Raloxifene

Raloxifene is a SERM that acts as an antiestrogen in breast and uterine tissue and an estrogen in bone.

It is increasingly being chosen over tamoxifen because it helps prevent osteoporosis with use of GnRH blockers, and also because it has less or no risk of increasing chances of getting uterine cancer in the general population.

It can also be used to treat gynecomastia, and has been shown effective in reducing breast size in those with the condition.

It has been shown to reduce ERα and PR expression in breast tissue in premenopausal women. Additionally, it was shown to decrease the presence of Ki-67, a biomarker for cell proliferation, in breast tissue of premenopausal women.

Raloxifene has favorable effects on lipids, including cholesterol. Additionally, it may promote feminine fat distribution: in a study on 56-66 year old postmenopausal women, there was an increase in fat in the legs and buttocks and a decrease in fat in the abdomen and trunk after 1 year on 60 mg/day raloxifene. It is not yet known how pronounced this effect is, as there have been no comparisons of body fat distribution between raloxifene and estradiol.

Pharmacodynamics
In in vitro assays, raloxifene appears to be a mixed ERα agonist/antagonist and a ERβ antagonist.

Availability
Note that (as of 2018) Raloxifene can be quite expensive (~US$5 per pill), so it may not be a practical option unless covered by insurance.

Side effects
Rare, but serious adverse events:


 * Increased risk of stroke in those predisposed to cardiovascular issues. In postmenopausal women at high risk of cardiovascular events, there was an 50% increase in death due to stroke. In postmenopausal women with no cardiovascular heath issues, there was not an increased risk of stroke.
 * Increased risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism). In postmenopausal women, there was a 210% increase in the incidence of deep vein thrombosis and a 117% increase in the incidence of pulmonary embolism. The magnitude of this risk is similar to the risk of venous thromboembolism with estrogen-progestin therapy (specifically, conjugated equine estrogens plus medroxyprogesterone acetate ).

Other adverse events:


 * Flu-like symptoms. 16% increase with 60 mg raloxifene daily versus placebo.
 * Hot flashes. 49% increase with 60 mg raloxifene daily versus placebo.
 * Leg cramps. 53% increase with 60 mg raloxifene daily versus placebo.
 * Peripheral edema (swelling due to fluid accumulation, typically legs). 17% increase with 60 mg raloxifene daily versus placebo.

This list is non-exhaustive. All research referenced in this section was performed on postmenopausal women. Other populations may experience different rates of adverse effects.