What Causes Ovarian Cancer?- Hormones Matter

Ovarian cancer is the most difficult to diagnose of all the gynecologic cancers, which are uterine, fallopian, vulva, and cervical. The symptoms of bloating, back or pelvic pain, digestive issues, changes in bowels, urinary frequency, and fatigue are the most commonly reported. Other symptoms include vaginal bleeding or unusual discharge, change in weight, painful intercourse, and menstrual changes. Any one of these can be symptomatic of other diseases or disorders such as Irritable Bowel Syndrome, Gastritis, Back Strain, or Menopause to name a few.

Risk Factors for Ovarian Cancer

Scientists do not know what exactly causes ovarian cancer, but according to the American Cancer Society, there are “some factors that make a woman more likely to develop epithelial ovarian cancer,” which is the most common form of ovarian cancer. The three most prominently researched factors include:

Estrogen exposure – synthetic and endogenous
Genetics
Family history

Ovarian Cancer and the Estrogens

Estradiol is a female hormone that plays an important role in normal sexual and reproductive development. It is one of many estrogenic hormones produced by the ovaries. The ovaries produce most of the estrogenic hormones, though a far lesser amount comes from the adrenal glands. After menopause, the adrenal glands produce the majority of estrogens.

Estradiol and the other endogenous estrogens affect skin, hair, mucus membranes, pelvic muscles, breasts, bones, urinary tract, heart and blood vessels, and the brain. Perhaps more importantly, the estrogens affect mitochondrial energy metabolism in the heart, but also in the brain, and everywhere else as well. In light of that, it is understandable that synthetic estrogens might influence these same systems.

Oral contraceptives. According to the Center for Disease Control and Prevention, “there is no known way to prevent ovarian cancer.” However those who used birth control pills “has consistently been found to be associated with a reduced risk of ovarian cancer….Oral contraceptive formulations with high levels of progestin were associated with a lower risk ….” Various studies have shown a 10-12% decrease after just one year of use and as much as a 50% decrease after five years.

Some research suggests that total duration of exposure to estrogenic hormones, whether endogenously produced or synthetic (and there is some debate about this), decreases a woman’s risk for ovarian cancer. With this line of reasoning, some researchers have argued that the use of oral contraceptives may reduce the risk of ovarian cancer because contraceptives prevent ovulation. The theory is that each time she ovulates the woman is exposed to more hormones. According to researchers at Johns Hopkins “It is hypothesized that the longer a woman is exposed to estrogen, the higher her risk of ovarian cancer…. The longer the woman menstruates, the higher her risk.” This may not be the case for all women, however.

For those who carry the BRCA1 and BRCA2 mutations, oral contraceptives may or may not reduce the risk for ovarian cancer, but pregnancy does. A study published in 2001 stated that “We believe that it is premature to prescribe oral contraceptives for the chemoprevention of ovarian cancer in carriers of a BRCA1 or BRCA2 mutation, particularly in the light of the report of a possible increased risk of breast cancer in such women.” In contrast, a study in May of 2014 the Journal of the National Cancer Institute wrote, “Although we were not able to undertake meta-analyses of the existing data, it is likely that oral contraceptives are associated with ovarian cancer risk reduction. For those who carry the BRCA1 or BRCA2 mutations, oral contraceptives did reduce the risk for ovarian cancer.” More research is required to fully determine if or how oral contraceptives affect the occurrence of ovarian cancer, for those women with or without BRCA1 or BRCA2 mutations.

Other researchers speculate that it is not the estrogens but exposure to androgens that increases risk. Regardless of the mechanisms by which oral contraceptives may or may not confer protection against ovarian cancer, they are not without other risks. When a woman takes birth control pills she is also increasing her risk for breast, cervical, and liver cancer. Therefore, it is imperative that she understand and discuss with her physician these risk factors, as well as her personal and family history.

Since the introduction of oral contraception in the 1960’s there have been many studies on its relationship to various cancers. The studies have been on birth control pills of estrogen only, estrogen-progesterone, and those with androgenic properties (testosterone effects). How much a factor estrogen alone is in causing ovarian cancer requires more research.

I chose to not take birth control pills because I did not believe it was healthy to control when a woman was to have or not have a period. In other words, control her hormones and menstrual cycle. I am the mother of three healthy sons. If I had taken the birth control pills between pregnancies, would I now have ovarian cancer? No one knows for sure. I made my decision many years ago believing it was best for my health so I do not have any regrets.

Hormone Replacement Therapy. For many years women have used Hormone Replacement Therapy (HRT) to help relieve the hot flashes, mood swings, and other symptoms due to menopause. According to a study published in the Lancet in February, 2015, a study of 21,488 postmenopausal women with ovarian cancer, concluded an increase risk from the use of both estrogen-only and progesterone and estrogen combinations of Hormone Replacement Therapy. “Women who had taken HRT for at least 5 years were still at increased risk of ovarian cancer 10 years later.”

An interesting article about HRT and its affects on ovarian and breast cancers, a historical review of HRT, and post oophorectomies written by Chandler Marrs raises the question if HRT is “largely or wholly causal in ovarian cancer.” More research is needed to answer the questions raised by Dr. Marrs.

There are additional factors for the woman and her physician to take into consideration if HRT is right for her. Has she had a hysterectomy? What are her menopausal side effects, and how severely are they affecting her quality of life? Has she had breast cancer, or have a family history? “Based on the WHI (Women’s Health Initiative) study, taking EPT is linked to a higher risk of breast cancer.” It is recommended that a woman be on as low a dose and for as short a period of time as possible to reduce her risk of ovarian cancer. There are also over-the-counter herbs and supplements that might help reduce or eliminate the menopausal side effects.

Once again I chose not to take any HRT for three reasons: one, I did not want to manipulate my hormones; two, I had a family history of breast cancer from one aunt; and three, menopausal symptoms of hot flashes and insomnia were not severe enough for me to take any HRT. I used over the counter meds for the insomnia.

Another theory suggests that tubal ligation or hysterectomies might lower the risk of ovarian cancer. This is based on “some cancer-causing substances may enter the body through the vagina and pass through the uterus and fallopian tubes to the ovaries.” This theory also requires more research.

Finally, there appears to be a link between polycystic ovarian syndrome (PCOS), an imbalance of the female hormones, and ovarian and endometrial cancers. Any personal or familial breast cancer history also puts women at higher risk. More research is required for this complex and familial disease.

Ovarian Cancer and Genetic Risk Factors

Is ovarian cancer caused by some defect in our DNA or genes? Our DNA carries instructions for each cell in our body. Any defect in our genes can cause or lead to any type of cancer. What causes the genes to be defective is not completely known. Most often the body is able to correct any damage to a gene, but due to not fully understood factors sometimes the mutated gene is not reversed. “Usually, it takes multiple mutations over a lifetime to cause cancer” which is why aging is a high risk factor for ovarian cancer.

Lynch Syndrome, an inherited cancer of the digestive tract causes a 12% risk increase for ovarian cancer because of the mutation in DNA repair genes.
BRCA1 and BRCA2 are inherited genes that produce tumor suppressor proteins. If these genes are mutated they increase the risk of developing breast and ovarian cancers. Unfortunately women of Eastern Jewish descent (Ashkenazi) are at greatest risk. Norwegian, Dutch and Icelandic peoples also have a higher incidence of these mutations. BRCA1 and BRCA2 mutations account for about 15% of ovarian cancers overall. BRCA1 and 2 carriers also have a higher concentration of female hormones. Research is examining how estrogen affects the Fallopian tubes where most ovarian cancers begin. Many women with BRCA1 and 2 gene mutations choose to have their breasts and ovaries removed, which is a drastic and difficult decision.

“Most DNA mutations related to ovarian cancer are not inherited but instead occur during a woman’s life….So far, studies haven’t been able to specifically link any single chemical in the environment or in our diets to mutations that cause ovarian cancer. The cause of most acquired mutations remains unknown.”

Genetic testing is recommended. The process will include your family health history and environmental factors as well as the gene test. The information can be valuable for the patient, family members, and future generations. If tested positive, family members have the opportunity to make prophylactic decisions as to their health care options.

I chose to be genetically tested though I did not have any of the ethnic risk factors associated with BRCA1 and BRCA2. I wanted to be sure I had not passed on a mutated gene. I am glad to say that I tested negative.

Family History and Ovarian Cancer

How much of a factor is family history? Any family history of ovarian, breast, or colon cancers might raise a red flag to the physician. How close the relative is to the patient is a question to be considered.

My aunt on my mother’s side had breast cancer and we do not know if she had a mutated gene (other than BRCA) that got passed on to me. My great grandfather had colon cancer but it was decided that he was too far removed from me to be a factor. My mother died from stomach cancer and my uncle who was a habitual smoker died of throat cancer. To sciences present knowledge there is no connection with my ovarian cancer.

Do you know your family history? This knowledge may be important along with the presenting symptoms for your physician in determining a diagnosis. From a small, non-scientific, and anonymous questionnaire of gynecologic survivors, here are some unfortunate and interesting statistics:

Did your physician(s) ask about your family history? Yes from 35 out of 131MD’s
Did your physician(s) ask about your symptoms? Yes from 34 out of 131 MD’s

Only about 25% of the doctors discussed the family history or symptoms. The women mainly saw their family physician or gynecologist for an initial appointment with presenting symptoms. Here are the most common symptoms:

55%–Bloating
42%–Abdominal pain
28%–Digestive problems
28%–Fatigue
20%–Frequent urination
16% –Constipation
13%–Vaginal bleeding
11%–Weight change
11%–Back pain
8%–Painful intercourse
4%–Shortness of breathe
4%–Menstrual issues
2%–Temperature
2%–Overweight

Here are some comments from the women who completed the questionnaire:

“My family doctor only did testing because I demanded it after she sent me home the first time and I still didn’t feel better after 2 months later.” (Diagnosed Stage IIIC)

“Had I not demanded the ultrasound my diagnosis would have been missed….” (Diagnosed Stage IIIC)

“I look back and I do believe I did have subtle symptoms, but my male doctor ignored my complaints….with a family history I feel I should be been looked at more closely.” (Diagnosed IIC)

“I found that the best doctor is the one that listens.” (Diagnosed Stage IC)

The following patient had a hysterectomy 14 years prior to diagnosis, removing only her uterus. “…I was on Estrogen only for all those years.” (Diagnosed IIIC)

It is important to recognize that there are many possible risk factors that have not been substantiated in various case studies. Such factors are infertility drugs, talcum powder, smoking, aspirin and NSAIDS, and dietary considerations. According to the National Cancer Institute (May 15, 2015) more research is needed for these possible contributors.

Early Detection Is Key

In closing, early detection & diagnosis are a woman’s best opportunity to treat gynecologic cancers. From Johns Hopkins, “…the combination of bloating, increased abdominal size, and urinary problems was found in 43% of women with ovarian cancer…. Women presenting with non-specific symptoms, particularly if severe intensity or rapid onset, should be thoroughly evaluated for the possibility that the symptoms are due to an ovarian mass.”

When we experience any of the symptoms of ovarian cancer for two weeks without any relief despite medications, women need to seek out medical attention quickly. We must advocate for ourselves that the physician listen to our symptoms, discuss our family history, and insist that an abdominal ultrasound and CA125 be parts of the diagnostic tools.

About the author: Karen Ingalls is the author of the award-winning book, Outshine: An Ovarian Cancer Memoir, which discusses the symptoms, risk factors, and statistics of this lesser known disease; shares her journey; and how she used traditional medicine and complementary therapies together. She writes how “the beauty of the soul, the real me and the real you, outshines the effects of cancer, chemotherapy, and radiation.”

Corrections. On June 26, the word ‘increases’ was changed to ‘decreases’ in the following sentence: ‘…whether endogenously produced or synthetic (and there is some debate about this), decreases a woman’s risk for ovarian cancer.’ The 2014 study was added to the discussion of BRCA mutations and oral contraceptives.