Genetic causes of early menopause
What determines the age when menopause begins? It’s known that lifestyle factors, especially smoking, can accelerate the onset of menopause. However, early menopause is often caused by factors beyond our control. Today, we’ll explore the role of genetics in the age of menopause onset. Which genes should be tested, and what insights can this provide us with?
Menopause is like a clock that typically chimes around the age of 50, signaling the end of our reproductive years. But sometimes, that chime arrives earlier – before 45, it’s called early menopause, and before 40, it’s known as premature menopause or premature ovarian insufficiency.
So, why does it matter to know when your personal menopause clock will strike?
Well, one big reason is to help you predict your natural fertility window. In today’s world, life often leads us to delay having children for various reasons. If your menopause starts early, it can throw a curveball into your family planning. But there’s more to it; early menopause has some health implications too. It’s been linked to an increased risk of conditions like diabetes, osteoporosis, and even dementia. We all know that prevention is better than cure, so wouldn’t it be great to have a heads-up on whether your biological clock is ‘ticking’ a bit faster than expected?”
Tests that tell you when menopause is around the corner
You might have heard of hormone tests that can signal a low ovarian reserve. They measure the level of your female hormones in the blood or in the urine. There is just one problem with them: but by the time they pick it up, the decline has often already started. There’s no crystal ball for predicting exactly when this decline kicks in. That’s why scientists are turning to genetic research. Can we use genetic changes as a clue to spot early menopause on the horizon?
Believe it or not, your genes have a say in when menopause comes knocking. It’s a highly heritable condition, meaning it runs in families. Genetic variants contribute to around 50% of the variation in the age at which menopause occurs.
In 2021, a team of international scientists delved into this genetic puzzle. They analyzed data from 200,000 women of European descent and uncovered a whopping 290 gene variants that influence the timing of menopause. What’s interesting is that many of these genes are linked to DNA repair processes.
In simple terms, if these genetic systems don’t work as they should, it can lead to cell damage, cell death, and even speed up the aging process. It’s like our genes have a role in accelerated aging of the reproductive system and the whole body.
Can genes predict the exact age of menopause?
The short answer is no, a single gene that can tell you precisely when menopause will hit doesn’t exist. Even if you have ‘unfavorable’ gene variants, you could still experience menopause at the average age, which was shown in a recent study.
Why? Well, the process of menopause onset is quite complex, influenced by multiple genes working together. Scientists are currently working on creating a panel of genetic tests that could estimate your risk of early menopause. The score on this genetic risk scale is currently more telling than the well-known factor of smoking versus not smoking, which was previously considered one of the best predictors of early menopause.
However, it’s worth noting that such a commercial test panel isn’t available just yet. But progress is being made in this field. For example, among women carrying rare variants of two genes, TWNK and SOHLH2, menopause tends to arrive 3-5 years earlier.
So, if there isn’t a single ‘early menopause’ gene, why bother with genetic testing? To be aware of possible health problems and prevent them!
Early Menopause and its Connection to Health Issues
The researchers also delved into the health implications of experiencing menopause earlier or later. Their genetic analysis revealed that earlier menopause can increase the risk of type 2 diabetes, impact bone health negatively, and raise the chances of fractures. However, there’s a silver lining – earlier menopause seems to decrease the risk of certain hormone-sensitive cancers, like ovarian and breast cancer.
Dr. Katherine Ruth from the University of Exeter, one of the study’s co-authors, shed light on this finding: ‘We found that earlier menopause was causally associated with a lower risk of hormone-sensitive cancers. We believe this is likely due to a shorter lifetime exposure to high levels of sex hormones, which are at their peak while a woman is still menstruating.’
So, while there isn’t a magical ‘menopause date’ gene, there are genes that play a role in how our cells function. When these genes misbehave, it can increase the likelihood of certain health issues and potentially push menopause to come knocking sooner.
So, imagine you can’t predict the exact date on the calendar when menopause will show up, but you can get some valuable insights from your genetic makeup. These insights help you lower the odds of health problems and empower you to make smart choices for your well-being.
Which Genes Can Predict Early Menopause and Manage Individual Risks?
Among hundreds of genes associated with early menopause, we’ve singled out five that hold significant importance for understanding not only the speed of your biological clock but also for guiding your everyday choices:
F5 (Leiden Mutation) Gene: If you carry a polymorphism in this gene, early menopause is more likely, and if you smoke, the risk increases. Moreover, this gene mutation significantly elevates the risk of blood clots, especially when using hormonal therapy or birth control pills. A potential solution is opting for transdermal treatments like patches, which don’t increase clot risk.
APOE Gene: APOE is a versatile gene that influences Alzheimer’s risk, menopause timing, and susceptibility to fatty liver disease. The APOE4 allele may lead to earlier menopause and it is the greatest risk factor for dementia. Conversely, the APOE2 allele offers a longer life, a longer reproductive window, and protection from Alzheimer’s, but elevated fatty liver risk. Preventive strategies include lifestyle choices, like avoiding smoking, alkohol and certain diet type. Also, gene therapy trials for APOE4-carriers are ongoing.
CHEK1 and CHEK2 Genes: Polymorphisms in these genes can affect the age of menopause onset and reproductive lifespan. Which is also important, mutations in these genes significantly increase the risk of breast and ovarian cancer, making regular check-ups with your doctor vital for preventive care.
CYP1B1 Gene: Mutations in this gene can influence environmental toxin sensitivity and increase the risk of early menopause. Avoiding smoking is crucial, as the gene plays a role in detoxifying toxins like cigarette smoke components.
While genetics can’t offer an exact calendar date for menopause, understanding your genetic makeup can provide valuable insights to help you make informed decisions and lower the risk of health issues. By exploring these genetic factors and taking proactive measures, you can empower yourself to navigate the unique journey of menopause with confidence and resilience.
