raloxifene

Raloxifene is used for the treatment and prevention of osteoporosis in postmenopausal women.{{Cite web |title=Raloxifene: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a698007.html |access-date=2018-11-07 |website=medlineplus.gov |language=en}} It is used at a dosage of 60 mg/day for both the prevention and treatment of osteoporosis.{{Cite book |last=Mosby |url=https://books.google.com/books?id=41z07XtCfa0C&pg=PA1379 |title=Mosby's Drug Reference for Health Professions - E-Book |date=5 March 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-18760-2 |pages=1379–}} In the case of either osteoporosis prevention or treatment, supplemental calcium and vitamin D should be added to the diet if daily intake is inadequate.{{Cite journal |vauthors=Ohta H, Hamaya E, Taketsuna M, Sowa H |date=January 2015 |title=Quality of life in Japanese women with postmenopausal osteoporosis treated with raloxifene and vitamin D: post hoc analysis of a postmarketing study |journal=Current Medical Research and Opinion |volume=31 |issue=1 |pages=85–94 |doi=10.1185/03007995.2014.975339 |pmid=25299349 |s2cid=24671531}}

Raloxifene is used to reduce the risk of breast cancer in postmenopausal women. It is used at a dosage of 60 mg/day for this indication. In the Multiple Outcomes of Raloxifene (MORE) clinical trial, raloxifene decreased the risk of all types of breast cancer by 62%, of invasive breast cancer by 72%, and of invasive estrogen receptor-positive breast cancer by 84%. Conversely, it does not reduce the risk of estrogen receptor-negative breast cancer. There were no obvious differences in effectiveness of raloxifene in the MORE trial for prevention of breast cancer at a dosage of 60 mg/m²/day relative to 120 mg/m²/day. In the Study of Tamoxifen and Raloxifene (STAR) trial, 60 mg/day raloxifene was 78% as effective as 20 mg/day tamoxifen in preventing non-invasive breast cancer. Women with undetectable levels of estradiol (<2.7 pg/mL) have a naturally low risk of breast cancer and, in contrast to women with detectable levels of estradiol, do not experience significant benefit from raloxifene in terms of reduction of breast cancer risk.

Raloxifene is contraindicated in lactating women or women who are or who may become pregnant. It also may be of concern to women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.{{Cite journal |vauthors=Gizzo S, Saccardi C, Patrelli TS, Berretta R, Capobianco G, Di Gangi S, Vacilotto A, Bertocco A, Noventa M, Ancona E, D'Antona D, Nardelli GB |year=2013 |title=Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications |journal=Obstet Gynecol Surv |volume=68 |issue=6 |pages=467–81 |doi=10.1097/OGX.0b013e31828baef9 |pmid=23942473 |s2cid=9003157}}

Common side effects of raloxifene include hot flashes (25–28% vs. 18–21% for placebo), vaginal dryness, and leg cramps (generally mild; 5.5% vs. 1.9% for placebo).[http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022042lbl.pdf Raloxifene label] Last updated 09/2007] Raloxifene does not cause breast tenderness, endometrial hyperplasia, menstrual bleeding, or endometrial cancer.{{Cite journal |vauthors=Seeman E |year=2001 |title=Raloxifene |journal=J. Bone Miner. Metab. |volume=19 |issue=2 |pages=65–75 |doi=10.1007/s007740170043 |pmid=11281162 |s2cid=249888642}} It does not appear to affect cognition or memory. Raloxifene is a teratogen; i.e., it can cause developmental abnormalities such as birth defects.{{cn|date=January 2025}}

Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, and vision changes. Black box warnings were added to the label of raloxifene in 2007 warning of increased risk of death due to stroke for postmenopausal women with documented coronary heart disease or at increased risk for major coronary events, as well as increased risk for deep vein thrombosis and pulmonary embolism. The risk of venous thromboembolism with raloxifene is increased by several-fold in postmenopausal women ({{abbrlink|RR|relative risk}} = 3.1). Raloxifene has a lower risk of thromboembolism than tamoxifen. In the MORE trial, raloxifene caused a 40% decrease in risk of cardiovascular events in women who were at increased risk for coronary artery disease, although there was no decrease in cardiovascular events for the group as a whole.

A report in September 2009, from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene used to treat breast cancer, significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.{{Cite press release |title=Medications Effective in Reducing Risk of Breast Cancer But Increase Risk of Adverse Effects |date=September 2009 |publisher=Agency for Healthcare Research and Quality |location=Rockville, MD |url=http://archive.ahrq.gov/news/newsroom/press-releases/2009/brcanmed.html |access-date=2009-09-14}}

A human case report in July 2016, suggests that raloxifene may in fact, at some point, also stimulate breast cancer growth leading to a reduction of advanced breast cancer disease upon the withdrawal of the drug.{{Cite journal |vauthors=Lemmo W |date=September 2016 |title=Anti-Estrogen Withdrawal Effect With Raloxifene? A Case Report |journal=Integrative Cancer Therapies |volume=15 |issue=3 |pages=245–249 |doi=10.1177/1534735416658954 |pmc=5739193 |pmid=27411856}}

Unlike other SERMs, such as tamoxifen, raloxifene has no risk of uterine hyperplasia or endometrial cancer ({{abbrlink|RR|relative risk}} = 0.8).{{Cite journal |vauthors=Park WC, Jordan VC |date=February 2002 |title=Selective estrogen receptor modulators (SERMS) and their roles in breast cancer prevention |journal=Trends in Molecular Medicine |volume=8 |issue=2 |pages=82–88 |doi=10.1016/S1471-4914(02)02282-7 |pmid=11815274}}{{Cite book |url=https://books.google.com/books?id=hJwqDwAAQBAJ&pg=PA231 |title=The Breast E-Book: Comprehensive Management of Benign and Malignant Diseases |vauthors=Bland KI, Copeland EM, Klimberg VS, Gradishar WJ |date=29 June 2017 |publisher=Elsevier Health Sciences |isbn=978-0-323-51187-2 |pages=231–}}

Raloxifene does not increase the incidence of breast pain or tenderness in postmenopausal women.{{Cite journal |vauthors=Haskell SG |date=May 2003 |title=Selective estrogen receptor modulators |journal=Southern Medical Journal |volume=96 |issue=5 |pages=469–476 |doi=10.1097/01.SMJ.0000051146.93190.4A |pmid=12911186 |s2cid=40607634}}

Raloxifene has been studied in clinical trials across a dosage range of 30 to 600 mg/day, and was well-tolerated at all dosages.

Raloxifene is a selective estrogen receptor modulator (SERM) and hence is a mixed agonist and antagonist of the estrogen receptor (ER) in different tissues. It has estrogenic activity in some tissues, such as bone and the liver, and antiestrogenic activity in other tissues, such as the breasts and uterus. Its affinity (K_d) for the ERα is approximately 50 pM, which is similar to that of estradiol.{{Cite journal |vauthors=Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L |year=2000 |title=A pharmacological review of selective oestrogen receptor modulators |journal=Human Reproduction Update |volume=6 |issue=3 |pages=212–224 |doi=10.1093/humupd/6.3.212 |pmid=10874566 |doi-access=free}} Relative to estradiol, raloxifene has been reported to possess about 8 to 34% of the affinity for the ERα and 0.5 to 76% of the affinity for the ERβ.{{Cite journal |vauthors=Weatherman RV, Clegg NJ, Scanlan TS |date=May 2001 |title=Differential SERM activation of the estrogen receptors (ERalpha and ERbeta) at AP-1 sites |journal=Chemistry & Biology |volume=8 |issue=5 |pages=427–436 |doi=10.1016/S1074-5521(01)00025-4 |pmid=11358690 |doi-access=free}}{{Cite journal |display-authors=6 |vauthors=Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, Nicolas JC, Cavaillès V, Balaguer P |date=May 2006 |title=Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta |journal=Biochemical Pharmacology |volume=71 |issue=10 |pages=1459–1469 |doi=10.1016/j.bcp.2006.02.002 |pmid=16554039}} Raloxifene acts as a partial agonist of the ERα and as a pure antagonist of the ERβ.{{Cite book |title=New Molecular Mechanisms of Estrogen Action and Their Impact on Future Perspectives in Estrogen Therapy |vauthors=Greene GL, Shiau AK, Nettles KW |journal=Ernst Schering Research Foundation Workshop |year=2004 |isbn=978-3-662-05388-1 |pages=33–45 |chapter=A Structural Explanation for ERα/ERβ SERM Discrimination |doi=10.1007/978-3-662-05386-7_3 |pmid=15248503 |issue=46}}{{Cite journal |vauthors=Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S |date=July 1998 |title=Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists |journal=Molecular Pharmacology |volume=54 |issue=1 |pages=105–112 |doi=10.1124/mol.54.1.105 |pmid=9658195}} In contrast to the classical ERs, raloxifene is an agonist of the G protein-coupled estrogen receptor (GPER) ({{abbrlink|EC₅₀|half-maximal effective concentration}} = 10–100 nM), a membrane estrogen receptor.{{Cite journal |vauthors=Prossnitz ER, Arterburn JB |date=July 2015 |title=International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators |journal=Pharmacological Reviews |volume=67 |issue=3 |pages=505–540 |doi=10.1124/pr.114.009712 |pmc=4485017 |pmid=26023144}}{{Cite journal |display-authors=6 |vauthors=Petrie WK, Dennis MK, Hu C, Dai D, Arterburn JB, Smith HO, Hathaway HJ, Prossnitz ER |date=2013 |title=G protein-coupled estrogen receptor-selective ligands modulate endometrial tumor growth |journal=Obstetrics and Gynecology International |volume=2013 |pages=472720 |doi=10.1155/2013/472720 |pmc=3863501 |pmid=24379833 |doi-access=free}}

Raloxifene has antiestrogenic effects in the mammary glands in preclinical studies. In accordance, raloxifene reduces breast density in postmenopausal women, a known risk factor for breast cancer.{{Cite journal |last=Jeon-Hor, Chen |display-authors=etal |date=September 15, 2003 |title=Reduction of Breast Density Following Tamoxifen Treatment Evaluated by 3-D MRI: Preliminary Study |journal=Magn Reson Imaging |volume=29 |issue=1 |pages=91–8 |doi=10.1016/j.mri.2010.07.009 |pmc=3005955 |pmid=20832226}} It does not stimulate the uterus in postmenopausal women, and results in no increase in risk of endometrial thickening, vaginal bleeding, endometrial hyperplasia, or endometrial cancer. At the same time, raloxifene has minimal antiestrogenic effect in the uterus in premenopausal women. This may possibly be due to inadequate tissue exposure of the uterus to raloxifene in these estrogen-rich individuals.

In premenopausal women, raloxifene increases levels of follicle-stimulating hormone (FSH) and estradiol. Conversely, in postmenopausal women, raloxifene has been found to reduce levels of the gonadotropins, luteinizing hormone (LH) and FSH, while not affecting levels of estradiol. Raloxifene also decreases prolactin levels in postmenopausal women. In men, raloxifene has been found to disinhibit the hypothalamic–pituitary–gonadal axis (HPG axis) and thereby increase total testosterone levels.{{Cite journal |vauthors=Corona G, Rastrelli G, Ratrelli G, Maggi M |date=February 2015 |title=The pharmacotherapy of male hypogonadism besides androgens |journal=Expert Opin Pharmacother |volume=16 |issue=3 |pages=369–87 |doi=10.1517/14656566.2015.993607 |pmid=25523084 |s2cid=8891640}}{{Cite journal |vauthors=Birzniece V, Sutanto S, Ho KK |date=April 2012 |title=Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=4 |pages=E521–7 |doi=10.1210/jc.2011-3347 |pmid=22319035 |doi-access=free}}{{Cite journal |vauthors=Uebelhart B, Herrmann F, Pavo I, Draper MW, Rizzoli R |date=September 2004 |title=Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels |journal=J. Bone Miner. Res. |volume=19 |issue=9 |pages=1518–24 |doi=10.1359/JBMR.040503 |pmid=15312253 |s2cid=36104038}} Due to the simultaneous increase in sex hormone-binding globulin (SHBG) levels however, free testosterone levels often remain unchanged in men during therapy with raloxifene.

Raloxifene has estrogenic effects on liver protein synthesis. It increases SHBG levels in both pre- and postmenopausal women as well as in men.{{Cite journal |vauthors=Fabian CJ, Kimler BF |date=March 2005 |title=Selective estrogen-receptor modulators for primary prevention of breast cancer |journal=Journal of Clinical Oncology |volume=23 |issue=8 |pages=1644–1655 |doi=10.1200/JCO.2005.11.005 |pmid=15755972 |doi-access=free}} The medication decreases levels of total and low-density lipoprotein (LDL) cholesterol, C-reactive protein, apolipoprotein B, and homocysteine.{{Cite journal |vauthors=Draper MW, Chin WW |date=June 2003 |title=Molecular and clinical evidence for the unique nature of individual selective estrogen receptor modulators |journal=Clinical Obstetrics and Gynecology |volume=46 |issue=2 |pages=265–297 |doi=10.1097/00003081-200306000-00008 |pmid=12808380 |s2cid=5132467}} Conversely, it has little effect on levels of triglycerides and high-density lipoprotein (HDL). Raloxifene has been shown to inhibit the oxidation of LDL cholesterol in vitro. The medication has been found to decrease insulin-like growth factor 1 (IGF-1) levels in pre- and postmenopausal women as well as in men.{{Cite journal |vauthors=Duarte FH, Jallad RS, Bronstein MD |date=November 2016 |title=Estrogens and selective estrogen receptor modulators in acromegaly |journal=Endocrine |volume=54 |issue=2 |pages=306–314 |doi=10.1007/s12020-016-1118-z |pmid=27704479 |s2cid=10136018}} It has also been found to increase insulin-like growth factor binding protein 3 (IGFBP-3) levels in pre- and postmenopausal women. Due to activation of estrogen receptors in the liver, raloxifene has procoagulatory effects, such as decreasing levels of fibrinogen and influencing levels of other coagulation factors. For these reasons, raloxifene increases the risk of thrombosis.

Raloxifene increases bone mineral density in postmenopausal women but decreases it in premenopausal women. In the MORE trial, the risk of vertebral fractures was decreased by 30%, and bone mineral density was increased in the spine (by 2.1% at 60 mg, 2.4% at 120 mg) and femoral neck (2.6% at 60 mg, 2.7% at 120 mg). It has been found to possess estrogenic effects in adipose tissue in postmenopausal women, promoting a shift from an android fat distribution to a gynoid fat distribution.{{Cite journal |vauthors=Xu B, Lovre D, Mauvais-Jarvis F |date=May 2016 |title=Effect of selective estrogen receptor modulators on metabolic homeostasis |journal=Biochimie |volume=124 |pages=92–97 |doi=10.1016/j.biochi.2015.06.018 |pmid=26133657 |quote=In healthy postmemopausal women, raloxifene treatment for one year prevented body weight gain and abdominal adiposity by promoting a shift from an android to gynoid fat distribution [46].}}{{Cite journal |vauthors=Francucci CM, Daniele P, Iori N, Camilletti A, Massi F, Boscaro M |year=2014 |title=Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women |journal=Journal of Endocrinological Investigation |volume=28 |issue=7 |pages=623–631 |doi=10.1007/BF03347261 |pmid=16218045 |s2cid=28467435 |quote=These results [...] suggest, for the first time, that RLX promotes the shift from android to gynoid fat distribution, and prevents the uptrend of abdominal adiposity and body weight compared with untreated women.}} The medication has been found to increase levels of leptin, an adipokine.

{{Tissue-specific estrogenic and antiestrogenic activity of SERMs}}

The absorption of raloxifene is approximately 60%.{{Cite journal |vauthors=Hochner-Celnikier D |date=July 1999 |title=Pharmacokinetics of raloxifene and its clinical application |journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology |volume=85 |issue=1 |pages=23–29 |doi=10.1016/s0301-2115(98)00278-4 |pmid=10428318}} However, due to extensive first-pass metabolism, the absolute bioavailability of raloxifene is only 2.0%. Raloxifene is rapidly absorbed from the intestines upon oral administration.{{Cite journal |vauthors=Morello KC, Wurz GT, DeGregorio MW |year=2003 |title=Pharmacokinetics of selective estrogen receptor modulators |journal=Clinical Pharmacokinetics |volume=42 |issue=4 |pages=361–372 |doi=10.2165/00003088-200342040-00004 |pmid=12648026 |s2cid=13003168}} Peak plasma levels of raloxifene occur 0.5 to 6 hours after an oral dose. In healthy postmenopausal women treated with 60 mg/day raloxifene, peak circulating raloxifene levels normalized by dose and body weight were (i.e., divided by (mg/kg)), 0.50 ng/mL (500 pg/mL) after a single dose and 1.36 ng/mL (1,360 pg/mL after multiple doses).

Raloxifene is widely distributed throughout the body. There is extensive distribution of raloxifene into the liver, serum, lungs, and kidneys. The volume of distribution of raloxifene with a single 30 to 150 mg oral dose is approximately 2348 L/kg, which corresponds to ~170,000 L for a 72 kg person.{{Cite journal |vauthors=Snyder KR, Sparano N, Malinowski JM |date=September 2000 |title=Raloxifene hydrochloride |journal=Am J Health Syst Pharm |volume=57 |issue=18 |pages=1669–75; quiz 1676–8 |doi=10.1093/ajhp/57.18.1669 |pmid=11006795 |doi-access=free}} Both raloxifene and its glucuronide metabolites show high plasma protein binding (>95%), including to both albumin and α₁ acid glycoprotein, but not to sex hormone-binding globulin. More specifically, raloxifene is 98.2 ± 0.4% bound to plasma proteins.{{Cite journal |vauthors=Miller JW, Skerjanec A, Knadler MP, Ghosh A, Allerheiligen SR |date=July 2001 |title=Divergent effects of raloxifene HCI on the pharmacokinetics and pharmacodynamics of warfarin |journal=Pharm Res |volume=18 |issue=7 |pages=1024–8 |doi=10.1023/a:1010904815275 |pmid=11496940 |s2cid=1713984}}

Raloxifene is metabolized in the liver and undergoes enterohepatic recycling. It is metabolized exclusively by glucuronidation and is not metabolized by the cytochrome P450 system. Less than 1% of radiolabeled material in plasma comprises unconjugated raloxifene. The metabolites of raloxifene include several glucuronides. The elimination half-life of raloxifene after a single dose is 27.7 hours (1.2 days), whereas its half-life at steady state at a dosage of 60 mg/day is 15.8 to 86.6 hours (0.7–3.6 days), with an average of 32.5 hours (1.4 days). The extended half-life of raloxifene is attributed to enterohepatic recirculation and its high plasma protein binding. Raloxifene and its glucuronide conjugates are interconverted by reversible metabolism and enterohepatic recycling, which prolongs the elimination half-life of raloxifene with oral administration. The medication is deconjugated into its active form in a variety of tissues, including liver, lungs, spleen, bone, uterus, and kidneys.

Raloxifene is mainly excreted in bile and is eliminated in feces. Less than 0.2% of a dose is excreted unchanged in urine and less than 6% of a dose is excreted in urine as glucuronide conjugates.

{{See also|List of selective estrogen receptor modulators|Benzothiophene}}

Raloxifene hydrochloride has the empirical formula C₂₈H₂₇NO₄S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene hydrochloride is an off-white to pale-yellow solid that is slightly soluble in water.

Raloxifene is a benzothiophene derivative and is structurally distinct from the triphenylethylene SERMs like tamoxifen, clomifene, and toremifene.{{Cite book |url=https://books.google.com/books?id=iX31BwAAQBAJ&pg=PA320 |title=Osteoporosis: Pathophysiology and Clinical Management |vauthors=Orwoll ES, Bliziotes M |date=2 August 2002 |publisher=Springer Science & Business Media |isbn=978-1-59259-278-4 |pages=320–}} It is the only benzothiophene SERM to have been marketed. A benzothiophene SERM that was not marketed is arzoxifene (LY-353381).{{Cite book |url=https://books.google.com/books?id=5bFPCwAAQBAJ&pg=PA24 |title=The Duration and Safety of Osteoporosis Treatment: Anabolic and Antiresorptive Therapy |vauthors=Silverman S, Abrahamsen B |date=29 December 2015 |publisher=Springer |isbn=978-3-319-23639-1 |pages=24–}} Bazedoxifene (Duavee, Viviant) and pipendoxifene (ERA-923) are structurally related to raloxifene but are technically not benzothiophenes and instead are indoles.

Raloxifene was approved in the United States for the prevention of postmenopausal osteoporosis in 1997, the treatment of postmenopausal osteoporosis in 1999, and to prevent or reduce the risk of breast cancer in certain postmenopausal women in 2007.{{Cite book |url=https://books.google.com/books?id=HnYyeNIY3WwC&pg=PT113 |title=Rare Diseases and Orphan Products: Accelerating Research and Development |date=3 April 2011 |publisher=National Academies Press |isbn=978-0-309-15806-0 |pages=113–}}{{Cite book |url=https://books.google.com/books?id=jpNsg_Sx2wMC&pg=PA10 |title=Reducing Breast Cancer Risk with Drugs |publisher=Am Cncl on Science, Health |pages=10– |id=GGKEY:CBEALLAHP8W}}{{Cite book |last=Sydney Lou Bonnick |url=https://books.google.com/books?id=0NGsgFAf_9QC&pg=PA277 |title=Bone Densitometry for Technologists |date=10 November 2007 |publisher=Springer Science & Business Media |isbn=978-1-59259-992-9 |pages=277–}}{{Cite book |url=https://books.google.com/books?id=NtdT5maa_pMC&pg=RA2-PA73 |title=Modern Drug Synthesis |vauthors=Li JJ, Johnson DS |date=27 March 2013 |publisher=John Wiley & Sons |isbn=978-1-118-70124-9 |pages=2–}} It received orphan designation in 2005.

File:Rolaxifene.jpg

Raloxifene is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while raloxifène is its {{abbrlink|DCF|Dénomination Commune Française}} and raloxifene hydrochloride is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.{{Cite book |last=J. Elks |url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1063 |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=1063–}}{{Cite book |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA909 |title=Index Nominum 2000: International Drug Directory |publisher=Taylor & Francis |year=2000 |isbn=978-3-88763-075-1 |pages=909–}}{{Cite book |url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA245 |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms |vauthors=Morton IK, Hall JM |date=31 October 1999 |publisher=Springer Science & Business Media |isbn=978-0-7514-0499-9 |pages=245–}} It has also been known by the name keoxifene.

Raloxifene is sold mainly under the brand name Evista and to a lesser extent the brand name Optruma.{{Cite web|url=https://www.drugs.com/mtm/raloxifene.html|title=Raloxifene Uses, Side Effects & Warnings|website=Drugs.com}} It is also sold under a variety of other brand names in various countries.

Raloxifene is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, Australia, New Zealand, South Africa, Latin America, Southern, Eastern, and Southeastern Asia, and elsewhere in the world such as in Israel and Egypt.

Raloxifene is provided in the form of 60 mg oral tablets.

An editorial in Lancet Oncology criticized the way that research about the medication for breast cancer prevention was released.{{Cite journal |last=Thelancetoncology |year=2006 |title=A STARring role for raloxifene? |journal=Lancet Oncol |volume=7 |issue=6 |pages=443 |doi=10.1016/S1470-2045(06)70701-X |pmid=16750489}}

Clinical studies of raloxifene for metastatic breast cancer in women have been conducted but found little effectiveness at 60 mg/day in those previously treated with tamoxifen, though modest effectiveness has been observed at higher doses.{{Cite journal |vauthors=Provinciali N, Suen C, Dunn BK, DeCensi A |date=October 2016 |title=Raloxifene hydrochloride for breast cancer risk reduction in postmenopausal women |journal=Expert Rev Clin Pharmacol |volume=9 |issue=10 |pages=1263–1272 |doi=10.1080/17512433.2016.1231575 |pmid=27583816 |s2cid=26047863}} In contrast to tamoxifen, raloxifene is not approved for the treatment of breast cancer.{{Cite book |url=https://books.google.com/books?id=R0FbhLsWHBEC&pg=PA743 |title=Holland-Frei Cancer Medicine 8 |vauthors=Holland JF, Pollock RE |publisher=PMPH-USA |year=2010 |isbn=978-1-60795-014-1 |pages=743–}}

Raloxifene has been studied in men for a variety of uses, such as for treatment of schizophrenia, prostate cancer, and osteoporosis.{{Cite journal |vauthors=Blum A, Hathaway L, Mincemoyer R, Schenke WH, Csako G, Waclawiw MA, Panza JA, Cannon RO |year=2000 |title=Hormonal, lipoprotein, and vascular effects of the selective estrogen receptor modulator raloxifene in hypercholesterolemic men |journal=Am. J. Cardiol. |volume=85 |issue=12 |pages=1491–4; A7 |doi=10.1016/s0002-9149(00)00802-x |pmid=10856400}}{{Cite journal |vauthors=Doran PM, Riggs BL, Atkinson EJ, Khosla S |year=2001 |title=Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men |journal=J. Bone Miner. Res. |volume=16 |issue=11 |pages=2118–25 |doi=10.1359/jbmr.2001.16.11.2118 |pmid=11697809 |s2cid=28216610 |doi-access=free}}{{Cite journal |vauthors=Dimaraki EV, Symons KV, Barkan AL |year=2004 |title=Raloxifene decreases serum IGF-I in male patients with active acromegaly |journal=Eur. J. Endocrinol. |volume=150 |issue=4 |pages=481–7 |doi=10.1530/eje.0.1500481 |pmid=15080777 |doi-access=free}}{{Cite journal |vauthors=Duschek EJ, Gooren LJ, Netelenbos C |year=2004 |title=Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men |url=http://www.eje-online.org/content/150/4/539.full.pdf |journal=Eur. J. Endocrinol. |volume=150 |issue=4 |pages=539–46 |doi=10.1530/eje.0.1500539 |pmid=15080785 |doi-access=free}}{{Cite journal |vauthors=Smith MR, Fallon MA, Lee H, Finkelstein JS |year=2004 |title=Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial |journal=J. Clin. Endocrinol. Metab. |volume=89 |issue=8 |pages=3841–6 |doi=10.1210/jc.2003-032058 |pmid=15292315 |doi-access=free}}{{Cite journal |vauthors=Ho TH, Nunez-Nateras R, Hou YX, Bryce AH, Northfelt DW, Dueck AC, Wong B, Stanton ML, Joseph RW, Castle EP |year=2017 |title=A Study of Combination Bicalutamide and Raloxifene for Patients With Castration-Resistant Prostate Cancer |journal=Clin Genitourin Cancer |volume=15 |issue=2 |pages=196–202.e1 |doi=10.1016/j.clgc.2016.08.026 |pmid=27771244 |s2cid=19043552}}{{Cite journal |vauthors=Khodaie-Ardakani MR, Khosravi M, Zarinfard R, Nejati S, Mohsenian A, Tabrizi M, Akhondzadeh S |year=2015 |title=A Placebo-Controlled Study of Raloxifene Added to Risperidone in Men with Chronic Schizophrenia |journal=Acta Med Iran |volume=53 |issue=6 |pages=337–45 |pmid=26069170}}{{Cite journal |vauthors=Weickert TW, Weinberg D, Lenroot R, Catts SV, Wells R, Vercammen A, O'Donnell M, Galletly C, Liu D, Balzan R, Short B, Pellen D, Curtis J, Carr VJ, Kulkarni J, Schofield PR, Weickert CS |year=2015 |title=Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia |journal=Mol. Psychiatry |volume=20 |issue=6 |pages=685–94 |doi=10.1038/mp.2015.11 |pmc=4444978 |pmid=25980345}} It has been studied in combination with castration and bicalutamide, a nonsteroidal antiandrogen, for the treatment of prostate cancer.{{Cite journal |vauthors=Fujimura T, Takayama K, Takahashi S, Inoue S |date=January 2018 |title=Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine |journal=Cancers |volume=10 |issue=2 |pages=29 |doi=10.3390/cancers10020029 |pmc=5836061 |pmid=29360794 |doi-access=free}}

Raloxifene has been studied as an adjunct in the treatment of schizophrenia in postmenopausal women.{{Cite journal |vauthors=Wang Q, Dong X, Wang Y, Li X |year=2017 |title=Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a meta-analysis of randomized controlled trials |journal=Arch Womens Ment Health |volume=21 |issue=1 |pages=31–41 |doi=10.1007/s00737-017-0773-2 |pmid=28849318 |s2cid=4524617}} A 2017 meta-analysis concluded that it was safe and effective for this indication, although further studies with larger sample sizes are needed for confirmation. It may be effective in women with less severe symptoms.

A tissue-selective estrogen-receptor complex (TSEC) of estradiol and raloxifene has been studied in postmenopausal women.{{Cite journal |vauthors=Carneiro AL, de Cassia de Maio Dardes R, Haidar MA |date=July 2012 |title=Estrogens plus raloxifene on endometrial safety and menopausal symptoms--semisystematic review |journal=Menopause |volume=19 |issue=7 |pages=830–4 |doi=10.1097/gme.0b013e31824a74ce |pmid=22549172 |s2cid=196380398}}

Raloxifene (60 mg/day) was reported to be effective in the treatment of pubertal gynecomastia in adolescent boys in a small retrospective chart review.{{Cite journal |vauthors=Nordt CA, DiVasta AD |date=August 2008 |title=Gynecomastia in adolescents |journal=Current Opinion in Pediatrics |volume=20 |issue=4 |pages=375–382 |doi=10.1097/MOP.0b013e328306a07c |pmid=18622190 |s2cid=205834072}}{{Cite journal |vauthors=Leung AK, Leung AA |year=2017 |title=Gynecomastia in Infants, Children, and Adolescents |journal=Recent Patents on Endocrine, Metabolic & Immune Drug Discovery |volume=10 |issue=2 |pages=127–137 |doi=10.2174/1872214811666170301124033 |pmid=28260521}}{{Cite journal |vauthors=Lawrence SE, Faught KA, Vethamuthu J, Lawson ML |date=July 2004 |title=Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia |journal=The Journal of Pediatrics |volume=145 |issue=1 |pages=71–76 |doi=10.1016/j.jpeds.2004.03.057 |pmid=15238910}} Other SERMs are also known to be effective in the treatment of gynecomastia.{{Cite journal |display-authors=6 |vauthors=Kanakis GA, Nordkap L, Bang AK, Calogero AE, Bártfai G, Corona G, Forti G, Toppari J, Goulis DG, Jørgensen N |date=November 2019 |title=EAA clinical practice guidelines-gynecomastia evaluation and management |journal=Andrology |volume=7 |issue=6 |pages=778–793 |doi=10.1111/andr.12636 |pmid=31099174 |doi-access=free}}

Raloxifene has been reported to augment the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs).{{Cite journal |vauthors=Sugiyama N, Barros RP, Warner M, Gustafsson JA |date=September 2010 |title=ERbeta: recent understanding of estrogen signaling |journal=Trends in Endocrinology and Metabolism |volume=21 |issue=9 |pages=545–552 |doi=10.1016/j.tem.2010.05.001 |pmid=20646931 |s2cid=43001363}}

{{Reflist}}

{{refbegin}}

• {{Cite journal |last=Barrett-Connor E |year=2001 |title=Raloxifene: risks and benefits |journal=Ann N Y Acad Sci |volume=949 |issue=1 |pages=295–303 |bibcode=2001NYASA.949..295B |doi=10.1111/j.1749-6632.2001.tb04036.x |pmid=11795366 |s2cid=41412601}}
• {{Cite journal |last=Heringa M |year=2003 |title=Review on raloxifene: profile of a selective estrogen receptor modulator |journal=Int J Clin Pharmacol Ther |volume=41 |issue=8 |pages=331–45 |doi=10.5414/cpp41331 |pmid=12940590}}
• {{Cite journal |vauthors=Sporn MB, Dowsett SA, Mershon J, Bryant HU |year=2004 |title=Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action |journal=Clin Ther |volume=26 |issue=6 |pages=830–40 |doi=10.1016/s0149-2918(04)90127-0 |pmid=15262454}}
• {{Cite journal |vauthors=Vogel VG |year=2009 |title=The NSABP Study of Tamoxifen and Raloxifene (STAR) trial |journal=Expert Rev Anticancer Ther |volume=9 |issue=1 |pages=51–60 |doi=10.1586/14737140.9.1.51 |pmc=2785111 |pmid=19105706}}
• {{Cite book |title=Cancer Prevention II |vauthors=Wickerham DL, Costantino JP, Vogel VG, Cronin WM, Cecchini RS, Ford LG, Wolmark N |work=Recent Results Cancer Res. |year=2009 |isbn=978-3-540-69296-6 |series=Recent Results in Cancer Research |volume=181 |pages=113–9 |chapter=The Use of Tamoxifen and Raloxifene for the Prevention of Breast Cancer |doi=10.1007/978-3-540-69297-3_12 |pmc=5110043 |pmid=19213563}}
• {{Cite journal |vauthors=Vogel VG |year=2011 |title=Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women |journal=Breast Cancer: Targets and Therapy |volume=3 |pages=127–37 |doi=10.2147/BCTT.S11288 |pmc=3846694 |pmid=24367182 |doi-access=free}}
• {{Cite journal |vauthors=Yang ZD, Yu J, Zhang Q |year=2013 |title=Effects of raloxifene on cognition, mental health, sleep and sexual function in menopausal women: a systematic review of randomized controlled trials |journal=Maturitas |volume=75 |issue=4 |pages=341–8 |doi=10.1016/j.maturitas.2013.05.010 |pmid=23764354}}

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