Tuesday 3 September 2019

What is the menopause and when does it strike?

It’s a natural part of the female life cycle – so why don’t we talk more about the menopause, its debilitating effects and possible mitigation?

What is the menopause?
The menopause is when a woman’s fertile period comes to a halt. This is generally a gradual process over months or even years, but technically the menopause is defined as when a woman has gone 12 months without a period. In the UK, the average age for this happening is 52 years, but about one in 100 women have a menopause before the age of 40.

How does the body know when to start ramping things down?
The menopause is programmed into female biology. It begins when the ovaries have too few eggs to keep powering the ovulation cycle. From childhood, the ovaries have thousands of eggs (200,000, say, but the number varies widely). These cells are constantly moving along a fertility conveyor belt, taking months to grow from primitive follicle to the mature egg which is released during ovulation. The process operates in a knock-out pyramid, with most eggs dying off along the way and only about 400 ever graduating to ovulation.

The primordial follicles activate in clusters that grow and compete, with one egg (normally just one) winning out each month. But as women approach the menopause, the remaining follicles become more sparsely spaced. Beyond some critical threshold, they are no longer packed densely enough to exchange the chemical signals with their neighbours that allow them to activate in clusters. So even though eggs remain, they are dormant.

“It’s almost like they’re losing their friends,” says Prof Evelyn Telfer, of the University of Edinburgh. “When the woman gets older and when there’s a very low number they just don’t activate.”

The follicles release oestrogen as they grow. So when they stop maturing, there is a steep drop in the levels of the hormone being produced, and that’s what leads to menopausal symptoms.

How long does the typical menopause last?
Symptoms usually start a few months or years before a woman’s periods stop – a phase known as the perimenopause – and on average last about four years from the last period. However, around one in 10 women experience symptoms for up to 12 years.

What are the symptoms?
The first indication of the menopause is a change in the normal pattern of a woman’s periods – they may become either unusually light or heavy and could arrive with shorter breaks or be absent for months at a time.

Hot flushes are the most striking symptom, although they don’t affect everyone. About 20% of women report having none at all, about 80% have some and about 25% have hot flushes that are problematic. They normally involve a rush of heat over the upper body and face, sweating and possibly a reddened blotchy appearance. Night sweats can disturb sleep. Trying to disguise or distract from hot flushes in the workplace as a result of actual or perceived stigma around the menopause can be stressful and affect confidence.
 Illustration: Guardian Design

Other symptoms include vaginal dryness, changes in libido, mood swings, memory problems and higher risk of osteoporosis.

Can a woman still have a baby after menopause?
It is possible, through IVF treatment using either eggs frozen pre-menopause or donor eggs. Biomedical progress might open up other options. Post-menopause, women still have hundreds of follicles left in the ovaries and scientists have demonstrated that it is possible to grow these follicles into mature eggs in the lab.

A Japanese team is using a version of this technique in a clinical trial of an experimental fertility treatment called IV-activation, in which ovarian tissue is extracted, treated in the lab to encourage the follicles to mature and then grafted back into the ovary. They speculate that in the future, post-menopausal women might be able to have babies using such treatment.

Can a woman predict when she’s going to hit the menopause?
The age at which a woman enters menopause is partly inherited. So asking your mother or grandmother is a good place to start. Some clinics offer ultrasound tests aimed at assessing the ovarian reserve. The scans can only see the most mature egg cells – the follicles are too small to spot – and the tests are not very accurate at predicting when the menopause will begin.

Scientists are identifying ever more genes that contribute to the age menopause begins, but since it is a trait that is influenced by a large number of genes, it is not yet possible to get an accurate readout from a genetic test.

In terms of evolution, what’s the point of the menopause?
One of the most compelling evolutionary explanations for menopause is the “reproductive conflict hypothesis”. The idea is that when multiple generations live together in a patrilocal set up (that’s to say, a woman moving in with her husband’s parents), a woman would compete with her mother-in-law for the resources needed for babies and children if their reproductive schedules overlapped.

Research by Prof Virpi Lummaa, of the University of Turku in Finland, using a 200-year dataset on pre-industrial Finns, showed that simultaneous reproduction by daughters-in-law and mothers-in-law was linked to a far worse chance of children surviving.

The daughter-in-law is unrelated to the children of her mother-in-law, so – evolutionarily – has no motivation to contribute to their survival. For the mother-in-law there’s a trade-off as she has 25% of genes in common with her grandchildren. And so if at some point in ancient history a “menopause gene” emerged, it would carry the evolutionary advantage of boosting the chances of survival of grandchildren.

“Our modelling work showed that such costs of two women reproducing simultaneously in the same household were sufficient to generate selection against continued reproduction beyond 51 years,” Lummaa says.

It’s interesting to note that this evolutionary trade-off only happens when males continue to live with their families as adults. Lummaa’s team studied Asian elephants employed in timber camps in Myanmar and found that calves survived better if their grandmother was nearby. However, Asian elephants do not show a clear-cut menopause and have been observed to reproduce into their late 60s.

A crucial difference could be that elephants live in matriarchal herds, led by a dominant older female. So, thanks, prehistoric patriarchy.

Do other animals have a menopause?
There are a few contenders – guppies gasp on for a few weeks after their last litter, which some have suggested is the fish menopause. But whales are the only real parallel. Killer whales, short-finned pilot whales, belugas and narwhals all live substantial periods beyond their reproductive years.

Do men go through a “manopause”?
Not really. The symptoms of the female menopause are linked to rapid hormonal changes. In men, testosterone peaks at around the age of twenty20 and is on a gentle downward slope thereafter. A typical adult male testosterone concentration range is 10 – -30 nanomoles per litre. Some men suffer from testosterone deficiency as they get older and might notice physical effects including reduced muscle mass, the appearance of “man boobs”, decreased sex drive, problems sleeping and hot flushes. “Once you go to 8eight or 6six ([nanomoles]) that’s when people think about treatment,” said Waljit Dhillo, professor in endocrinology and metabolism at Imperial, said. While we’re on the male menopause, it’s worth mentioning that researchers have also found little supporting evidence for the existence of the midlife crisis.

What treatments are available?
The main one is hormone replacement therapy (HRT). Hot flushes and other symptoms are caused by the loss of oestrogen in the body as the ovaries stop producing it. However, oestrogen causes the womb lining to grow, which raises the risk of endometrial cancer. To protect the lining of the uterus, combined HRT is normally given, which contains progesterone as well. It can be taken in the form of pills, patches, gels or implants.

What are the pros and cons of HRT?
Pros: controls menopause symptoms really effectively.

Cons: increases the chances that a woman will get breast cancer and ovarian cancer. The extent of this cancer risk has been at the heart of the controversy surrounding HRT. A large study by the Institute of Cancer Research in London found that women who took combined HRT for five years were 2.7 times more likely to get breast cancer than those who did not. Other studies have found slightly lower increases in risk. However, a major study last year found that HRT does not shorten lives – so while women on HRT were more likely to develop breast cancer they are not more likely to die at a younger age.

Also, on stopping HRT some but not all women will experience a return of menopause symptoms.

Are there other treatment options?
Some people find alternative therapies such as acupuncture, phytoestrogens or black cohosh helpful, although systematic reviews have not found strong evidence to support these approaches making a measurable difference.

There is some evidence that psychological approaches can help. A team of researchers published a study last year that showed when women were offered cognitive behavioural therapy and support on how to discuss the menopause at work, 82% said the intervention had reduced the impact of their symptoms.

There are also new drugs on the horizon that work in different ways to HRT. One of the most promising is a compound called MLE4901, originally developed by AstraZeneca. It targets a chemical in the brain called neurokinin B, which is known to increase in response to oestrogen deficiency. The idea is that it would control symptoms without affecting hormone levels – and so hopefully sidestepping the downsides of HRT.

A trial, published by a team at Imperial College London, recruited women who were having seven or more hot flushes a day. The drug resulted in a 73% decrease in hot flushes. That trial and one other have prompted interest from big pharma.

Astellas, a Japanese pharmaceutical company, is now running a phase 2 trial. “It works ridiculously well,” says Waljit Dhillo, a professor in endocrinology and metabolism at Imperial, who led the trial. “The patients in our study were saying please can we carry on with the drug.”

So, is there anything to look forward to?
It’s clearly subjective, but many women would view no more periods and not needing to worry about unplanned pregnancies as positives. There is also evidence that women generally feel good post-menopause. One study by Australian scientists, which followed women for 20 years from the early 1990s found that negative mood scores and depressive symptoms decreased significantly as they transitioned from midlife (50–64) to late-life (over 65).

(Source: The Guardian)

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