Should psychiatrists be prescribing oestrogen therapy to their female patients?

Some studies have indicated that oestrogen therapy may be beneficial in the treatment of a number of neuropsychiatric disorders. However, it has been suggested that psychiatrists fail to prescribe oestrogen therapy to their patients, as they are 'not aware of' or 'do not believe' studies supporting their use. This paper reappraises the putative role of hormone treatments, particularly oestrogen therapy, in psychiatry.

Reversibility of the effects of acute ovarian hormone suppression on verbal memory and prefrontal function in pre-menopausal women.

BACKGROUND: Whilst acute loss of ovarian function is associated with memory deficits, the biological basis of this is poorly understood. We have previously reported that acute loss of function during Gonadotropin Hormone Releasing Hormone agonists (GnRHa) treatment is associated with impaired verbal memory and a disruption of corresponding left inferior frontal gyrus (LIFG) during the encoding stage. In the current study, we provide a critical extension to this work by determining whether this memory deficit is reversible following normalization of ovarian function. To do this we carried out a further imaging study using the same verbal memory recognition task after cessation of GnRHa-induced ovarian suppression. METHOD: We used event-related fMRI to study verbal episodic memory performance and brain activation at the LIFG in 13 healthy pre-menopausal women pre-, during, and post-acute ovarian hormone suppression using GnRHa. RESULTS: Following resolution of acute GnRHa-induced ovarian suppression, verbal recognition scores returned to their initial levels and this restoration was associated with a restored level of left frontal activation during successful encoding of words. CONCLUSIONS: Our findings suggest that the memory deficits associated with acute ovarian suppression are reversed following resolution of normal ovarian function and are associated with reversible attenuation of LIFG activation during encoding. These findings lend further support to the hypothesis that memory difficulties reported by some women following acute ovarian hormone withdrawal are reversible and may have a clear neurobiological basis.

A study of visuospatial working memory pre- and post-Gonadotropin Hormone Releasing Hormone agonists (GnRHa) in young women.

Gonadotropin Hormone Releasing Hormone agonists (GnRHa) produce an acute decline in ovarian hormone production leading to a 'pseudo' menopause. This is therapeutically useful in the management of a variety of gynaecological conditions but also serves as a powerful model to study the effects of ovarian hormones on cognition. Animal and human behavioral studies report that memory is particularly sensitive to the effects ovarian hormone suppression (e.g. post GnRHa). Further, it has recently been reported that ovariectomy in young women increases the risk of cognitive impairment in later life. However, the underlying brain networks and/or stages of memory processing that might be modulated by acute ovarian hormone suppression remain poorly understood. We used event-related fMRI to examine the effect of GnRHa on visual working memory (VWM). Neuroimaging outcomes from 17 pre-menopausal healthy women were assessed at baseline and 8 weeks after GnRHa treatment. Seventeen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. We report GnRHa was associated with attenuation of left parahippocampal (BA 35) and middle temporal gyri (BA 21 ,22, 39) activation, with a significant group-by-time interaction at left precuneus (BA 7) and posterior cingulate cortex (PCC) (BA 31) at encoding, and with cerebellar activation at recognition in the context of unimpaired behavioral responses. Our study suggests that acute ovarian hormone withdrawal following GnRHa, and perhaps at other times, (e.g. following surgical menopause and postpartum) alters the neural circuitry underlying performance of VWM.

Physiological variation in estradiol and brain function: a functional magnetic resonance imaging study of verbal memory across the follicular phase of the menstrual cycle.

Women frequently complain of memory problems at times in their reproductive lives that are associated with changes in estrogen concentration (e.g. around menopause and childbirth). Further, behavioural studies suggest that memory performance may fluctuate across the menstrual cycle. For example, performance on verbal tasks has been reported to be greatest during phases associated with high estrogen concentrations whereas the opposite has been reported with visuo-spatial tasks. The biological basis of these reported effects remains poorly understood. However, brain imaging studies into the effects of estrogen therapy in postmenopausal women suggest that estrogen modulates the metabolism and function of brain regions sub-serving memory. Furthermore, we have recently reported that acute suppression of ovarian function in young women (with a Gonadotropin Hormone Releasing Hormone agonist) is associated with decreased activation in left prefrontal cortex, particularly the left inferior frontal gyrus (LIFG), during successful verbal memory encoding. We therefore investigated whether physiological variation in plasma estradiol concentration is associated with differences in activity of the LIFG during successful verbal encoding. We hypothesised that higher plasma concentrations of estradiol would be associated with increased brain activity at the LIFG and improved recall performance. Although we did not find a significant relationship between plasma estradiol concentration and verbal recall performance, we report a positive correlation between brain function and estradiol concentration at the LIFG.

Gonadotropin hormone releasing hormone agonists alter prefrontal function during verbal encoding in young women.

Gonadotropin hormone releasing hormone agonists (GnRHa) are commonly used in clinical practice to suppress gonadal hormone production in the management of various gynaecological conditions and as a treatment for advanced breast and prostate cancer. Animal and human behavioural studies suggest that GnRHa may also have significant effects on memory. However, despite the widespread use of GnRHa, the underlying brain networks and/or stages of memory processing that might be modulated by GnRHa remain poorly understood. We used event-related functional magnetic resonance imaging to examine the effect of GnRHa on verbal encoding and retrieval. Neuroimaging outcomes from 15 premenopausal healthy women were assessed at baseline and 8 weeks after Gonadotrophin Releasing Hormone analogue (GnRHa) treatment. Fifteen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. GnRHa was associated with changes in brain response during memory encoding but not retrieval. Specifically, GnRHa administration led to a change in the typical pattern of prefrontal activation during successful encoding, with decreased activation in left prefrontal cortex, anterior cingulate, and medial frontal gyrus. Our study suggests that the memory difficulties reported by some women following GnRHa, and possibly at other times of acute ovarian hormone withdrawal (e.g. following surgical menopause and postpartum), may have a clear neurobiological basis; one that manifest during encoding of words and that is evident in decreased activation in prefrontal regions known to sub-serve deep processing of to-be-learned words.

Effects of acute ovarian hormone suppression on the human brain: an in vivo 1H MRS study.

A previous proton magnetic resonance spectroscopy ((1)H MRS) study carried out by our group indicated that post-menopausal women who started taking oestrogen therapy (ET) at or around the menopause had a significantly lower choline (Cho) concentration in the hippocampus and parietal lobe than those who were ET naïve, suggesting that long-term ET positively modulates neuronal/glial membrane turnover in older females. The objective of the current study was to determine whether neuronal membrane turnover is modulated by sex hormones in younger women following a pharmacologic challenge that induced acute ovarian hormone suppression. We carried out an in vivo(1)H MRS study in a group of 10 premenopausal women pre- and post-8 weeks of acute ovarian suppression with a Gonadotrophin Releasing Hormone analogue (GnRHa) (two Zoladex 3.6 mg implants). We report that young women, post-ovarian suppression, had a significant increase in Cho concentration (and Cho/Cr ratio) in the dorsolateral prefrontal cortex (DLPFC). They also showed a trend to a significant increase in Cho concentration in the hippocampus. This supports our previous findings and adds to the evidence that neuronal/glial membrane metabolism is affected by sex hormones in women.