Q&A: Early diagnosis key in successful uterine fibroid prevention, treatment

Key takeaways:

• The likelihood of uterine fibroids increases with age and regresses at menopause.
• Early identification of fibroids can prevent tumor progression and worsening symptoms.

Uterine fibroids are common hormone-dependent tumors that can develop after puberty, with likelihood increasing with age and regressing after menopause when estrogen and progesterone are no longer produced.

“Woman can experience more than one tumor in the same uterus,” Mohamed Ali, PhD, staff scientist in the department of obstetrics and gynecology at the University of Chicago, told Healio. “They usually come in numbers not only one tumor, but there are many. They are different in size, in their location and they can be submucosal, subserosal or intramural.”

According to Ali, the likelihood of future uterine fibroids can increase to 70% to 80% by the time a woman is aged 50 years, and uterine fibroids are more common among Black women compared with white women. Regarding where uterine fibroids derive from, Ali noted that there are four genetic mutations or abnormalities that are known to lead to tumor-initiating stem cells.

Healio spoke with Ali about uterine fibroid symptoms, risk factors, diagnosis and treatment.

Healio: What are the main symptoms and risk factors women with uterine fibroids experience? How do these symptoms impact day-to-day life?

Ali: For the symptoms, the most common and the most annoying is bleeding. Women experience heavy menstrual bleeding. They experience a lot of abnormal uterine bleeding. It’s heavier, more frequent and it stays longer. Because of the nature of the tumor, these are big masses, so they cause pelvic symptoms because they exert some pressure in the pelvis, so they can cause pain, constipation and pain during sexual intercourse. Those are the two main symptoms.

There are long-term complications that can affect the integrity of the endometrium. Those women can experience some obstetric complications during pregnancy, and uterine fibroids can affect endometrial receptivity when the implantation of the embryo happens for the women to get pregnant. The presence of the tumor can affect the integrity of this endometrium, so it affects how the endometrium is receptive to the embryo. Also, there are a lot of studies connecting fibroids to infertility as well.

There are several risk factors. One of the most common is age, because as women increase in age, the risk of having fibroids increases. That’s why the peak of incidence is 50 years of age. Also, vitamin D deficiency is one of the main risk factors, and that might justify why Black women are likely having fibroids more than white women, because Black women are at higher risk of vitamin D deficiency. They have a 10 times higher risk of vitamin D deficiency because of many reasons that the color of the skin can affect. Vitamin D’s biological source is from the UV light of the sun, so having darker skin might interfere. Also, there are reports that the consumption of dairy products is more challenging for Black women because they have more lactase deficiency, which is an enzyme that processes the lactose sugar in milk.

Speaking of Black women, race is also one of the main risk factors for uterine fibroids. Uterine fibroids are about three- to fourfold more likely in Black women vs. white women. Black women experience earlier tumors, bigger tumors, more aggressive symptoms and even when they hit menopause, the rate of tumor regression is much slower. Also, environmental exposures to pollution or to endocrine-disrupting chemicals is a risk factor. There are epidemiological studies that connect in utero exposure when the mother of those women who are going to develop uterine fibroids while the fetus is still in the uterus. When those women are exposed to endocrine-disrupting chemicals — compounds you can find in plastics, beauty products — those endocrine-disrupting chemicals can disrupt the hormonal signaling. And, later in life, the children of those women who are exposed to endocrine-disrupting chemicals have a higher chance of developing uterine fibroids.

Another risk factor is stress. There are reports about the stress of low socioeconomic levels. Those can be a risk factor and that also might contribute to why women of color, Black women, have higher risk, considering they are more likely to have lower socioeconomic levels vs. white women.

Healio: How difficult is it to diagnose uterine fibroids? Are there any barriers to diagnosis or care access?

Ali: I’m a basic scientist, I’m not a clinician. What I know is that it’s not difficult to diagnose, but the problem is a late diagnosis. If we suspect a woman has fibroids, it’s easy to do imaging — or ultrasound or MRI — and you can very easily know that this woman has fibroids. The problem is late diagnosis. The woman might have fibroids for a while, and you have no idea because the symptoms don’t appear in every woman that has fibroids. They appear in only 25% to 50% of women. The problem is that the woman has fibroids for a while, and you have no idea, and when she experiences bleeding, it can be an incidental diagnosis due to other causes, when she goes to hospital and then she finds out she has fibroids. That’s the main problem.

That’s what our lab is trying to work on — to develop a kit for early diagnosis. Early diagnosis means early intervention. We are exploring the possibility of natural compounds that are nonhormonal and are fertility friendly, so those women can consume those compounds early in life, and it can decrease the aggressiveness of the tumor. So that’s a comment on the diagnosis — it’s not difficult to diagnose, but the problem is the late diagnosis.

Healio: It is said that uterine fibroids are the main reason women receive hysterectomies in the U.S. What are some other treatment methods for uterine fibroids?

Ali: Hysterectomy has been the main treatment, the only curative treatment, because it’s removing the whole uterus, so there is no place for regrowth of the tumor. But this comes with many expenses, like those women cannot get pregnant anymore and there is a lot of economic burden on the patient. There is also myomectomy, which is surgical removal of only the fibroid and keeping the uterus, but it also has some economic drawbacks, and there is a possibility that the tumor can come again and regrow. Also, removal of the fibroid can usually leave a scar on the endometrium, so it is also linked with poor outcomes of those women having future fertility.

There have been a lot of studies and clinical trials exploring pharmacological treatment, like oral treatment. In the 1990s, the FDA approved a gonadotropin hormone-releasing hormone (GnRH) receptor agonist, leuprolide acetate, which desensitizes GnRH receptors that suppresses secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses ovarian production of estrogen and progesterone so they are simply shutting down the hormones in the body, but those have menopause-like side effects. Because you’re blocking the hormones, those women can have low bone mineral density and they cannot get pregnant during use of this drug. So, this drug was only approved for short term, 3 to 6 months only, before surgery to shrink the tumor so it can be easily removed and to reduce the frequency of bleeding, because those women have anemia. This drug was the only approved FDA drug [for treating uterine fibroids] until 2 or 3 years ago.

We have two approved oral treatments belonging to the same GnRH analog family, but those are antagonists, not agonists [relugolix and elagolix]. The agonist needs a longer time to produce an effect because it acts first as an agonist and then the long-term exposure of a few days of a drug can traverse and block the receptor. These new drugs have advantages. They are nonpeptide, so they can be taken orally. Because leuprolide was a peptide, it cannot be consumed orally because it’s going to be degraded in the stomach. It was only used as an injection. However, these new approved drugs cannot be used alone. You must combine them with estrogen and progesterone because they completely shut down the hormones in the body with several side effects. So, you must combine them with add-back therapy. They must be combined with an external source of estrogen and progesterone. So, elagolix is taken twice a day, and relugolix can be used only once daily, so it’s more convenient. These two drugs can be used relatively short term — up to 2 years.

The main limitation for drugs is that they cannot eradicate the fibroid, the fibroid is still there. They just improve the bleeding. They reduce the frequency and the amount of bleeding and they can shrink the tumors a little bit, not much because you’re already giving the patient external sources of hormones, so you don’t expect the tumor to regress a lot, but it improves a lot in reducing the bleeding.

There is a third compound, linzagolix (ObsEva), close to FDA approval from an ongoing clinical phase 3 trial, and it belongs to the same family.

Healio: What might OB/GYNs not know about uterine fibroids?

Ali: They need to know that vitamin D deficiency is one of the main risk factors, and they need to advise those vitamin D deficient patients to consume vitamin D. They can order a serum vitamin D and 99% of the time they’re going to find out that they are vitamin D deficient, and they need to correct their vitamin D level. That’s what I heard from my mentor. He is a physician, and whenever he sees patients, especially Black women, he ordered for serum vitamin D. Most of the cases, almost 100%, are vitamin D deficient, and he must replenish the vitamin D stores in the body, and, once this happens, they feel improvements in symptoms. Vitamin D is a natural compound, so it doesn’t have any side effects if it’s used in the regular recommended dose and check serum level regularly to avoid any overdose-related toxicities.

Healio: How can the landscape surrounding uterine fibroid care be improved?

Ali: There is a challenge admitting all the women. Early diagnosis is the key. We need to do more awareness so women can know if they are experiencing early symptoms, if they have the risk factors that are known for uterine fibroids, and if they have a family history, like if their mothers have uterine fibroids or if they are Black women or not consuming enough amount of vitamin D, or they are living in a lower socioeconomic level.

If they have multiple risk factors, they can take some early precautions like consuming vitamin D or other natural compounds that are proven to have anti-fibroid effects, like green tea. The main active ingredient in green tea is epigallocatechin gallate. This is also available OTC, so you don’t need a prescription for this and it’s also safe if they are using the recommended dose. They can consume those compounds if they have those risk factors, early diagnosis or still small size of fibroid. That can help a lot in the patient’s symptoms and economic perspective to avoid surgery in the future.

Healio: Is there anything else you would like to add?

Ali: There is primary prevention and secondary prevention. Primary prevention means that women have never developed fibroids, but they have enough risk factors to know that they are at risk. They can consume natural compounds. The secondary prevention are women who developed fibroids, but they removed it by surgery, and we are trying to give them some supplements to prevent reoccurrence of the fibroids. So, to conclude, it’s important to work on either primary prevention or secondary prevention.

For more information:

Mohamed Ali, PhD, can be reached at mohamed.ali@bsd.uchicago.edu.