Uterine fibroids (UFs) are one of the most prevalent benign abnormal cell growth diseases worldwide, with approximately 80% of premenopausal women experiencing their symptoms of heavy menstrual bleeding, pain, and infertility, according to a estudiar publicado en la revista Medicina [1]. Here we cover UF treatment with a class of medications called selective progesterone receptor modulators (SPRMs), better known as emergency contraceptives.
Uterine fibroids and hormonal birth control recap
In a previous article (aquí) looking at the relationship between hormonal birth control and fibromas uterinos, we covered the conflicting reports on whether or not HBC reduces fibroid risk. Per that article, the fact that “there are currently 259 different formulations of hormonal birth control on the market” likely contributes to a lack of conclusive evidence on whether HBC can, in fact, reduce fibroid risk. Additionally, “the conflicting reports may be a result of the wide variety of concentrations of estrogen and/or progestin in each medication.”
The problem of progesterone when it comes to uterine fibroids
En progesterona is a vital hormone for women’s reproductive health (maintaining and preparing the revestimiento uterino for a fertilized egg, sustaining the early stages of pregnancy, as well as other day-to-day functions like blood sugar regulation), if progesterone levels become abnormally low or the body becomes less sensitive to the progesterone it produces, a host of reproductive issues can appear.
Progesterone resistance happens when the body becomes less and less sensitive to the progesterone it produces, much like insulin resistance in Type II Diabetes. While researchers are still not sure what causes progesterone resistance, it is clear that it leads to reproductive issues like infertility, miscarriage, endometriosis, SOP, and uterine fibroids.
At the cellular level, disrupted progesterone signaling affects the body in ways that can lead to all the aforementioned reproductive issues; oftentimes the disrupted signaling itself is a result of decreased sensitivity in the progesterone receptor. To reference a helpful image from our previous look at uterine fibroids and hormonal birth control: imagine your cells as little houses with mailboxes on the outside. These mailboxes are cell receptors. These cell receptors are special proteins that sit on the surface of the cell and wait for specific messages like a mailbox slot that will only accept letters–in this case, only progesterone “letters.”
The progesterone resistance at the receptor level can affect cells in many ways, including:
- Stimulating Cell Growth: Progesterone encourages fibroid cells to grow and multiply by increasing certain proteins that tell the cells to keep dividing. This leads to more fibroid cells and bigger fibroid tumors [3]
- Preventing Cell Death: Normally, the body removes damaged or unnecessary cells through a natural process called apoptosis (programmed cell death). Progesterone stops this from happening in fibroid cells, so they live longer and keep growing [3]
- Affecting Chemical Signals: Fibroid growth is influenced by special signaling chemicals called cytokines. Progesterone changes how these chemicals are made, which can further support fibroid development [3]
- Changing DNA Behavior: Progesterone interacts with genetic changes (like gene mutations) to turn on certain genes that make fibroid stem cells grow, helping tumors form and expand [3]
- Building Blood Supply: For fibroids to grow, they need more blood vessels to bring in nutrients and oxygen. Progesterone helps create these new blood vessels by increasing VEGF, a factor that promotes blood vessel growth [3]
Selective progesterone receptor modulators (SPRMs) as a treatment for uterine fibroids
Enter selective progesterone receptor modulators (SPRMs), man-made compounds found in emergency contraceptives like Mifepristone and Ella that compete with progesterone at the progesterone receptor binding sites, selectively turning progesterone signals “on” or “off” depending on where in the body they’re acting. These SPRMs have been shown to prevent cell growth by targeting fibroid cells and inducing programmed cell death by turning these signals “off” [2].
A word about Plan B and uterine fibroids
Note that while Plan B or the “morning-after pill” (also known by the drug name levonorgestrel) es an emergency contraceptive, it is a progestogen (a synthetic form of progesterone that acts similarly to naturally made progesterone in the body) and “feeds” the progesterone receptors. In contrast, SPRM’s “starve” the receptors [4]. For this reason, Plan B would not be taken as a uterine fibroid treatment.
SPRMs aren’t just used for ‘emergency contraception’
While most commonly used as an emergency contraceptive by either preventing ovulation or terminating a very early pregnancy, SPRMs are used in clinical practice to treat PMS, abnormal uterine bleeding, and endometriosis, for breast cancer prevention, and, of course, to treat uterine fibroids [3].
There are 5 types of SPRM’s commonly used in clinical practice–Mifepristone (also known as Mifeprix or the abortion pill), Ulipristal Acetate (sold under the brand name Ella or ellaOne), Asoprisnil, Telapristone Acetate (sold under the names Proellex and Progenta), and Vilaprisan. Let’s take a look at the two most popular ones, keeping in mind that all SPRMs perform in relatively the same way. (If you’d like to read about all 5 types, check out the meta-analysis published in the medical journal Células aquí.)
Mifepristone (aka the abortion pill)
A 2023 comprehensive review of literature examined the role of progesterone in uterine fibroid growth as well as pharmaceutical approaches to modulate UF growth [3].
One study in the review examined 42 women with symptomatic uterine fibroids over the course of 26 weeks. These women were split into two groups–one group taking 2.5 mg of mifepristone per day, the other group taking 5 mg/day. At the end of the 26 week study, 78% of women in the 2.5 mg/day group experienced therapeutic amenorrea (more on this below), or the absence of menstruation, and on average the fibroid volume decreased by 27.9%. In the group of women taking 5 mg/day, 94% experienced amenorrhea and they had a 45.5% decrease in fibroid volume. The side effects were rather mild between the 2.5 and 5 mg/day groups, with 9 and 16% respectively reporting hot flashes, 2 and 4% respectively experiencing nausea or vomiting, and liver enzymes elevated in 13 and 7% respectively (an important finding, as SPRMs have been correlated with liver toxicity) [3].
Note that while in saludable women, amenorrhea is seen as a symptom of a serious disorder, in women with UFs, induced amenorrhea has been used as a therapeutic treatment: UFs often lead to heavy menstrual bleeding, pelvic pain, iron-deficiency anemia, and cramps. Inducing temporary amenorrhea may also help reduce fibroid size, since it leads to lower levels of estrogen (see our HBC and Fibroid article for more information)
Ulipristal Acetate (UPA)
Ulipristal acetate (UPA) is the most well-known and most tested SPRM. However, chronic use of UPA is also known for causing liver toxicity, abnormal liver enzymes, and in rare cases, liver failure [3].
A rigorous four-part study was performed on the effect of UFs, using UPA in what’s called the PEARL (PGL4001 Efficacy Assessment in Reduction of symptoms because of uterine Leiomyomata) trials [5]. Women with symptomatic UFs seeking surgery were randomly divided into three groups: 96 women were given 5 mg UPA per day, 98 were given 10 mg/day, and 48 received a placebo.
After 13 weeks, 91% of women taking 5mg/day saw a decrease in uterine bleeding using an objective assessment called pictorial blood-loss assessment chart (PBAC). 92% of women on 10 mg/day saw a decrease in bleeding, and only 19% of women on the placebo reported a decrease. For women on 5mg/day, 73% experienced amenorrhea compared to 82% of women taking 10 mg/day, and compared to only 6% of women on the placebo. For total fibroid volume, women on 5 mg/day saw a 21% decrease in size, women on 10 mg/day saw a 12% decrease, and women on the placebo saw growth of 3% [5].
As with any medication we put into our bodies, there are always side effects. The liver toxicity risks of SPRMs can be life-threatening, likely caused because progesterone (and therefore also the SPRMs bound to the progesterone receptors) are broken down by the liver. Ulipristal acetate was used by over 765,000 women in Europe between 2012 and 2018: five women were diagnosed with drug-induced liver injury, four of whom required a liver transplant [6].
Comparing liver damage risks with UPA for uterine fibroids vs. liver damage risks with the abortion pill
To put this in context, UPA used for uterine fibroids is only one-sixth of the dosage used for the abortion pill, yet after the long-term course of treatment at about 12 weeks long, it’s strongly recommended to monitor liver function for up to four weeks after the end of the treatment to make sure liver function remains normal [7]. Mifepristone (the abortion pill) can be anywhere from 300mg to 1200 mg daily, with one study finding that after 2-3 months on the higher end of the dosage, women were starting to show signs of liver injury, including severe, long-lasting jaundice [8].
The bottom line: what’s the best treatment for uterine fibroids?
Unlike the lack of conclusive evidence in our look at HBC and uterine fibroids, it seems quite clear that emergency contraception, specifically SPRMs, dramatically improve uterine fibroid size as well as the negative side effects of the growths like heavy menstrual bleeding and painful cramps. However, the amount of research on SPRM’s as a long-term treatment has been halted due to very real concerns of liver toxicity.
It’s also important to point out that SPRMs induce amenorrhea, or the cessation of periods, and mujeres necesita healthy, regular periods for optimal health and well-being. SPRMs are also unhelpful to the woman struggling with fibroids who wants to get pregnant now or in the future. An ideal treatment would therefore address the root cause of fibroids, restoring a woman’s natural cycle, and preserving her fertility.
In forthcoming articles, we will address research on plant-based treatments for uterine fibroids, as well as the various surgical approaches used to address fibroids.
