Mindfulness, cognitive behavioural and behaviour‐based therapy for natural and treatment‐induced menopausal symptoms:

Systematic Review

Mindfulness, cognitive behavioural and behaviour‐based therapy for natural and treatment‐induced menopausal symptoms: a systematic review and meta‐analysis

CMG van Driel

Corresponding Author

E-mail address:cmg.driel@umcg.nl

Department of Obstetrics & Gynaecology, University Medical Centre Groningen, Groningen, the Netherlands

Department of Epidemiology, University Medical Centre Groningen, Groningen, the Netherlands

Correspondence: CMG van Driel, Department of Epidemiology, University Medical Centre Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands. Email



During menopause women experience vasomotor and psychosexual symptoms that cannot entirely be alleviated with hormone replacement therapy (HRT). Besides, HRT is contraindicated after breast cancer.


To review the evidence on the effectiveness of psychological interventions in reducing symptoms associated with menopause in natural or treatment‐induced menopausal women.

Search strategy

Medline/Pubmed, PsycINFO, EMBASE and AMED were searched until June 2017.

Selection criteria

Randomised controlled trials (RCTs) concerning natural or treatment‐induced menopause, investigating mindfulness or (cognitive‐)behaviour‐based therapy were selected. Main outcomes were frequency of hot flushes, hot flush bother experienced, other menopausal symptoms and sexual functioning.

Data collection and analysis

Study selection and data extraction were performed by two independent researchers. A meta‐analysis was performed to calculate the standardised mean difference (SMD).

Main results

Twelve RCTs were included. Short‐term (<20 weeks) effects of psychological interventions in comparison to no treatment or control were observed for hot flush bother (SMD −0.63, 95% CI −0.80 to −0.46, < 0.001, I2 = 0%) and menopausal symptoms (SMD −0.34, 95% CI −0.52 to −0.15, < 0.001, I2 = 0%). Medium‐term (≥20 weeks) effects were observed for hot flush bother (SMD −0.49, 95% CI −0.80 to −0.19, = 0.002, I2 = 63%). In the subgroup treatment‐induced menopause, consisting of exclusively breast cancer populations, as well as in the subgroup natural menopause, hot flush bother was reduced by psychological interventions. Too few studies reported on sexual functioning to perform a meta‐analysis.


Psychological interventions reduced hot flush bother in the short and medium‐term and menopausal symptoms in the short‐term. These results are especially relevant for breast cancer survivors in whom HRT is contraindicated. There was a lack of studies reporting on the influence on sexual functioning.

What uterine bleeding is abnormal?

What uterine bleeding is abnormal?

Here’s a breakdown of reasons for abnormal bleeding and what to do if something’s off.

What counts as abnormal?

There are different categories of abnormal: bleeding that occurs between periods (spotting), regular periods that are heavy or longer, or erratic periods. Menstrual cycles more often than every 21 days or farther apart than 35 days are abnormal. Normal bleeding lasts five to seven days. Heavy bleeding during a menstrual cycle or bleeding that lasts more than 7 days is called menorrhagia.

shutterstock women talking

What causes abnormal uterine bleeding?

A variety of issues can cause abnormal uterine bleeding. The cause of abnormal uterine bleeding usually depends on your age.

  • Pregnancy is a common cause. Many women have abnormal bleeding in the first few months of a normal pregnancy. Sometimes bleeding can indicate a miscarriage or an ectopic pregnancy.
  • Polyps or fibroids (small and large growths) in the uterus
  • Birth control pills or the intrauterine device (IUD)
  • Perimenopause or menopause. In the years before menopause and when menopause begins, women have months when they don’t ovulate. Women are menopausal once they have been 12 months without a menstrual cycle. ANY bleeding after menopause is considered abnormal.
  • Hormone replacement therapy
  • A thyroid problem. Hypothyroidism can cause heavy bleeding. Both hypo- and hyperthyroidism are associated with the absence of periods.
  • Infection of the cervix (sexually transmitted infections)
  • Hormonal imbalances (PCOS)
  • Endometrial or cervical cancer

Hormone Imbalances

In most premenopausal women who experience abnormal uterine bleeding, it is caused by a hormone imbalance. When hormones are the problem, this is called dysfunctional uterine bleeding (DUB). DUB occurs when the normal cycle of menstruation is disrupted usually due to failure to ovulate. Hormone imbalances are common in teenagers experiencing puberty or women entering menopause. This causes sporadic bleeding, heavy bleeding, or spotting. Many teenage girls have episodes of irregular bleeding during the first few months after their first menstrual period. This usually resolves without treatment. Hormones are often used to treat DUB, such as progestin, the contraceptive pill or an intrauterine device.

Polyps and fibroids can be removed surgically without compromising fertility in young women.

Sometimes, it is challenging to identify those women who are premenopausal but have abnormal bleeding from causes other than hormonal imbalances. Women need to be up to date with their pap smear (to make sure she does not have cervical cancer) and a pelvic ultrasound may be useful to investigate the endometrium (inner lining of the uterus), myometrium (the muscle layer), tubes and ovaries. Sometimes, a Pipelle is recommended to sample the endometrium.

Non-hormonal causes of bleeding

In postmenopausal women, any bleeding is abnormal. Therefore, even a streak of blood (spotting) needs to be investigated.

The GP will need to make sure your PAP smear is recent. The GP may also order an ultrasound to look at your reproductive pelvic organs. A gynaecological specialist may suggest to look inside your uterus by conducting a hysteroscopy (a thin tube with a tiny camera). An endometrial biopsy may be requested if abnormal growths are found (a sample of the uterine tissue for testing).

Uterine fibroids can be removed surgically. Young women can have fibroids removed and keep the uterus and the ability to have children. For postmenopausal women this may not be a priority any longer and needs to be balanced against the risk of cancer.

However, cancer is not always the cause of abnormal uterine bleeding. Many benign and treatable problems can also cause abnormal bleeding. From our research on many thousand women, the GP or the gynaecological specialist provide information that is most trusted and valuable – even before Dr Google or girlfriends.

Prior to your appointment, it is helpful to keep a record of your menstrual cycle and irregular bleeding to bring to your appointment.

Putting up with irregular bleeding is never a good idea because it can mask serious conditions that cannot be detected otherwise

What is listeria and how does it spread in rockmelons?

What is listeria and how does it spread in rockmelons?

Listeriosis is caused by eating food contaminated with a bacterium called Listeria monocytogenes. It’s an uncommon illness but can be deadly if it causes septicaemia (blood poisoning) or meningitis (inflammation of the membranes around the brain).

The ten reported cases are among people aged over 70. The elderly are particularly susceptible to listeriosis, as are pregnant women and their fetuses, and those with weakened immune systems.

Past outbreaks have been linked with raw milk, soft cheeses, salads, unwashed raw vegetables, cold diced chicken, pre-cut fruit and fruit salad.

Read more: Understanding the recent listeria-linked cheese recall

How does it spread?

Listeria is found widely in soil, water and vegetation, and can be carried by pets and wild animals.

A vegetable or fruit food product can become contaminated anywhere along the chain of food production: planting, harvesting, packing, distribution, preparation and serving.

Even on a farm, sources of contamination can include irrigated waters, wash waters and soil. Listeria can survive for up to 84 days in some soils.

Heavy rains on a crop can splash listeria from soils onto the surface or skin of the vegetable, especially those that grow low to the ground, such as rockmelons.

Read more: Scary berries: how food gets contaminated and what to do

Listeria contamination can also occur in restaurants and home kitchens, where the bacterium can be found – and spread – in areas where foods are being handled.

Listeria monocytogenes is quite a hardy bacterium. It can survive at refrigerated temperatures and has adapted mechanisms to survive acidic environments such as the stomach.

What are the symptoms?

First, it’s important to note that eating foods that contain listeria bacteria won’t necessarily make you sick.

Listeria monocytogenes can survive in the body, moving between cells (human phagocytes) for a long time. This is, in part, why there can be a long “incubation period” between ingestion and onset of illness. This can be as long as 70 days but is usually around three weeks.

Symptoms include fever, muscle aches and gastrointestinal problems such as nausea, vomiting and diarrhoea.

In severe cases, symptoms can include collapse and shock, particularly if there is septicaemia. If the infection has spread to the central nervous system, more worrying symptoms will occur, such as headache, stiff neck, confusion, seizures and the person may go into a coma. In such cases, the fatality rate is as high as 30%.

In pregnant women, the bacteria are thought to cross the lining of maternal blood vessels and then enter the fetal circulation of the placenta. Infection during pregnancy can lead to miscarriage, stillbirth and newborn infections.

Treatment for confirmed infections involves antibiotics and supportive measures such as intravenous fluids for dehydration.

When infection does occur in pregnancy, the early use of antibiotics can often prevent infection of the fetus or newborn.

But even with very prompt treatment, infections can be deadly in high-risk groups.

Why are some groups at higher risk?

Pregnant women are a special group known to be at higher risk for listeriosis. The underlying mechanisms for why pregnant women are susceptible to listeriosis are not well understood but it’s thought an altered immune system is involved.

Read more: How to keep school lunches safe in the heat

People with weakened immune systems, such as those on cancer treatment or medications that suppress the immune system, are more susceptible to developing listeriosis because their bodies are less able to fight off the bug.

Newborn babies are also extremely vulnerable as their immune systems have not yet matured, as are the elderly, whose immune systems are declining.

Tracking and finding the source

The life cycle of the bacteria can make it difficult to track the source of the outbreak. Listeria is able to contaminate a variety of foods, which may have a long shelf life, and listeriosis has a long incubation period.

All ten people in the current outbreak consumed rockmelon before they fell sick and state and territory health departments were able to pinpoint the source to a farm in the NSW Riverina district.

But it’s not always that easy. The current South African listeriosis outbreak is the worst outbreak in recorded history with 172 deaths recorded to date. The source has not yet been identified.

Read more: How we can prevent more Listeria deaths

How can you prevent listeriosis?

Here are some practical things you can do to prevent the spread of listeria:

  • thoroughly cook raw food from animal sources, such as beef, lamb, pork and poultry
  • wash raw vegetables and fruit thoroughly before eating
  • use separate cutting boards for raw meat and foods that are ready to eat
  • wash your hands with soapy water before and after preparing food
  • wash knives and cutting boards after handling uncooked foods
  • wash your hands after handling animals.

If you are at greater risk for listeriosis, consider avoiding:

  • pre-cut melons such as rockmelon or watermelon
  • pre-packed cold salads including coleslaw and fresh fruit salad
  • pre-cooked cold chicken, cold delicatessen meats, pâté
  • raw and uncooked smoked seafood (such as smoked salmon)
  • unpasteurised milk or milk products, soft cheeses (such as brie, camembert, ricotta or blue-vein)
  • sprouted seeds
  • raw mushrooms.

The NSW Food Authority is also advising consumers who are most at risk of listeriosis to avoid eating rockmelon and discard any rockmelon they already have at home.

Hearing in women at menopause.

Interesting study showing the HRT, mainly oestrogen, protects against hearing loss in menopausal women.
Acta Otolaryngol. 2007 Feb;127(2):149-55.

Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy.

Author information

Department of Audiology, Karolinska University Hospital, Stockholm, Sweden. christina.hederstierna@karolinska.se



Hormone replacement therapy (HRT) may have a protective effect on hearing impairment in postmenopausal women. New guidelines for classification of audiometric configuration in age-related hearing loss are suggested.


To describe prevalence of hearing loss and audiometric configuration in a group of middle-aged women with respect to menopausal stage and HRT.


A total of 143 women around menopause were sampled through the Swedish population register. The mean hearing threshold levels were compared according to menopausal status. The audiograms in the 57 women with hearing loss were classified according to audiometric configuration.


In all, 57 women (40%) had any kind of hearing loss; 42 had very minute hearing loss; 15 had a 4FA (average of thresholds at 0.5, 1, 2, and 4 kHz) of at least 20-39 dB HL in at least one ear. Two of these had a 4FA of 40-69 dB HL in at least one ear. The most common configurations were: gently sloping (47%), steeply sloping (14%), and high-frequency U-shaped (14%). The postmenopausal women who were not on HRT had poorer hearing mainly at 2 and 3 kHz, compared with pre- and perimenopausal women, and postmenopausal women on HRT.

You’ve been diagnosed with depression, now what

You’ve been diagnosed with depression, now what? October 15, 2015 4.08pm AEDT

Therapy, drugs or exercise? The depression treatment journey can be difficult to navigate. Eduardo Millo/Flickr, CC BY-NC-ND

First stop: talking therapies

Psychotherapy remains the cornerstone of treatment. Cognitive behavioural therapy (CBT) is the most studied of the therapies, but other forms are effective too. CBT works by addressing the thoughts and behaviours that act to entrench depression.

When people are depressed they tend to withdraw from their social networks. They no longer enjoy social interactions and think they’re unappealing company. By spending more time alone, and less time around people whose company they would usually enjoy, the depression gets worse, leading to even more time spent alone, and so on.

CBT and most other therapies act to break this feedback loop by challenging the thoughts and behaviours that reinforce social isolation, and getting people engaged again.

How do you find a therapist?

Your GP should be able to recommend one, or you can find names in the directories at the Australian Psychological Society and Royal Australian and New Zealand College of Psychiatrists. If you’re between 12 and 25, headspace is a good option.

Most therapists are psychologists or psychiatrists, but some have backgrounds in occupational therapy and social work. There is actually no need for a formal qualification to work as a therapist; my five-year-old daughter could put up her shingle. But it becomes important for claiming rebates, as well as feeling confident you’re seeing someone with a degree of competence.

The Medicare Better Access scheme provides rebates for up to ten sessions of therapy a year to see a psychologist, social worker, or occupational therapist.

To access it you need a GP referral, and the amount of the rebate you get will depend on the qualification of the therapist. It might cover all of the therapist’s fee, or there might be a gap.

You can get a higher rebate still if you see a psychiatrist, who can offer up to 50 sessions of therapy a year. Their fees are likely to be higher, though, meaning a bigger gap between what you pay and the rebate you get.

CBT aims to break unhelpful thinking patterns. Photographee.eu/Shutterstock

The funding for ten sessions per calendar year for non-medical therapists introduces an oddity to the process. If you start seeing a therapist towards the end of the year you can get 20 continuous sessions (ten in one year and ten in the next). But if your depression hits at the beginning of a calendar year you will be cut off after ten.

There are other options, though: you might be eligible for rebates from your health insurance fund and of course, if you can afford to, you can pay for the sessions yourself.

Then there is online therapy, which research suggests is very effective. There are a number of options available in Australia, including MoodGYM, e-couch and This Way Up. They are worth investigating.


Medications for depression have got a lot of bad press in the past few years, with suggestions that pharmaceutical companies have exaggerated their effectiveness by burying equivocal or negative results.

A fair assessment of the evidence suggests that overall they are effective: only modestly so, but taking an antidepressant medication is, on average, more effective than taking a sugar tablet.

Antidepressant medications might be considered when therapy hasn’t been effective, when it isn’t wanted (not everyone wants to see a therapist), or when the depression is severe.

One of the problems with antidepressant medications is they’re often not well-managed. Too often doctors write a script and the person stays on a low and ineffective dose of the medication without review for many months, even years.

Antidepressant use should be closely managed. Photographee.eu/Shutterstock

Antidepressant medications take four to six weeks before they start working. If there hasn’t been any effect by then, something needs to happen. In the first instance that is usually a dose increase.

But if the medication still hasn’t had any positive effect after another six to eight weeks, another medication should be considered. You need to get to this point before you can determine that a medication hasn’t been effective, but beyond this point there seems little sense in staying on a medication that hasn’t helped.

Any decisions about stopping medication, or changing dose, should be made in consultation with a doctor. Not only can they discuss the options, but they can also monitor your mood while changes are made.

Diet and exercise

People with depression are increasingly told that doing more exercise and eating better – the contemporary version of pulling their socks up – will alleviate their symptoms.

The science shows people who eat well and exercise regularly have lower levels of depression. Good physical health is associated with good mental health. Whether or not interventions that aim to improve diet or increase physical fitness are effective treatments for depression is, however, less certain.

The main problem with these prescriptions, as anyone who has been on a diet or joined a gym will know, is that filling them is hard.

It is always good to be fit and eat well, and doctors should more often recommend that these can help depression. But at this stage, while we work out how best exercise and diet can work as interventions, they should be seen as adjuncts to the more established treatments: pursue them, but in addition to psychotherapy, not instead of it.

Do I need a skin cancer check?

Health Check: do I need a skin cancer check?

November 9, 2015 4.14pm AEDT

Talk to your GP if you notice any moles or lesions that have grown, or changed shape or colour. charnsitr/Shutterstock

Australia has one of the highest rates of skin cancer in the world. Two-thirds of Australians will be diagnosed with skin cancer by the age 70.

The vast majority are non-melanoma skin cancers such as squamous cell carcinomas (SCC) and basal cell carcinomas (BCC). These are relatively easy to treat and rarely spread to other parts of the body.

Thirty years of SunSmart campaigns have raised community awareness – and anxiety – about skin cancer. But while most people know early detection is best, there’s a lot of confusion about whether you need to undergo regular skin checks.

Breast, bowel and cervical cancer prevention programs recommend population-wide screening with mammograms, pap tests and stool tests. But this isn’t the case for skin cancer checks.

Opportunistic screening

Current clinical guidelines recommend examining your own skin and asking your GP for a skin check if you notice anything suspicious.

This means familiarising yourself with your skin and looking for new moles, sores, lumps or lesions – or those that have changed size, shape or colour.

Australian guidelines favour self-detection and opportunistic screening over a population-wide program of regular skin checks because such a program would be incredibly costly and there is insufficient evidence that checking everybody would save lives. This is because:

  • very few people die from non-melanoma skin cancer
  • while advanced melanoma is deadly, the frequency of melanoma in the community does not justify a mass population screening program on economic grounds
  • the instrument that would be used for mass screening (assessment by a general practitioner) is not sufficiently accurate – in other words, GPs may remove too many benign lesions and also fail to diagnose and remove the skin cancers.

What should you do if you find a suspicious spot?

If you find a suspicious spot on your skin, ask your GP for a skin check. Your family doctor knows you, your medical history, your family history and is your first point of call.

There are only three possible diagnoses your doctor can make for you skin lesion: clearly malignant, clearly benign and too close to call.

If your doctor is 100% sure the lesion is a skin cancer, they will arrange for it to be removed. Each GP knows the limits of their surgical skill and will refer you on to a dermatologist as necessary. If you’re particularly concerned about scarring, you can request a referral to a dermatologist or plastic surgeon.

If your doctor is 100% certain the lesion is benign, no treatment is required and you will be reassured. Your doctor will examine any other skin lesions and provide you with advice about sun protection and early diagnosis of skin cancer.

If after examining your skin lesion, your doctor is only 99% sure that the lesion is benign, then a definitive diagnosis is required. Options include diagnostic biopsy, excision biopsy or referral to a dermatologist.

Access to specialists varies and patients may have to wait weeks or months for a definitive diagnosis for a “suspicious lesion”. So GPs often excise lesions they feel are low (but not zero) risk.

Consequently, the number of benign lesions needed to be excised for every skin cancer removed is approximately 20 for melanoma and three for non-melanoma skin cancers.

Some dermatology centres provide rapid assessment clinics for GP-referred patients with suspicious lesions.

High-risk groups

People at higher risk of skin cancer may benefit from asking their doctor for a skin check.

Apart from facilitating early diagnosis, the skin check is an opportunity to discuss your individual risk, what to look for when examining your skin, and ways to protect yourself in the sun.

Medical photography is increasingly popular and there is some evidence to support its use in high-risk patients to help detect melanomas early.

But photographs are not the best way to detect non-melanoma skin cancers. Nor are they a substitute for an examination by an experienced clinician.

People who have had previous skin cancer should see their dermatologist once a year for a skin check.

Those who have had more than 20 solar keratosis (lesions caused by UV rays) treated should see a dermatologist for an initial assessment and then once every two to three years.

People with a first-degree relative who has had a melanoma should ask their GP for a skin check and to assess their risk.

Those with red hair, fair skin, blue eyes and those with lots of moles (more than 50) should consider a skin assessment once they hit 30.

People with blond hair, fair skin and blue eyes could wait until they are 40.

And the rest of us might consider having a check when we turn 50.

Further reading: Spot the difference: harmless mole or potential skin cancer

How our brain controls movement and makes new connections when parts are damaged


How our brain controls movement and makes new connections when parts are damaged

September 29, 2016 6.09am AEST

Disclosure statement

Ross Cunnington receives funding from the Australian Research Council and the National Health and Medical Research Council


University of Queensland provides funding as a member of The Conversation AU.


The brain is key to our existence, but there’s a long way to go before neuroscience can truly capture its staggering capacity. For now though, our Brain Control series explores what we do know about the brain’s command of six central functions: language, mood, memory, vision, personality and motor skills – and what happens when things go wrong.

Having voluntary control over body movements is the only way we can interact with people, objects and our environment. Body movement is not just about controlling arms and legs; it’s also for our head and eyes to visually explore the world, for our facial expressions to show emotion, and for articulation of our lips, tongue and mouth to communicate.

Further reading: What brain regions control our language? And how do we know this?

The devastating effects of the brain losing its ability to control body movements are seen in motor neuron disease – where progressive degeneration and muscle wasting leads to some patients becoming “locked-in”, meaning they can’t move or communicate in any way.

The motor system and primary motor cortex

The brain’s motor system is contained mostly in the frontal lobes. It starts with premotor areas, for planning and coordinating complex movements, and ends with the primary motor cortex, where the final output is sent down the spinal cord to cause contraction and movement of specific muscles.

The primary motor cortex on the left side of the brain controls movement of the right side of the body, and vice-versa, the right motor cortex controls movement of the left side of the body.

Different areas of the primary motor cortex connect to and control movement of different body parts. Wikimedia Commons

Different areas of the primary motor cortex connect to, and control, movement of different parts of the body, forming a kind of body map known as the homunculus.

The size of the area on the homunculus determines the level of fine movement control we have with that part of the body. So, for instance, a large proportion of the motor cortex is devoted to our thumb, fingers, mouth and lips, as they are vital for manipulating objects and speech articulation.

The connection from the primary motor cortex to muscles of the body is so important that any damage leads to an impaired ability to move. If someone suffers a stroke, for instance, that causes damage to the primary motor cortex on one side of their brain, they will develop an impaired ability to move on the opposite side of their body.

Further reading: Some people can’t see, but still think they can: here’s how the brain controls our vision.

If the area of damage is specific to only part of the primary motor cortex, such as the hand area of the homunculus, it will affect movements only of the corresponding part of their body, for example, the hand.

The Conversation, CC BY-SA

Neuroplasticity and movement rehabilitation

As with other parts of the brain, when neurons of the primary motor cortex are damaged they will never regrow or repair. However, the brain can heal itself and regain some lost function through neuroplasticity. This means undamaged parts can change their connections and remap to other areas of the body to take over function, compensating for damaged parts of the motor cortex.

Neuroplasticity is the fundamental principle in physical rehabilitation, such as physiotherapy for patients following stroke, that allows patients to regain motor function and recover. Through neuroplasticity, the more a particular movement is performed, the stronger the brain pathways for that movement become and the easier it gets to perform that movement in the future.

Neuroplasticity is the fundamental principle in physical rehabilitation, such as physiotherapy, for patients following stroke. from shutterstock.com

Let’s look at an example of a stroke patient, Harry, who has problems with movement in his left leg. Harry might have altered patterns of walking due to damage in the leg area of the motor cortex of the right side of his brain. To help Harry regain efficient walking ability, the physiotherapist helps him perform sequences or patterns of walking by practising activation and control of specific muscle groups in his left leg.

Further reading: We’re capable of infinite memory, but where in the brain is it stored, and what parts help retrieve it?

At first, Harry will need lots of concentration to use the correct muscles as his brain is laying down new neural pathways to compensate for the damaged areas. But as this practice is repeated and the new pathways are established and strengthened, correct movement becomes easier without much concentration.

This same principle of neuroplasticity also applies for learning in the healthy brain. Anytime we acquire a new skill such as learning to ride a bike, writing our signature or dancing the tango, it’s our brain’s ability to strengthen or make new connections to adapt and change that allows us to learn.

So if you are a ballet dancer or a gymnast, a swimmer or a soccer player, a watch-maker or micro-surgeon, your brain connections in your motor system will be different depending on the practice and skill you have with fine movement of different parts of your body.

This article was co-written with Zita Arends, who is a physiotherapist in stroke rehabilitation and aged care.

More on estrogen and brain function.

Here is more information of the brain benefits of estrogen for those who still remain unconvinced.
Brain Res. 2016 Aug 15;1645:79-82. doi: 10.1016/j.brainres.2016.06.016. Epub 2016 Jun 16.

Reprint of: From the 90׳s to now: A brief historical perspective on more than two decades of estrogen neuroprotection.

Author information

Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV 26506, USA; Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506, USA. Electronic address: elengler@hsc.wvu.edu.
Department of Pharmacology and Neuroscience, University of North Texas, Fort Worth, TX 76107, USA. Electronic address: Meharvan.Singh@unthsc.edu.
Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV 26506, USA; Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506, USA. Electronic address: jwsimpkins@hsc.wvu.edu.


Historical perspective abstract:From the 90׳s to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90׳s, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer׳s Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen׳s neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be among these.


Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats: We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-βE2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions. ChAT activity was decreased in the hippocampus but not the frontal cortex of 5-week OVX animals. E2 replacement resulted in a reversal of this effect. At the 28-week time period, an unexpected decrease in ChAT activity was observed across all treatment groups. Interestingly, E2-pellet animals demonstrated the least severe decline in ChAT. This phenomenon was most evident in the frontal cortex where ChAT decreased by 61 and 56% in INTACT and OVX animals, respectively, whereas the decline in E2-pellet animals was only 16% over the same time period, suggesting a previously unreported cytoprotective effect of E2. Taken together, these findings demonstrate important effects of estrogens on cholinergic neurons and support the potential use of estrogen therapy in treatment of dementias in postmenopausal women. © 1994. This article is part of a Special Issue entitled SI:50th Anniversary Issue.

Role of Estrogen and Other Sex Hormones in Brain Aging.

I have been beating the drum for years now about the benefits of estrogen for women, yet I still get women who say that have been advised to stop their HRT or not to start taking them, by their doctors or friends. I get a bit hot under the collar when I hear this as I know the damage this poor advice will do to these women. Here is more positive reasons for staying on hormones long-term – note the date of this study – a few months ago.
Front Aging Neurosci. 2017 Dec 22;9:430. doi: 10.3389/fnagi.2017.00430. eCollection 2017.

Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair.

Author information

Instituto de Investigaciones Biomédicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Departamento de Histología, Embriología, Biología Celular y Genética, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Danish Center for Molecular Gerontology and Danish Aging Research Center, Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark.
Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain.


Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity.

Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD).

Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain.

Can’t teach old dogs new tricks? Nonsense. Tips for learning later in life

Can’t teach old dogs new tricks? Nonsense. Tips for learning later in life

As 90-year-old Thumekile Mthiyane proves, you’re never too old to learn or try new things. Reuters/Rogan Ward

Change, often rapid and disorienting, is today’s norm. Even things our grandparents took for granted – manual typewriters, telegrams, smelling salts, corsets – have disappeared into antique shops and museums. We change jobs and even careers many times in one lifetime. We travel more. It seems like we adapt to new technologies almost weekly.

What hasn’t changed is that human beings need to learn so they can adapt and thrive in new circumstances. Is this possible for older people? It’s common knowledge that children are voracious learners but the famous cliche suggests that you can’t teach an old dog new tricks. This simply isn’t true.

As research conducted by my colleagues and I has shown, learning is a lifelong process. It’s also life-wide: we learn in all kinds of situations besides schools and colleges – in our families, workplaces, communities and through leisure activities. And it’s life-deep: it’s about emotions, morality, cultural and spiritual development, not just the intellect.

Here’s what you need to know to continue on your own lifelong learning process, and to encourage others around you to keep learning.

What older people have going for them

Ageing brings a slight deterioration in functions like short-term memory. But it has the advantage of accumulated experience. This means you know what you want to learn and how you want to apply it, and can link it to experience and concepts you’ve already acquired. Children at school typically learn a prescribed curriculum for future application. Adults tend to choose their learning and want it to count here and now.

Learning as an adult is not easy. You have to admit what you don’t know. Sometimes past learning experiences have been negative and associated with feelings of fear and failure. And adults have multiple responsibilities: work, family, social involvements and ageing parents, to name a few. Learning means negotiating these commitments and your own feelings. When you decide to embark on new studies, it’s important to let those around you know; explain how it will change things and enlist their support.

It’s also good to learn with others so that you can share the challenges and triumphs. Isolation can drive people away from learning at any stage of their lives. Study groups and learning partners, whether online, face-to-face or both, can be a great way of deepening and sustaining learning.

What and where

But what, and where, should you study? Firstly, it’s important to realise that not all, or even most, learning is formal. There’s an enormous modern emphasis on educational institutions, which for the masses is generally only a few hundred years old. And so the ways that humans have always learnt are often taken for granted.

We often learn the most important things informally from others and from experience: how to parent, how to get on with our neighbours, how to surf the Internet, where to find a job; and, perhaps most importantly, how to direct our own learning. Developing social capital – networks of friends, mentors, advisers, instructors – is as important for learning as it’s ever been.

These networks also allow us to connect with people whose voices we don’t usually hear; that helps us to avoid ghettoising our own minds and opens up new opportunities for thought and action.

Local organisations such as churches, mosques and temples often offer learning opportunities. NGOs as diverse as the World Wildlife Fund and Alcoholics Anonymous provide both face-to-face and eLearning opportunities.

In South Africa, community-based organisations such as stokvels – financial cooperatives – can be a great way to learn about money and saving. Keeping the country’s own radical tradition alive, Popular Education South Africa is a catalytic project that “seeks to inspire alternative forms of education provision that benefit working class and poor people”.

The government system of Community Learning Centres, linked to a Community College in each province, offers adult basic education and an alternative route to writing the National Senior Certificate. This is the final school-leaving exam (“matric”) that can equip you to enter tertiary institutions. Although these centres are of uneven quality, many do an outstanding job under difficult circumstances.

Navigating the Internet

The Internet offers a flood of learning opportunities. But how do you negotiate the deluge of options and pathways? It is important to check out the credentials of the websites you use because search engines don’t discriminate. Look out for websites that are linked to universities and research institutes. These and other credible online sources abound.

Though Wikipedia often gets a bad rap, it’s a vast public resource of information on almost every conceivable topic and a fascinating human invention. It’s a good spot to supplement your learning or answer quick queries.

TED Talks are devoted to “ideas worth spreading”, usually in the form of short powerful talks. You can learn anything from how to spot a liar to how to land on a comet. Each talk also offers access to a transcript, a reading list for more sources and an option for posting your own comments and joining the debate.

Learning as never before

It doesn’t matter whether your learning preferences are formal or informal; institutional or self-directed; online, face-to-face or blended.

We live in a learning world as never before, and the quality of our learning as a species is likely to determine our future. So don’t let cliches about old dogs hold you back: keep learning.