Uterine fibroids

Uterine fibroids are a problem for a lot of women, especially after age 30. Fibroids are benign tumors that grow in the muscle cells of the uterus. While estimates vary, at least half of American women who are of reproductive age have fibroids. [ref ]

This article will dig into the causes of fibroids, explain how your genetic variants can add to the susceptibility, and offer solutions that are backed by research.

Uterine fibroids:

Symptoms of fibroids include:

  • painful or heavy periods
  • anemia
  • frequent need to urinate
  • painful sex
  • low back pain

Fibroids can also play a role in infertility for some women. But not all women have symptoms with fibroids – it depends on the location and size.

Fibroids are also known as uterine leiomyoma, which means smooth muscle tumor.

Causes of fibroids

You would think that something that affects more than half of women would be well understood and have good solutions available. Oddly enough, there are still questions surrounding the causes of fibroids, and a lot of the solutions available are either ineffective or come with significant side effects.

Genetics plays a role in the susceptibility to fibroids, but, as you will see,  lifestyle factors are also important. [ref ]

Stem cells and growth

Fibroids are medically classified as benign tumors, which means that they are nearly always non-cancerous growths.

Genetics studies show that a fibroid will arise from one cell that has somewhat unchecked growth. Stem cells are present in the muscle of the uterus, which needs to be able to grow and change both monthly and in pregnancy.  [ref ][ref ]

The stem cells in the uterine muscle are capable of replicating into more muscle tissue – that is their whole purpose. When there is DNA damage in a growth related gene, the stem cell to go on a growth spree and become a fibroid. Additionally, the conditions for growth and proliferation of the cell need to be right (see below). The body’s normal way of dealing with damaged DNA also needs to be overridden. [ref ]

Estrogen, progesterone, and growth

Estrogen and progesterone are involved in the formation and growth of fibroids, which occurs mainly during the reproductive years when estrogen and progesterone levels are high. Fibroids usually decrease in size once a woman reaches menopause.

The cells in a fibroid have increased estrogen and progesterone receptors. Animal studies show that the addition of estrogen alone, or estrogen plus progesterone, can increase the size of fibroids.[ref ]

In the uterus, estrogen upregulates IFG-1 (insulin-like growth factor 1), EGFR, TGF-beta1.  All of these are growth-related molecules. [ref ]

Interleukin-1 is an inflammatory cytokine that can inhibit REST, which is a tumor suppressor. Interleukin-1 is also upregulated in fibroid tissue. [ref ]

Environmental exposure

Adding fuel to the fibroid fire, exposure to endocrine-disrupting chemicals such as BPA and phthalates also increases the risk and growth of fibroids.

BPA is a component of plastics and a known endocrine disruptor, similar in structure to estrogen. A cell study shows that exposure to low levels of BPA increases the proliferation of fibroid cells. [ref ] A study of 495 women who were diagnosed with fibroids found that they had higher concentrations of BPA in them than women without fibroids.[ref ]

2-hydroxy-4-methyoxybenzophenone, a UV filter found in sunscreens, is also linked to an increase in fibroids. [ref ]

Phthalates, which are found in plastics, vinyl, and fragrances, are also endocrine-disrupting chemicals that are linked with an increased risk of fibroids. This was especially true in women who carry the GSTM1 null genotype.[ref ]

In-utero and infant exposures:

Early-onset fibroids are linked with exposure to diethylstilbestrol (DES) in-utero. DES is an estrogen medication that was used from 1940 to 1971 for pregnant women. The daughters of women who took DES were at a higher risk of fibroids and at a younger age.  [ref ]

Infectious agents:

Infection with cytomegalovirus in the uterine tissue is associated with a 6-fold increase in the risk of fibroids. On the other hand, Chlamydia trachomatis decreased the risk of fibroids. [ref ][ref ]


Genetic variants that increase the risk of fibroids:

None of these genetic variants cause fibroids on their own. Instead, they all add to the susceptibility. You will notice that these variants are involved in the vascular system (important for blood vessels for the fibroid), DNA repair pathways (important in proliferation), and estrogen pathways.

ACE gene: codes for the angiotensin-converting enzyme which is important in vascular diseases.

Check your genetic data for rs4343  (23andMe v4, v5; AncestryDNA):

  • A/A: normal (ACE insertion/insertion)
  • A/G: increased risk of fibroids (ACE deletion/insertion)
  • G/G: increased risk of fibroids (ACE deletion/deletion)

XPC gene: codes for part of the DNA repair pathway

Check your genetic data for rs2228000 (23andme v4, v5; AncestryDNA):

  • G/G: normal risk of fibroids
  • A/G: decreased risk of fibroids
  • A/A: decreased risk of fibroids[ref ]

XPG gene: codes for part of the DNA repair pathway

Check your genetic data for rs873601 (23andMe v5; AncestryDNA):

  • A/A: increased risk of fibroids [ref ]
  • A/G: normal risk of fibroids
  • G/G: normal risk of fibroids

CYP1B1 gene: estrogen metabolism

Check your genetic data for rs1056827 A119S (23andMe v4 only):

  • C/C: normal
  • A/C: somewhat increased risk of uterine fibroids
  • A/A: increased risk of breast cancer [ref ] increased risk of uterine fibroids [ref ]

ESR1 gene: estrogen alpha receptor1

Check your genetic data for rs2234693 Pvull (23andMe v4, v5; AncestryDNA):

  • T/T: slightly lower risk of fibroids [ref ]
  • C/T: normal risk of fibroids
  • C/C: normal risk of fibroids

CCND1 gene: cell cycle regulatory protein

Check your genetic data for rs9344 (AncestryDNA only):

  • G/G: normal risk of fibroids
  • A/G: slightly increased risk of fibroids
  • A/A: increased risk of fibroids[ref ]

FASN gene: fatty acid synthase

Check your genetic data for rs4247357 (23andMe v4; AncestryDNA):

  • T/T: increased risk of fibroids [ref ]
  • G/T: increased risk of fibroids
  • G/G: normal risk of fibroids

GSTM1 gene: glutathione-S transferase, part of phase II detoxification

Check your genetic data for rs366631 (23andMe v4 only):

  • A/A: deletion (null) GSTM1 gene. Five-fold increased risk of fibroids with higher phthalate exposure [ref ] (This is actually the most common genotype in most populations.)
  • A/G: GSTM1 present
  • G/G: GSTM1 present

 


Lifehacks for fibroids:

Dietary associations:

Women eating more than 2 servings of fruits in a day had a slightly decreased risk of uterine fibroids compared to women eating less than 2 servings per week.  A higher intake of animal sources of vitamin A was also linked to a slightly decreased risk of uterine fibroids.[ref ]

Another study found that frequent milk and soybean use was linked with an increased risk of fibroids.[ref ] Unfortunately, the study lumped both of those together as a category, so I’m not sure which one was important. The implication here is that additional phytoestrogens or bovine hormones could increase fibroids.

Food additives, sweeteners, and preserved foods have also been linked to an increased risk of fibroids. (Not really helpful since the study doesn’t really narrow down or define those terms.) [ref ]

Oral contraceptive use is linked to an increased risk of fibroids.[ref ] Alternatively, some types of oral contraceptives can also be used to slow menstrual bleeding and decrease the symptoms of fibroids.

Flavonoids:

The fact that increased fruit intake and decreased preserved foods are linked to fewer fibroids leads one to think that natural polyphenols in fruits and vegetables may be good for fibroids.

EGCG:  A randomized controlled trial of green tea extract (800 mg, 45% EGCG) found that the women consuming the green tea extract had a reduction in fibroid size and a decrease in blood loss. The women in the placebo arm of the trial had an increase in fibroid size.  [ref ] You can get green tea extract on Amazon or at your local health food store. Be sure to read the label to determine the amount and percentage EGCG.

Kaempferol is a flavonoid that has been shown in cell culture studies to inhibit the proliferation of fibroid cells.  It also decreased IGF1 and VEGF, both of which are thought to be involved in the growth of fibroids. [ref ]

Resveratrol has been shown in a cell study to reduce the growth of fibroids. [ref ]

Curcumin has also been shown in tissue studies to stop the growth of fibroid tissue.[ref ]

Avoid phthalates and BPA:

Phthalates are a chemical found in plastics, vinyl, and artificial fragrances (personal care products, air fresheners, and laundry products). They act as estrogen mimics in the body. The level of phthalate metabolites is associated with the size of fibroids – more phthalates in the body = bigger fibroids. [ref ][ref ]

Similarly, higher BPA levels have also been linked with increased odds of fibroids. BPA can be found in some plastics, household dust, and thermal printed receipts.

What can you realistically do to avoid phthalates and BPA? Check your personal care products for phthalates, and look for laundry products without artificial fragrances included. Dusting and vacuuming regularly has been shown to decrease BPA. Handling thermal printed receipts, especially with wet hands, has been shown to increase BPA fairly significantly in the body.

NSAIDs and aspirin:

While not without potential drawbacks, using anti-inflammatory drugs, such as ibuprofen, can be effective for reducing heavy menstrual flow.  [ref ] Aspirin has been shown in cell studies to reduce fibroid proliferation. [ref ]

 

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.