II. Mechanism

  1. Positive Estrogen effects
    1. Stimulates bone mineralization
    2. Improves lipid profile
  2. Anti-Estrogenic effects
    1. No Breast stimulation
    2. No uterine stimulation

III. Indication

  1. Osteoporosis Prevention in postmenopausal women
  2. Hormone Replacement in postmenopausal women
    1. Beyond hot flash stage
    2. Estrogen Replacement contraindicated (Breast Cancer)
  3. Breast Cancer Prevention in post-menopausal women with Breast Cancer risk >1.66% in 5 years
    1. Lower efficacy than Tamoxifen for breast Cancer Prevention, but also lower Venous Thromboembolism and Endometrial Cancer Risks

IV. Contraindications

  1. Venous Thromboembolism
  2. Perioperative period
  3. Prolonged immobilization
  4. History of Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)

V. Advantages

  1. No Uterine endometrial stimulation (unlike Estrogen)
    1. Does not require concurrent Progestin use
  2. Does not stimulate Breast tissue (unlike Estrogen)
    1. No Breast swelling, tenderness, or pain
    2. No data yet on Breast Cancer
  3. Increases Bone Mineral Density
    1. Modest effect (1-2%) at hip, spine, and long bones
    2. Not as effective as Estrogen Replacement
  4. Positive lipid effects
    1. Lowers LDL 10-12%
    2. Lowers Total Cholesterol 6-7%
  5. Helps stabilize pelvic floor
    1. Protects against Uterine Prolapse
    2. Decreases Incidence of Urinary Incontinence
    3. Reduces pelvic surgery rate by 50%
    4. Goldstein (2001) Obstet Gynecol 98:91-6 [PubMed]

VI. Precautions

  1. DVT, PE and cardiovascular risk is an FDA black box warning

VII. Disadvantages

  1. Expensive: $65/month (Premarin is $20/month)
  2. Anti-Estrogen effects (Hot Flashes)

VIII. Adverse Effects

  1. Hot Flashes (24.6%)
  2. Leg Cramps (5.9%)
  3. Increased Deep Vein Thrombosis and Thromboembolism risk
    1. More likely to occur in first 4 months of treatment
    2. Similar to risk with Estrogen Replacement

IX. Dosing

  1. Raloxifene 60 mg PO daily
    1. Course of 5 years if used for breast Cancer Prevention

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Cost: Medications

evista (on 4/19/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
EVISTA 60 MG TABLET Generic $1.24 each
raloxifene (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
RALOXIFENE HCL 60 MG TABLET Generic $1.24 each

Ontology: droloxifene (C0047498)

Definition (NCI) A phenolic analogue of tamoxifen, a nonsteroidal selective estrogen receptor modulator (SERM). Droloxifene competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. (NCI)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C038345
English meta-hydroxytamoxifen, Phenol, 3-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenyl-1-butenyl)-, (E)-, 3-Hydroxytamoxifen, (E)--1-[4'-(2-dimethylaminoethyoxy)phenyl]-1(3-hydroxyphenyl)-2-phenyl-but-1-ene, (E)-3-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol, (E)-alpha[p-[2-(dimethylamino)ethoxy]phenyl]-alpha'-ethyl-3-stilbenol, droloxifene, 3-hydroxytamoxifen, DROLOXIFENE, Droloxifene

Ontology: Toremifene (C0076836)

Definition (NCI) A nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which are manifested according to tissue type or species. (NCI04)
Definition (NCI_NCI-GLOSS) An anticancer drug that belongs to the family of drugs called antiestrogens. Toremifene blocks the effect of the hormone estrogen in the body. It may help control some cancers from growing, and it may delay or reduce the risk of cancer recurrence.
Definition (MSH) A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.
Definition (PDQ) A nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which are manifested according to tissue type or species. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41103&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41103&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1256" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D017312
SnomedCT 387588002, 96378009
English Ethanamine, 2-(4-(4-chloro-1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-, (Z)-, (Z)-2-[4-(4-Chloro-1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine, (Z)-4-Chloro-1,2-diphenyl-1[4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-butene, toremifene citrate, toremifene citrate (medication), toremifene citrate (Fareston), Toremifene [Chemical/Ingredient], toremifene, TOREMIFENE, Toremifene (product), Toremifene (substance), TOR, Toremifene
Swedish Toremifen
Czech toremifen
Finnish Toremifeeni
Russian TOREMIFEN, ТОРЕМИФЕН
Japanese トレミフェン
Polish Toremifen
Spanish toremifeno (producto), toremifeno (sustancia), toremifeno, Toremifeno
French Torémifène
German Toremifen
Italian Toremifene
Portuguese Toremifeno

Ontology: idoxifene (C0139560)

Definition (NCI_NCI-GLOSS) A drug that blocks the effects of estrogen.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C071362
English 1-(4-iodophenyl)-1-(4-(2-pyrrolidinoethoxy)phenyl)-2-phenyl-1-butene, 4-iodopyrrolidinotamoxifen, Pyr-I-Tam, Pyrrolidino-4-iodotamoxifen, 1-[2-[4-[(1E)-1-(4-Iodophenyl)-2-phenyl-1-butenyl]phenoxy]ethyl]pyrrolidine, idoxifene, pyrrolidino-4-iodotamoxifen, IDOXIFENE, Idoxifene
Japanese イドキシフェン

Ontology: Raloxifene (C0244404)

Definition (NCI_NCI-GLOSS) The active ingredient in a drug used to reduce the risk of invasive breast cancer in postmenopausal women who are at high risk of the disease or who have osteoporosis. It is also used to prevent and treat osteoporosis in postmenopausal women. It is also being studied in the prevention of breast cancer in certain premenopausal women and in the prevention and treatment of other conditions. Raloxifene blocks the effects of the hormone estrogen in the breast and increases the amount of calcium in bone. It is a type of selective estrogen receptor modulator (SERM).
Definition (NCI) A selective benzothiophene estrogen receptor modulator (SERM). Raloxifene binds to estrogen receptors (ER) as a mixed estrogen agonist/antagonist; it displays both an ER-alpha-selective partial agonist/antagonist effect and a pure ER-beta-selective antagonist effect. This agent functions as an estrogen agonist in some tissues (bones, lipid metabolism) and as an estrogen antagonist in others (endometrium and breasts), with the potential for producing some of estrogen's beneficial effects without producing its adverse effects. (NCI04)
Definition (CSP) a selective estrogen receptor modulator; has both agonist and antagonist estrogen action.
Definition (MSH) A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
Definition (PDQ) A selective benzothiophene estrogen receptor modulator (SERM). Raloxifene binds to estrogen receptors (ER) as a mixed estrogen agonist/antagonist; it displays both an ER-alpha-selective partial agonist/antagonist effect and a pure ER-beta-selective antagonist effect. This agent functions as an estrogen agonist in some tissues (bones, lipid metabolism) and as an estrogen antagonist in others (endometrium and breasts), with the potential for producing some of estrogen's beneficial effects without producing its adverse effects. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43109&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43109&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1518" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D020849
SnomedCT 109029006, 419530003
LNC LP171633-3
English Methanone, (6-hydroxy-2-(4-hydroxyphenyl)benzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)-, raloxifene, [6-Hydroxy-2-(4-hydroxyphenyl)-benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone, raloxifene (medication), Raloxifene, Raloxifene [Chemical/Ingredient], RALOXIFENE, Raloxifene (substance), RALOX, Keoxifene, Raloxifene (product)
Spanish raloxifeno (producto), raloxifeno (sustancia), raloxifeno, Raloxifeno
Swedish Raloxifen
Czech raloxifen
Finnish Raloksifeeni
Russian RALOKSIFEN, РАЛОКСИФЕН
Italian Keoxifene, Raloxifene
Polish Raloksyfen
Japanese ケオキシフェン, ラロキシフェン
French Raloxifène
German Raloxifen
Portuguese Raloxifeno

Ontology: Evista (C0720318)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D020849
English ELi Lilly Brand of Raloxifene, Lilly Brand of Raloxifene, Raloxifene Lilly Brand, evista, Evista

Ontology: Selective Estrogen Receptor Modulators (C0732611)

Definition (NCI_NCI-GLOSS) A drug that acts like estrogen on some tissues but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are selective estrogen receptor modulators.
Definition (CSP) structurally diverse group of compounds distinguished from estrogen by their ability to bind and activate the estrogen receptor, but act as either an estrogen agonist or antagonist depending on the tissue type and hormonal milieu; classified as either first generation because they demonstrate estrogen agonist properties in the endometrium or second generation based on their patterns of tissue specificity.
Definition (MSH) A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63)
Concepts Pharmacologic Substance (T121) , Hormone (T125)
MSH D020845
SnomedCT 109030001, 415515000
French Modulateurs sélectifs des récepteurs estrogéniques, Modulateurs sélectifs des récepteurs oestrogéniques, Modulateurs spécifiques des récepteurs aux oestrogènes, Modulateurs spécifiques des récepteurs aux estrogènes, SERM (Selective Estrogen Receptor Modulators), Modulateurs sélectifs des récepteurs des oestrogènes, Modulateurs sélectifs du récepteur aux oestrogènes, Modulateurs sélectifs du récepteur des oestrogènes
Swedish Selektiva estrogenreceptormodulatorer
English ESTROGEN RECEPT MODULATORS SELECTIVE, SELECTIVE ESTROGEN RECEPT MODULATORS, Select estrogen recpt modultor, Estrogen Receptor Modulator, Selective, Estrogen Receptor Modulators, Selective, Selective Estrogen Receptor Modulator, SERM, SERMs, Selective Estrogen Receptor Modulators, serms, selective estrogen receptor modulator (SERM), serm, Selective estrogen receptor modulators, selective estrogen receptor modulator, Selective estrogen receptor modulator, Selective oestrogen receptor modulator, Selective estrogen receptor modulator (product), Selective estrogen receptor modulator (substance), SERM - Selective estrogen receptor modulator, SERM - Selective oestrogen receptor modulator, Selective Estrogen Receptor Modifying Agents
Czech receptory estrogenů - selektivní modulátory, SERMs
Finnish Selektiiviset estrogeenireseptorin modulaattorit
Russian ESTROGENNYKH RETSEPTOROV MODULIATORY IZBIRATEL'NYE, ЭСТРОГЕННЫХ РЕЦЕПТОРОВ МОДУЛЯТОРЫ ИЗБИРАТЕЛЬНЫЕ
Japanese エストロゲン受容体モジュレーター-選択的, 選択的エストロゲン受容体モジュレーター, 選択的エストロゲン受容体修飾薬, 選択的エストロゲン受容体調節薬
Spanish Moduladores Selectivos de los Receptores de Estrógeno, Moduladores Selectivos de Receptores de Estrógeno, modulador selectivo del receptor estrógénico (producto), modulador selectivo del receptor estrógénico, modulador selectivo del receptor estrogénico (producto), Moduladores Selectivos de los Receptores Estrogénicos, Moduladores Selectivos del Receptor Estrogénico, Moduladores Selectivos de los Receptores de Estrógenos, modulador selectivo del receptor de estrógeno (producto), modulador selectivo del receptor de estrógeno (sustancia), modulador selectivo del receptor de estrógeno, modulador selectivo del receptor estrogénico, modulador selectivo de receptor de estrógeno (sustancia), modulador selectivo de receptor de estrógeno, Mress
Italian Modulatori selettivi dei recettori estrogenici, Modulatori selettivi degli estrogeno-recettori, SERM, Modulatori selettivi dei recettori degli estrogeni
Polish Modulatory receptora estrogenowego selektywne
Norwegian Selektive østrogenreseptormodulerende stoffer, Østrogenreseptormodulerende stoffer, selektive, SERM, SERMs
Portuguese Moduladores Seletivos dos Receptores de Estrógenos, Moduladores Seletivos dos Receptores Estrogênicos, Moduladores Seletivos de Receptor de Estrógeno, Moduladores Seletivos de Receptores Estrogênicos, Moduladores Seletivos de Receptor Estrogênico, SERMs, Moduladores Seletivos de Receptor de Estrogênio
German SERMs, Östrogen-Rezeptor-Modulatoren, selektive, Selektive Östrogen-Rezeptor-Modulatoren