DOCSLIB.ORG

Estrogen As a Regulator of Ethanol Reward and Drinking Behavior

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Estrogen As a Regulator of Ethanol Reward and Drinking Behavior Ethanol and the Female Brain: Estrogen as a Regulator of Ethanol Reward and Drinking Behavior BY ELISA RACHEL HILDERBRAND B.A., Knox College, 2010 DISSERTATION Submitted as partial fulfillment of the requirements for the degree of Doctor of Philosophy in Neuroscience in the Graduate College of the University of Illinois at Chicago, 2020 Chicago, Illinois Defense Committee: Amy W. Lasek, Advisor David Wirtshafter, Chair Mark Brodie, Physiology & Biophysics Subhash Pandey, Psychiatry Jamie Roitman, Psychology TABLE OF CONTENTS CHAPTER PAGE 1. INTRODUCTION....................................................................................................................1 1.1. Alcohol Use Disorder (AUD) .............................................................................................1 1.2. Sex Differences in AUD………………………………………………………………. ....3 1.3. Sex Differences in Animal Models of AUD .......................................................................5 1.3.1. Operant Self-Administration ...................................................................................6 1.3.2. Conditioned Place Preference (CPP) .......................................................................8 1.3.3. Two-Bottle Choice Ethanol Consumption .............................................................10 1.4. Ovarian Hormones and AUD ...........................................................................................13 1.4.1. Human Studies .......................................................................................................14 1.4.2. Animal Studies.......................................................................................................15 1.5. The Ovarian Steroid Hormone 17β-Estradiol and Its Receptors ......................................17 1.5.1 Estrogen Biochemistry and Synthesis ....................................................................18 1.5.2 Estrogen Receptors .................................................................................................20 1.6. Neural Substrates of Reward and Their Regulation by Estradiol .....................................26 1.6.1. The Reward System ...............................................................................................27 1.6.2. Estradiol as a Reward Modulator ..........................................................................29 1.7. Summary and Project Overview .......................................................................................35 2. ESTRADIOL ENHANCES ETHANOL REWARD IN FEMALE MICE THROUGH ACTIVATION OF ERα AND ERβ .........................................................................................................................39 2.1. Introduction .......................................................................................................................39 2.2. Materials and Methods .....................................................................................................41 2.2.1. Experimental Animals ...........................................................................................41 2.2.2. Ovariectomy (OVX) ..............................................................................................42 2.2.3. Drug Treatments ....................................................................................................42 2.2.4. Behavioral Procedure .............................................................................................43 2.2.5. Ethanol Metabolism ...............................................................................................45 2.2.6. Lentiviral Construct ...............................................................................................45 2.2.7. Stereotaxic Injection of Virus ................................................................................46 2.2.8. Histology................................................................................................................46 2.2.9. Statistical Analysis.................................................................................................48 2.3. Results...............................................................................................................................48 2.3.1. Estradiol (E2) enhances ethanol CPP in OVX mice ..............................................48 2.3.2. E2 does not alter preference for the initially non-preferred Side of the CPP chamber in the absence of ethanol conditioning ....................................................49 2.3.3. E2 does not Alter the rate of ethanol metabolism in OVX mice ...........................50 2.3.4. Activation of ERα or ERβ individually is not sufficient to enhance ethanol CPP in OVX mice ..................................................................................................50 2.3.5. Activation of both ERα and ERβ enhances ethanol CPP in OVX mice ................51 2.3.6. Lentiviral infection may induce damage in the CeA .............................................51 2.4. Discussion .........................................................................................................................58 2.5. Acknowledgements ...........................................................................................................62 ii 3. VTA ESTROGEN RECEPTORS REGULATE BINGE-LIKE DRINKING IN GONADALLY INTACT FEMALE C57BL/6J MICE ........................................................................................................63 3.1. Introduction .......................................................................................................................63 3.2. Material and Methods .......................................................................................................65 3.2.1. Experimental Animals ...........................................................................................65 3.2.2. OVX .......................................................................................................................65 3.2.3. Drug Treatments ....................................................................................................66 3.2.4. Lentiviral Construct ...............................................................................................66 3.2.5. Stereotaxic Injection of Virus ................................................................................66 3.2.6. Vaginal Cytology ...................................................................................................67 3.2.7. Behavioral Procedure .............................................................................................68 3.2.8. Confirmation of Viral Placement and in vivo Knockdown Efficiency ..................69 3.2.9. Statistical Analysis.................................................................................................72 3.3. Results...............................................................................................................................72 3.3.1. Systemic treatment with PPT (an ERα agonist) suppresses fluid intake in OVX mice ..............................................................................................................72 3.3.2. Ventral Tegmental Area (VTA) ERα and ERβ regulate binge-like EtOH intake in female, but not male, mice ......................................................................73 3.3.3. Intra-VTA ER knockdown does not alter sucrose intake in female mice .............75 3.3.4. Viral vector expressing shEsr1 reduces ERα protein levels in male mouse VTA .......................................................................................................................76 3.3.5. qPCR analysis was not effective for measuring in vivo knockdown of viral constructs shEsr1-1785 and shEsr2-1089 in VTA tissue ......................................76 3.4. Discussion .........................................................................................................................82 3.5. Acknowledgements ...........................................................................................................85 4. ESTROGEN RECEPTORS REGULATE THE EXPRESSION OF GENES INVOLVED IN ETHANOL REWARD-RELATED BEHAVIORS IN THE AMYGDALA AND VENTRAL TEGMENTAL AREA ........86 4.1. Introduction .......................................................................................................................86 4.2. Material and Methods .......................................................................................................90 4.2.1. Experimental Animals ...........................................................................................90 4.2.2. Drug Treatments and Tissue Processing ................................................................91 4.2.3. RNA Extraction, cDNA Synthesis, and qPCR ......................................................93 4.2.4. Statistical Analysis.................................................................................................94 4.3. Results...............................................................................................................................94 4.3.1. E2 regulates gene expression in the amygdala ......................................................94 4.3.2. ER-selective agonists modulate Npy and Crh expression in the amygdala and VTA .......................................................................................................................96 4.4. Discussion .......................................................................................................................102
Load more

Recommended publications
  • Clomifene Citrate(BANM, Rinnm) ⊗
    2086 Sex Hormones and their Modulators Profasi; UK: Choragon; Ovitrelle; Pregnyl; USA: Chorex†; Choron; Gonic; who received the drug for a shorter period.6 No association be- 8. Werler MM, et al. Ovulation induction and risk of neural tube Novarel; Ovidrel; Pregnyl; Profasi; Venez.: Ovidrel; Pregnyl; Profasi†. tween gonadotrophin therapy and ovarian cancer was noted in defects. Lancet 1994; 344: 445–6. Multi-ingredient: Ger.: NeyNormin N (Revitorgan-Dilutionen N Nr this study. The conclusions of this study were only tentative, 9. Greenland S, Ackerman DL. Clomiphene citrate and neural tube 65)†; Mex.: Gonakor. defects: a pooled analysis of controlled epidemiologic studies since the numbers who developed ovarian cancer were small; it and recommendations for future studies. Fertil Steril 1995; 64: has been pointed out that a successfully achieved pregnancy may 936–41. reduce the risk of some other cancers, and that the risks and ben- 10. Whiteman D, et al. Reproductive factors, subfertility, and risk efits of the procedure are not easy to balance.7 A review8 of epi- of neural tube defects: a case-control study based on the Oxford Clomifene Citrate (BANM, rINNM) ⊗ Record Linkage Study Register. Am J Epidemiol 2000; 152: demiological and cohort studies concluded that clomifene was 823–8. Chloramiphene Citrate; Citrato de clomifeno; Clomifène, citrate not associated with any increase in the risk of ovarian cancer 11. Sørensen HT, et al. Use of clomifene during early pregnancy de; Clomifeni citras; Clomiphene Citrate (USAN); Klomifeenisi- when used for less than 12 cycles, but noted conflicting results, and risk of hypospadias: population based case-control study.
    [Show full text]
  • Clomid (Clomiphene Citrate USP)
    PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory Agent sanofi-aventis Canada Inc. Date of Revision: 2905 Place Louis-R.-Renaud August 9, 2013 Laval, Quebec H7V 0A3 Submission Control No.: 165671 s-a Version 5.0 dated August 9, 2013 Page 1 of 23 PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory agent. ACTION AND CLINICAL PHARMACOLOGY CLOMID (clomiphene citrate) is an orally-administered, non-steroidal agent which may induce ovulation in anovulatory women in appropriately selected cases.1-16 The ovulatory response to cyclic CLOMID therapy appears to be mediated through increased output of pituitary gonadotropins, which in turn stimulate the maturation and endocrine activity of the ovarian follicle and the subsequent development and function of the corpus luteum. The role of the pituitary is indicated by increased plasma levels of gonadotropins and by the response of the ovary, as manifested by increased plasma level of estradiol. Antagonism of competitive inhibition of endogenous estrogen may play a role in the action of CLOMID on the hypothalamus. CLOMID is a drug of considerable pharmacologic potency. Its administration should be preceded by careful evaluation and selection of the patient, and must be accompanied by close attention to the timing of the dose. With conservative selection and management of the patient, CLOMID has been demonstrated to be a useful therapy for the anovulatory patient. Based on studies with 14C-labeled clomiphene, the drug is readily absorbed orally in humans, and is excreted principally in the feces. Cumulative excretion of the 14C-label averaged 51% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 8% and mean fecal excretion of 42%; less than 1% per day was excreted in fecal and urine samples collected from 31 to 53 days after 14C-labelled clomiphene administration.
    [Show full text]
  • Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – an Evidence Based Approach
    1 Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – An Evidence Based Approach Hatem Abu Hashim Department of Obstetrics & Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 1. Introduction World Health Organisation (WHO) type II anovulation is defined as normogonadotrophic normoestrogenic anovulation and occurs in approximately 85% of anovulatory patients. Polycystic ovary syndrome (PCOS) is the most common form of WHO type II anovulatory infertility and is associated with hyperandrogenemia (1,2). Moreover, PCOS is the most common endocrine abnormality in reproductive age women. The prevalence of PCOS is traditionally estimated at 4% to 8% from studies performed in Greece, Spain and the USA (3-6). The prevalence of PCOS has increased with the use of different diagnostic criteria and has recently been shown to be 11.9 ± 2.4% -17.8 ± 2.8 in the first community-based prevalence study based on the current Rotterdam diagnostic criteria compared with 10.2 ± 2.2% -12.0 ± 2.4% and 8.7 ± 2.0% using National Institutes of Health criteria and Androgen Excess Society recommendations respectively (7). Importantly, 70% of women in this recent study were undiagnosed (7). Clomiphene citrate (CC) is still holding its place as the first-line therapy for ovulation induction in these patients (2,8,9). CC contains an unequal mixture of two isomers as their citrate salts, enclomiphene and zuclomiphene. Zuclomiphene is much the more potent of the two for induction of ovulation, accounts for 38% of the total drug content of one tablet and has a much longer half-life than enclomiphene, being detectable in plasma 1 month following its administration (10).
    [Show full text]
  • Clomifene Or Letrozole Ovulation Induction Treatment
    What happens next? For most women (once the correct dose has been established) we would encourage you to continue for six months without having to be scanned. After this, if you are still not pregnant, please ring your Fertility Nurse for advice. If, during the time you are receiving treatment, your periods become irregular ie. longer than 33-34 days, or you lose over a stone in weight (gaining is not an option!), please contact your Fertility Nurse. Clomifene or Letrozole Good Luck (Please call if you are pregnant!) Ovulation Induction Cornwall Centre for Reproductive Medicine treatment Wheal Unity Clinic Administrator – 01872 253044 Fertility Nurses – 01872 252061 If you would like this leaflet in large print, braille, audio version or in another language, please contact the General Office on 01872 252690 RCHT 557 © RCHT Design & Publications 2002 Revised 12/2018 V3 Review due 12/2021 What is clomifene? There is also a theoretical, but not proven, concern that prolonged use may Clomifene citrate or Letrozole are the most commonly used drug in the make the development of ovarian cancer more likely. Therefore it is treatment of women who fail to ovulate (produce an egg) regularly. Clomifene recommended to be taken for a year only, taking it for any longer is unlikely to or Letrozole drugs have the effect of boosting the production of those give any significant benefit. hormones that stimulate eggs to grow. When and how is it taken? Does it work for everyone? Take clomifene/letrozole for four days starting the day after your period starts Over half of women will respond to clomifene/letrozole treatment (more so if (ie.
    [Show full text]
  • 6. Endocrine System 6.1 - Drugs Used in Diabetes Also See SIGN 116: Management of Diabetes, 2010
    1 6. Endocrine System 6.1 - Drugs used in Diabetes Also see SIGN 116: Management of Diabetes, 2010 http://www.sign.ac.uk/guidelines/fulltext/116 Insulin Prescribing Guidance in Type 2 Diabetes http://www.fifeadtc.scot.nhs.uk/media/6978/insulin-prescribing-in-type-2-diabetes.pdf 6.1.1 Insulins (Type 2 Diabetes) 6.1.1.1 Short Acting Insulins 1st Choice S – Insuman ® Rapid (Human Insulin) S – Humulin S ® S – Actrapid ® 2nd Choice S – Insulin Aspart (NovoRapid ®) (Insulin Analogues) S – Insulin Lispro (Humalog ®) 6.1.1.2 Intermediate and Long Acting Insulins 1st Choice S – Isophane Insulin (Insuman Basal ®) (Human Insulin) S – Isophane Insulin (Humulin I ®) S – Isophane Insulin (Insulatard ®) 2nd Choice S – Insulin Detemir (Levemir ®) (Insulin Analogues) S – Insulin Glargine (Lantus ®) Biphasic Insulins 1st Choice S – Biphasic Isophane (Human Insulin) (Insuman Comb ® ‘15’, ‘25’,’50’) S – Biphasic Isophane (Humulin M3 ®) 2nd Choice S – Biphasic Aspart (Novomix ® 30) (Insulin Analogues) S – Biphasic Lispro (Humalog ® Mix ‘25’ or ‘50’) Prescribing Points For patients with Type 1 diabetes, insulin will be initiated by a diabetes specialist with continuation of prescribing in primary care. Insulin analogues are the preferred insulins for use in Type 1 diabetes. Cartridge formulations of insulin are preferred to alternative formulations Type 2 patients who are newly prescribed insulin should usually be started on NPH isophane insulin, (e.g. Insuman Basal ®, Humulin I ®, Insulatard ®). Long-acting recombinant human insulin analogues (e.g. Levemir ®, Lantus ®) offer no significant clinical advantage for most type 2 patients and are much more expensive. In terms of human insulin. The Insuman ® range is currently the most cost-effective and preferred in new patients.
    [Show full text]
  • Supplementary Methods
    1 Supplementary Methods Definitions of the reproductive traits used in the analysis Reproductive trait Definition Age at first birth (years) Age at first live birth (females only). Age at last birth (years) Age at last live birth (females only). Age at menarche (years) Age at menarche between 9 and 17 years. Age at natural menopause (years) Age at last menstrual period excluding those with surgical menopause or taking hormone replacement therapy. Bilateral oophorectomy Ever had bilateral oophorectomy (case) vs. never (control). Breast cancer Breast cancer on registry (ICD10 C50, ICD9 174&175), vs no cancer reported (control). Dysmenorrhea Dysmenorrhea listed as an illness (reported at interview). Early menarche Youngest 5% of BMI adjusted age at menarche(case) vs oldest 5% (control). Age at menarche defined as above. Early menopause Age at natural menopause (as defined above) at 20-45 years (case) vs. 50-60 years (control). Endometrial cancer Endometrial cancer on registry (ICD10 C54, ICD9 182) vs no cancer reported. Endometriosis Endometriosis listed as an illness (reported at interview). Fibroids Fibroids listed as an illness (reported at interview). Hysterectomy Ever had hysterectomy (case) vs. never (control). Irregular menstrual cycles Women still menstruating reporting irregular cycles (case) vs. regular cycles (control). Length of menstrual cycle (days) Women still menstruating reporting regular cycles. Excludes women taking oral contraceptives, HRT or hormone medications (see list below) and pregnant women. Long menstrual cycle (vs average) Length of menstrual cycle >31 days (case) vs 28 days (control). As defined above. Menopausal symptoms Menopausal symptoms listed as an illness (reported at interview). Menorrhagia Menorrhagia listed as an illness (reported at interview).
    [Show full text]
  • In Vitro and in Silico Analyses of the Inhibition of Human Aldehyde Oxidase By
    JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 In Vitro and In Silico Analyses of the Inhibition of Human Aldehyde Oxidase by Bazedoxifene, Lasofoxifene, and Structural Analogues Shiyan Chen, Karl Austin-Muttitt, Linghua Harris Zhang, Jonathan G.L. Mullins, and Aik Jiang Lau Downloaded from Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore jpet.aspetjournals.org (S.C., A.J.L.); Institute of Life Science, Swansea University Medical School, United Kingdom (K.A-M, J.G.L.M.); NanoBioTec, LLC., Whippany, New Jersey, U.S.A. (L.H.Z.); at ASPET Journals on September 29, 2021 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (A.J.L.) 1 JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 Running Title In Vitro and In Silico Analyses of AOX Inhibition by SERMs Corresponding author: Dr. Aik Jiang Lau Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. Downloaded from Tel.: 65-6601 3470, Fax: 65-6779 1554; E-mail: [email protected] jpet.aspetjournals.org Number of text pages: 35 Number of tables: 4 Number of figures: 8 at ASPET Journals on September 29, 2021 Number of references 60 Number of words in Abstract (maximum
    [Show full text]
  • Tamoxifen: Drug Information
    Official reprint from UpToDate® www.uptodate.com ©2017 UpToDate® Tamoxifen: Drug information Copyright 1978-2017 Lexicomp, Inc. All rights reserved. (For additional information see "Tamoxifen: Patient drug information" and see "Tamoxifen: Pediatric drug information") For abbreviations and symbols that may be used in Lexicomp (show table) ALERT: US Boxed Warning Ductal carcinoma in situ/women at high risk for breast cancer: Serious and life-threatening events associated with tamoxifen in the risk-reduction setting (women at high risk for cancer and women with ductal carcinoma in situ [DCIS]) include uterine malignancies, stroke, and pulmonary embolism (PE). Incidence rates for these events were estimated from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial. Uterine malignancies consist of endometrial adenocarcinoma (incidence rate per 1,000 women-years of 2.2 for tamoxifen versus 0.71 for placebo) and uterine sarcoma (incidence rate per 1,000 women-years of 0.17 for tamoxifen versus 0.4 for placebo) (updated long-term follow-up data [median length of follow-up is 6.9 years] from NSABP P-1 study). For stroke, the incidence rate per 1,000 women-years was 1.43 for tamoxifen versus 1 for placebo. For PE, the incidence rate per 1,000 women-years was 0.75 for tamoxifen versus 0.25 for placebo. Some of the strokes, PE, and uterine malignancies were fatal. Discuss the potential benefits versus the potential risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risks of developing breast cancer.
    [Show full text]
  • Assessment Report
    25 January 2018 EMA/88321/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report EnCyzix International non-proprietary name: enclomifene Procedure No. EMEA/H/C/004198/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Administrative information Name of the medicinal product: EnCyzix Applicant: Renable Pharma Limited 20-22 Bedford Row WC1R 4JS UNITED KINGDOM Active substance: ENCLOMIFENE CITRATE International Non-proprietary Name/Common Enclomifene Name: Not assigned Pharmaco-therapeutic group (ATC Code): Treatment of hypogonadotropic hypogonadism (secondary hypogonadism) in Therapeutic indication(s): adult men aged ≤60 years with a body mass index (BMI) ≥25 kg/m2 which has been confirmed by clinical features and biochemical tests in patients which have not responded to diet and exercise Pharmaceutical form(s): Capsule, hard Strength(s): 8.5 mg and 17 mg Route(s) of administration: Oral use Packaging: bottle (HDPE) Package size(s): 30 capsules EMA/88321/2018 Page 2/111 Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ....................................................................................
    [Show full text]
  • Fertility Treatment Using Clomifene Tablets
    Patient Information Fertility Treatment using Clomifene Tablets Women’s Services Introduction This information leaflet is for women undergoing fertility treatment who have been prescribed Clomifene (Clomid) tablets. What is Clomifene? Clomifene is a drug used in fertility treatment to stimulate the ovaries to produce eggs (ovulation). It is not a hormone but alters your ‘hormone’ balance to help your ovaries produce eggs. What are the benefits of Clomifene? The aim is to increase ovulation and increase the chance of you becoming pregnant. The tablet works best if your BMI is between 19 and 30; any lower or higher will affect the success rates. If you are significantly overweight, you will be advised to lose weight before commencing Clomifene tablets. What are the risks of Clomifene? There are a few small risks and side effects as with most medications, these include: Multiple pregnancy - Approximately 1 in 10 women who conceive using Clomifene have twins. Less than 1 in 1,000 have triplets. Headaches Abdominal pain Ovarian cysts Hot flushes Blurring of vision or yellow colouration of vision; if this occurs stop taking your tablets and consult your GP Ovarian hyperstimulation (where the ovaries have over responded to Clomifene) – this is very uncommon 2 What are the alternative treatments to Clomifene? There are a few different treatment options to induce ovulation which include: Tamoxifen tablets Letrozole tablets Metformin (may be combined with Clomifene) in women with PCOS Laparoscopy (key hole surgery) and ‘drilling’ of ovaries in women with PCOS Injections of follicle stimulating hormone (FSH) Assisted conception treatment, e.g. IVF/ICSI These different treatment options may not be suitable for everyone.
    [Show full text]
  • Clomifene Pharmacokinetic Data Bioavailability High (>90
    Clomifene Pharmacokinetic data Bioavailability High (>90%) Metabolism Hepatic (with enterohepatic circulation) Half-life 5-7 days Excretion Mainly renal, some biliary Clomifene (INN) or clomiphene (USAN) (trademarked as Androxal, Clomid and Omifin) is a selective estrogen receptor modulator (SERM) that increases production of gonadotropins by inhibiting negative feedback on the hypothalamus. This synthetic drug comes supplied as white, round tablets in 50 mg strength only. It has become the most widely prescribed of all fertility drugs. It is used in the form of its citrate to induce ovulation. Use in female infertility It is used mainly in female infertility, in turn mainly as ovulation induction to reverse oligoovulation or anovulation such as in infertility in polycystic ovary syndrome, as well as being used for ovarian hyperstimulation, such as part of an in vitro fertilization procedure. In April 1989, a patent was awarded to Yale University Medical researchers Dr. Florence Comite and Dr. Pamela Jensen for the use of clomiphene to predict fertility in women. A woman capable of sustaining pregnancy would develop denser bone mass while on clomiphene; the bone mass increase would be predictive of fertility, and the changes could be detected on a CT scanner. Mode of action Clomifene inhibits estrogen receptors in hypothalamus, inhibiting negative feedback of estrogen on gonadotropin release, leading to up-regulation of the hypothalamic–pituitary–gonadal axis. Zuclomifene, a more active isomer, stays bound for longer periods of time. The drug is non-steroidal. In normal physiologic female hormonal cycling, at 7 days past ovulation, high levels of estrogen and progesterone produced from the corpus luteum inhibit GnRH, FSH and LH at the hypothalamus and anterior pituitary.
    [Show full text]
  • Hormone Therapy for Sexual Function in Perimenopausal and Postmenopausal Women (Review)
    Hormone therapy for sexual function in perimenopausal and postmenopausal women (Review) Nastri CO, Lara LA, Ferriani RA, Rosa-e-Silva ACJS, Figueiredo JBP, Martins WP This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 6 http://www.thecochranelibrary.com Hormone therapy for sexual function in perimenopausal and postmenopausal women (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 5 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 9 Figure1. ..................................... 10 Figure2. ..................................... 12 Figure3. ..................................... 13 Figure4. ..................................... 15 Figure5. ..................................... 17 Figure6. ..................................... 19 Figure7. ..................................... 20 Figure8. ..................................... 22 ADDITIONALSUMMARYOFFINDINGS . 23 DISCUSSION ..................................... 25 AUTHORS’CONCLUSIONS . 27 ACKNOWLEDGEMENTS . 27 REFERENCES ..................................... 27 CHARACTERISTICSOFSTUDIES . 36 DATAANDANALYSES. 77 Analysis 1.1. Comparison
    [Show full text]