Uterine Cancer and Abnormal Vaginal Bleeding

Abnormal Vaginal Bleeding

When there is abnormal vaginal bleeding, it is vitally important that this be discussed with your doctor and the cause looked into.

There are many possible reasons, some more serious than others. You can’t tell what the cause is just by symptoms alone.

Two of the possible causes are endometrial hyperplasia and endometrial cancer – cancer of the uterus. Endometrial hyperplasia can progress over time to be endometrial cancer. At the point in time when the abnormal bleeding starts, you don’t know which it is.

One of the risk factors for these two conditions is obesity. Sometimes abnormal vaginal bleeding first shows up when the medication metformin is started. Metformin is not the cause of the abnormality in the uterus, it is just triggering some shedding of the already abnormal lining of the uterus. More on that below.

First, some basic information to understand this condition. Here is a link to a patient education page published by the American College of Obstetricians and Gynecologists:

“Endometrial Hyperplasia”

or this page LINK

Researchers are studying the possible benefit of metformin as one part of an approach to the prevention or treatment of both endometrial hyperplasia and endometrial cancer.

For example, the major cancer centre MD Anderson Cancer Center is currently studying this. From their web page:

“Project 1: Metformin for the Chemoprevention of Endometrial Cancer in Obese, Insulin-Resistant Women
Obese women clearly are at increased risk for developing endometrial cancer. Numerous epidemiologic studies have demonstrated that obesity is strongly associated with an increased risk of endometrial cancer. While an average woman has a 3% lifetime risk of endometrial cancer, obese women have a 9-10% lifetime risk of endometrial cancer. In a review of diet and cancer by the American Institute for Cancer Research and World Cancer Research Fund (WCRF), authors stated that the evidence relating body mass index and cancer is strongest for endometrial cancer. While excessive production of extragonadal estrogens (estrone) in the adipose tissue of obese women is presumed to be the major contributor to the risk of endometrial cancer, increased serum estrogen levels alone are unlikely to fully account for this effect.
Studies by our group and others suggest that insulin resistance associated with obesity contributes to the increased risk of endometrial cancer. In addition, data from our previous funding period suggest that other mechanisms are involved in activating pro-proliferative signaling pathways in the obese endometrium.

For the current studies, our central hypothesis is that metformin can decrease endometrial hyperproliferation and can act as a chemopreventive agent in insulin-resistant obese women.”

http://www.mdanderson.org/education-and-research/research-at-md-anderson/early-detection-and-treatment/research-programs/spores/uterine-cancer-spore/research/index.html

The story of one woman’s experience related to this was recently published in the medical journal “Annals of Pharmacotherapy”

http://aop.sagepub.com/content/47/11/1581.abstract

A 57-year-old woman was started on metformin for pre-diabetes and metabolic syndrome.

Abnormal Vaginal Bleeding Following Pharmacist Prescribing of Metformin Leads to the Detection of Complex Endometrial Hyperplasia

“The pharmacist prescribed metformin 500 mg twice daily for prediabetes and metabolic syndrome, resulting in vaginal bleeding 1 week following initiation of therapy. Bleeding stopped following discontinuation of metformin, and recurred on retrial. The symptoms were dose dependent as bleeding did not occur at a dose of 500 mg once daily, but recurred at a total dose of 1000 mg/d.”

When she received proper investigation, it was discovered that she had endometrial hyperplasia.

The current understanding of this phenomenon is that the metformin actually promotes a (somewhat) more healthy endometrial (uterine) lining. With this improvement, the thickened abnormal lining at least partially is shed, showing up as vaginal bleeding. The higher dose was more helpful to the health of the uterine lining than the lower dose, so the bleeding appeared at the higher dose.

In this case, the woman had an unknown (“silent”) serious medical condition – endometrial hyperplasia – which could have progressed to endometrial cancer without first there being any warning bleeding to call attention to the problem.  In fact, until she was investigated, it would have been an open question as to whether uterine cancer was already present.

When abnormal vaginal bleeding, or a change in the usual menstrual pattern, appears in association with metformin use and/or changes in metformin dose, this needs prompt medical attention. Metformin has no means to cause abnormal vaginal/menstrual bleeding directly. It can only do so when there is an underlying disease or condition that affects the lining layer of the uterus.

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