Surprise weight gain can also happen due to certain medications, especially if you just started them, according to Deb St. Cyr-Paul, RD. “Calcium-channel blockers, which are medications for high blood pressure, can cause fluid retention in lower legs and hands, also known as peripheral edema, in many people who take them,” she explains. Non-steroidal anti-inflammatory drugs (NSAIDs) and birth control pills can also cause fluid retention, she adds.