Dependence on some drugs can be hard to recognize. Hormone replacement therapy (HRT) has been widely prescribed only in the past two decades, and the indications for treatment and the risk/benefit ratio are still disputed. Oestrogens are psychoactive: they lift mood, can be given by injection, and their use has powerful psychological effects. Reports of women with supraphysiological oestradiol concentrations may represent tolerance and withdrawal. Dependence on substances occurring naturally in the body has been reported before. We propose that HRT dependence occurs.