raloxifene
Regulatory sources consulted
Approved indications
- Treatment and prevention of osteoporosis in postmenopausal women; it reduces vertebral fracture risk, not hip fracture risk.
Contraindications
Absolute
- Active or prior venous thromboembolism, including deep-vein thrombosis, pulmonary embolism, or retinal vein thrombosis.
- Women of reproductive potential, liver disease, severe renal impairment, unexplained uterine bleeding or signs of endometrial cancer, or hypersensitivity.
Clinical warnings
- Major warning · It increases venous thromboembolism risk, especially early in treatment. Stop at least 3 days before and during prolonged immobilization and resume only after full mobility returns. — CIMA/AEMPS, ficha técnica 87122
- Major warning · It does not treat vasomotor symptoms and may worsen hot flushes. Investigate any uterine bleeding. — CIMA/AEMPS, ficha técnica 87122
- Major warning · In a trial of postmenopausal women with coronary disease or high coronary risk, deaths due to stroke increased with raloxifene without an increase in overall stroke incidence. Carefully assess benefit versus risk in women with a history of or risk factors for stroke. — CIMA/AEMPS, ficha técnica 87122
- Major warning · In patients with prior oral-estrogen-induced hypertriglyceridemia, raloxifene may significantly increase serum triglycerides; monitor them during treatment. — CIMA/AEMPS, ficha técnica 87122
Drug interactions
- HighCholestyramine or other anion-exchange resins
Mechanism: They significantly reduce raloxifene absorption and enterohepatic circulation.
Recommendation: Coadministration is not recommended.
CIMA/AEMPS, ficha técnica 87122https://cima.aemps.es/cima/dochtml/ft/87122/FT_87122.html
- ModerateWarfarin and other coumarin derivatives
Mechanism: It may modestly shorten prothrombin time.
Recommendation: Monitor prothrombin time when starting or stopping raloxifene.
CIMA/AEMPS, ficha técnica 87122https://cima.aemps.es/cima/dochtml/ft/87122/FT_87122.html
Adverse events
Common (≥1%)
Hot flushes · Leg cramps · Flu-like symptoms · Peripheral edema
Rare but serious
Deep-vein thrombosis · Pulmonary embolism · Retinal vein thrombosis · Fatal stroke in women at coronary risk
Pregnancy and lactation
Indicated only in postmenopausal women and contraindicated in women of reproductive potential. Do not use while breastfeeding.
Recent literature (PubMed)
The prevalence of osteoporosis is increasing in the United States. To evaluate low bone mass and osteoporosis treatments to prevent fractures. Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. Bisphosphonates, denosumab, abalopara
Postmenopausal osteoporosis is a chronic progressive disease related to estrogen deficiency at menopause, aging, and superimposed genetic and environmental factors. Many patients with osteoporosis are not diagnosed, and the majority are not treated. Current therapies for osteoporosis include antiresorptive treatments, including bisphosphonates, denosumab, and raloxifene, and osteoanabolic treatments, including teriparatide, abaloparatide, and romosozumab, which is a dual-action agent. Sequential therapies aim to optimize fracture prevention and bone density outcomes for long-term management. Recent guidelines have suggested categorical risk stratification and a goal-directed individualized therapy strategy. New treatments under investigation also hold promise for further improving bone health in postmenopausal osteoporosis.
Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM). To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms. Medline, Embase, and CINAHL through 11 December 2023. Randomized controlled trials (RCTs) of at least 8 weeks' duration enrolling postmenopausal women with at least 1 GSM symptom and reporting effectiveness or harms of hormonal interventions or vaginal moisturizers. Risk of bias and data extraction were performed by one reviewer and verified by a second reviewer. Certainty of evidence (COE) was assessed by one reviewer and verified by consensus. From 11 993 citations, 46 RCTs evaluating vaginal estrogen (k = 22), nonestrogen hormones (k = 16), vaginal moisturizers (k = 4), or multiple interventions (k = 4) were identified. Variation in populations, interventions, comparators, and outcomes precluded meta-analysis. Compared with placebo or no treatment, vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction. Compared with placebo, vaginal dehydroepiandrosterone (DHEA) may improve dryness, dyspareunia, and distress, bother, or interference from genitourinary symptoms; oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction; and vaginal moisturizers may improve dryness (all low COE). Vaginal testosterone, systemic DHEA, vaginal oxytocin, and oral raloxifene or bazedoxifene may provide no benefit (low COE) or had uncertain effects (very low COE). Although studies did not report frequent serious harms, reporting was limited by short-duration studies that were insufficiently powered to evaluate infrequent serious harms. Most studies were 12 weeks or less in duration and used heterogeneous GSM diagnostic criteria and outcome measures. Few studies enrolled women with a history of cancer. Vaginal estrogen, vaginal
The physiological role of estrogen in the female endometrium is well established. On the basis of responses to steroid hormones (progesterone, androgen, and estrogen), the endometrium is considered to have proliferative and secretory phases. Estrogen can act in the endometrium by interacting with estrogen receptors (ERs) to induce mucosal proliferation during the proliferative phase and progesterone receptor (PR) synthesis, which prepare the endometrium for the secretory phase. Mouse knockout studies have shown that ER expression, including ERα, ERβ, and G-protein-coupled estrogen receptor (GPER) in the endometrium is critical for normal menstrual cycles and subsequent pregnancy. Incorrect expression of ERs can produce many diseases that can cause endometriosis, endometrial hyperplasia (EH), and endometrial cancer (EC), which affect numerous women of reproductive age. ERα promotes uterine cell proliferation and is strongly associated with an increased risk of EC, while ERβ has the opposite effects on ERα function. GPER is highly expressed in abnormal EH, but its expression in EC patients is paradoxical. Effective treatments for endometrium-related diseases depend on understanding the physiological function of ERs; however, much less is known about the signaling pathways through which ERs functions in the normal endometrium or in endometrial diseases. Given the important roles of ERs in the endometrium, we reviewed the published literature to elaborate the regulatory role of estrogen and its nuclear and membrane-associated receptors in maintaining the function of endometrium and to provide references for protecting female reproduction. Additionally, the role of drugs such as tamoxifen, raloxifene, fulvestrant and G-15 in the endometrium are also described. Future studies should focus on evaluating new therapeutic strategies that precisely target specific ERs and their related growth factor signaling pathways.