Metformin for ovarian cancer

Could A Diabetes Medication Prevent Ovarian Cancer?

A laboratory study published in Clinical Cancer Research offers a new hypothesis about how ovarian cancer forms and suggests how an insulin resistance/diabetes medicine may prevent it.

Ovarian Cancer Facts.

  • Ovarian cancer is the fifth most common cancer in women, and
  • Ovarian cancer is a leading cause of cancer death in women
  • The five-year survival rate for ovarian cancer is 45 percent.
  • Women who have a family history of ovarian cancer or a mutation of the BRCA gene are at greatest risk of the disease.
  • There is no reliable screening test to catch this cancer early
  • The only options for prevention are birth control pills, which reduce the risk of ovarian cancer by half, or removing the ovaries and fallopian tubes.
  • Common symptoms are bloating, abdominal pain, gastrointestinal upset and weight loss/gain.

For more information on Ovarian Cancer please click the link to my article Let’s Talk About Ovarian Cancer

The New Research.

The study is the first to show that the natural stiffening of the ovaries called “fibrosis” occurs with age. It also suggests that the diabetes drug metformin may be able to halt this process.

This is an interesting hypothesis, which then begs many questions. It also then leads to looking at other supplements and medications that help with insulin resistance and regulation.

So, should we just be looking at the medications, or looking at the underlying cause of the issue, which seems to be insulin resistance?

After all, insulin resistance is a big driver on inflammation and disease processes in the body. But let’s look at Fibrosis first.

What is Fibrosis?

Fibrosis happens when body tissues are repeatedly injured and inflamed, leaving behind hard collagen fibres that pile up over time, like a scar on the skin. Research has shown that cancer cells tend to like growing in these fibrotic tissues. Fibrosis is also a normal part of aging and usually appears around the menopausal stage of life.

The Findings of The Study

The first part of the investigation was for the team to find out what was causing the fibrosis of the ovaries. They thought the answer might lie in ovulation. Every time an ovary releases an egg it becomes inflamed, creating a monthly cycle of wound and repair.

During the study the research was surprised to find an ovary from a 69-year-old woman that had no fibrosis. The woman’s medical records showed she had been taking metformin, a drug for Type 2 diabetes. What was interesting is that a Taiwanese study had previously noted an 82% reduction of ovarian cancer rates among Type 2 diabetes patients taking metformin.

The research team performed a series of experiments to investigate the links between ovarian fibrosis, aging and metformin.

The first part of the research, the team used mice studies and used a drug to prevent mice from ovulating. They noticed that the treated mice did not develop fibrosis with age, which then suggested that ovulation might be linked to the development of fibrosis. The team also noted that more detailed studies are needed to confirm these findings.

The second part of the research was to examine the ovaries that had been removed from women of all ages. What they found was that the ovaries of most of the postmenopausal women had fibrosis. But, they also notices the when the ovaries of postmenopausal women where were taking metformin were examined, none of these showed any evidence of fibrosis.

With these new finding the team set about looking at the rationale of targeting ovarian fibrosis as new option to reduce the risk of ovarian cancer. They also added in the rationale for the use of metformin to prevent ovarian cancer, based on these findings as well. The team are currently doing more research into learning how fibrosis develops in the ovaries and how metformin may be stopping this from happening.

These findings will need to be confirmed with more studies before clinical trails can take place. But, this could lead to a non-invasive test to measure fibrosis and help with early detection of ovarian cancer.

The team are hoping that metformin may prove to be an effective preventative treatment for younger women who are at high risk of ovarian cancer, but who can’t remove their ovaries because they still want to have children.

Added thoughts

While any research into ovarian cancer is welcomed, as mentioned previously, if metformin is helping with prevention of fibrosis, then surely we need to be looking insulin resistance as being a major cause of this?

It also begs the question, do other natural insulin regulators such as inositol do the same thing and would be better to use because Metformin does have a high side effect profile?

Insulin Resistance and Disease

We do know that insulin is a big driver of inflammation and disease states in the body. Insulin resistance is the name given to when cells of the body don’t respond properly to the hormone insulin.

Insulin resistance is the driving factor that leads to many disease states and health conditions such as:

  • Obesity and being overweight
  • Metabolic Syndrome
  • Type 2 diabetes,
  • Gestational diabetes
  • Pre-diabetes.
  • Stroke
  • Cardiovascular disease
  • Stroke
  • PCOS
  • Reproductive conditions
  • Infertility

Insulin Resistance is linked to certain cancers

Meanwhile, insulin resistance and metabolic syndrome are also linked with higher risk for cancers of the bladder, breast, colon, cervix, pancreas, prostate and uterus. 

The connection: High insulin levels early in insulin resistance seem to fuel the growth of tumours and to suppress the body’s ability to protect itself by killing off malignant cells.

Insulin resistance is closely associated with obesity; however, it is possible to be insulin resistant without being overweight or obese. We see this in women who have PCOS and who are not overweight, or obese.

Modern research has shown that insulin resistance can be combatted by treatment methods that reduce how much insulin the body is producing. Reducing insulin resistance can be achieved by following a grain free, low refined food diet.

Final note

If found to metformin to helping with fibrosis and this then leads to ovarian cancer, surely we need to look at what the root cause it. As mentioned above, one could assume it would have to be insulin resistance and we already know that insulin resistance is a driver of certain cancers and tumours.

Surely then, it would make sense to educate women, especially those with family history of ovarian cancer, about the importance of low GI diets and maintaining optimum health and optimum weight etc, in the prevention of not only ovarian cancer, but other disease states that affect women as well.

There are also valid alternatives to using Metformin, which has a very high side effect profile and has some long-term health consequences. There are valid alternatives such as using inositol, which has lots of research behind it and has been compared to Metformin in several research studies. Something to think about and I always like to give people something to think about important issues such as this. Just remember that you heard it here first.

 

Journal References:

  1. Curtis W. McCloskey, David P. Cook, Brendan S. Kelly, Feryel Azzi, Christian H. Allen, Amanda Forsyth6, Jeremy Upham, Katey J. Rayner, Douglas A. Gray, Robert W. Boyd, Sangeeta Murugkar, Bryan Lo, Dominique Trudel, Mary K. Senterman, Barbara C. Vanderhyden. Metformin abrogates age-associated ovarian fibrosisClinical Cancer Research, Oct 9, 2019
  2. Mehri Jamilian; Pegah Farhat; Fatemeh Foroozanfard; Faraneh Afshar Ebrahimi; Esmat Aghadavod; Fereshteh Bahmani; Bita Badehnoosh; Hamidreza Jamilian; Zatollah Asemi. Comparison of Myo-inositol and Metformin on Clinical, Metabolic and Genetic Parameters in Polycystic Ovary Syndrome. A Randomized Controlled Clinical TrialClin Endocrinol. 2017;87(2):194-200.
  3. Fruzzetti F, Perini D, Russo M, et al. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017;33:39–42.
  4. Chiu TT, Rogers MS, Law EL, et al. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod. 2002;17:1591–1596.
  5. Artini PG, Di Berardino OM, Papini F, et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013;29:375–379.
  6. Zacche MM, Caputo L, Filippis S, et al. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25:508–513.
  7. Costantino D, Minozzi G, Minozzi E, et al. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13:105–110.
  8. Orgel: The Links Between Insulin Resistance, Diabetes, and Cancer. Curr Diab Rep. 2013 Apr; 13(2): 213–222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595327/
  9. Dijiogue S: Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer February 1, 2013 20 R1-R17. http://erc.endocrinology-journals.org/content/20/1/R1.full
  10. Orgel: The Links Between Insulin Resistance, Diabetes, and Cancer. Curr Diab Rep. 2013 Apr; 13(2): 213–222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595327/

 

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Let’s Talk About Ovarian Cancer

Ovarian cancer often has no symptoms in the early stages. Later stages are associated with symptoms, but they can be non-specific, such as loss of appetite and weight loss.

Ovarian cancer often goes undetected until it has spread within the pelvis and stomach. At this late stage, ovarian cancer is more difficult to treat and can be fatal. This is why early intervention is something I am very big on and why we all need to not put things off when they present themselves.

Ovarian cancer is the 9th most common cancer diagnosed in Australian women.

Ovarian cancer is the 6th most common cause of cancer death in Australian women.

The present life expectancy of Australian women is 84 years. One in 77 women will be diagnosed with ovarian cancer before the age of 85.The risk of ovarian cancer increases with age. About 83% of all new cases of ovarian cancer diagnosed in 2005 were in women 50 years or older. The median age of first diagnosis is 64 years.

The five year survival rate for ovarian cancer is 45%.

Symptoms
Most women with ovarian cancer experience at least one symptom of the disease in the year prior to their diagnosis. The following can all be signs of ovarian cancer:

  • Abdominal bloating
  • Abdominal or back pain
  • Appetite loss or feeling full quickly
  • Changes in bowel habit
  • Urinary frequency or incontinence
  • Pain during intercourse
  • Menstrual irregularities
  • Unexplained weight loss or gain
  • Indigestion or heartburn

Why is bloating a sign of ovarian cancer?

Ascites (a build-up of fluid in the abdomen and a sign of advanced ovarian cancer) is probably the major cause of bloating in women with ovarian cancer. Therefore, waiting for bloating as a key ‘sign’ is too late and we want to encourage all women to ‘know your normal’ and if this changes, to seek medical help. This is why any changes in the body need to be looked into. Many may think that they are reacting to foods, or they have a gut issue etc, but it may actually be the signs of ovarian cancer. This is why proper investigations and proper differential diagnosis by a trained professional is so important.

Family history
While having a family history of ovarian cancer increases a woman’s risk of developing ovarian cancer, 90-95 per cent of all ovarian cancers occur in women who do not have a family history.

Key factors associated with increased risk include:

  • Multiple relatives on the same side of the family affected by breast cancer (male or female) or ovarian cancer
  • Younger age at cancer diagnosis in relatives
  • Relatives affected by both breast and ovarian cancer
  • Relatives affected with bilateral breast cancer
  • An increase in age
  • Inheriting a faulty gene (called a gene mutation) that increases the risk of ovarian cancer
  • Being Caucasian (white) and living in a Western country with a high standard of living having few or no full-term pregnancies
  • Starting your menstrual cycle early (before the age of 12) and beginning menopause after the age of 50
  • Taking hormone therapy (HT) after menopause. Some studies suggest this may increase your risk of developing ovarian cancer, but others don’t make this connection
  • Never having taken the contraceptive pill – the pill has been found to reduce the risk of cancer of the ovaries and uterus
  • Only five to 10 per cent of all ovarian cancers are associated with a family history. The risk of developing ovarian cancer increases with the number of affected first degree relatives (parents, siblings, children)
  • Ashkenazi Jewish ancestry.

Diagnosis for Ovarian Cancer

There is currently no evidence to support the use of any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or a combination of tests, to screen for ovarian cancer. The only way to properly screen for it is through histology done at the time of laparoscopy.

While CA126 can be a diagnostic, it really has limited value and I have to let people know that it isn’t the best diagnostic at all. 50% of ovarian cancers will actually have a normal CA125 reading.

The cancer council’s guidelines are quite clear about this after numerous research studies show that CA125 has limited diagnostic value for Ovarian cancer. If markers and symptoms are suggestive of Ovarian Cancer, the only true diagnostic is Laparoscopy with histology to really get an accurate diagnosis.

Treatment for Ovarian Cancer

At such an advanced stage, the cancer is more difficult to cure. As ovarian cancer advances, cells from the original tumor can spread (metastasize) throughout the pelvic and abdominal regions and travel to other parts of the body. Cancer cells are carried through the body through lymph vessels and the bloodstream.

If a woman is suspected of having ovarian cancer, she should be referred to a gynaecological oncologist. Research shows survival for women with ovarian cancer is improved when their surgical care is directed by a gynaecological oncologist.

Treatment for ovarian cancer usually involves surgery and chemotherapy. It may also include radiotherapy.

Usually your healthcare practitioner, or GP, will generally arrange for initial tests and looks after your general health as well as coordinating with your specialists. Depending on your treatment you will be seen by several specialists, such as: medical oncologist, radiation oncologist, radiologist, gynaecological pathologist, cancer nurses and other health professionals such as a dietitian, physiotherapist, social worker and a counsellor.

With any condition that affects the body, we often get early warning signs and this is why early intervention and making sure you are investigated and management properly is so important.

Regards

Andrew Orr

-Women’s and Men’s Health crusader

-No Stone Left Unturned

-The Women’s Health Experts

01 Dr Andrew Orr