Is menopause hereditary? The genetic influence explained

You might’ve inherited your mother’s eyes or your father’s sense of humour, but when it comes to the menopausal journey, can we predict its path by looking at our family tree? To what degree is menopause hereditary?

While every woman’s experience is as distinctive as her fingerprint, our genetic blueprint carries hints about this transformative phase of life. How much do genes influence the onset and symptoms of menopause? Let’s delve into the science to unravel the connections.

Your genes have a powerful effect in determining when you’ll experience menopause

Many genetic and environmental factors affect the timing of menopause.

Some of these are lifestyle choices (smoking brings menopause forward by 18 months on average, as does a diet rich in refined carbs like rice and pasta, while a diet high in oily fish can delay it by three and a half years). There are also environmental factors (not finishing high school, having an income of less than $20,000, or experiencing childhood poverty are all associated with earlier menopause). However, as we’ll see, even these can have a genetic component.

Your family history is the best predictor of age at menopause

A woman whose mother, sister, aunt or grandmother experienced menopause before age 46 is six times more likely to have early menopause herself. If more than one female relative had early menopause, that risk doubles to twelve times. The age at which your mother underwent menopause is probably the best guide to when you will.

Genetics plays a critical role in this similarity in age of menopause within families. Let’s delve deeper into the specifics.

The genetics of age at menopause

Genetic studies have shown that at least 290 genes are involved in deciding when you’ll experience menopause. It’s thought that between them, they account for about half of the variation in age at natural menopause. These include genes involved in repairing damaged DNA and producing sex hormones like estrogen and progesterone.

Some genes have minor effects in deciding when you’ll reach menopause, but others are much more powerful

The vital importance of DNA repair

DNA damage is a critical factor in ageing. It leads to many of the signs, symptoms and diseases associated with ageing, so our body’s DNA repair mechanisms are vital.

Imagine your DNA as a vast library of books. Over time, some pages get torn or smudged. Our body has its own librarians – genes like BRCA2 and CHEK2 – which help repair or replace these damaged pages. But what if the librarians are a bit forgetful?

Menopause comes along when your ovaries have run out of viable eggs, and damage to their DNA is one reason why their numbers diminish. If their DNA can’t be repaired, the eggs self-destruct.

It’s no surprise that faulty DNA repair and maintenance genes are linked to premature menopause. Some scientists believe that menopause at an early age may be linked to more rapid ageing of the body as a whole rather than just the ovaries. It’s a sad fact that women who experience premature menopause have a slightly shorter average lifespan.

Two genes involved in repairing damaged DNA are BRCA2 and CHEK2. Genetic variants of BRCA2 and CHEK2 are associated with an increased risk of breast cancer, and other hormone-sensitive cancers (including ovarian and uterine). Variants of BRCA2 are also associated with menopause one and a half years earlier. At the same time, those of CHEK2 can bring menopause forward by more than two and a half years. That’s because the proteins produced by these ‘faulty’ genes are less effective at repairing damaged DNA.

Menopause timing is linked to weight

Around 10% of the genes associated with the timing of menopause also affect our weight.

Carrying excess weight delays menopause by, on average, about six months. Some of that delay may be due to genes influencing both weight and age at menopause. However, fat tissue also produces oestrogen, and that’s also thought to be a factor in delaying menopause in women with a higher body mass index.

While our maternal lineage provides several clues, our paternal side remains intriguingly enigmatic.

Genetic effects from our fathers’ side remain mysterious

Women inherit a copy of every gene from each parent, so while we’re used to looking at mothers to predict what menopause will be like, it’s just as valid to ask our father’s mother and female relatives. This is an aspect that’s far less well-understood. In large part, that’s because the research just hasn’t been done. It’s also because it’s usually much easier to ask your mother what her menopause was like than your mother-in-law!

Having seen the powerful effect of genetic variance on menopause timing, let’s now ask if our genes also dictate how intensely we experience menopausal symptoms?

Do genetic factors affect the severity of menopausal symptoms?

We know much less about this. We do know that certain gene variants (of the neurokinin 3 receptor) are associated with worse hot flashes and night sweats in women of European ancestry. These genes are rare in East Asia and are not linked to hot flashes in those with African ancestry. This suggests you can’t assume genetic factors significant in one racial/ethnic group will be equally important in others. 

The gene sits on chromosome 4, so you’ll get one copy from your mum and one from your dad. Again, this means you need to look at your mum and your dad’s mum for an idea of how likely you are to suffer from hot flashes. Bear in mind, however, that 8 in 10 women experience hot flashes, and most rate them as moderate to severe. Any influence from your genes is likely to be hard to notice.

Medicines like fezolinetant (Veozah®), which block the neurokinin 3 receptor, are effective at treating hot flashes and night sweats.    

There’s also a genetic link between depression and other menopause symptoms, so you might inherit an increased susceptibility to depression around menopause. Around half of women experience perimenopausal depression.

Other than these, there’s little research exploring how our genes influence menopausal symptoms.

Beyond symptom intensity, our lifestyle choices, which we typically view as personal decisions, might also have genetic underpinnings. Let’s explore this further.

Lifestyle factors have genetic aspects too

As we mentioned earlier, lifestyle choices have a profound effect on when we experience menopause, and that may feel like a different realm from the genetic factors we’ve been discussing. However, delve more deeply, and it becomes fiendishly complicated. 

Each daily cigarette you smoke brings menopause forward by about two and a half weeks. That’s around a year for a pack-a-day smoker. On average, smokers experience menopause 18 months earlier than non-smokers. Lifestyle choices, right?

You may not know that your genetic makeup helps determine whether and how many cigarettes you smoke. The strongest effect is for the gene that codes for the nicotine receptor. However, before you blame your smoking on your genes, that gene is responsible for only half a percent of the variation in how much someone smokes.

Of course, you inherit these genes from your parents, but a far more powerful influence is their behaviour. If your parents smoke, you’re four times more likely to smoke yourself. Cultural aspects, like where you live and your social groups, also powerfully influence how likely you and your parents are to smoke.

Drinking more than the recommended daily allowance of alcohol can bring menopause forward by a year. Genetic variants are at play here too. Studies have linked half the variation in how much we drink to our genes. Once again, if a parent suffers from alcoholism, we’re four times more likely to have problem drinking.

See how tricky it is to tease genetic and cultural factors and personal choice apart? This complex interplay between genetics and choice also extends to the broader cultural contexts we live in.

Cultural factors play a huge role

Cultural factors can profoundly shape how we experience menopause and confound attempts to tease out the underlying genetics.

Generalising is always wrong (see what I did there?), but cultural attitudes are real and do shape the menopause experience. It is important not to reduce people to stereotypes, but many cultural differences have been observed in how menopause may be experienced. For example, Western cultures often value youthfulness over fertility. In this context, menopause can be seen as the final loss of youth. Arab culture, greatly values fertility, so the passing of the reproductive years is often traumatic for Arab women.

In contrast, Mayan women experience enhanced respect when they reach menopause, which is seen as a marker of experience. They become respected elders, freed from much of the responsibility for household chores. Chinese culture has a similar viewpoint, so many Chinese women see menopause as a time of rebirth.

The bottom line

Genetics undeniably influence when menopause begins, but they’re just one piece of the puzzle when it comes to the severity of symptoms.

Navigating through the interplay of multiple genes as well as environmental and lifestyle factors is like solving a complex mystery. Every woman’s story is unique, influenced not just by her genetic code but also by many external factors.

Our understanding of this genetic tapestry is expanding rapidly thanks to ongoing technological advancements. This now allows researchers to conduct genome-wide association studies to look for links between our genes and many characteristics of our life and health. As research unfolds, it promises to shed more light on the intricate ways our genes intersect with our experiences.

Wondering what other mysteries your genes might hold? Unlock more insights by subscribing to our mailing list and stay ahead in understanding your body’s mysteries. For more insights into all aspects of menopause, grab yourself a copy of The Menopause Handbook.

Further reading

Louwers YV, Visser JA. Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits. Front Genet. 2021;12:676546. doi:10.3389/fgene.2021.676546

Zhao W, Smith JA, Yu M, et al. Genetic variants predictive of reproductive aging are associated with vasomotor symptoms in a multiracial/ethnic cohort. Menopause. 2021;28(8):883. doi:10.1097/GME.0000000000001785

Ruth KS, Day FR, Hussain J, et al. Genetic insights into biological mechanisms governing human ovarian ageing. Nature. 2021;596(7872):393-397. doi:10.1038/s41586-021-03779-7

Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010;42(5):441-447. doi:10.1038/ng.571