DOCSLIB.ORG

Eraas for Menopause Treatment: Welcome the ‘Designer Estrogens’

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Eraas for Menopause Treatment: Welcome the ‘Designer Estrogens’ REVIEW CME LEARNING OBJECTIVE: Readers will tailor hormone therapy to the needs of the patient CREDIT HEATHER D. HIRSCH, MD, MS, NCMP ELIM SHIH, MD, NCMP HOLLY L. THACKER, MD, NCMP Assistant Professor, Clinical Internal Medicine, Division Department of Obstetrics and Gynecology, Director of Center for Specialized Women’s Health, of General Internal Medicine, The Ohio State University, Women’s Health Institute, Cleveland Clinic Department of Obstetrics and Gynecology, Women’s Columbus, and Center for Women’s Health, Health Institute, Cleveland Clinic; Professor, Cleveland The Ohio State University Wexner Medical Center, Clinic Lerner College of Medicine of Case Western Upper Arlington, OH Reserve University, Cleveland, OH ERAAs for menopause treatment: Welcome the ‘designer estrogens’ ABSTRACT strogen receptor agonist-antagonists E(ERAAs), previously called selective es- Estrogen receptor agonist-antagonists (ERAAs) selec- trogen receptor modulators (SERMs), have tively inhibit or stimulate estrogen-like action in targeted extended the options for treating the vari- tissues. This review summarizes how ERAAs can be used ous conditions that menopausal women suffer in combination with an estrogen or alone to treat meno- from. These drugs act differently on estrogen pausal symptoms (vasomotor symptoms, genitourinary receptors in different tissues, stimulating re- syndrome of menopause), breast cancer or the risk of ceptors in some tissues but inhibiting them breast cancer, osteopenia, osteoporosis, and other female in others. This allows selective inhibition or midlife concerns. stimulation of estrogen-like action in various target tissues.1 KEY POINTS This article highlights the use of ERAAs Tamoxifen is approved to prevent and treat breast cancer. to treat menopausal vasomotor symptoms It may also have beneficial effects on bone and on car- (eg, hot flashes, night sweats), genitourinary diovascular risk factors, but these are not approved uses. syndrome of menopause, osteoporosis, breast cancer (and the risk of breast cancer), and other health concerns unique to women at Raloxifene, a second-generation ERAA, was initially ap- midlife. proved for preventing and treating osteoporosis and later received approval to reduce the risk of invasive estro- ■ SYMPTOMS OF MENOPAUSE: gen receptor-positive breast cancer in postmenopausal COMMON AND TROUBLESOME women. Vasomotor symptoms such as hot flashes and night sweats are common during perimeno- Ospemifene is approved for treatment of genitourinary pause—most women experience them. They syndrome of menopause. are most frequent during the menopause tran- sition but can persist for 10 years or more af- The combination of conjugated estrogen and bazedoxi- terward.2 fene is approved for treating moderate to severe vasomo- Genitourinary syndrome of menopause tor symptoms associated with menopause and also for is also common and often worsens with years preventing postmenopausal osteoporosis in women with after menopause.3 It can lead to dyspareunia an intact uterus. and vaginal dryness, which may in turn result in lower libido, vaginismus, and hypoactive sexual desire disorder, problems that often arise at the same time as vaginal dryness and atrophy.4 Osteopenia and osteoporosis. A drop in systemic estrogen leads to a decline in bone doi:10.3949/ccjm.84a.15140 mineral density, increasing the risk of fractures.5 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 84 • NUMBER 6 JUNE 2017 463 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. DESIGNER ESTROGENS TABLE 1 Designer estrogens and their uses Agent Approved uses Other possible benefits Adverse effects Tamoxifen To treat metastatic breast cancer Positive effect on bone Venous thromboembolism and ductal carcinoma in situ Positive effect on cardiovascular Uterine neoplasia To reduce the risk of estrogen risk receptor-positive breast cancer in Vasomotor symptoms women at high risk Raloxifene To prevent and treat osteoporosis Reduction in breast cancer risk Venous thromboembolism To reduce the risk of invasive estro- Stroke gen receptor-positive breast cancer in postmenopausal women Ospemifene To treat genitourinary syndrome of Positive effect on bone Venous thromboembolism menopause Conjugated In women with a uterus: to prevent Positive effects on uterus, genito- Venous thromboembolism estrogen- osteoporosis and treat vasomotor urinary syndrome of menopause bazedoxifene symptoms of menopause ■ ESTROGEN-PROGESTIN TREATMENT: have estrogen receptor-positive breast cancer THE GOLD STANDARD, BUT NOT IDEAL cannot take estrogen. The current gold standard for treating moder- Individualized options are needed for women who have progestin-related side ef- ERAAs have ate to severe hot flashes is estrogen, available in oral, transdermal, and vaginal formulations.6 fects, unwanted vaginal bleeding, or a higher extended Estrogen also has antiresorptive effects on bone risk of breast cancer. the options and is approved for preventing osteoporosis. Systemic estrogen may also be prescribed for ■ WELCOME THE ERAAs for treating genitourinary syndrome of menopause if local An ideal treatment for menopause would relieve the various vaginal treatment alone is insufficient. vasomotor symptoms and genitourinary syn- conditions If women who have an intact uterus receive drome of menopause and increase bone mineral estrogen, they should also receive a progestin to density without causing breast tenderness, vagi- menopausal protect against endometrial hyperplasia and re- nal bleeding, or endometrial proliferation. women suffer duce the risk of endometrial cancer. The “designer estrogens,” or ERAAs, have from Despite its status as the gold standard, es- specific positive effects on the bone, heart, and trogen-progestin therapy presents challenges. brain with neutral or antagonist effects on estro- In some women, progestins cause side effects gen receptors in other tissues such as the breasts such as breast tenderness, bloating, fatigue, and endometrium.8 While not entirely free of and depression.7 Estrogen-progestin therapy adverse effects, these agents have been devel- often causes vaginal bleeding, which for some oped with the aim of minimizing the most com- women is troublesome or distressing; bleed- mon ones related to estrogen and progestin. ing may be the reason for repeated evalua- Several ERAAs are currently approved by tions, can increase anxiety, and can lead to the US Food and Drug Administration (FDA) poor adherence with hormonal treatment. for various indications, each having a unique Women who carry a higher-than-normal risk profile. Clomifene was the first agent of this of developing breast cancer or fear that taking class, and it is still used clinically to induce hormones will lead to breast cancer may show ovulation. This article highlights subsequent- decreased adherence to therapy. Women who ly approved agents, ie, tamoxifen, raloxifene, 464 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 84 • NUMBER 6 JUNE 2017 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. HIRSCH AND COLLEAGUES ospemifene, and the combination of conju- The IBIS-I trial (International Breast gated estrogens and bazedoxifene (Table 1). Cancer Intervention Study I)13 found that, in All ERAAs increase the risk of venous throm- healthy women at high risk of breast cancer, boembolism, and therefore none of them should be the benefit of taking tamoxifen for 5 years as used in women with known venous thromboem- preventive treatment persisted long afterward. bolism or at high risk of it. The investigators estimated that at 20 years of follow-up the risk of breast cancer would ■ TAMOXIFEN: be 12.3% in placebo recipients and 7.8% in CANCER TREATMENT AND PREVENTION tamoxifen recipients, a 4.5% absolute risk re- After clomiphene, tamoxifen was the second duction; number needed to treat (NNT) 22. ERAA on the market. Although researchers Data on tamoxifen and osteoporosis were looking for a new contraceptive drug, The Breast Cancer Prevention Trial revealed they found tamoxifen to be useful as a chemo- a 19% reduction in the incidence of osteopo- therapeutic agent for breast cancer. First used rotic fractures with tamoxifen, but the differ- in 1971, tamoxifen continues to be one of the ence was not statistically significant.14 The most commonly prescribed chemotherapeutic 1-year rates of fracture in women age 50 and medications today. older were 0.727% with placebo and 0.567% The FDA has approved tamoxifen to treat with tamoxifen, an absolute difference of breast cancer as well as to prevent breast can- 0.151%; therefore, if the effect is real, 662 cer in pre- and postmenopausal women at risk. women age 50 or older would need to be treat- It may also have beneficial effects on bone and ed for 1 year to prevent 1 fracture. Tamoxifen on cardiovascular risk factors, but these are is not FDA-approved to treat osteoporosis. not approved uses for it. Data on tamoxifen and cardiovascular risk Trials of tamoxifen for cancer treatment reduction The Early Breast Cancer Trialists’ Collab- Chang et al,15 in a study in women at risk of orative Group9 performed a meta-analysis and breast cancer, incidentally found that tamoxi- found that 5 years of adjuvant treatment with fen was associated with a 13% reduction in Women with tamoxifen is associated with a 26% reduction total cholesterol compared with placebo. a uterus 16 in mortality and a 47% reduction in breast Herrington and Klein, in a systematic
Load more

Recommended publications
  • Clinical Update on the Use of Ospemifene in the Treatment of Severe Symptomatic Vulvar and Vaginal Atrophy
    Journal name: International Journal of Women’s Health Article Designation: Review Year: 2016 Volume: 8 International Journal of Women’s Health Dovepress Running head verso: Palacios and Cancelo Running head recto: The use of ospemifene in the treatment of severe symptomatic VVA open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJWH.S110035 Open Access Full Text Article REVIEW Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy Santiago Palacios1 Abstract: The physiological decrease in vaginal estrogens is accountable for the emergence of María Jesús Cancelo2 vulvar and vaginal atrophy (VVA) and its related symptoms such as vaginal dryness, dyspareunia, vaginal and/or vulvar irritation or itching, and dysuria. The repercussion of these symptoms 1Palacios Institute of Women’s Health, Madrid, Spain; 2Gynecology and on quality of life often makes it necessary to initiate treatment. Up until now, the treatments Obstetrics Department, Guadalajara available included vaginal moisturizers and lubricants, local estrogens, and hormonal therapy. University Hospital, University of Alcalá, Spain However, therapeutic options have now been increased with the approval of 60 mg ospemifene, the first nonhormonal oral treatment with an agonist effect on the vaginal epithelium and an endometrial and breast safety profile which makes it unique. This is the first selective estrogen receptor modulator indicated in women with moderate-to-severe vaginal atrophy not eligible For personal use only. for local estrogen treatment. Considering that “local estrogen noneligible women” are those in whom such treatment cannot be administered either because it is contraindicated or due to skill issues, who are averse to the mode and convenience of vaginal products’ administration or to their use on account of potential systemic absorption, or those who demonstrate dissatisfac- tion in terms of efficacy and safety, it is clear that there is a significant unmet medical need in VVA management.
    [Show full text]
  • Management of Women with Premature Ovarian Insufficiency
    Management of women with premature ovarian insufficiency Guideline of the European Society of Human Reproduction and Embryology POI Guideline Development Group December 2015 1 Disclaimer The European Society of Human Reproduction and Embryology (hereinafter referred to as 'ESHRE') developed the current clinical practice guideline, to provide clinical recommendations to improve the quality of healthcare delivery within the European field of human reproduction and embryology. This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. The aim of clinical practice guidelines is to aid healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients. However, adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not override the healthcare professional's clinical judgment in diagnosis and treatment of particular patients. Ultimately, healthcare professionals must make their own clinical decisions on a case-by-case basis, using their clinical judgment, knowledge, and expertise, and taking into account the condition, circumstances, and wishes of the individual patient, in consultation with that patient and/or the guardian or carer. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. ESHRE shall not be liable for direct, indirect, special, incidental, or consequential damages related to the use of the information contained herein.
    [Show full text]
  • CP.PMN.168 Ospemifene (Osphena)
    Clinical Policy: Ospemifene (Osphena) Reference Number: CP.PMN.168 Effective Date: 08.28.18 Last Review Date: 11.20 Line of Business: Commercial, HIM, Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Ospemifene (Osphena®) is a selective estrogen receptor modulator (SERM). FDA Approved Indication(s) Osphena is indicated for the treatment of moderate to severe dyspareunia and vaginal dryness, symptoms of vulvar and vaginal atrophy, due to menopause. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Osphena is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Dyspareunia or Vaginal Dryness (must meet all): 1. Diagnosis of dyspareunia or vaginal dryness due to menopause; 2. Age ≥ 18 years; 3. Failure of two vaginal lubricants or vaginal moisturizers at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 4. Failure of ≥ 4 weeks of one vaginal estrogen at up to maximally indicated doses (e.g., estradiol vaginal cream, Premarin vaginal cream), unless contraindicated or clinically significant adverse effects are experienced; 5. Dose does not exceed 60 mg (1 tablet) per day. Approval duration: Medicaid/HIM – 12 months Commercial – Length of Benefit B. Other diagnoses/indications 1. Refer to the off-label use policy for the relevant line of business if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized): CP.CPA.09 for commercial, HIM.PHAR.21 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    [Show full text]
  • HRT Communications 23.08.20191.Pdf
    DHSC - 23/8/2019 Hormone replacement therapy (HRT) supply issues The Department of Health and Social Care (DHSC) are aware of the ongoing manufacturing issues that have affected the supply of some hormone replacement therapy (HRT) products throughout 2019. Please see Table 1, which provides the latest update on the availability of all HRT products marketed in the UK and the known resupply date for products that are currently experiencing supply issues. This table also provides an update of all HRT preparations that remain available. Clinicians may be required to switch patients to alternative HRT products that contain the same active ingredients for a temporary period. Prescribing information regarding HRT equivalence to support local decision making is available through various sources such as the British National Formulary, Summary of Product Characteristics (SPC), The Monthly Index of Medical Specialities (MIMS), and other sources including local Medicines Information Centres. Clinicians are advised to work closely with community pharmacies to understand local availability of HRT products and use the table below to help make decision about appropriative HRT products for patients who are affected by the supply issues. DHSC will continue to provide updates on HRT availability in the monthly supply report, which is uploaded to the Specialist Pharmacist Services website. All registered user can access this update via this following link: https://www.sps.nhs.uk/articles/department-of-health-and- pharmaceutical-market-strategy-group-pmsg-supply-updates/ Please share this information with relevant networks locally including GP practices and community pharmacies. Table 1. HRT Availability Oestrogen Only Brand Strength Current Availability Anticipated resupply Ingredient (s) Manufacturer Oral preparations date Continued availability 1mg In stock to be confirmed.
    [Show full text]
  • OSPHENA) National Drug Monograph October 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives
    Ospemifene Monograph Ospemifene (OSPHENA) National Drug Monograph October 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information Description/Mechanism of Ospemifene is a selective estrogen receptor modulator (SERM) with agonist Action actions on vaginal tissue, the endometrium and bone. Antagonist actions suggest antitumor effects in experimental breast cancer models. Ospemifene is not interchangeable with other SERMs such as raloxifene or tamoxifen, nor they with it. Indication(s) Under Review in Ospemifene is an estrogen agonist/antagonist indicated for the treatment this document (may include of moderate to severe dyspareunia, a symptom of vulvar and vaginal off label) atrophy, due to menopause. Dosage Form(s) Under Tablet (oral), 60 mg Review REMS REMS X No REMS Postmarketing Requirements See Other Considerations for additional REMS information Pregnancy Rating X Executive Summary Efficacy After 12 weeks ospemifene reduced the symptom score of dyspareunia significantly more than placebo. Thirty-eight percent of postmenopausal women taking ospemifene reported no pain upon intercourse compared to 28% taking placebo. Ospemifene significantly improved the Maturation Index (composed of percent of vaginal parabasal and superficial cells, and vaginal pH) after 12 and 52 weeks of treatment. Vaginal dryness symptom scores improved significantly more with ospemifene than placebo. Use of vaginal lubricant decreased more in women taking ospemifene than placebo.
    [Show full text]
  • Reference List Abraham L, Pinkerton JV, Messig M, Ryan KA, Komm BS, Mirkin S
    SERM Education Project Reference List Abraham L, Pinkerton JV, Messig M, Ryan KA, Komm BS, Mirkin S. Menopause-specific quality of life across varying menopausal populations with conjugated estrogens/bazedoxifene. Maturitas. 2014;78(3):212-218. Archer DF, Carr BR, Pinkerton JV, Taylor HS, Constantine GD. Effects of ospemifene on the female reproductive and urinary tracts: translation from preclinical models into clinical evidence. Menopause. 2015;22(7):786-796. Archer DF, Lewis V, Carr BR, Olivier S, Pickar JH. Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women. Fertil Steril. 2009;92(3):1039-1044. Archer DF. The gynecologic effects of lasofoxifene, an estrogen agonist/antagonist, in postmenopausal women. Menopause. 2011;18(1):6-7. Bachmann G, Bobula J, Mirkin S. Effects of bazedoxifene/conjugated estrogens on quality of life in postmentopausal women with symptoms of vulvar/vaginal atrophy. Climacteric. 2010;13(2):132-140. Bachmann G, Gass M, Kagan R, Moffett A, Barcomb L, Symons J. Lasofoxifene (LASO), a next generation selective estrogen response modulator (SERM) improves dyspareunia in postmenopausal women with vaginal atrophy (VA) [abstract]. Menopause. 2005;12(2):238. Bachmann G, Gass M, Moffett A, Portman D, Symons J. Lasofoxifene improves symptoms associated with vaginal atrophy [abstract]. Menopause. 2004;11(6):669. Abstract P-63. Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010;17(3):480-486. Barrett-Connor E, Grady D, Sashegyi A, et al; MORE Investigators (Multiple Outcomes of Raloxifene Evaluation). Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial.
    [Show full text]
  • OSPHENA Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION Active DVT, pulmonary embolism (PE), or a history of these conditions These highlights do not include all the information needed to use (4, 5.1) OSPHENA safely and effectively. See full prescribing information for Active arterial thromboembolic disease (for example, stroke and OSPHENA. myocardial infarction [MI]), or a history of these conditions (4, 5.1) Known or suspected pregnancy (4, 8.1) OSPHENATM (ospemifene) tablets, for oral use Initial U.S. Approval: 2013 ---------------WARNINGS AND PRECAUTIONS------------ WARNING: ENDOMETRIAL CANCER AND CARDIOVASCULAR Venous Thromboembolism: Risk of DVT and pulmonary embolism DISORDERS (5.1) See full prescribing information for complete boxed warning. Known, suspected, or history of breast cancer (5.2) OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. Severe Hepatic Impairment (5.3, 8.7, 12.3) There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen -------------------ADVERSE REACTIONS---------------------- therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer [see Warnings and Precautions (5.2)]. Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis. (6.1) Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). OSPHENA 60 mg had cerebral thromboembolic To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc. and hemorrhagic stroke incidence rates of 0.72 and 1.45 per thousand at 1-855-OSPHENA (1-855-677-4362) or FDA at 1-800-FDA-1088 or women, respectively vs.
    [Show full text]
  • MSAN(2020)67 – Hormone Replacement Therapy
    NHS Circular: MSAN (2020) 67 Chief Medical Officer Directorate Pharmacy and Medicines Division 23 July 2020 Medicine Supply Alert Notice Hormone Replacement Therapy (all formulations) Priority: Level 3* - update to MSAN (2020)3 Valid until: See table at Annex A Issue 1. The Chief Pharmaceutical Officer previously wrote in circular PCA(P)(2019)18 to community pharmacy contractors and NHS Boards regarding information on the availability of all Hormone Replacement Therapy (HRT) products marketed in the UK. This was updated in January 2020 by MSAN (2020)3. 2. This MSAN gives an update on the information provided in MSAN (2020)3, as issued by the UK Department of Health and Social Care Medicine Supply Team in July 2020. Advice and Actions 4. The table 1 attached at Annex A provides the latest update on the availability of all HRT products marketed in the UK and the known resupply date for products that are currently experiencing supply issues. The table also provides an update of all HRT preparations that remain available. 5. Clinicians may be required to switch patients to alternative HRT products that contain the same active ingredients for a temporary period. Prescribing information regarding HRT equivalence to support local decision making is available through various sources such as the British National Formulary, Summary of Product Characteristics (SPC), The Monthly Index of Medical Specialities (MIMS), and other sources including local Medicines Information Centres. Additional Information 6. Clinicians are advised to work closely with community pharmacies to understand local availability of HRT products and use the table below to help make decision about appropriative HRT products for patients who are affected by the supply issues.
    [Show full text]
  • Ospemifene for the Treatment of Dyspareunia Associated with Vulvar and Vaginal Atrophy: Potential Benefits in Bone and Breast
    International Journal of Women’s Health Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy: potential benefits in bone and breast Lin H Soe Abstract: Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor Gregory T Wurz agonist/antagonist, that was recently approved by the US Food and Drug Administration for the Chiao-Jung Kao treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that Michael W DeGregorio affects up to 60% of postmenopausal women. Ospemifene is the first and only nonestrogen com- pound approved for this indication. Compared with other approved SERMs, such as tamoxifen, Department of Internal Medicine, Division of Hematology and Oncology, toremifene, bazedoxifene, and raloxifene, the estrogen-like effects of ospemifene in the vaginal School of Medicine, University of epithelium are unique. This review first discusses the rationale for developing ospemifene, includ- California, Davis, Sacramento, CA, ing its mechanism of action, and then focuses on the clinical development of ospemifene for the USA treatment of dyspareunia associated with vulvar and vaginal atrophy. Included are discussions For personal use only. of the effects of ospemifene on the endometrium, serum lipids, coagulation markers, bone, and breast cancer. In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist Video abstract tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. Ospemifene warrants further clinical investigation for the treatment and prevention of osteoporosis and breast cancer.
    [Show full text]
  • 2017 Hormone Therapy Position Statement of the North American Menopause Society
    Menopause: The Journal of The North American Menopause Society Vol. 24, No. 7, pp. 728-753 DOI: 10.1097/GME.0000000000000921 ß 2017 by The North American Menopause Society POSITION STATEMENT The 2017 hormone therapy position statement of The North American Menopause Society Abstract The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women’s health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees. Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genito- urinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture.
    [Show full text]
  • Senshio, INN-Ospemifene
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Senshio 60 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains 60 mg ospemifene. Excipient with known effect Each film-coated tablet contains 1.82 mg lactose as monohydrate. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet). Oval biconvex, white to off-white, film-coated tablets of dimensions 12 mm x 6.45 mm, debossed with “60” on one side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Senshio is indicated for the treatment of moderate to severe symptomatic vulvar and vaginal atrophy (VVA) in post-menopausal women who are not candidates for local vaginal oestrogen therapy. 4.2 Posology and method of administration Posology The recommended dose is one 60 mg tablet once daily with food taken at the same time each day. If a dose is missed it should be taken with food as soon as the patient remembers. A double dose should not be taken in the same day. Special populations Elderly (>65 years old) No dose adjustment is necessary in patients above the age of 65 years (see section 5.2). Renal impairment No dose adjustment is necessary for patients with mild, moderate or severe renal impairment (see section 5.2). 2 Hepatic impairment No dose adjustment is necessary for patients with mild to moderate hepatic impairment.
    [Show full text]
  • 208564Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 208564Orig1s000 CLINICAL REVIEW(S) Clinical Review Theresa H. van der Vlugt, M.D., M.P.H. Resubmission NDA 208564 Imvexxy™ (estradiol vaginal inserts) 4 mcg and 10 mcg CLINICAL REVIEW Application Type Class 2 Resubmission Application Number(s) NDA 208564 Priority or Standard Standard Submit Date(s) November 29, 2017 Received Date(s) November 29, 2017 PDUFA Goal Date May 29, 2018 Division/Office Division of Bone, Reproductive, and Urologic Products/Office of Drug Evaluation III Reviewer Name(s) Theresa H. van der Vlugt, M.D., M.P.H. Review Completion Date May 15, 2018 Established/Proper Name Estradiol vaginal insert (Proposed) Trade Name Imvexxy™ Applicant TherapeuticsMD Dosage Form(s) Intravaginal inserts Applicant Proposed Dosing 4 mcg insert administer intravaginally daily for 2 weeks, then 4 Regimen(s) mcg insert administered intravaginally two times per week (approximately 3 to 4 days apart) 10 mcg insert administered intravaginally daily for 2 weeks, then 10 mcg insert administered intravaginally two times per week (approximately 3 to 4 days apart) Applicant Proposed Treatment of moderate to severe dyspareunia, a symptom of Indication(s)/Population(s) vulvar and vaginal atrophy, due to menopause Recommendation on Approval Regulatory Action Recommended Postmenopausal women Indication(s)/Population(s) (if applicable) CDER Clinical Review Template 1 Version date: September 6, 2017 for all NDAs and BLAs Reference ID: 42696514271237 Clinical Review Theresa H. van der Vlugt, M.D., M.P.H. Resubmission NDA 208564 Imvexxy™ (estradiol vaginal inserts) 4 mcg and 10 mcg Table of Contents Glossary ..........................................................................................................................................6 1. Executive Summary.................................................................................................................8 1.1.
    [Show full text]