Trough oestradiol levels associated with cognitive impairment in post-menopausal women after 10 years of oestradiol implants

Rationale: Oestrogen treatment has been found to improve memory in healthy post-menopausal women, but the effects are small, especially when socio-economic status is controlled. There is some evidence that with long-term treatment the benefits decline, or reverse. Objective: To examine the effects of 10 years of oestradiol implants on attention, memory and frontal lobe function in healthy women (aged 51-72 years) who had undergone a surgical menopause. Methods: In an open study, patients were recruited from the Guy's Hospital menopause clinic and were tested just before receiving a new implant. Exclusion criteria included any form of psychoactive medication, IQ<90, English not the first language and anxiety or depression scores in the clinical range. All patients had been receiving HRT with an oestradiol implant for about 10 years. Each patient was pair-matched to a woman who had never received HRT. Eighteen pairs were matched for age, IQ, socio-economic status, years of secondary education, and occupation. They completed questionnaires, mood rating scales and a battery of cognitive tests. Results: The patients with oestradiol implants had significantly greater psychological and somatic menopausal symptoms and significantly worse mental flexibility (rule reversal) and long-term episodic memory than did the control group who had never received HRT. Analysis of covariance showed that the difference in menopausal symptoms did not account for the cognitive differences. There were no differences in a test of sustained attention or in a category generation task or in self-ratings of mood after the stress of cognitive testing. Conclusions: Long-term treatment with oestradiol implants does not convey cognitive benefits and may lead to impaired function.