Update on Raloxifene: Mechanism of Action, Clinical Efficacy, Adverse Effects, and Contraindications

  title={Update on Raloxifene: Mechanism of Action, Clinical Efficacy, Adverse Effects, and Contraindications},
  author={Salvatore Gizzo and Carlo Saccardi and Tito Silvio Patrelli and Roberto Berretta and Giampiero Capobianco and Stefania di Gangi and Antonio Vacilotto and Anna Bertocco and Marco Noventa and Emanuele Ancona and Donato D'Antona and Giovanni Battista Nardelli},
  journal={Obstetrical \& Gynecological Survey},
Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in postmenopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene… 
Selective estrogen receptor modulators in the prevention of breast cancer in premenopausal women: a review
The studies reviewed here demonstrate the modulation of Ki-67 expression and changes in breast density, suggesting an important preventive role for this group of drugs in prevention for premenopausal women at high risk of developing breast cancer.
Statins as Targeted “Magical Pills” for the Conservative Treatment of Endometriosis
Evidence supporting statins as the potential therapeutic agent for a targeted conservative treatment of endometriosis, but the uncertainties regarding their impact on gonadal function may not define them as an appropriate therapy for all young fertile women.
Effects of Raloxifene Combined with Low-dose Conjugated Estrogen on the Endometrium in Menopausal Women at High Risk for Breast Cancer
Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as ral oxifene alone on the endometrium.
Raloxifene as Treatment for Various Types of Brain Injuries and Neurodegenerative Diseases: A Good Start †
  • L. Veenman
  • Biology
    International journal of molecular sciences
  • 2020
An overview of potential treatments of neurodegenerative disease by raloxifene is presented, and attention is paid to subcellular molecular biological pathways that may be involved.
Translational Significance of Selective Estrogen Receptor Modulators in Psychiatric Disorders
  • M. Khan
  • Psychology, Medicine
    International journal of endocrinology
  • 2018
Results together with potent neurocognitive, neuroprotective, and cardiometabolic properties suggest that selective estrogen receptor modulators (SERMs) could be the potential targets for designing effective and safer therapies for psychiatric disorders.
Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies
Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients.
Could in-vitro studies on Ishikawa cell lines explain the endometrial safety of raloxifene? Systematic literature review and starting points for future oncological research
  • S. Gizzo, M. Noventa, G. Nardelli
  • Biology, Medicine
    European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation
  • 2015
If the endometrial safety profile of RAL is confirmed, in the near future, selective estrogen receptor modulators could represent an efficient alternative adjuvant treatment to tamoxifen (TAM) in women with breast cancer considered to be at an increased risk ofendometrial disease.
Neurocognitive, Neuroprotective, and Cardiometabolic Effects of Raloxifene: Potential for Improving Therapeutic Outcomes in Schizophrenia
  • M. Khan
  • Psychology, Medicine
    CNS Drugs
  • 2016
In postmenopausal women, raloxifene reduces the risks for atherosclerosis, diabetes mellitus, and weight gain, which are serious adverse effects associated with long-term antipsychotics treatment in schizophrenia; therefore, it may improve the safety and efficacy of antipsychotic drugs.
Levonorgestrel Intrauterine System in Adjuvant Tamoxifen Treatment
A systematic review of clinical trials on Mirena pharmacological features to establish whether systemic levels of progesterone could increase breast cancer recurrence in patients with breast patients taking tamoxifen to prevent endometrial proliferation.
Perioperative Use of Antiestrogen Therapies in Breast Reconstruction
Evidence indicates patients using SERMs at the time of operation are at an increased risk of flap loss and those taking either SERMs or AIs have higher rates of donor site complications.


Raloxifene hydrochloride.
  • K. Snyder, N. Sparano, J. M. Malinowski
  • Medicine, Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2000
Raloxifene is an alternative to traditional hormone replacement therapy for the prevention and treatment of osteoporosis in selected postmenopausal women and seemed to reduce the risk of breast cancer and positively influenced blood lipid markers of cardiovascular disease.
Recommendations for raloxifene use in daily clinical practice in the Swiss setting
The clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene were characterized based on published scientific evidence to date and a board of Swiss experts in the fields of menopause and metabolic bone diseases agreed about translating these insights into daily practice.
Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.
Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides.
Safety and Adverse Effects Associated With Raloxifene: Multiple Outcomes of Raloxifene Evaluation
Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increase risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrian cancer.
Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women.
The results of this study show that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density lipoprotein cholesterol and total cholesterol in healthy older women and may have a favorable effect on the incidence of cardiovascular disease in older women.
Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years
The main objectives of these analyses are to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and to evaluate the effect on the endometrium and incidence of vaginal bleeding.
Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update
Raloxifene is effective to prevent and treat postmenopausal vertebral osteoporosis, with reduction of spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects and the overall risk-benefit profile is favorable.
Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in vivo: results from a pilot clinical study.
The data show that RAL can modulate circulating levels of cytokines involved in osteoclastogenesis and bone resorption, suggesting that modulation of soluble factors could play a pivotal role in the mechanisms of the osteoprotective effect of RAL.
Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk.
Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers.