DOCSLIB.ORG

Developments in Jaundice

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Developments in Jaundice Postgrad Med J: first published as 10.1136/pgmj.45.521.196 on 1 March 1969. Downloaded from Postgrad. med. J. (March 1969) 45, 196-201. Developments in jaundice R. P. H. THOMPSON ROGER WILLIAMS B.M., M.R.C.P. M.D., M.R.C.P. JAUNDICE is a large subject, but two topical aspects OH OH are the potential hepatic toxicity of oral contracep- 8eH3 vt OH3 C-CH tives, and the possible use of hepatic enzyme induction in therapy. Hepatic effects of oral contraceptives Oral contraceptives are usually prescribed as a Testosterone cH3 Norethisterone cH3 combined pill containing 1-4 mg of a progestagen, C=o (ond 19-norprogestogens) C=0 and 0-05-0-15 mg of an oestrogen, taken for 3 weeks sH-OHCHH15 from the 5th day of each menstrual cycle. Less commonly sequential administration is used, when CH-OH OHC -COH oestrogen is taken for the first 2 weeks, and oestrogen OCH3~I -H_o^^^ CH-Cho^ modinone plus progestagen for the next week. These doses are ozzwJ^ Nomestronl)(and small compared to the normal production of pro- Hydroxyprogesterone OH gesterone and oestradiol, for the corpus luteum of menstruation secretes 20-30 mg/day of the former and 1 mg/day of the latter, and in late pregnancy the copyright. placenta up to 300 mg, and 15-30 mg/day, respec- tively. HO HO The progestagens used in contraceptive pills are Oestradiol Ethynyl oestrodiol synthetic and of two types (Fig. 1). Most are derivatives of testosterone but, lacking its C19methyl group, are called 19-norsteroids. They include OH norethisterone (norethindrone), norethynodrel and CH3CH2CH3 ethynodiol; and lynoestrenol. The two other pro- gestagens used, megestrol and chlormadinone, are http://pmj.bmj.com/ derivatives of hydroxyprogesterone, and have a or different structure. Either ethynyloestradiol Norethondrolone ('nilevor') mestranol are used for the oestrogen component. None of these steroids are 17c-alkyl-substituted, but FIG. 1. The structure of some steroid molecules. the 19-norprogestagens and these oestrogens do have unsaturated hydrocarbon groups in the 17a position. women developed raised serum transaminase levels Unlike testosterone, 19-norprogestagens are partly and retention of bromsulphthalein (BSP) after on October 4, 2021 by guest. Protected converted to oestrogens in vivo (Bishop, 1968). 1 month's treatment with an oral contraceptive pre- About 10 % of norethisterone acetate is metabolized paration for menstrual irregularities. Since then to urinary 17a-ethynyloestradiol (Brown & Blair, approximately 100 cases of jaundice have been 1960) which has twenty times the oestrogenic effect recorded in the world literature, although this of oestradiol, and although Paulsen (1966) found reaction probably occurs in less than 1 in 10,000 of that it produced gynaecomastia, other oestrogenic the millions of women taking the pill (Schaffner, effects surprisingly are not marked. Megestrol and 1966). Initial symptoms of vague nausea and pruritus chlormadinone are not so metabolized (Cooper & are followed by jaundice which is usually slight, but Kellie, 1968). occasionally severe. Biochemically and histologically the picture is of a mixed hepatocellular and chole- Occurrence ofimpaired hepatic function static lesion. This syndrome usually occurs in the In 1964 Eisalo, Jarvinen & Luukkainen reported first few weeks of treatment and rapidly regresses from Helsinki that twelve elderly post-menopausal when the pill is withdrawn. Postgrad Med J: first published as 10.1136/pgmj.45.521.196 on 1 March 1969. Downloaded from Developments in jaundice 197 Minor abnormalities of liver function and histo- 1964), while the serum transaminase levels and logy probably occur in a much higher percentage of routine liver histology were unaffected. In rats, women on the pill. Kleiner, Kresch & Arias (1965) Gallagher, Mueller & Kappas (1966) have demon- used the infusion test of Wheeler et al. (1960) to strated abnormal BSP retention with oestradiol and measure both the hepatic storage capacity and the mestranol, but progesterone and norethynodrel were transport maximum (Tm) for bromsulphthalein. inactive, as was progesterone in man (Kappas, Both these are concerned in the hepatic excretion of 1968). this dye, and this test may detect changes in liver Further information comes from the relationship function when the routine BSP test (measurement of contraceptive liver damage to recurrent intra- of retention in blood 30-45 min after intravenous hepatic cholestasis of pregnancy (Haemmerli, 1966). injection) is within normal limits. They found that In this condition pruritus alone, or pruritus and contraceptive doses of norethynodrel and mestranol moderate obstructive jaundice develop in the last given for several months impaired BSP transport trimester of succeeding pregnancies, returning to maxima in all nine normal women studied, storage normal soon after delivery. Serum alkaline phos- capacities remaining normal (Fig. 2). The electron phatase levels are raised and retention of BSP occurs. Centrizonal cholestasis in needle liver biopsies is 8 surprisingly mild. These women are particularly liable to develop jaundice with oral contraceptives, and they account for about half of the cases of such The condition is commoner in 7~ - jaundice reported. E Scandinavia and where the incidence of 60 Chile, C' contraceptive jaundice is also highest (Orellana- Alcade & Dominguez, 1966). In addition, abnor- ->' _ 50 5 malities of liver function without jaundice are commoner in women on the in these Cu,LcoE C probably pill g2 4040 -4 areas for serum transaminase levels are raised in c.rs VQa~ up L0 to 18% of pre-menstrual women in some Scandi- copyright. o C' ~E30 - navian series (Eisalo, Jarvinen & Luukkainen, 1965), but are normal in series from Mexico (Rice-Wray, E 1964), Holland (Swaab, 1964), London (Swyer & a~~~~~2I0 2 Little, 1965) and Los Angeles (Tyler, 1964). There is C some or e3a co 0 presumably genetic environmental factor 10 behind this geographical variation. Kreek et al. (1967) treated seven patients with 0 - OL previous pruritus or jaundice of pregnancy with FIG. 2. The effect of norethynodrel and mestranol on 0-5-1-5 mg of 17a-ethynyloestradiol alone for up to http://pmj.bmj.com/ BSP storage capacity and maximum excretory rates of two weeks, but did not try a progestagen. This dose normal women. Open columns, Before; stippled columns, is ten times that in the pill, but in six control women norethynodrel + mestranol; solid columns, after. it produced only nausea. In the seven patients their previous symptoms in pregnancy were reproduced, microscope will also often show changes of choles- liver function was variably impaired, and one tasis in the liver during contraceptive treatment, with patient became temporarily jaundiced. dilated canaliculi, distortion and loss of canalicular microvilli, and increased numbers of abnormal on October 4, 2021 by guest. Protected mitochondria. Light microscopy is usually normal Progestagens (Larsson-Cohn & Stenram, 1967). In most studies, administration of progestagens has had little effect. Adlercreutz & Ikonen (1964) Cause of abnormalities gave the progestagen lynoestrenol to a patient with It is uncertain whether the progestagen, the previous pruritus of pregnancy without change, but oestrogen component, or both are responsible. two progestagen and oestrogen contraceptive com- Combes et al. (1963) have shown selective impair- binations induced jaundice before and after. In the ment of the BSP transport maxima in the last original twelve patients of Eisalo et al. (1964) trimester of pregnancy, when large amounts of lynoestrenol was inactive, and Borglin (1965) had progesterone and oestrogen circulate. When equiva- similar results. In other studies, however, the 19- lently large amounts of oestradiol were given to norprogestagens without oestrogens have been thirty-one non-pregnant women, retention of BSP shown to impair liver function and rarely to cause frequently occurred (Mueller, Kappas & Damgaard, jaundice (Perez-Mera & Shields, 1962). In a recent Postgrad Med J: first published as 10.1136/pgmj.45.521.196 on 1 March 1969. Downloaded from 198 R. P. H. Thompson and Roger Williams report, remarkably prolonged and deep jaundice Oral contraceptives should not be given to developed in two sisters, one treated with norethis- patients with a previous history of jaundice or terone alone, the other with norethisterone plus pruritus ofpregnancy, nor to patients with hereditary ethynyloestradiol (Somayaji et al., 1968). hepatic excretory defects, nor with any of the diff- Other 19-norsteroids, such as methyltestosterone erent varieties of intrahepatic cholestasis. It is and norethandrolone, are well known to impair probably best not to prescribe them to patients with BSP excretion (Marquardt et al., 1961) and to cause hepatitis or other liver disease within recent months, cholestatic jaundice. These steroids have an alkyl although opinions on this are divided (Ockner & group in the 17cc-position (Fig. 1), which increases Davidson, 1967). their cholestatic action (Gallagher et al., 1966). Contraceptive pills which have a progesterone- There is some evidence that the similar but un- derived progestagen such as megestrol or chlor- saturated substitution groups in the 17a-position in madinone, rather than the testosterone-derived 19- 19-norprogestagens do likewise, and Eisalo, Heino nor-progestagens may be safer, and the long term & Rasanen (1968), for example, have recently found contraceptive use ofchlormadinone alone (Martinez- that the 19-norprogestagen lynoestrenol induced
Load more

Recommended publications
  • Part I Biopharmaceuticals
    1 Part I Biopharmaceuticals Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 3 1 Analogs and Antagonists of Male Sex Hormones Robert W. Brueggemeier The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, Ohio 43210, USA 1Introduction6 2 Historical 6 3 Endogenous Male Sex Hormones 7 3.1 Occurrence and Physiological Roles 7 3.2 Biosynthesis 8 3.3 Absorption and Distribution 12 3.4 Metabolism 13 3.4.1 Reductive Metabolism 14 3.4.2 Oxidative Metabolism 17 3.5 Mechanism of Action 19 4 Synthetic Androgens 24 4.1 Current Drugs on the Market 24 4.2 Therapeutic Uses and Bioassays 25 4.3 Structure–Activity Relationships for Steroidal Androgens 26 4.3.1 Early Modifications 26 4.3.2 Methylated Derivatives 26 4.3.3 Ester Derivatives 27 4.3.4 Halo Derivatives 27 4.3.5 Other Androgen Derivatives 28 4.3.6 Summary of Structure–Activity Relationships of Steroidal Androgens 28 4.4 Nonsteroidal Androgens, Selective Androgen Receptor Modulators (SARMs) 30 4.5 Absorption, Distribution, and Metabolism 31 4.6 Toxicities 32 Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 4 Analogs and Antagonists of Male Sex Hormones 5 Anabolic Agents 32 5.1 Current Drugs on the Market 32 5.2 Therapeutic Uses and Bioassays
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Guidelines for the Management of Heavy Menstrual Bleeding
    i GUIDELINES FOR THE MANAGEMENT OF HEAVY MENSTRUAL BLEEDING Prepared by a Working Party on behalf of the National Health Committee ii MAY 1998 Women reporting with heavy menstrual bleeding 50% of women have menstrual blood loss Full menstrual history ● Examination ● Full blood count note1 Yes Prolonged irregular cycles No Refer Yes Abnormal exam specialist uterine size >12wks note 2 No mild or severe anaemic moderate treat < 80 g/l (80-115g/l) anaemia No Assess risk of endometrial hyperplasia low Offer medical therapy ● risk Unexplaine bodyweight 90kg heavy menstrual ● note5 note 6 age 45 years <2% bleeding ● other risk factors have 90% of women note 3 ● levonorgestrel endometrial >8% have hyperplasia intrauterine system ● tranexamic acid ● Assess endometrium nonsteroidal ● transvaginal ultrasound antiinflammatory agents ● (TVS) norethisterone long course or normal ● oc pill endometrium ● ● endometrial biopsy if danazol if one medical therapyfails endometrium 12mm others can be used note 7 or if TVS not available note 4 Treatment Hyperplastic endometrium success? or carcinoma No Yes Refer to specialist for hysteroscopic evaluation Continue Refer specialist me d i c a l for surgery therapy note8 note9 iii note 1 O In women <20 years old pelvic examination is unlikely to contribute to management of heavy bleeding (C) and the likelihood of pathology is small (C) O Increased likelihood (70%) of heavy menstrual blood loss >80mls/cycle if Hb <120g/l (A) O Consider pictorial blood loss assessment charts (appendix 6.5) for women with normal
    [Show full text]
  • MMC International BV
    M.M.C. International Steroid Substances Steroid Test A Colour Steroid Test B Colour Steroid Test B Colour with UV Light Stanozolol/ Oxandrolone Test Clenbuterol/ Oxymetholone Test Ephedrine Test Alfadolone Orange Yellow Nil - - - Androsterone Orange Yellow White - - - Beclometasone Brown–yellow Orange Nil - - - Betamethasone Orange–brown Pink–Orange Nil - - - Boldenone Base (Equipoise, Ganabol) (pure powder) Warm red after 2 min. Dark Orange after 2 min. Bright Light Orange - - - Boldenone Undecanoate (oil) Dark brownish-red Dark Red Bright Light Orange - - - Boldenone Undecylenate (oil) Orange - Light Brown Dark Orange → Brown Bright Light Orange-Yellow - - - Carbenoxolone (CBX) Orange Yellow Yellow - - - Cholesterol Violet Orange White - - - Clenbuterol (Spiropent, Ventipulmin) - - - - Purple - Dark brown with yellow-green on the Dark brown with yellow-green on the Clomiphene (Androxal, Clomid, Omifin) Nil Dark brown to black No reaction Dark brown to black sides of the ampoule sides of the ampoule Cortisone Orange Yellow Green - - - Desoxycortone Blue–black Yellow Yellow - - - Dexamethasone Yellow Orange–pink Nil - - - Dienestrol Yellow Orange–red Nil - - - Diethylstilbestrol (DES) Orange (→yellow–green) Nil - - - Dimethisterone Brown–green Orange–red Yellow - - - Drostanolone Propionate (Masteron) (oil) Bright green Yellow-Orange Orange - - - Dydrogesterone (Duphaston) - Orange Green-Yellow - - - Enoxolone Orange Yellow Green-Yellow - - - Ephedrine (also for Pseudo- and Nor-Ephedrine) - - - - - Orange Estradiol (Oestradiol) Orange
    [Show full text]
  • NORETHISTERONE This Document Should Be Read in Conjunction with This DISCLAIMER
    King Edward Memorial Hospital Obstetrics & Gynaecology ADULT NORETHISTERONE This document should be read in conjunction with this DISCLAIMER Presentation Tablets: 350microg Tablets: 5mg Combination products: Tablets (Norimin 28®): norethisterone 500microg with ethinylestradiol 35microg As part of HRT: see Estrogen (Oestrogen) HRT Dose Contraception Oral: Progesterone only pill (POP): 350microg daily Combined oral contraceptive pill (COCP): ONE tablet daily Endometriosis Oral: 5-10mg once daily for at least 4-6 months Menstrual disorders (e.g. heavy menstrual bleeding) Oral: Initially: 5mg 3 times daily for 10 days. Higher doses have been used; seek specialist advice. To prevent recurrence (anovulatory): 5mg once or twice daily for 10- 14 days in seconf half of cycle To prevent recurrence (ovulatory): 5mg 3 times daily for days 5-26 of cycle Hormone replacement therapy (HRT) Oral: 1.25mg daily for 10-14 days each month, to be taken with continuous estrogen. Refer to Estrogen (Oestrogen) HRT Adult Medication Monograph Page 1 of 1 Norethisterone – Adult Administration Oral To be taken at the same time each day (or within 3 hours of the usual dose time). For Contraception: Start 4 weeks after the birth of baby (increased risk of abnormal vaginal bleeding if started earlier) Pregnancy 1st Trimester: Contraindicated 2nd Trimester: Contraindicated 3rd Trimester: Contraindicated Breastfeeding Considered safe to use. Progestogens are the preferred hormonal contraceptives as they do not inhibit lactation. Clinical Guidelines Estrogen (Oestrogen) HRT and Policies Progesterone Only Pill Contraception: Post Partum Gynaecology (Non-Oncological) Australian Medicines Handbook. Norethisterone. In: Australian References Medicines Handbook [Internet]. Adelaide (South Australia): Australian Medicines Handbook; 2017 [cited 2017 Apr 12].
    [Show full text]
  • Nur-Isterate Injection
    SELECT THE REQUIRED INFORMATION PROFESSIONAL INFORMATION PATIENT INFORMATION LEAFLET SCHEDULING STATUS: S4 PROPRIETARY NAME AND DOSAGE FORM: NUR-ISTERATE Oily solution for intramuscular injection COMPOSITION: 1 ml contains norethisterone enantate (17-ethinyl-17-heptanoyloxy-4-estrene-3-one) 200 mg. Other ingredients are: benzyl benzoate, castor oil for injection. PHARMACOLOGICAL CLASSIFICATION: A. 21.8.2 Progesterones without estrogens. PHARMACOLOGICAL ACTION: Pharmacodynamic properties: Protection against conception is based primarily upon an alteration of the cervical mucous. This alteration is present for the whole of the duration of action and prevents the ascent of the sperm into the uterine cavity. Radioimmunological studies have shown that, during the first 5 to 7 weeks after injection, ovulation is suppressed as a result of the high plasma level of norethisterone. In addition, NUR- ISTERATE causes morphological changes in the endometrium which have the effect of rendering nidation of a fertilised egg difficult. Pharmacokinetic properties: Norethisterone enantate was completely absorbed after intramuscular injection. The ester was eventually completely hydrolysed to its pharmacologically active compound norethisterone once it was released from the depot. Maximum levels of norethisterone were measured at about 3 to 10 days after IM administration. They amounted on average to 13.4 5.4 ng/ml and 12.2 2.7 ng/ml about 7 days (median) after IM administration of 200 mg norethisterone enantate in 2 ml and 1 ml oily solution, respectively. Plasma levels of norethisterone declined in two disposition phases with half-lives of 4 to 5 days and 15 to 20 days, respectively, which were due to a biphasic release of norethisterone enantate from the depot.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Control Be Implemented. the First Large-Scale Systematic Olympic Games
    Br J Sports Med: first published as 10.1136/bjsm.11.4.162 on 1 December 1977. Downloaded from 162 Brit. J. Sports Med. - Vol. 1 1, No. 4, December 1977, pp. 162-169 RADIOIMMUNOASSAY OF ANABOLIC STEROIDS: AN EVALUATION OF THREE ANTISERA FOR THE DETECTION OF ANABOLIC STEROIDS IN BIOLOGICAL FLUIDS Robert DUGAL, Ph.D., Claire DUPUIS, Ph.D. and Michel J. BERTRAND, Ph.D. Centre de Recherches en Sciences de la Sante, Institut National de la Recherche Scientifique, Centre Hospitalier Louis-H. Lafontaine, Montrdal, Quebec, Canada ABSTRACT Recently developped radioimmunoassays (RIA) for the analysis of anabolic steroids and their metabolites in biological fluids were tested for cross-reactivity with other types of steroids. Results show that the degree of desirable cross-reactivity within the two classes of orally active anabolic steroids vary widely and that the antiserum for 19-Nortestosterone (the active principle of intramuscular, preparations) has a very high degree of undesirable cross- reactivity with components of oral contraceptives. Single and multiple dose studies in human volunteers demonstrate that the detection level and degree of retrospectivity are likewise variable but that the test easily detects most anabolic steroids during treatment. At the present time, the combination of the three antisera for the assay of a sample appears to be a relatively rapid and economic method for screening large numbers of samples in situations where doping control of anabolic steroids is required. The importance of utilizing physico-chemical means for identification of RIA potential positives is emphasized. INTRODUCTION (Sumner, 1974: Brooks et al, 1975) and identification procedures for a limited number of them have also been copyright.
    [Show full text]
  • Polycystic Ovarian Syndrome
    Polycystic Ovarian Syndrome What we understand and how we can help October 2017 Presentation Title | 27 January 2014 History Stein and Leventhal 1935 Stein IF, Leventhal ML. Amenorrhoea associated with bilateral polycystic ovaries. Am J Obstet Gynaecol 1935; 29:181-191 Presentation Title | 7 January, 2019 Presentation Title | 7 January, 2019 Diagnosis Rotterdam criteria – Two of the three criteria 1. PCOS on USS 2. Oligo or anovulation (less than 6 periods each year) 3. Hyperandrogenism Presentation Title | 7 January, 2019 Presentation Title | 7 January, 2019 Diagnosis – ovarian morphology PCO ultrasound appearance in 22% of normal population PCOS is present in • 7% of women • 32% of women with amenorrhoea • 87% of women with hirsuitism/ acne • 73% of women with anovulatory infertility Presentation Title | 7 January, 2019 Diagnostic tests The biochemical tests are to identify hyperandrogenism… Testosterone Can be measured at any time during the cycle. Consider testosterone secreting tumour if rapid virilisation. Consider High total testosterone or normal total testosterone with low SHBG and high bio-testosterone (measure the free androgen index) GTT All PCOS women who are obese and all women PCOS women over the age of 40. LH and FSH AMH Ovarian reserve and number of antral follicles. – may be raised in PCOS, however not currently used in diagnsois. Presentation Title | 7 January, 2019 Presentation Title | 7 January, 2019 Managing Symptoms Presentation Title | 7 January, 2019 Obesity Supportive strategies for weight loss and diet. Consider Metformin Bariatric surgery Presentation Title | 7 January, 2019 Hirsuitism and Acne Weight loss Cosmetic methods Oral contraceptive pill consider Yasmin as it has an antiandrogenic action.
    [Show full text]
  • Study on Sperm Suppression Using Norethisterone Enanthate and Testosterone Undecanoate
    Study on sperm suppression using Norethisterone enanthate and testosterone undecanoate Objectives Overall goal: and The study was designed to address the following primary objectives: Background 1. The rate of suppression of spermatogenesis induced by a regimen of NET-EN and TU administered every 8 weeks for up to 4 injection visits; and 2. The level of contraceptive protection provided by the continued administration of NET-EN and TU every 8 weeks for an efficacy period of up to 56 weeks. Background: The study was designed to evaluate whether the combination of a progestin, norethisterone enantate (NET-EN), and an androgen, testosterone undecanoate (TU), represents a safe and effective method of male fertility regulation. The study had 3 phases. The suppression phase was to initiate a status of decreased sperm count and activity to a level which would be considered as contraceptive. When this was reached it was sustained with subsequent injections in the efficacy phase, which would end after 56 weeks, or if a pregnancy occurs. After these, the participant was then placed in the recovery phase, and was observed until normal sperm counts and activity returns to normal. 487 participants were screened for eligibility, of which 167 were excluded. The remaining 320 were enrolled into the study, into the suppression phase. A total of 274 completed the suppression phase. Of these 8 discontinued before transitioning to the Efficacy phase, and were moved to recovery phase. A total of 266 transitioned to the efficacy phase, among which 111 completed 56 weeks follow up or until a pregnancy occurred. The remaining 155 were discontinued, either because of the stopping of the study by the sponsor (96), death (1, unrelated to the study), or for other reasons (58).
    [Show full text]
  • Other Data Relevant to an Evaluation of Carcinogenicity and Its Mechanisms
    COMBINED ESTROGEN−PROGESTOGEN CONTRACEPTIVES 143 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms 4.1 Absorption, distribution, metabolism and excretion in humans The metabolism and disposition of various formulations of oral contraceptives used in humans differ. After entering the small intestine, estrogenic and progestogenic compounds in combined oral contraceptives undergo metabolism by bacterial enzymes and enzymes in the intestinal mucosa to varying extents. The mixture of metabolized and unmetabolized compounds then undergoes intestinal absorption, and thus enters the portal vein blood, which perfuses the liver. In the liver, the compounds can be metabolized extensively, which leads to variations in the amount of active drug. A fraction of the absorbed dose of ethinyl- estradiol and some progestogens is also excreted in the bile during its first transit through the liver. Although some of these compounds are partially reabsorbed via the enterohepatic circulation, a fraction may also be excreted in this ‘first pass’, which reduces overall bio- availability. Since steroids penetrate normal skin easily, various systems have also been developed that deliver estrogens and progestogens parenterally, e.g. transdermal patches, nasal sprays, subcutaneous implants, vaginal rings and intrauterine devices (Fanchin et al., 1997; Dezarnaulds & Fraser, 2002; Meirik et al., 2003; Sarkar, 2003; Wildemeersch et al., 2003; Sturdee et al., 2004). These different modes of administration have been described previously (IARC, 1999). In general, all parenteral routes avoid loss of the drug by hepatic first-pass metabolism and minimally affect hepatic protein metabolism. The absorption rates of orally administered estrogens and progestogens are usually rapid; peak serum values are observed between 0.5 and 4 h after intake.
    [Show full text]
  • Steroidal Estrogens
    FINAL Report on Carcinogens Background Document for Steroidal Estrogens December 13 - 14, 2000 Meeting of the NTP Board of Scientific Counselors Report on Carcinogens Subcommittee Prepared for the: U.S. Department of Health and Human Services Public Health Service National Toxicology Program Research Triangle Park, NC 27709 Prepared by: Technology Planning and Management Corporation Canterbury Hall, Suite 310 4815 Emperor Blvd Durham, NC 27703 Contract Number N01-ES-85421 Dec. 2000 RoC Background Document for Steroidal Estrogens Do not quote or cite Criteria for Listing Agents, Substances or Mixtures in the Report on Carcinogens U.S. Department of Health and Human Services National Toxicology Program Known to be Human Carcinogens: There is sufficient evidence of carcinogenicity from studies in humans, which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer. Reasonably Anticipated to be Human Carcinogens: There is limited evidence of carcinogenicity from studies in humans which indicates that causal interpretation is credible but that alternative explanations such as chance, bias or confounding factors could not adequately be excluded; or There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) in multiple species, or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor or age at onset; or There is less than sufficient evidence of carcinogenicity in humans or laboratory animals, however; the agent, substance or mixture belongs to a well defined, structurally-related class of substances whose members are listed in a previous Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.
    [Show full text]