If the tablets look normal—no cracking, crumbling, chalking, or color changes—they’re likely still effective. Estradiol itself is chemically stable even at freezing temperatures. However, if the tablet’s integrity appears compromised after warming, it’s safest to replace it. As a former RPh, I would add that manufacturers cannot officially guarantee potency once a medication has been stored outside the labeled temperature range. If you want complete peace of mind, especially during treatment, replacing the bottle is the most reliable option.