Review
10 January 2023
10.3389/fphar.2022.1045783
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EDITED BY
Reza Shirazi,
Medicine, UNSW Sydney, Australia
REVIEWED BY
Sajad Razavi Bazaz,
University of Technology Sydney,
Australia
Nguyen Minh Duc,
Pham Ngoc Thach University of
Medicine, Vietnam
*CORRESPONDENCE
Ayman Al-Hendy,
aalhendy@bsd.uchicago.edu
Andrews Akwasi Agbleke,
agbleke@sitghana.org
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This article was submitted to Obstetric
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Frontiers in Pharmacology
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12 December 2022
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CITATION
Sefah N, Ndebele S, Prince L, Korasare E,
Agbleke M, Nkansah A, Thompson H,
Al-Hendy A and Agbleke AA (2023),
Uterine fibroids — Causes, impact,
treatment, and lens to the
African perspective.
Front. Pharmacol. 13:1045783.
doi: 10.3389/fphar.2022.1045783
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© 2023 Sefah, Ndebele, Prince,
Korasare, Agbleke, Nkansah, Thompson,
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Frontiers in Pharmacology
Uterine fibroids — Causes,
impact, treatment, and lens to
the African perspective
Narvella Sefah 1, Sithembinkosi Ndebele 1, Lillian Prince 1,
Elizabeth Korasare 2, Michael Agbleke 3, Annabella Nkansah 3,
Humphrey Thompson 3, Ayman Al-Hendy 1* and
Andrews Akwasi Agbleke 3*
1
University of Chicago, Chicago, United States, 2Fibroid Foundation Africa, Accra, Ghana, 3Sena
Institute of Technology, Penyi, Ghana
Leiomyomas, or uterine fibroids as they are commonly known, are mostly seen
in women of reproductive age. However, they can go undetected in most
women, and approximately 25% of women show clinical symptoms. Although
fibroids are a global burden impacting 80% of premenopausal women, they are
more prevalent among Black women than among women of other races. Based
on clinical diagnosis, the estimated cumulative incidence of fibroids in
women ≤50 years old is significantly higher for black (>80%) versus white
women (~70%). The cause of leiomyomas is not clearly known, but studies
have shown evidence of factors that drive the development or exacerbation of
the disease. Evidence has linked risk factors such as lifestyle, age, environment,
family history of uterine fibroids, and vitamin D deficiencies to an increased risk
of uterine fibroids, which impact women of African descent at higher rates.
Treatments may be invasive, such as hysterectomy and myomectomy, or noninvasive, such as hormonal or non-hormonal therapies. These treatments are
costly and tend to burden women who have the disease. Sub-Saharan Africa is
known to have the largest population of black women, yet the majority of
uterine fibroid studies do not include populations from the continent.
Furthermore, the prevalence of the disease on the continent is not well
determined. To effectively treat the disease, its drivers need to be
understood, especially with regard to racial preferences. This paper aims to
review the existing literature and build a case for conducting future research on
African women.
KEYWORDS
fibroid, Africa, causes and treatment, perspective, types and classification, race,
lifestyle
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Introduction
2008; Marsh et al., 2013; Giuliani et al., 2020). It is hypothesized
that the size and location of the fibroid may play a role. Fibroids
up to the size of a watermelon have been recorded, while some are
as small as a tiny stone (Peddada et al., 2008; Fasubaa et al., 2018;
Maanongun et al., 2021). Fibroids can be singular tumors or, less
commonly, a cluster and are not limited in size (Hodge et al.,
2008; Bulun, 2013).
Uterine fibroids, also known as leiomyomas, are tumors
made of smooth muscle and connective tissue from the
myometrium or muscular outer layer of the uterus (Nowak,
1993; Fleischer et al., 2008; Suo et al., 2009; Bulun, 2013; Ke et al.,
2013). They can be found in premenopausal women and are
observed to regress post-menopause (Levy, 2008; Giannubilo
et al., 2015; Sarkodie et al., 2016; Ghosh et al., 2018; Giuliani et al.,
2020; Ulin et al., 2020; Ali et al., 2021). Uterine fibroids are
common in over 70% of women by the onset of menopause and
are clinically apparent in 25% of women of reproductive age
(Stewart et al., 2017). These tumors are benign neoplasms and are
not predicted to lead to cancer (Bulun, 2013; Orellana et al.,
2021).
Fibroids can form in various locations around the uterus and
can take different forms (Bulun, 2013; Zepiridis et al., 2016).
Approximately 20%–50% of women with fibroids show
symptoms of heavy menstrual bleeding, which can lead to
anemia, bladder dysfunction, and pregnancy complications
(Khan et al., 2014; Stewart et al., 2017; Marsh et al., 2018).
Notably, most fibroids go undetected by women and may be
small and asymptomatic (Laughlin et al., 2011; Zimmerman
et al., 2012; Sheng et al., 2020). Although extensive research
has been done, it is still inconclusive as to what causes some
fibroids to be asymptomatic and others symptomatic (Divakar,
Location
Fibroids can develop within 3 anatomical parts of the
uterus and are classified as subserosal, intramural, and
submucosal fibroids (Bajekal, 2000; Cook et al., 2010;
Zepiridis et al., 2016) (Figures 1–3). Myomas have been
found to originate from the plasticity of myometrial cells
during tissue development and maintenance; the cells
undergo cellular reprogramming and mutations (Longo and
Bulun, 2013; Navarro et al., 2021). According to the
International Federation of Gynecology and Obstetrics
(FIGO), uterine fibroids are categorized into eight different
subtypes (Table 1). The FIGO categorization also has a type 8,
which includes lesions on extrauterine locations such as the
cervix or broad ligament (Gomez et al., 2021). Subtypes are
determined by the position of the myoma in relation to the
endometrial cavity.
FIGURE 1
Typical healthy uterus. In a healthy uterus, there are no lesions. The endometrium is a thin layer that surrounds the uterine cavity and
myometrium. Both fallopian tubes and ovaries are present. The uterine cavity is empty. No part of the uterus is distended or disformed.
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FIGURE 2
Uterus with multiple fibroid types 0: Pedunculated submucosal, 100% of the fibroid is in the uterine cavity. 1: Submucosal, greater than 50% of
the fibroid is within the myometrium and the other portion is distorting the endometrium and uterine cavity. 2: Submucosal, less than 50% of the
fibroid is within the myometrium and the majority is distorting the endometrium and uterine cavity. 3: Intramural, the fibroid is within the
myometrium but touches the endometrium, and it does not distort the uterine cavity. 4: Intramural, the fibroid is completely within the
myometrium. 5: Intramural, the fibroid is predominantly within the myometrium with less than 50% extending outside of the myometrium. 6:
Subserosal, greater than 50% of the fibroid is located outside of the myometrium. 7: Pedunculated subserosal, 100% of the fibroid is outside of the
myometrium. See Table 1 for classification details.
Submucosal
Intramural fibroids produce significantly lower pregnancy rates,
implantation rates, and ongoing pregnancy/live birth rates and
even significantly higher rates of spontaneous abortion (Pritts
et al., 2009). This effect on implantation is seen even when the
fibroid does not reach the uterine cavity (Zepiridis et al., 2016;
Farhi et al., 1995; Ramzy et al., 1998; Surrey et al., 2001; Jun et al.,
2001). One study found that in women who underwent
myomectomy, intramural fibroids were the most common
type of fibroid to be removed (Casini et al., 2006).
Myomas that cause intramural distortion or reside within the
uterine cavity are submucosal fibroids (Puri et al., 2014) (Figures 2, 3).
Submucosal fibroids disrupt the endometrial blood supply, which
impacts implantation of the embryo (Garcia and Tureck, 1984; EldarGeva et al., 1998). In a systematic review completed by Pritts et al.,
submucosal fibroids were found to lower fertility rates. Submucosal
fibroids are also likely to be symptomatic, as they can lead to
intermenstrual bleeding and hemorrhage (Divakar, 2008; Wilde
and Scott-Barrett, 2009; Bulun, 2013; Puri et al., 2014).
Submucosal fibroids can negatively impact the implantation rates
of assisted reproductive technology (ART) because the uterine cavity
is occupied (Eldar-Geva et al., 1998; Guo and Segars, 2012).
Subserosal
Subserosal fibroids reside predominantly outside the
myometrium (Klatsky et al., 2008) (Figures 2, 3). Subserosal
myomas have been found to impact the establishment of early
pregnancy (Pritts et al., 2009). However, they have been
associated with a very minimal effect on fertility (Zepiridis
et al., 2016). Women with subserosal fibroids were found to
have no significant differences from those without fibroids (Pritts
Intramural
Intramural fibroids reside in the myometrium cavity without
distorting the endometrial cavity (Wilde & Scott-Barrett, 2009)
(Figures 2, 3). Intramural myomas impact the establishment of
early pregnancy (Eldar-Geva et al., 1998; Pritts et al., 2009).
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et al., 2009). Subserosal fibroids tend to be asymptomatic unless
they are large, which can cause substantial pressure or pain
(Bulun, 2013; Gomez et al., 2021).
Pedunculated
Fibroids of the final subtype do not reside in a specific
location. Pedunculated fibroids can occur both within and
outside the uterine cavity (Klatsky et al., 2008), and they are
attached to the uterus by a vascular stalk (Gomez et al., 2021)
(Figures 2, 3). These fibroids are likely to be asymptomatic unless
they are torsioned (Divakar, 2008; Wilde and Scott-Barrett,
2009), but they can also become symptomatic if they grow
and begin to push on other masses or detach and become
parasitic to the pelvis (Gomez et al., 2021). Parasitic myomas
are rare cases where a pedunculated subserosal myoma detaches
from the uterus and develops an alternative blood supply from
other sources, such as the omental or mesenteric vessels
(Cucinella et al., 2011).
Fibroid cell types and architecture
FIGURE 3
Side view of the uterus with multiple fibroid types -Key: See
Table 1. 0: Pedunculated submucosal, 100% of the fibroid is in the
uterine cavity. 1: Submucosal, greater than 50% of the fibroid is
within the myometrium and the other portion is distorting the
endometrium and uterine cavity. 2: Submucosal, less than 50% of
the fibroid is within the myometrium and the majority is distorting
the endometrium and uterine cavity. 3: Intramural, the fibroid is
within the myometrium but touches the endometrium and does
not distort the uterine cavity. 4: Intramural, the fibroid is
completely with the myometrium. 5: Intramural, the fibroid is
predominantly within the myometrium with less than 50%
extending outside of the myometrium. 6: Subserosal, greater than
50% of the fibroid is located outside of the myometrium. 7:
Pedunculated subserosal, 100% of the fibroid is outside of the
myometrium. See Table 1 for classification details.
Fibroids have several specific cellular characteristics
(Figure 4). A study performed in mice found myometrial
proliferation of fusiform smooth muscle cells in the tissue
area of the tumor (Romagnolo et al., 1996). The cytoplasm
and nuclei of the tumor cells had a normal appearance but
displayed high mitotic factors (Romagnolo et al., 1996). There
were several fibrous stroma, and within each stroma, spindle cells
with high cell proliferation and fibrosis occurred simultaneously.
Additionally, it was suggested that fibroids caused narrowing of
the lumen in the uterine horn based on their placement
(Romagnolo et al., 1996).
Broader slicing of fibroid tissues reveals various patterns in
the tissues (Figure 4). These patterns fit into a few main
categories. One is the whorled pattern, which is spiraled or
twisted; this is the typical pattern expected for fibroids (Khan
et al., 2014). In a study that sliced 19 fibroid tissues,
approximately 40% of the fibroids examined displayed a
whorled pattern (Jayes et al., 2019). Furthermore,
approximately 50% displayed a nodular pattern with
numerous nodes ranging in size. Another 50% displayed an
interweaving trabecular pattern, which is beam-like. Many of
the tissues displayed multiple patterns and were classified in both
categories (Jayes et al., 2019).
TABLE 1 Classification of uterine fibroids by FIGO.
Classification of uterine fibroids by anatomical positioning
FIGO
Subtype
Positioning
0
Submucosal - Subtype 0
100% endometrial cavity or intracavity
1
Submucosal - Subtype 1
> 50% intramural
2
Submucosal - Subtype 2
< 50% intramural
3
Intramural
In contact with the endometrium
4
Intramural
100% intramural
5
Intramural
Subserosal >50% intramural
6
Subserosal
Subserosal <50%
7
Subserosal
Pedunculated
Frontiers in Pharmacology
Effects
Uterine fibroids also play a drastic role in various aspects of
reproductive health; they cause approximately 5%–10% of
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FIGURE 4
Representative photographs of tissue slices showing differences in the gross appearance of fibroids. (A) Classical irregular whorled pattern.
(B–D) Patterns of nodules. (E,F) Trabecular structures. (G) Characteristics of multiple patterns. This example shows a trabecular/nodular pattern. (H)
Not categorized. This example shows a tightly gyrated pattern. (I) Myometrial tissue shown for comparison. Note the seedling fibroid embedded in
the tissue (white). Ruler (cm) shown for size. This figure and description were adapted from Jayes et al., 2019.
the placenta is torn from the uterine wall, causing immense blood
loss. To alleviate this blood loss, the uterus experiences clotting,
reducing blood flow and also cutting off the blood supply to the
myomas, causing them to shrink (Burbank, 2004).
Symptomatic fibroids are associated with two other classes of
symptoms, abnormal uterine bleeding and pelvic pressure and
pain (Stewart, 2001; Al-Mahrizi ad Tulandi, 2007; Khan et al.,
2014; Whitaker and Critchley, 2016; Giuliani et al., 2020).
Abnormal bleeding tends to occur during menstruation and is
known as menorrhagia or hypomenorrhea. This bleeding pattern
is prolonged and excessively heavy (Gupta et al., 2014; Ghosh
et al., 2018; Sohn et al., 2018), causing women in some cases to
infertility cases (Desai & Patel, 2011; Guo and Segars, 2012;
Zepiridis et al., 2016). This can be caused by the location of
fibroid growth, which can block the fallopian tubes and disable
the passage of the gamete. In addition, fibroids can impact the
success rate of women using assisted reproductive technologies
(ARTs) (Eldar-Geva et al., 1998; Guo and Segars, 2012).
However, due to the increased hormones during pregnancy,
many pregnant women tend to experience large growth of their
fibroids. Importantly, after giving birth, 70% of postpartum
women experience shrinkage of their fibroids (Laughlin et al.,
2011; Guo and Segars, 2012; Delli Carpini et al., 2019). This
shrinkage is hypothesized to be caused by uterine ischemia when
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Causes
have to change sanitary products every hour. This symptom is
most often seen in submucosal fibroids due to their location, as
mentioned previously. Pelvic pressure and pain are caused by
enlargement of the uterus. The placement of fibroids can distort
the shape of the uterus. Anterior fibroids have been linked to
urinary issues and constipation. Rarely, as mentioned above,
pedunculated fibroids can cause pain if there is a torsion (Stewart,
2001).
The causes of leiomyomas are not well known, and research
is still needed to understand their formation. However, some
drivers of the disease are discussed below.
Non-hormonal
Genetic modifications
Prevalence
Several studies point to specific genetic mutations that lead to
the development of fibroids, specifically the “MED12, HMGA2,
COL4A5/COL4A6, FAS or FH genes” (Eggert et al., 2012; Segars
et al., 2014). MED12 is one of the more frequently studied genes.
MED12, the gene that codes for the mediator subunit 12 protein,
is found on chromosome X. Alterations to MED12 have been
found in the majority of women with fibroids in whom
chromosomal changes have been noticed (Markowski et al.,
2012; Bulun, 2013). These alterations can range from clonal
chromosomal abnormalities to simple or complex
rearrangements or deletions. In addition to MED12, another
common alteration that has been found in fibroids with
chromosomal changes is HMGA2. HMGA2 codes for the
high mobility group AT2 hook proteins. In some cases of
fibroid chromosomal rearrangement, the HMGA2 locus has
been targeted and upregulated. MED12 and HMGA2 make up
approximately 80%–90% of fibroids with chromosomal
abnormalities, but these two alterations are mutually exclusive
(Markowski et al., 2012; Bulun, 2013).
Additionally, approximately 40% of women with these
tumors have chromosomal abnormalities in “trisomy 12,
translocation involving chromosomes (t12; 14) (q14–q15;
q23–q24), deletions on chromosome 7 (q22q32), 3q and 1p,
and rearrangements of 6p21, 10q22 and 13q21–q22” (Hodges
et al., 2002) (Table 2). In a study of Japanese women, there was an
association between chromosomes 10, 11, and 22 and
leiomyomas, and in white women, there was an association
with chromosome 17 (Ordulu, 2016). In a UK-based study,
the United Kingdom-based biobank that contains Icelandic
(Rafnar et al., 2018) and Finnish (Välimäki et al., 2018) data
found a variant among loci in chromosomes 16 and 22 in white
women. A study on African women and European women also
found an association between chromosome six and fibroids (Giri
et al., 2017). In Black women, there was a strong link between
chromosomes 22 and eight and fibroids (Hellwege et al., 2017).
An additional study by Zhang et al., 2015, found an association
between chromosome one and fibroids in Black women.
Studies have shown that the prevalence of uterine fibroids is
difficult to determine. As a majority of the cases are
asymptomatic, methods of prevalence determination can
impact the incidence recorded. A study found that using only
clinical diagnosis, the prevalence of fibroids is approximately
33%, but when using ultrasound, it rises to approximately 50% of
women, and with histological assessment, the incidence rises to
approximately 77% of women (Okolo, 2008).
Uterine fibroids have been noted to be present at a high
rate, especially in Black women. A study conducted
approximately 30 years ago found that fibroids are 3 to
4 times more likely to occur in Black women than white
women (Marshall, 1997). This percentage difference has
been determined to be statistically significant; it is
approximately 3 times more likely for Black women to
develop fibroids than white women even when adjusted for
age (Baird et al., 2003). Another study that included multiple
races supported the significantly higher prevalence for Black
women. They found a prevalence rate of 25.5% in Black
women, 7.5% in white women, 5.8% in East Asian women,
and 5.5% in South Asian women (Chibber et al., 2016). Studies
that include Black, white and Asian women are sparse and
generally focus on Black and white women. This may be due to
the lower prevalence of fibroids in the Asian race indicated in
the literature. Recent studies in the United Kingdom have
recorded a rate of 70% of white women and approximately
80% of Black women suffering from uterine fibroids (Bulun,
2013; Khan et al., 2014; Florence and Fatehi, 2022).
Furthermore, studies have shown that Black women are
more likely to have multiple fibroids. In a study performed
in 28 hospitals in Maryland, 57% of Black women had seven or
more fibroids, whereas 36% of white women had seven or
more fibroids (Kjerulff et al., 1996).
In addition to race being an established risk factor, early age
at menarche has been associated with an increased risk of uterine
fibroids (Dragomir et al., 2010; D’Aloisio et al., 2010; Faerstein,
2001; Wise, 2004; Marshall et al., 1998; Samadi et al., 1996).
However, the cumulative incidence of UFs increases as women
approach menopause to more than 80% (Cramer, 1990; Baird
et al., 2003). This finding could provide further clinical
implications for studies.
Frontiers in Pharmacology
Inflammation
Another factor that has been linked to fibroid development is
inflammation. Studies on the association between chronic
inflammation and leiomyomas are minimal. One study
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TABLE 2 Chromosomal associations by race.
Race
Chromosomes/Genes
Sources
White
17, 6, 16, 22
Ordulu, (2016)
Giri et al. (2017)
Rafnar et al. (2018)
Välimäki et al. (2018)
Asian
10,11,22
Ordulu, (2016)
Black
6, 22, 8, 1
Giri et al. (2017)
Hellwege et al. (2017)
Zhang et al. (2015)
Population
MED12, HMGA2, COL4A5/COL4A6, FAS or FH genes
Segars et al. (2014)
Eggert et al. (2012)
Bulun, (2013)
Markowski et al. (2012)
2016). These studies do not provide vast racialized data, often
only focusing on one or two races.
conducted by Protic et al. found an abundance of CD68-positive
macrophages, which are associated with inflammation, and
inflammatory cells in leiomyoma tissues. They found that
there were far more CD68 macrophages in leiomyomas and
their surrounding tissues than in the distant myometrium.
Furthermore, they found an abundance of inflammatory cells
in early-stage cellular leiomyomas, thus forming a link between
leiomyomas and inflammation (Protic et al., 2016). Fibrotic
disorders such as uterine fibroids are associated with altered
ECM pathology, which can be a result of excessive wound healing
initiated by the inflammatory response (Zannoti et al., 2021). The
results of a study by Kabodmehri et al., 2022, which looked at
chronic endometriosis and uterine fibroids, displayed different
results than hypothesized. Women with fibroids showed a higher
rate of chronic endometriosis than those without fibroids, but
that difference was not significant. Within the fibroid group,
women with submucosal fibroids were more likely to have
endometriosis than women with subserosal or intramural
fibroids (64% vs. 37%), and this difference was significant
(Kabodmehri et al., 2022). The sample size in the Kabodmehri
et al. study was small, but it drew attention to the overall role
inflammation plays. If inflammation is frequent in women with
submucosal fibroids, then it could play a role in the excessive
bleeding that these women experience.
Estradiol
Cancerous diseases, such as breast cancer, are heavily
impacted by hormones such as estradiol and progesterone.
Additionally, there are racial differences in hormone levels.
Black women had the highest level of estradiol at
approximately 166 pg/ml adjusted for BMI, whereas white
women had an adjusted level of approximately 142 pg/ml.
Asian women were in the middle, with 156 pg/ml (Pinheiro
et al., 2005) (Table 3). Several other studies have confirmed
this trend. A Haiman et al., 2002, study reported estradiol levels
in Black women of 136.1 pg/ml and in white women of 115.9 pg/
ml. A study with Asian and white women reported estradiol
levels of 547 pg/ml for Asian women and 359 pg/ml for white
women, which were again higher for Asian women than for white
women (Huddleston et al., 2011). A study with Black and Asian
women reported estradiol levels in Black women of 21.4 pg/ml
and in Asian women of 16.6 pg/ml (Song et al., 2018). Although
these estradiol concentrations were low, they still showed a
similar trend as that observed in the Pinheiro study, with
Black women having a higher estradiol concentration than
Asian women.
Hormonal
Cholesterol-based hormones have been shown to impact
tumor growth (Obochi et al., 2009; Chimento et al., 2019).
Such hormones include progesterone, estradiol, and vitamin
D3 (Table 3). Furthermore, estradiol and progesterone work
together to maintain viability for tumor development (Ishikawa
et al., 2010; Reis et al., 2016). Progesterone completes the
development and proliferation of leiomyomas (Kim et al.,
2009; Ishikawa et al., 2010; Reis et al., 2016), and estradiol
increases the availability of progesterone receptors on the cells
and allows for more sensitivity to progesterone, thus increasing
development (Ishikawa et al., 2010; Kim et al., 2013; Reis et al.,
Frontiers in Pharmacology
Progesterone
Progesterone is vital to the growth of fibroids, as it works to
proliferate cells and maintain their rapid growth (Kim et al.,
2009; Ishikawa et al., 2010; Reis et al., 2016). Black women had a
concentration of 1,321 ng/d adjusted for BMI, white women had
an adjusted concentration of 1,289 ng/d, and Asian women had
the lowest concentration of 1,205 ng/d (Pinheiro et al., 2005).
Although these differences were not statistically significant, there
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TABLE 3 BMI and hormonal levels by race.
Hormonal levels by race
Average BMI
Estradiol Level
Black
White
2
2
24.7 kg/m
33.1 kg/m2
29.2 kg/m2
–
Thomas et al. (2013)
32.2 kg/m2
–
–
Dodgen and Spence-Almaguer, (2017)
–
–
25.54 kg/m2
Zhou et al. (2020)
Liu et al. (2021)
156 pg/ml
Pinheiro et al. (2005)
166 pg/ml
142 pg/ml
136.1 pg/ml
115.9 pg/ml
–
Haiman et al. (2002)
225.2 pg/ml
191.5 pg/ml
–
Marsh et al. (2011)
–
359 pg/ml
16.6 pg/ml
Song et al. (2018)
547 pg/ml
Huddleston et al. (2011)
–
–
195.66 pmol/L
Needham et al. (2015)
–
–
74.1 pmol/L
Ausmanas et al. (2007)
1321 ng/d
1289 ng/d
1205 ng/d
Pinheiro et al. (2005)
15.0 ng/ml
11.0 ng/ml
–
Haiman et al. (2002)
20.3 ng/ml
26.7 ng/ml
–
Alzaman et al. (2016)
18.3 ng/ml
38.0 ng/ml
–
Zhu et al. (2016)
–
–
19.15 ng/ml
Siddiqee et al. (2021)
–
–
53.7 nmol/L
Chen et al. (2017)
–
–
45.1 nmol/L
Wei et al. (2019)
and can induce apoptosis in cancer cells (Halder et al., 2012).
Vitamin D is introduced into the body through the skin from UV
rays or from 7-dehydrocholesterol or dietary resources in the
inactive form. In the liver, it is converted to 25(OH)D and then
converted to the active form of 1,25(OH)D in the kidney. It is
then carried by vitamin D-binding protein (VDBP) to the skin
and different cells (Pike & Christakos, 2017; Ciebiera et al., 2018).
VDBP is necessary for maintaining “circulating vitamin D and
modulation of the bioavailability, activation, and end-organ
responsiveness of the hormone and its metabolites” (Alzaman
et al., 2016).
White Americans had a vitamin D level of 26.7 ng/ml in
the body, whereas Black Americans had a level of 20.3 ng/ml
(Alzaman et al., 2016). Asians may lie in the middle in terms of
vitamin D levels, although it is unclear, but they do show a
lower level of vitamin D than whites (Siddiqee et al., 2021).
However, a population study showed that from 1999 to 2018,
white people had a crude cancer rate of 559.1 per
100,000 people, and Black people had a rate of 408.5 per
100,000 people (CDC Wonder). This contradicts the
association between VitD levels among the various races, as
shown in Table 3.
was a difference (Pinheiro et al., 2005). This kind of difference
was also seen in the Haiman et al., 2002, study, where Black
women again had the highest progesterone levels of 15.0 ng/ml
and white women had a level of 11.0 mg/ml (Table 3).
Vitamin D
Another discovered cause of uterine fibroids appears to be a
lack of vitamin D. One study found that Black women are
severely more likely than white women to be vitamin D
deficient, with 42% of Black women being deficient and only
4% of white women being deficient (Kakarala et al., 2007). Using
an assay of 25-hydroxyvitamin D (25(OH)D), which is a
commonly recognized marker of vitamin D, researchers were
able to determine the status of vitamin D in women. The results
showed that only 10% of black women and 50% of white women
had sufficient vitamin D levels, and women with sufficient
vitamin D levels were 32% less likely to have fibroids than
women who were deficient (Baird et al., 2013). An optimal
level of vitamin D is 25(OH)D at 40–60 ng/ml (Ciebiera et al.,
2018).
1,25-Dihydroxyvitamin D3, a biologically active form of
vitamin D3, has been shown to decrease tumor proliferation
Frontiers in Pharmacology
Sources
29.0 kg/m
–
Vitamin D Level (25(OH)D)
2
32.4 kg/m
21.4 pg/ml
Progesterone Level
Asian
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TABLE 4 Hormonal levels by BMI.
Average BMI
Estradiol Level
Progesterone Level
Vitamin D Level (25(OH)D)
≤24 kg/m2
25 − 29 kg/m2
≥ 30 kg/m2
Sources
37.7 pg/ml
33.6 pg/ml
30.3 pg/ml
Freeman et al. (2010)
34.8 pmol/L
43.2 pmol/L
54.9 pmol/L
Key et al. (2003)
278.9 pg/ml
279.9 pg/ml
258.2 pg/ml
Bellver et al. (2022)
117.81 pg/ml
149.83 pg/ml
0.19 ng/ml
0.17 ng/ml
0.96 ng/ml
1.60 ng/ml
90.4 nmol/L
83.3 nmol/L
77.9 nmol/L
Wei et al. (2019)
84.9
76.5
73.2 (serum)
Lagunova et al., 2009
Lifestyle
0.17 ng/ml
Esfahlan et al. (2011)
Bellver et al. (2022)
—
Esfahlan et al. (2011)
and vitamin D (Table 4). In terms of estradiol, some of the
findings contradict what is hypothesized about the correlation
between estradiol and BMI. In a study by Freeman et al., it was
observed that as BMI increases, estradiol level decreases. This
refutes the previous hypothesis that estradiol increases as BMI
increases. Although a study done by Key et al., 2003, supports the
hypothesis of estradiol increasing as BMI increases, they found
an estradiol level of 34.8 pmol/L for women with a
BMI ≤24 kg/m2 , 43.2 pmol/L for women with a BMI of
25 − 29 kg/m2 , and 54.9 pmol/L for women with a BMI
≥ 30 kg/m2 (Table 4).
There is also an unclear association between progesterone
levels and BMI. One study found a decrease in progesterone
levels as BMI increased, from 0.19 ng/ml in women with a
BMI ≤24 kg/m2 to 0.17 ng/ml in women with a BMI 25 −
29 kg/m2 and ≥ 30 kg/m2 (Bellver et al., 2022). Another study
found that progesterone levels increased as BMI increased,
from 0.96 ng/ml in women with a BMI ≤24 kg/m2 to 1.60 ng/
ml in women with a BMI of 25 − 29 kg/m2 (Esfahlan et al.,
2011).
In terms of vitamin D, there was a trend of vitamin D levels
decreasing as BMI increased in a Wei et al., 2019, study that
reviewed the United Kingdom population. Individuals with a
BMI ≤24 kg/m2 had an average level of 90.4 nmol/L,
individuals with a BMI of 25 − 29 kg/m2 had a level of
83.3 nmol/L, and individuals with a BMI ≥ 30 kg/m2 had a
level of 77.9 nmol/L.
Some studies have associated obesity with uterine fibroids.
A literature review performed by Qin et al., 2021, including
relevant literature from 1992 to 2020, found a positive
correlation between obesity and fibroids. A study on
Ghanaian women also showed that there is a greater
likelihood of fibroids in obese women (Sarkodie et al.,
2016). One study found that obese women accounted for
24%
of
those
undergoing
myomectomies
and
hysterectomies for leiomyomas (Camanni et al., 2010). It is
important to note that the correlation has not been completely
determined, as some studies have found no association
between BMI and fibroids. Possible explanations for obesity
increasing the incidence of uterine fibroids include altered sex
hormone metabolism, reduced sex hormone binding globulin
(SHGB) level, and systematic inflammation (Soave and Marci,
2018).
In terms of altered sex hormone metabolism, it is
hypothesized that since adipose tissue is known to affect
endocrine tissue, an increase in body fat would increase the
amount of estrogen in the body, and estrogen is a driver for
uterine fibroids (Soave and Marci, 2018). The reduced SHGB
level poses a similar problem, because if there are fewer
binding sites, there will be more free estrogen in the bodies
of obese women. Finally, systemic inflammation could be a
driver, as when fat cells accumulate, there is an increase in
inflammatory cytokines in the body that could drive the
growth of ECM in fibroids (Soave and Marci, 2018).
Various studies show that Black women have the highest
average BMI, followed by white women and Asian women,
at approximately 32.6, 29.1, and 25.1, respectively (Thomas
et al., 2013; Zhou et al., 2020; Liu et al., 2021) (Table 3).
Hormonal levels seemed to fluctuate between the BMI
categories, but some overall trends were observed for estradiol
Frontiers in Pharmacology
—
Treatments
UFs have been associated with fertility complications, and
depending on the location of the fibroids, they can contribute
to recurrent pregnancy loss (Freytag et al., 2021). Fibroid
categorizations are dependent on the location of the fibroid in
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TABLE 5 Uterine fibroid treatments.
Treatment type
Procedure type
Description
References/Source
Surgical
Endometrial ablation
Endometrium thickness reduction
Florence and Fatehi, (2022)
Giuliani et al. (2020)
Uterine artery embolization
Blood flow reduction
Florence and Fatehi, (2022)
Yerezhepbayeva et al. (2022)
Giuliani et al. (2020)
High-frequency magnetic resonance-guided focused ultrasound surgery
Fibroid size reduction
Yerezhepbayeva et al. (2022)
Khan et al. (2014)
Keserci et al. (2020)
Duc et al. (2018)
Myomectomy
Fibroid removal
Florence and Fatehi, (2022)
De La Cruz & Buchanan, (2017)
Giuliani et al. (2020)
Hysterectomy
Uterus removal
Stewart et al. (2016)
Bala et al., 2015
Giuliani et al. (2020)
Mifepristone, Prollex, asoprismil, ulipristal acetate
SPRM
Farris et al. (2019)
Donnez et al. (2019)
Doherty et al. (2014)
Combined oral contraceptives
Control menstrual bleeding
Florence and Fatehi, (2022)
Kashani et al. (2016)
Khan et al. (2014)
Giuliani et al. (2020)
Leuprolide acetate, centrorelix, gamirelix, elagolix, relugolix, linzagolix
GnRH antagonists
Kashani et al. (2016)
De La Cruz & Buchanan, (2017)
Bulun, (2013)
Giuliani et al. (2020)
Schlaff et al. (2020)
Al-Hendy et al. (2021)
Donnez and Donnez (2020)
Vitamin D
Fibroid size reduction
Baird et al. (2013)
Khan et al. (2014)
Tranexamic acid
Menstrual bleeding reduction
Kashani et al. (2016)
Khan et al. (2014)
Non-steroidal anti-inflammatory drugs
Menstrual bleeding reduction
Kashani et al. (2016)
Epigallocatechin gallate
Fibroid size reduction
Grandi et al. (2022)
Al-Hendy et al. (2021)
Khan et al. (2014)
Hormonal
Non-hormonal
Surgical
the uterus, and treatment is determined with consideration of
fertility preservation. Currently, the removal of UFs ranges
from invasive (hysterectomy, myomectomy) to minimally
invasive (uterine artery embolization, high-frequency
magnetic resonance-guided focused ultrasound surgery) to
non-invasive pharmaceuticals (Table 5). Pharmaceutical
therapies are classified by their mechanism: 1) therapies
aimed at controlling the symptoms of UFs, such as
progestins, oral contraceptives, and antifibrinolytics, and 2)
therapies aimed at reducing the size of fibroids, such as
gonadotropin-releasing hormone agonists and antagonists.
However, these therapies are not curative (Soliman et al.,
2015).
Frontiers in Pharmacology
Treatment for fibroids is often surgical, as it has proven to be
the most effective method (Ishikawa et al., 2010; Sheng et al.,
2020; Florence and Fatehi, 2022). Surgical options depend on the
severity of the case (Table 5). One non-invasive option is
endometrial ablation, which removes the thickness of the
endometrium but requires the use of permanent contraception
post-surgery. Another option is uterine artery embolization,
which reduces the blood flow to specific fibroids to alleviate
symptoms (Levy, 2008; Khan et al., 2014; Giuliani et al., 2020;
Florence and Fatehi, 2022). High-frequency magnetic resonanceguided focused ultrasound surgery is another non-invasive
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hypoestrogenic state caused by agonists is not sustainable, and a
study showed that women using agonists needed some add-back
therapy to reverse some of the symptoms of the hypoestrogenic
state (Kashani et al., 2016).
GnRH antagonists have also been used to treat symptomatic
fibroids (Levy, 2008; Khan et al., 2014; Kashani et al., 2016).
These antagonists work similarly to agonists, but antagonists
have an amino acid substitution from the original GnRH and
competes with it for the binding sites (Kashani et al., 2016).
Antagonists have been shown to decrease the volume and
symptoms of the fibroid. A study showed that when used for
19 days, there was a 41% decrease in the volume of the fibroids. A
downside of both antagonists and agonists is that they can cause
many adverse side effects because of the hypoestrogenic state and
cannot be used for an extended period of time. In the
United Kingdom, the injectable GnRH antagonists cetrorelix
and ganirelix are rarely used, as they have only been part of
observational studies (Kashani et al., 2016). One study with
nearly 400 women from across the world determined relugolix
to be a GnRH antagonist that is suitable for everyday use and has
been proven to reduce menstrual bleeding (Al-Hendy et al.,
2021). Another GnRH antagonist that has been shown to
decrease heavy menstrual bleeding is elagolix (Schlaff et al.,
2020).
Finally, an emerging therapy to treat uterine fibroids is
vitamin D. In Eker rats, the active metabolite in vitamin D
has been observed to stop the proliferation and production of
fibroid cells and their extracellular matrix, thus reducing their
volume (Baird et al., 2013; Khan et al., 2014; Sheng et al., 2020).
option that destroys the fibroid with high-frequency ultrasound
(Levy, 2008; Khan et al., 2014; De La Cruz and Buchanan, 2017;
Yerezhepbayeva et al., 2022).
A more invasive option is a myomectomy, which will remove
the fibroids themselves, although many women require multiple
myomectomies for recurrent fibroids (Levy, 2008; Florence and
Fatehi, 2022). The most invasive treatment is a hysterectomy, in
which the uterus is removed (Clayton, 2006; Levy, 2008; Stewart
et al., 2016; Faustino et al., 2017). Unfortunately, approximately
⅓ of hysterectomies performed are due to uterine fibroids
(Stewart et al., 2016). An analysis of the hysterectomy trends
in India found that fibroids were the cause of 40% of the
hysterectomies performed, followed by chronic cervicitis at
13.6% and dysfunctional uterine bleeding at 12%. The study
found that there was a wide array of diseases that could require a
hysterectomy, but fibroids were the most prominent (Bala et al.,
2015). A full hysterectomy is not always needed; if the risk of
bleeding out is low or the fibroids are smaller in size, doctors may
opt for more conservative treatment in hopes of saving the
uterus. As time progresses, there have been more advances in
less invasive techniques to attempt and treat fibroids, with hopes
that non-surgical treatments will be effective.
Hormonal
Progesterone and estrogen modulators along with other
hormonal interventions have shown an ability to slow and
reduce fibroid growth (Table 5) (Farris et al., 2019).
Progesterone modulators include mifepristone, which is a
selective progesterone receptor modulator (SPRM) that works
to decrease the size of leiomyomas (Farris et al., 2019; Giuliani
et al., 2020). Other utilized forms of SPRMs include but are not
limited to Proellex and asoprisnil (Farris et al., 2019).
Additionally, combined forms of oral contraceptives to
regulate both progesterone and estrogen levels in the body
have been shown to treat fibroids (Khan et al., 2014; Florence
and Fatehi, 2022). Combined oral contraceptive pills are
prescribed to women with or without fibroids to control
heavy menstrual bleeding. In women with fibroids, oral
contraceptives are not expected to shrink the tumor. They
work to suppress endometrial proliferation and thus reduce
menstrual bleeding (Kashani et al., 2016).
A common treatment to shrink fibroids involves GnRH
agonists. These agonists were accepted by the FDA in 1999 in
the form of leuprolide acetate for short-term use prior to surgery.
GnRH agonists are the synthetic model of the gonadotropinreleasing hormone GnRH. These agonists have been shown to
have greater binding affinity and longer half-lives (Kashani et al.,
2016). GnRH agonists work to bind to and downregulate the
GnRH receptors. This downregulation decreases the production
of follicle-stimulating hormone (FSH) and luteinizing hormone
(LH) and leads to a hypoestrogenic state, which causes the
tumors to shrink. GnRH agonists have been shown to
decrease fibroid size by 30%–65% (Kashani et al., 2016). The
Frontiers in Pharmacology
Non-hormonal
One non-hormonal treatment is tranexamic acid, which is
a lysine derivative that prevents fibrin degradation and
stabilizes clot formation (Table 5) (Florence and Fatehi,
2022). Fibrin is necessary to form clots and stop bleeding
(Litvinov and Weisel, 2016). Heavy menstrual bleeding is a
prevalent symptom for those suffering from uterine fibroids,
which affects the coagulation and homeostatic factors of
platelets. Thus, tranexamic acid is used to inhibit the
activation of plasminogen to plasmin. This inhibition
decreases fibrinolysis, clot breakdowns, menstrual flow and
blood loss (Khan et al., 2014; Kashani et al., 2016). Tranexamic
acid was FDA approved in 2009 and is given to women both
with fibroids and without fibroids to treat heavy menstrual
bleeding (Kashani et al., 2016).
Another non-hormonal treatment is non-steroidal antiinflammatory drugs (NSAIDs), which are used to control
uterine bleeding. NSAIDs reduce prostaglandin synthesis by
inhibiting
the
cyclooxygenase
enzyme.
Endometrial
prostaglandin receptors are known to promote the growth of
new vasculature in tumors, which can lead to abnormal bleeding.
Thus, reducing the synthesis of prostaglandin with NSAIDs
reduces the amount of menstrual bleeding (Kashani et al., 2016).
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FIGURE 5
Map of Fibroid prevalence across africa.
Furthermore, the rates of uterine fibroid prevalence varied
greatly among African countries (Figure 5). Even within
countries, the occurrence rates differed vastly. The smallest
prevalence was found to be 3.1% in a 5-year study conducted
in a teaching hospital in Kano, Nigeria (Muhammad et al.,
2013). Over 12,000 women were screened in this study, and
386 of them had leiomyomas. Another study performed in
Nigeria with 4500 women found an incidence of 67%
(Elugwaraonu et al., 2013). The highest occurrence was
found in Ghana, in a study at a teaching hospital in
Kumasi where histology showed that 79% of the women
had uterine fibroids (Titiloye et al., 2018).
The values found in many countries on the African
continent do not match those from the global perspective
(Figure 5), particularly those accepted as the prevalence
values for Black women. The majority of the studies
revealed fibroid occurrences of less than 30% (Mutai et al.,
2015; Ernest et al., 2016; Bineta et al., 2018; Hortence et al.,
2021; Adawe et al., 2022). There may be severe
undercoverage, as some of the available studies do not
have access to many regions and are usually conducted in
one hospital, resulting in a sampling bias.
Additionally, the green tea extract epigallocatechin gallate
(EGCG) has been shown to decrease the size of uterine fibroids
both in vivo and in vitro (Khan et al., 2014; Grandi et al., 2022).
EGCG has been shown to provide anti-inflammatory,
antiproliferative, antioxidant and anticancer effects (Al-Hendy
et al., 2021). These effects help shrink fibroids. One study found a
17.8% uterine fibroid size reduction (Grandi et al., 2022); another
study found a 32% size reduction after four months of use (AlHendy et al., 2021).
African perspective
Prevalence across africa
On the continent of Africa, other challenges arise for women
suffering from uterine fibroids. Upon reviewing several countries
on the continent, published documentations of prevalence were
difficult to obtain (Figure 5). Notably, there are publications
about uterine fibroids by authors across the African continent,
but many of them do not include prevalence data (MorhasonBello and Adebamowo, 2022). This may be due to the lack of
medical record digitization until recently.
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Diagnosis
Additionally, as mentioned in the discussion of overall
treatments, surgery is the standard of uterine fibroid
treatment worldwide, as it has proven to be effective
(Florence and Fatehi, 2022).
The non-surgical treatment methods that are being used in
other countries, such as progesterone modulators, are too
expensive for African women to afford (Igboeli et al.,
2019). One study assessed the costs of uterine fibroid
treatments in US dollars, and it was found that women
who chose surgical options, as opposed to hormonal or
non-hormonal options, overall incurred the lowest costs.
This was due to fewer missed days of work and less
repeated treatment and overall procedure cost (Carls et al.,
2008). Additionally, none of these non-surgical treatments
offer as permanent an option as myomectomies and
hysterectomies (Igboeli et al., 2019). Thus, the women
would have to continue ongoing treatment, which could
take away time and resources. In terms of treatments such
as vitamin D, which can be supplemented, there has not been
adequate research to formulate a standard treatment or
widespread acceptance of it as a treatment. As research
continues, this may become a helpful treatment used
worldwide.
Typically, to diagnose a fibroid, a woman must come to a
hospital or health facility equipped with an ultrasound system
(Sarkodie et al., 2016). The combined use of a physical
examination and ultrasound helps physicians identify the
presence of fibroids (Sarkodie et al., 2016; Igboeli et al., 2019).
The determination can also be made using patient history and
laboratory investigation. Further testing to detect specific
fibroids,
such
as
hysterosalpingography
and
hysterosonography, can be performed.
There can be challenges in obtaining a diagnosis, some
economic and some behavioral. Sociocultural stigma and
perceptions and financial handicaps of UF create a barrier to
seeking treatment and management of this chronic disease. In a
study employed to understand the delay in treatment and
diagnosis of disease, many attributed it to perceiving
symptoms as “normal” or stating “life must continue” or “bills
need to be paid” (Ghant et al., 2016). Furthermore, this delay
could be caused by women not having the time, transportation,
or money to see a professional (Igboeli et al., 2019). Avoidancebased coping, altered perception of normalcy, limited knowledge
of the disease, and lack of financial means deter women from
seeking care (Dominic et al., 2019). Thus, women will wait to seek
diagnosis until their situation becomes highly symptomatic.
Often, they will use orthodox options as a last resort (Okon
et al., 2020).
Future directions
Several issues exist surrounding our understanding of and
determination of appropriate treatment options for fibroids.
First, there is a common understanding that Black women are
at a higher risk of developing fibroids than women of any
other race. It is therefore necessary to assess the prevalence of
the disease on the African continent through a systematic
review of medical charts. The data generated can support or
refute current understandings and provide options for fibroid
prevention and treatment. A medical chart review will provide
a clearer picture of the prevailing burden and trend of the
disease across generations.
This article suggests that nearly half of uterine fibroids are
caused by chromosomal abnormalities. Further research into
genetic drivers of the disease, such as chromosomal aberrations,
and their stratification by race will shed more light on why the
burden is higher for Black women than for white or Asian
women. Additionally, by understanding the chromosomal
abnormalities that occur, there may be emerging technologies
to assess fibroid causes and prevention.
As mentioned previously, the present data covering the
association between BMI and fibroids vary. Some studies
found no association, while others found significant results
showing that fibroids increase as BMI increases. These studies
need to be continued with large populations and include data
from all races. Such findings are critical now, as average BMI
continues to increase across races. Lifestyle is a driver that
Treatment
After diagnosis of leiomyomas, treatment is
administered. Some women may opt to try traditional
practices before an orthodox method (Igboeli et al., 2019;
Okon et al., 2020). Orthodox treatments in Africa include
“expectant
management,
surgery,
uterine
artery
embolization,
ablative
techniques,
and
medical
management” (Akinola et al., 2003; Okon et al., 2020). Of
these treatments, surgery is utilized most often. In one study
with 656 women seeking gynecological treatment at Korle Bu
Teaching Hospital, of those who had fibroids, 79%
underwent surgical treatment (Ofori-Dankwa et al., 2019).
Furthermore, of the surgical treatments, myomectomy is the
most common, with one study reporting that 85% of fibroid
treatments were myomectomies and the other 15% were
hysterectomies (Okon et al., 2020). Hysterectomy is
performed at a lower rate than myomectomy because it
eliminates the possibility of further pregnancy. The high
usage of surgery as a treatment for uterine fibroids in Africa
could be due to numerous reasons. One is that, as discussed
previously, women tend to wait to seek a diagnosis, and in
those cases, the fibroids tend to be highly symptomatic or
large and reduce the possibility of using other treatments.
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often require patients to endure long-term therapy. These
treatments tend to be more costly than surgery. Further
research should be conducted to help mitigate the side
effects of hormonal treatments, provide women with
options outside of surgery, and find cost-effective treatment
for women. Fibroids have been shown to be highly hormone
dependent, which means that women suffering from them
could benefit from seeing an endocrinologist. During the
annual physical examination, hormone levels should be
assessed for high-risk women as a means to identify
fibroids, particularly as they evolve from asymptomatic to
symptomatic.
The current standard of care, which involves
myomectomy and hysterectomy, has evolved with precision
medicine. In many advanced countries, myomectomies and
hysterectomies can take place laparoscopically, which can
lower recovery times and overall costs for women. This is
not usually the case in sub-Saharan Africa. As technologies
advance, the proper equipment to perform these procedures
needs to be expanded worldwide.
patients and physicians can actively correct, whether by diet or
exercise. A woman with a history of fibroids in her family needs
to understand the role that lifestyle can play in the occurrence of
the disease. This understanding is especially important for Black
women, as they are known to have the highest BMI among other
races as well as the highest prevalence of leiomyomas.
Incorporating African women into these studies can help
determine if the correlation between fibroids and BMI also
exists in African women living outside of Western cultures,
where their diet and environment are different.
Similarly, a driver that requires further investigation is
inflammation. Inflammatory cells are present in the fibroid
tissue and extracellular matrix. This may be due to its
endogenous origins along the reproductive tract. Effort
should be directed at evaluating women with prior
inflammatory conditions and assessing whether treating
such inflammation can lead to a decrease in fibroid volume
or symptoms. Larger population studies will aid in
understanding the correlation between fibroids and
inflammation and help researchers design better research
interventions.
A key research area is understanding the fibroid internal
cellular architecture and the various patterns displayed in the
tissues. By creating personalized 3D fibroid organelles in the
laboratory using tissue samples from women with fibroids,
researchers across the African continent can 1) create a
fibroid biobank, 2) develop molecular tools to study the
drivers of the disease and 3) test both conventional
pharmaceutical and herbal drugs. This can help us to study
the role of locations in fibroid patterns. Additionally, beyond the
patterns identified, these 3D cultures will provide an
understanding of the fibroid tissue layers and their ECM. The
organelles will continue to produce important biomarkers, which
will aid in the establishment of new treatments for the disease and
mechanisms to inhibit their proliferation. Furthermore, the
establishment of an immortal cell line from African fibroid
tissues will be crucial in the sequencing of fibroids and
analysis between races. Additionally, by understanding the
signaling pathways that fibroid tissue undergoes as it grows in
a culture medium, researchers can provide clearer answers to
timelines women can expect for their fibroids, especially if
specific drivers are more likely to cause fibroids to grow.
Additionally, it has been demonstrated that histological
assessments provide the widest scope to accurately identify the
prevalence of uterine fibroids. Researchers should aim to develop
better diagnostic tools to identify emerging fibroids at an early
stage or as the condition changes from asymptomatic to
symptomatic.
Non-surgical treatments have proven to be effective in
many cases but unfortunately cause severe side effects and
Frontiers in Pharmacology
Author contributions
NS and AAA conceived, wrote and revised the paper. SN, LP,
EK, MA, AN, HT, and AAA wrote, edited and revised the paper.
Funding
This work was supported by a Burroughs Wellcome Fund
grant (CGT2110276) to AAA and the University of Chicago
Center for Global Health Fellowship Program to NS and SN.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
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