydrogen sulfate, Prasterone sulfate and so on. As DHEA-S is very closely connected with DHEA, both hormones are mentioned together in the following text. Biosynthesis DHEA-S is the major C19 steroid and is a precursor in testosterone and estrogen biosynthesis. DHEA-S originates almost exclusively in the zona reticularis of the adrenal cortex (Fig.2). Some may be produced by the testes, none is produced by the ovaries. The adrenal gland is the sole source of this steroid in women, whereas in men the testes secrete 5% of DHEA-S and 10 – 20% of DHEA. The production of DHEA-S and DHEA is regulated by adrenocorticotropin (ACTH). Corticotropin-releasing hormone (CRH) and, to a lesser extent, arginine vasopressin (AVP) stimulate the release of adrenocorticotropin (ACTH) from the anterior pituitary gland (Fig.3). In turn, ACTH stimulates the adrenal cortex to secrete DHEA and DHEA-S, in addition to cortisol.
    [Show full text]
  • Targeting Glycine Reuptake in Alcohol Seeking and Relapse
    JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. TITLE PAGE Targeting Glycine Reuptake in Alcohol Seeking and Relapse Valentina Vengeliene, Martin Roßmanith, Tatiane T. Takahashi, Daniela Alberati, Berthold Behl, Anton Bespalov, Rainer Spanagel Downloaded from The primary laboratory of origin: Institute of Psychopharmacology, Central Institute of jpet.aspetjournals.org Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; at ASPET Journals on September 30, 2021 VV, MR, TTT, RS: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; DA: Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, CH-4070 Basel, Switzerland; BB, AB: Department of Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; AB: Department of Psychopharmacology, Pavlov Medical University, St Petersburg, Russia JPET #244822 JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. RUNNING TITLE GlyT1 in Alcohol Seeking and Relapse Corresponding author with complete address: Valentina Vengeliene, Institute of Psychopharmacology, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany Email: [email protected], phone: +49-621-17036261; fax: +49-621- Downloaded from 17036255 jpet.aspetjournals.org The number of text pages: 33 Number of tables: 0 Number of figures: 6 Number of references: 44 at ASPET Journals on September 30, 2021 Number of words in the Abstract: 153 Number of words in the Introduction: 729 Number of words in the Discussion: 999 A recommended section assignment to guide the listing in the table of content: Drug Discovery and Translational Medicine 2 JPET #244822 JPET Fast Forward.
    [Show full text]
  • Estradiol (E2), Estriol (E3), Ethinylestradiol (EE2), Testosterone (TEST), Androstenedione (AND), and Progesterone
    UNIVERSITY OF CINCINNATI Date: 13-Aug-2010 I, Ruth Marfil Vega , hereby submit this original work as part of the requirements for the degree of: Doctor of Philosophy in Environmental Science It is entitled: Abiotic Transformation of Estrogens in Wastewater Student Signature: Ruth Marfil Vega This work and its defense approved by: Committee Chair: Makram Suidan, PhD Makram Suidan, PhD George Sorial, PhD George Sorial, PhD Margaret Kupferle, PhD, PE Margaret Kupferle, PhD, PE Marc Mills, PhD Marc Mills, PhD 11/8/2010 1,041 Abiotic Transformation of Estrogens in Wastewater A Dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy In the School of Energy, Environmental, Biological and Medical Engineering By Ruth Marfil-Vega B.S. Chemistry, University of Valladolid, Spain, 2001 Committee Chair: Makram T. Suidan, Ph.D. ABSTRACT The fate of seven steroids: estrone (E1), estradiol (E2), estriol (E3), ethinylestradiol (EE2), testosterone (TEST), androstenedione (AND), and progesterone (PROG), in the presence of synthetic wastewater was studied in order to establish the role abiotic processes play in the elimination of these chemicals from the environment. Comprehension of these mechanisms will foster the optimization of the existing wastewater treatment technologies and the development of sustainable alternatives. Distinctive behavior was encountered for the target compounds in accordance with their chemical structure, hence, different physico-chemical properties and reactivity. Estrogenic compounds, comprising E1, E2, E3 and EE2, were found to undergo a catalytic transformation when contacted with a model vegetable material present in the synthetic wastewater.
    [Show full text]
  • The Mechanisms and Managements of Hormone-Therapy Resistance in Breast and Prostate Cancers
    Endocrine-Related Cancer (2005) 12 511–532 REVIEW The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers K-M Rau1,2*, H-Y Kang3,4*, T-L Cha1,5,6, S A Miller1 and M-C Hung1 1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA 2Department of Hematology-Oncology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan 4The Center for Menopause and Reproductive Medicine Research, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan 5Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA 6Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (Requests for offprints should be addressed to M-C Hung; Email: [email protected]) *(K-M Rau and H-Y Kang contributed equally to this work) Abstract Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usually are effective in prevention and treatment. However, the emergence of resistance is common, especially for locally advanced tumors and metastatic tumors, in which case resistance is predictable. The phenotypes of these resistant tumors include receptor- positive, ligand-dependent; receptor-positive, ligand-independent; and receptor-negative, ligand- independent. The underlying mechanisms of these phenotypes are complicated, involving not only sex hormones and sex hormone receptors, but also several growth factors and growth factor re- ceptors, with different signaling pathways existing alone or together, and with each pathway possibly linking to one another.
    [Show full text]
  • A Simple Method to Measure Sulfonation in Man Using Paracetamol As Probe Drug Natália Marto 1,2*, Judit Morello1,3, Alexandra M
    www.nature.com/scientificreports OPEN A simple method to measure sulfonation in man using paracetamol as probe drug Natália Marto 1,2*, Judit Morello1,3, Alexandra M. M. Antunes3, Sofa Azeredo4, Emília C. Monteiro1,5 & Sofa A. Pereira1,5 Sulfotransferase enzymes (SULT) catalyse sulfoconjugation of drugs, as well as endogenous mediators, gut microbiota metabolites and environmental xenobiotics. To address the limited evidence on sulfonation activity from clinical research, we developed a clinical metabolic phenotyping method using paracetamol as a probe substrate. Our aim was to estimate sulfonation capability of phenolic compounds and study its intraindividual variability in man. A total of 36 healthy adult volunteers (12 men, 12 women and 12 women on oral contraceptives) received paracetamol in a 1 g-tablet formulation on three separate occasions. Paracetamol and its metabolites were measured in plasma and spot urine samples using liquid chromatography-high resolution mass spectrometry. A metabolic ratio (Paracetamol Sulfonation Index—PSI) was used to estimate phenol SULT activity. PSI showed low intraindividual variability, with a good correlation between values in plasma and spot urine samples. Urinary PSI was independent of factors not related to SULT activity, such as urine pH or eGFR. Gender and oral contraceptive intake had no impact on PSI. Our SULT phenotyping method is a simple non-invasive procedure requiring urine spot samples, using the safe and convenient drug paracetamol as a probe substrate, and with low intraindividual coefcient of variation. Although it will not give us mechanistic information, it will provide us an empirical measure of an individual’s sulfonator status. To the best of our knowledge, our method provides the frst standardised in vivo empirical measure of an individual’s phenol sulfonation capability and of its intraindividual variability.
    [Show full text]