Early menopause linked to mental decline

“Premature menopause is linked with poor thinking and reaction times,” The Daily Telegraph reports.

A large French study found that women who had their menopause before the age of 40 had memory problems and delayed reaction times.

Premature menopause is usually defined as occurring before or around the age of 40. This can happen because of an underlying condition, such as primary ovarian failure, or if the ovaries are damaged due to treatments such as chemotherapy, or if they are surgically removed for health reasons.

The women in the study had memory tests when they were aged 65, and these were repeated over seven years. The researchers analysed the results to see if there was any connection between memory difficulties and the age the woman had undergone the menopause.

Researchers found that premature menopause was linked to poorer verbal fluency and visual memory after the age of 65. To the researchers’ surprise, they found that hormone replacement therapy (HRT) improved visual memory, but seemed to worsen verbal ability.

Reassuringly, however, there was no significant link between premature menopause and increased risk of dementia.

Where did the story come from?

The study was carried out by researchers from Montpellier and Bordeaux Universities, and the Centre Memoire Ressources et Recherche in Montpellier (France); Murdoch Children’s Research Institute in Melbourne and the University of Melbourne (Australia); and Imperial College London. It was funded by numerous French institutes and regional governments.

The study was published in the peer-reviewed medical journal BJOG: An International Journal of Obstetrics and Gynaecology.

The media reported the study fairly accurately, but did not make it clear that the women were aged 65 at the beginning of the trial, meaning they could already have cognitive problems.

The most important finding – that premature menopause was not linked to dementia – was also ignored. The Mail Online also inaccurately called the menopause the time when “women run out of eggs”. Technically, during the menopause, the ovaries stop releasing mature eggs.

What kind of research was this?

This was a prospective cohort study of women who were participating in a larger study called the “Three-City Study”. The researchers wanted to see:

if early menopause was associated with poorer cognitive function later in life
whether the type of menopause (“natural” or “surgical”) had any influence on the results
whether the use of hormonal therapy could slow or reverse any decline

The average age for women to have the menopause is around 50, and premature menopause happens when a women is aged around 40.

What did the research involve?

The memory of 4,868 women aged 65 was assessed over seven years, and the researchers looked for any link between their age and type of menopause, taking other factors into consideration.

Women over the age of 65 were recruited between 1999 and 2001 from Montpellier, Bordeaux and Dijon, in France. This was done by random selection from electoral rolls. They were excluded from the study if they had dementia or did not report key elements, such as the age at menopause.

Each woman reported their age at the time of the menopause (defined as one year without menstruating), any history of hysterectomy or bilateral oophorectomy (surgical removal of both ovaries), or if the menopause was due to radiation or chemotherapy.

They were also asked to provide details of any current or previous use of hormonal therapies and if they were taken around the time of the menopause. Other data collected included age, education level, alcohol consumption, smoking status and activity level. Full medical and drug history was recorded.

The researchers assessed the women’s cognitive function at the beginning of the study and then after two, four and seven years. The tests included:

the Mini-Mental State Examination (MMSE), which measures global (total) cognitive function
Benton’s Visual Retention Test (BVRT), which assesses visual memory (the ability to accurately identify a line drawing just shown)
Isaacs’ Set Test, which measures verbal fluency (the ability to say as many words on a category as possible in 30 seconds, such as naming animals or colours)
Trail Making Tests, which measures mental speed and agility

A proportion of the women (3,739) were also assessed for dementia by a psychologist and then fully assessed by a neurologist if they were thought to have dementia.

Statistical analysis took the medical and sociodemographic data into account when comparing the results of the cognitive tests for women who had undergone early menopause.

What were the basic results?

The main results were that:

all of the women who had premature menopause had a 56% increased risk of poor performance on verbal fluency and 39% increased risk of visual memory, compared to women who had the menopause after the age of 50
there was no associated risk of poor visual memory if hormonal therapy was taken by women during premature menopause, but the risk of reduced verbal fluency was higher. If hormonal therapy was not taken by women during the premature menopause, there was an increased risk of poor visual memory
both natural and surgical premature menopause were associated with more than double the risk of poor verbal fluency
there was no significant difference in the cognitive tests for women who had the menopause between the ages of 41 and 50, compared to those over the age of 50
among the women assessed for dementia, premature menopause was associated with a 35% increased risk of reduced mental speed and global cognitive function over the seven-year study (from age 65 to 72), but there was no significant link to dementia risk
there was no significant link between the type of menopause or the use of hormonal therapy and the risk of cognitive decline and dementia
there was no significant difference in cognitive function in older postmenopausal women between surgical and natural menopause

The background results were that:

natural menopause was reported by 79% of the women, surgical in 10% and other causes in 11% (including radiotherapy and chemotherapy)
premature menopause occurred in 7.6% of the women
over a fifth of women used hormonal therapy at the time of menopause and this was mostly by oestrogen patches
dementia was diagnosed in 10.5% of the women assessed

How did the researchers interpret the results?

The researchers report that these results “add to the current literature providing evidence that both premature surgical menopause and premature ovarian failure can have long-lasting negative effects on cognitive function in later life”.

They go on to say that “in terms of surgical menopause, these results suggest that further caution should be used when recommending ovariectomy [oophorectomy] in younger women, and the potential long-term effects on cognitive function are a component of the risk/benefit ratio associated with such surgery”.

Conclusion

This study found a link between premature menopause and memory problems. Strengths of the study include the large number of participants and the fact they were followed prospectively, which reduces the chance of bias. However, as it was a cohort study, it cannot prove that the memory problems were caused by their premature menopause. The researchers analysed the results, taking multiple factors into consideration.

Patient recall, the age of menopause and the type and duration of taking any hormonal therapy may also have been inaccurate. A further limiting factor in this study is that it commenced when women were aged 65, with no diagnosis of dementia. This means it was unable to examine whether premature menopause was related to any cognitive decline or memory problems, including dementia, prior to this age.

It is also worth bearing in mind that 7.6% of the women had premature menopause, which is far higher than the widely believed prevalence estimate of 1%. This means that these results may not directly apply to the general population.

A positive final note is that the researchers found no link between premature menopause and more severe types of cognitive decline, such as dementia.