DOCSLIB.ORG

Areas of Future Research in Fibroid Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Areas of Future Research in Fibroid Therapy 9/18/18 Cumulative Incidence of Fibroids over Reproductive Lifespan RFTS Areas of Future Research Blacks Blacks UFS Whites in Fibroid Therapy CARDIA Age 33-46 William H. Catherino, MD, PhD Whites Professor and Chair, Research Division Seveso Italy Uniformed Services University Blacks Whites Associate Program Director Sweden/Whites (Age 33-40) Division of REI, PRAE, NICHD, NIH The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. Laughlin Seminars Reprod Med 2010;28: 214 Fibroids Increase Miscarriage Rate Obstetric Complications of Fibroids Complication Fibroid No Fibroid OR Abnormal labor 49.6% 22.6% 2.2 Cesarean Section 46.2% 23.5% 2.0 Preterm delivery 13.8% 10.7% 1.5 BreecH position 9.3% 4.0% 1.6 pp Hemorrhage 8.3% 2.9% 2.2 PROM 4.2% 2.5% 1.5 Placenta previa 1.7% 0.7% 2.0 Abruption 1.4% 0.7% 2.3 Guben Reprod Biol Odds of miscarriage decreased with no myoma comparedEndocrinol to myoma 2013;11:102 Biderman-Madar ArcH Gynecol Obstet 2005;272:218 Ciavattini J Matern Fetal Neonatal Med 2015;28:484-8 Not Impacting the Cavity Coronado Obstet Gynecol 2000;95:764 Kramer Am J Obstet Gynecol 2013;209:449.e1-7 Navid Ayub Med Coll Abbottabad 2012;24:90 Sheiner J Reprod Med 2004;49:182 OR = 0.737 [0.647, 0.840] Stout Obstet Gynecol 2010;116:1056 Qidwai Obstet Gynecol 2006;107:376 1 9/18/18 Best Studied Therapies Hysterectomy Option over Time Surgical Radiologic Medical >100 years of study Hysterectomy Open myomectomy GnRH agonists 25-34 years of study Endometrial Ablation GnRH agonists 20-24 years of study Laparoscopic myomectomy Uterine artery embolization Retinoic acid 10-19 years of study Uterine artery obstruction SPRMs: Mifepristone, ulipristal Robotic myomectomy GnRH antagonists 5-9 years of study Cryomyolysis MRI-guided high frequency ultrasound SPRMs: Asoprisnil, Telapristone, Laparoscopic ablation Vilaprisan SERMs: Tamoxifen, Raloxifene, Letrozole, Genistein Pitter MC, Simmonds C, Seshadri-Kreaden U, Hubert HB. JMIR 2014;3: Jacoby VLObstet Gynecol 2009;114:1041-8 2011 2012 2013 2014 2015 2016 2017 2018 Elagolix Vilaprisan Vilaprisan Vilaprisan Ulipristal Ulipristal Ulipristal Ulipristal Ulipristal Ulipristal Ulipristal Ulipristal Leuprolide Leuprolide Leuprolide Leuprolide Leuprolide Leuprolide Leuprolide Leuprolide Mifepristone Mifepristone Mifepristone Mifepristone Mifepristone Mifepristone Mifepristone Mifepristone Cetrorelix Cetrorelix Cetrorelix Cetrorelix Cetrorelix Retinoic Acid Retinoic Acid Retinoic Acid Retinoic Acid Retinoic Acid Retinoic Acid ECGC ECGC ECGC Berberine Berberine Tranilast Halofuginone Halofuginone Halofuginone >100 pubs Levonorgestrel Levonorgestrel Levonorgestrel Levonorgestrel Levonorgestrel 70-99 pubs Medical Therapy Triptorelin Triptorelin Triptorelin Triptorelin Triptorelin 10-69 pubs Letrozole Letrozole Letrozole Letrozole 1-9 pubs AG1478 AG1478 Last Pub Simvastatin Tamoxifen 2001 Goserelin Goserelin Goserelin Goserelin Targretin 2004 Raloxifene Raloxifene Raloxifene Raloxifene Pioglitazone 2005 Tibolone Tibolone Tibolone Tibolone Resveratrol 2005 Asoprisnil Asoprisnil Asoprisnil Asoprisnil E. alatus 2006 Liarozole Liarozole TKS050 2007 Celecoxib Celecoxib Ciglitazone 2007 Telapristone Telapristone Telepristone Isoliquiritigenin 2008 Lynesterol Lynesterol Curcumin 2011 Methoxyestradiol Methoxyestradiol Fulvestrant 2011 Buserelin Buserelin Perfenidone 2011 CDB-4124 2011 2 9/18/18 Leuprolide Acetate GnRH Analogues 10, patient reported - VisualAnalog Scale: 1 Palomba Fertil Steril 1998;70:111 Elagolix Selective Progesterone Receptor Modulators Archer Fertil Steril 2017;108:152 3 9/18/18 Chemical Structures: Selective Progesterone Receptor How do sPRMs work? Modulators (SPRMs) CH3 O OO N SS F FF F H3 C OCH3 F H OH F OCCH3 FF O CH3 N H3 C OH O OO C C CH3 Ulipristal Vilaprisan CH3 OCH3 HO N N O O H3 C OCH2 CH3 Mifepristone OCH3 CH2 OCH3 O Progesterone O Telapristone Asoprisnil Bouchard Fertil Steril 2011;96:1175 Mifepristone Clinical efficacy of each SPRM for fibroid N = 14 treatment Age: 40.8 BMI: 25.9 Decrease in fibroid size: 28% Engman Hum Reprod 2009;24:1870 4 9/18/18 PEARL I: Asoprisnil Ulipristal Controls bleeding faster than Placebo Bleeding Suppression Uterine Volume Donnez NEJM 2012;366:409 Chwalisz Fertil Steril 2007;87:1399 Donnez N Engl J Med 2012;366:409 PEARL II: Ulipristal Controls Bleeding Faster Vilaprisan: Optimal Dose than Leuprolide Acetate approximately 1-2 mg to induce Non-Bleeding Event Donnez NEJM 2012;366:421-32 Donnez N Engl J Med 2012;366:421 Schütt Hum Reprod 2016;31:1703 5 9/18/18 Vilaprisan: 1-2 mg decreases mean number of Bleeding Days Potential Future Therapies Schütt Hum Reprod 2016;31:1703 Simvastatin Retinoic Acid • hmg-CoA • Differentiating inhibitor agent • Hyperlipidemia • Relatively toxic therapy • Compounds that • Antitumor increase properties intracellular retinoic acid available for study Catherino WH, Malik M. Fertil Steril 2007;87:1388 Borahay J Biol Chem 2014;289:35075 Ben-Sasson Fertil Steril 2011;95:2080 Borahay Am J Obstet Gynecol 2015;213:196.e1-8 Gilden Fertil Steril 2012;98:1557 6 9/18/18 Vitamin D Green Tea Extract • Has • High therapeutic antiproliferative index and apoptotic • Consumption function associated with • Vit D depletion lower cancer associated with incidence high risk of fibroids Halder Biol Reprod 2012;86:116 Zhang Am J Obstet Gynecol 2010;202:289 Halder Biol Reprod 2013;89:150 Roshdy Int J Womens Health 2013;5:477 Berberine Tranilast • Chinese herb • Anti-allergic • Anti-inflammatory • Inhibits mast cell • Used to treat degranulation chronic • Inhibits release of inflammatory inflammatory conditions mediators • Prevents keloid tumor formation Chuang Reprod Sci 2017;24:1005 Wu Fertil Steril 2015;103:1098 Islam Fertil Steril 2014;102:597 7 9/18/18 Cabergoline / Aromatase Inhibitor Summary 500 Before • Dopamine After receptor agonist • There is an increasing interest in moving from surgical • Combined with to medical management. 0 aromatase Co ntro l Ca berg oli ne • GnRH analogues and SPRMs effectively decrease inhibitor menorrhagia and leiomyoma size • No value in • Novel therapies that function without regulating addition of gonadal hormones are currently under investigation cabergoline Vahdat Eur J Obstet Gynecol Reprod Biol 2016;206:74 Sayyah-Melli Eur J Obstet Gynecol Reprod Biol 2017;210:257 Thank you! 8.
Load more

Recommended publications
  • Mifepristone
    1. NAME OF THE MEDICINAL PRODUCT Mifegyne 200 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 200-mg mifepristone. For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet. Light yellow, cylindrical, bi-convex tablets, with a diameter of 11 mm with “167 B” engraved on one side. 4. CLINICAL PARTICULARS For termination of pregnancy, the anti-progesterone mifepristone and the prostaglandin analogue can only be prescribed and administered in accordance with New Zealand’s abortion laws and regulations. 4.1 Therapeutic indications 1- Medical termination of developing intra-uterine pregnancy. In sequential use with a prostaglandin analogue, up to 63 days of amenorrhea (see section 4.2). 2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester. 3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester). 4- Labour induction in fetal death in utero. In patients where prostaglandin or oxytocin cannot be used. 4.2 Dose and Method of Administration Dose 1- Medical termination of developing intra-uterine pregnancy The method of administration will be as follows: • Up to 49 days of amenorrhea: 1 Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue: misoprostol 400 µg orally or per vaginum. • Between 50-63 days of amenorrhea Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of misoprostol.
    [Show full text]
  • Transplantation and Immunology 1
    Transplantation and Immunology 1 Transplantation and Immunology บรรยายโดย อ.นพ.สมชัย ลิ้มศรีจ าเริญ เรียบเรียง นพ.กิตติ์รวี จิรธานีเรืองกิจ อาจารย์ที่ปรึกษา อ.นพ.ราวิน วงษ์สถาปนาเลิศ Outline 1. Immunology 2. Immunosuppression: drug use in transplantation 3. Clinical transplant: liver pancreas intestine and kidney transplant ในอเมริกา ท า Transplant เยอะมาก และ resident ศัลยกรรมทุกคนต้องผ่าน rotation transplant ดังนั้น ในอนาคต บ้านเรา จะท ากันมากขึ้น และอาจจะบรรจุ เป็น requirement ให้ resident ต้องผ่าน • Immunology ประวัติศาสตร์ เริ่มจาก Jensen reported in 1902 - มีการทดลอง ศึกษาเกี่ยวกับ tumor และ immunology ของ tumor พบว่า สามารถน าเอา tumor จากหนูไป transplant ให้ตัวอื่นได้ ( ท าใน 19 successive generation) - พบว่าหนูบางส่วนจะ reject tumor ไม่ให้เติบโต (50% of mice) - โดยจะ reject ทุกครั้ง ที่น า tumor มา transplant ใหม่ (มี resistant to subsequent challenge) และ หากน า เอา normal tissue ใส่ไปก่อน และเอา tumor มา transplant ก็จะ reject ได้เร็วขึ้น - เกิด Theory อธิบายเหตุการณ์นี้ คือ Athrepsia theory (เกี่ยวกับ nutrition) เพราะ เวลาใส่ tumor เข้าไปแรกๆ จะยังเจริญได้ช่วงหนึ่งจากนั้น จึงตายไป เชื่อว่าเกิดจากการขาด สารอาหาร หลังจาก tumor ใช้สารอาหารหมด มันก็จะตายไป นับเป็นจุดเริ่มต้นที่ใช้ tumor ในการศึกษาหลักการเรื่อง Transplantation Medawar reported in 1943 (Nobel prize) - เมื่อมี rejection เกิดขึ้น หากเราใช้ graft ครั้งที่ 2 จาก donor เดิม จะเกิดการ reject เร็วขึ้น ซึ่งคิดว่าเกิดจาก Actively acquired immune reaction จากนั้นมีการศึกษาอีกหลายอย่างเพื่อศึกษา transplant immunology Owen reported in 1947 - ถ้าน าสัตว์เช่น ลูกวัว ที่เป็น dizygotic
    [Show full text]
  • Durham E-Theses
    Durham E-Theses Elemental Fluorine for the Greener Synthesis of Life-Science Building Blocks HARSANYI, ANTAL How to cite: HARSANYI, ANTAL (2016) Elemental Fluorine for the Greener Synthesis of Life-Science Building Blocks, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/11705/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk 2 Durham University A thesis entitled Elemental Fluorine for the Greener Synthesis of Life-Science Building Blocks by Antal Harsanyi (College of St. Hild and St. Bede) A candidate for the degree of Doctor of Philosophy Department of Chemistry, Durham University 2016 Antal Harsanyi: Elemental fluorine for the greener synthesis of life-science building blocks Abstract Fluorinated organic compounds are increasingly important in many areas of our modern lives, especially in pharmaceutical and agrochemical applications where the incorporation of this element can have a major influence on biochemical properties.
    [Show full text]
  • A Case Report on Treatment of Infertility Due to Premature Ovarian
    WORKSHOPS Wednesday, 07 September 2011, 13:00 - 16:30 W01 Diagnostic and operative hysteroscopic office surgery Stefano Angioni Abstract not available at the time of printing W02 Female sexual dysfunction: what gynaecologists should know! Johannes Bitzer Abstract not available at the time of printing W03 Obesity and reproduction Reynir Tomas Geirsson Abstract not available at the time of printing W04 Surgery in urogynecology the contemporary view Pallavi Latthe(1), Gunnar Lose(2), Douglas G Tincello(3), Søren Brostrøm(1), Søren Gräs(1) (1) Birmimgham Women's Hospital, Department of Urogynaecology, Birmingham, UK (2) Herlev Hospital, Department of Obstetrics and Gynecology. 63 C7F, Herlev, Copenhagen, Denmark (3) University of Leicester, Department of Obstetrics and Gynaecology, Leicester, UK Surgery for pelvic floor dysfunction in women have evolved in the last decades, especially since the introduction in the 1990'ies of synthetic slings for the treatment of stress urinary incontinence. The retropubic loose mid-urethral macroporous monofilament slings (e.g. TVT) revolutionized the surgical treatment of stress urinary incontinence, and have emerged as the new gold standard. However, copy-cat products and novel approaches (e.g. transobturatror and single-incision slings) were rapidly and successively introduced to the market without proper evidence to support their use. Furthermore, due to the marketing success and ease of use of the mid-urehral 'sling kits', the concept of synthetic vaginal implants was expanded to the more problematic area of pelvic organ prolapse. Recently, level 1 evidence have emerged on both new sling-types and vaginal prosthesis, and will be discussed in this workshop. Furthermore, the future role of novel approaches such as robotic surgery and stem cell therapy in urogynecological surgery will be discussed.
    [Show full text]
  • Antiprogestins, a New Form of Endocrine Therapy for Human Breast Cancer1
    [CANCER RESEARCH 49, 2851-2856, June 1, 1989] Antiprogestins, a New Form of Endocrine Therapy for Human Breast Cancer1 Jan G. M. Klijn,2Frank H. de Jong, Ger H. Bakker, Steven W. J. Lamberts, Cees J. Rodenburg, and Jana Alexieva-Figusch Department of Medical Oncology (Division of Endocrine Oncology) [J. G. M. K., G. H. B., C. J. K., J. A-F.J, Dr. Daniel den Hoed Cancer Center, and Department of Endocrinology ¡F.H. d. J., S. W. ]. L.J, Erasmus University, Rotterdam, The Netherlands ABSTRACT especially pronounced effects on the endometrium, decidua, ovaries, and hypothalamo-pituitary-adrenal axis. With regard The antitumor, endocrine, hematological, biochemical, and side effects of chronic second-line treatment with the antiprogestin mifepristone (RU to clinical practice, the drug has currently been used as a contraceptive agent or abortifacient as a result of its antipro 486) were investigated in 11 postmenopausal patients with metastatic breast cancer. We observed one objective response, 6 instances of short- gestational properties (2, 22-24). Based on its antiglucocorti term stable disease, and 4 instances of progressive disease. Mean plasma coid properties, this drug has been used or has been proposed concentrations of adrenocorticotropic hormone (/' < 0.05), cortisol (/' < for treatment of conditions related to excess corticosteroid 0.001), androstenedione (/' < 0.01), and estradici (P < 0.002) increased production such as Cushing's syndrome (19, 25-27) and for significantly during treatment accompanied by a slight decrease of sex treatment of lymphomas (24) and glaucoma (28); because of its hormone binding globulin levels, while basal and stimulated gonadotropi effects on the immune system, the drug has been suggested to levels did not change significantly.
    [Show full text]
  • Guidance on Bioequivalence Studies for Reproductive Health Medicines
    Medicines Guidance Document 23 October 2019 Guidance on Bioequivalence Studies for Reproductive Health Medicines CONTENTS 1. Introduction........................................................................................................................................................... 2 2. Which products require a bioequivalence study? ................................................................................................ 3 3. Design and conduct of bioequivalence studies .................................................................................................... 4 3.1 Basic principles in the demonstration of bioequivalence ............................................................................... 4 3.2 Good clinical practice ..................................................................................................................................... 4 3.3 Contract research organizations .................................................................................................................... 5 3.4 Study design .................................................................................................................................................. 5 3.5 Comparator product ....................................................................................................................................... 6 3.6 Generic product .............................................................................................................................................. 6 3.7 Study subjects
    [Show full text]
  • Mifepristone (Korlym)
    Drug and Biologic Coverage Policy Effective Date ............................................ 1/1/2021 Next Review Date… ..................................... 1/1/2022 Coverage Policy Number ............................... IP0092 Mifepristone (Korlym®) Table of Contents Related Coverage Resources Overview .............................................................. 1 Coverage Policy ................................................... 1 Reauthorization Criteria ....................................... 2 Authorization Duration ......................................... 2 Conditions Not Covered....................................... 2 Background .......................................................... 3 References .......................................................... 4 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • The Clinical Efficacy of Progesterone Antagonists in Breast Cancer ------ .__..__
    8 The clinical efficacy of progesterone antagonists in breast cancer --------_.__..__. Walter Jonat, Marius Giurescu, John FR Robertson CONTENTS • Introduction • Onapristone • Mlfepristone • Summary INTRODUCTION indication of a functional PgR.4 As described in Chapter 14, substantial in vitro and in vivo The search for active and safe alternatives to evidence suggests that PgR serves as a biologi­ current systemic therapies is one of the main cally important molecule in breast cancer objectives of current breast cancer research. behaviour. Moreover, preclinical studies indi­ Over the last three decades since the discovery cate that blockade of PgR function inhibits pro­ of the estrogen receptor (ER), the development liferation and induces apoptosis (see Chapter of new endocrine agents has in the main been 14). Therefore, clinically practical PgR inhibitors aimed at either preventing the production of have been developed. These are overtly active estrogens (e.g. ovarian ablation with small molecuk'S that appear to function by gonadotropin-releasing hormone (GnRH) ana­ binding to PgR and inhibiting pathways down­ logues, aromatase inhibition) or blocking their stream of PgR. Two agents, onapristone and effect by competition for ER (e.g. selective ER mifepristone, have been evaluated in clinical modulators (SERMs) and pure antiestrogens). trials, and, as described below, have activity in Such developments have focused, indirectly or patients with metastatic disease. Although com­ directly, on the ER as a target for manipulation mercial support for these two agents has of tumour growth. This approach is supported recently waned, the concept of PgR inhibition by the finding that the response to such thera­ in breast cancer is sufficiently well founded to pies is related to the expression of ER by breast justify its inclusion in any textbook of endocrine tumours.13 However, it is also known that therapy.
    [Show full text]
  • EC313-A Tissue Selective SPRM Reduces the Growth and Proliferation of Uterine Fbroids in a Human Uterine Fbroid Tissue Xenograft Model Hareesh B
    www.nature.com/scientificreports OPEN EC313-a tissue selective SPRM reduces the growth and proliferation of uterine fbroids in a human uterine fbroid tissue xenograft model Hareesh B. Nair1*, Bindu Santhamma1, Kalarickal V. Dileep2, Peter Binkley3, Kirk Acosta1, Kam Y. J. Zhang 2, Robert Schenken3 & Klaus Nickisch1 Uterine fbroids (UFs) are associated with irregular or excessive uterine bleeding, pelvic pain or pressure, or infertility. Ovarian steroid hormones support the growth and maintenance of UFs. Ulipristal acetate (UPA) a selective progesterone receptor (PR) modulator (SPRM) reduce the size of UFs, inhibit ovulation and lead to amenorrhea. Recent liver toxicity concerns with UPA, diminished enthusiasm for its use and reinstate the critical need for a safe, efcacious SPRM to treat UFs. In the current study, we evaluated the efcacy of new SPRM, EC313, for the treatment for UFs using a NOD-SCID mouse model. EC313 treatment resulted in a dose-dependent reduction in the fbroid xenograft weight (p < 0.01). Estradiol (E2) induced proliferation was blocked signifcantly in EC313-treated xenograft fbroids (p < 0.0001). Uterine weight was reduced by EC313 treatment compared to UPA treatment. ER and PR were reduced in EC313-treated groups compared to controls (p < 0.001) and UPA treatments (p < 0.01). UF specifc desmin and collagen were markedly reduced with EC313 treatment. The partial PR agonism and no signs of unopposed estrogenicity makes EC313 a candidate for the long-term treatment for UFs. Docking studies have provided a structure based explanation for the SPRM activity of EC313. Te unmet need for medical management of uterine fbroids (UFs) has led to the discovery of various novel agents in recent years.
    [Show full text]
  • Endometriosis
    CLINICAL REVIEW Endometriosis Follow the link from the online version of this article to obtain certi ed continuing 1 2 3 medical education credits Martha Hickey, Karen Ballard, Cindy Farquhar 1 Endometriosis is a relatively common and potentially Department of Obstetrics and SOURCES AND SELECTION CRITERIA Gynaecology, University of debilitating condition affecting women of reproductive We searched Medline and Pubmed, used personal archives Melbourne and the Royal Women’s age. Prevalence is difficult to determine, firstly because of Hospital, Melbourne, Victoria, of references, and consulted with other experts to inform Australia 3052 variability in clinical presentation, and, secondly because this manuscript. When available, data from systematic 2Faculty of Health and Medical the only reliable diagnostic test is laparoscopy, when endo- reviews and randomised controlled trials were used. We Sciences, University of Surrey, metriotic deposits can be visualised and histologically also used expert guidelines such as the recent European Guildford, Surrey, UK Society of Human Reproduction and Embryology (ESHRE) 3 confirmed. Population based studies report a prevalence Department of Obstetrics and consensus.4 Gynaecology, University of of around 1.5% compared with 6-15% in hospital based 1 Auckland, Auckland, New Zealand studies. Endometriosis can be asymptomatic, but those Correspondence to: M Hickey with symptoms generally present early in reproductive What are the causes of endometriosis? [email protected] life and improve after menopause. Symptomatic endome- The pathogenesis of endometriosis is unknown, but lead- Cite this as: BMJ 2104;348:g1752 triosis can result in long term adverse effects on personal ing theories include retrograde menstruation, altered doi: 10.1136/bmj.g1752 relationships, quality of life, and work productivity.
    [Show full text]
  • Clinical Study Protocol M12-815 a Phase 3 Study to Evaluate The
    NCT02654054 Elagolix (ABT-620) M12-815 Protocol Amendment 3 1.0 Title Page Clinical Study Protocol M12-815 A Phase 3 Study to Evaluate the Efficacy and Safety of Elagolix in Combination with Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated with Uterine Fibroids in Premenopausal Women Incorporating Amendments 1, 2 and 3 AbbVie Investigational Product: Elagolix (ABT-620) Date: 25 September 2017 Development Phase: 3 Study Design: Phase 3, randomized, double-blind, multicenter, placebo-controlled study evaluating the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women 18 to 51 years of age. Investigators: Multicenter Trial: Investigator information is on file at AbbVie Sponsor: AbbVie Sponsor/Emergency Contact: This study will be conducted in compliance with the protocol, Good Clinical Practice and all other applicable regulatory requirements, including the archiving of essential documents. Confidential Information No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie. 1 Elagolix (ABT-620) M12-815 Protocol Amendment 3 1.1 Protocol Amendment: Summary of Changes Previous Protocol Versions Protocol Date Original 06 November 2015 Amendment 1 01 December 2015 Amendment 2 23 June 2016 The purpose of this Amendment is to: ● Update Section 1.1 Protocol Amendment: Summary of Changes from Appendix Q to Appendix
    [Show full text]