Cancer and its treatment may cause leg cramps and other types of muscle cramps. Cramps or spasms are painful tightening of the muscles in the leg, ankle, or foot. Research and clinical evidence confirm that tamoxifen is associated with an increased risk of muscle and leg cramps. A 2023 study, known as the KARISMA trial, found that muscle cramps were one of five symptoms with a significant change in severity related to tamoxifen exposure. Common tamoxifen side effects include hot flashes, vaginal discharge or dryness, loss of libido, fatigue, and depression. Less common, but more serious side effects of tamoxifen include endometrial cancer, blood clots, and stroke. Common Evista side effects include hot flashes, leg cramps, swelling, flu-like symptoms, and joint pain. I started on Tamoxifen about four months ago and the leg cramps started almost immediately, first in one leg now in both. It is more or less permanent in both calves and I’m walking like an old woman. Tamoxifen side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. While tamoxifen can be an effective treatment for breast cancer, it can also cause a range of side effects, including muscle cramps. Muscle cramps, or spasms, are painful tightenings of the muscles in the leg, ankle, or foot. Tamoxifen causes leg cramps, which are sharp pains that last for a few seconds to several minutes. People are commonly affected by severe pain that causes them to wake up in the middle of the night, disrupting their sleep patterns and causing morning exhaustion.