February is Ovarian Cancer awareness month. This is a very tricky cancer to diagnose and treat. There are no screening tests available. Early symptoms can be very vague and are often dismissed. Most women are diagnosed at a late stage and this contributes to poor survival rates. Research towards a better understanding of the risk factors and better diagnostic strategies is essential. In the meantime, this is what we know and what we can do:
Do not dismiss vague symptoms – and talk to the doctor who takes them seriously
There is no early detection test for ovarian cancer, so being aware of the symptoms is crucially important. Here are the common ones:
- Increased abdominal size or persistent abdominal bloating
- Abdominal or pelvic pain
- Feeling full after eating a small amount, indigestion or nausea
- Needing to urinate often or urgently
- Changes in bowel habits
- Unexplained weight gain or loss
- Excessive fatigue
- Lower back pain
- Bleeding after menopause or in-between periods
- Pain during or after sex
Especially early on, symptoms can be vague. They can also be caused by other, less serious and more common medical conditions. But, you know your body better than anyone else. Always listen to what your body is saying and trust your instincts. Get checked out. If you are not comfortable with your doctor’s diagnosis or are still concerned about unexplained persistent symptoms, seek a second opinion.
Be aware of the risk factors – and change what you can (there are things you CAN do!)
- Increasing age – ovarian cancer is more common after menopause
- Genetics
- BRCA1 and BRCA2 genes
- Lynch Syndrome – a genetic condition that affects the function of genes that are necessary for DNA repair
- Strong family history of ovarian, breast, endometrial or colorectal cancer
- History of breast cancer or diabetes
- Endometriosis
- Hormone Replacement Therapy (HRT)
- Not having had children
- Being overweight
- Smoking
If you look at these risk factors you will notice that the only 2 that you can really influence are weight and smoking. These risk factors are connected with many other chronic illnesses and cancers, so it is not surprising that they are connected to ovarian cancer as well. However, at the first sight, it looks like we cannot do much about other risk factors. Yes, I know HRT is on the list but, for some women, HRT is not a question of choice. It can be something that is absolutely essential for the maintenance of the quality of life.
I do believe that there is something else that we can and should do. I will explain, but for it to make sense I first have to give you a little bit of science.
Let’s go back to those risk factors. The genes and genetic syndrome that I have listed are all connected to DNA repair and there is not a huge amount we can do about that (yet). But, let’s look at the next lot of risk factors – HRT, endometriosis, age, not having had children and being overweight. In one way or another, all of these are connected to increased exposure to estrogen. Why does this matter?
We can shift estrogen metabolism and make it safer
Most estrogen is metabolised in the liver by CYP enzymes. Here is a simple version of what happens: CYP-1A1 is the ‘good guy’ – it turns estrogen into 2-hydroxy-estrone (2-OHE) which is a benign metabolite. CYP-1B1 is the ‘bad guy’- it turns estrogen into 4-hydroxy-estrone (4-OHE) which causes DNA damage implicated in cancer initiation. We do have a mechanism that can help clear this dangerous metabolite. It involves another enzyme called COMT.
Here is how all of this is relevant to ovarian cancer. Women who have unbalanced estrogen metabolism, with a high level of 4-OHE, are more likely to develop ovarian and breast cancer. In fact, tissue samples from ovarian and breast cancers have been found to contain high concentrations of 4-OHE.
What makes you more likely to have high levels of 4-OHE? Some of it comes down to genetics. Women with genetic variants that make CYP-1B1 work very fast and COMT1 work slowly land themselves in a position where they accumulate lots of 4-OHE that cannot be cleared by their slow COMT.
The important thing is, we can test for both estrogen metabolites and gene variants that make it more likely for a woman to have an unbalanced estrogen metabolism. We can also intervene to shift biochemistry towards the production of safer metabolites. A diet high in cruciferous vegetables, DIM and sulphorafane supplements support estrogen detoxification pathways in the liver. COMT needs excellent Vit B levels, efficient methylation pathways and lots of magnesium to function optimally. Caffeine and EGCG (found in green tea) both inhibit COMT.
We can get our microbiome to work for us
We have known for some time that the microbiome regulates systemic estrogen levels through the action of microbial B-glucuronidase which converts estrogen metabolites back into their active form. Active estrogen in the gut can then be reabsorbed back into the bloodstream. When there is dysbiosis, microbial B-glucuronidase is more abundant, leading to the higher reabsorption of active estrogen from the gut. I measure microbial B-glucuronidase levels in my patients and often find it elevated in patients who have symptoms consistent with higher estrogen activity.
Close involvement of the microbiome in estrogen-related effects has been confirmed by a recent study that identified a compound (Quinic acid) produced by the microbiome, that stimulates the growth of endometriosis lesions. I am certain that we will soon be identifying other post-biotics (compounds produced by the microbiome) that have a wide range of influences. That is why I see supporting diverse and healthy microbiomes as one of the cornerstone interventions.
Supporting healthy estrogen metabolism can also help reduce the risk of breast and endometrial cancer, both of which can be estrogen-driven.
I have given you a lot of genetics and biochemistry in this post. But, the take-home message is super simple.
To reduce the risk of ovarian cancer:
- Be aware of the symptoms
- Listen to your body and be persistent in seeking help if you feel that something is not right
- Optimise your estrogen metabolism
- Ensure that your microbiome can support the effective elimination of estrogen metabolites
- Share the knowledge, and talk to your friends. Maybe you will save a life.
