Sponsored by the Campion Fund and the Fibroid Foundation of Africa
Prepared by Elizabeth Korasure. Edited by Phyllis Leppert for the Campion Fund
Abstract: Uterine Fibroids (UFs) are very common benign gynecological tumors, and they disproportionately impact black women at a much higher rate than their racial counterparts. In February 2022, clinicians, and researchers in the field of obstetrics and gynecology from nine African countries, USA, and Germany came together for a two-day conference on Uterine Fibroids. This meeting provided a learning opportunity to 1. discuss the prevalence of UFs in the African regions 2. discuss novel research on the management of UFs 3. identify and understand treatment options available for women in Africa 4. identify existing policy and policy change 5. understand existing tools to educate, advocate, and provide awareness across the continent within the cultural context. This was the first conference discussing the management issues of UFs in African regions with a focus on improving the quality of life for women living in these regions. The presenters collectively agreed on the need for collaborative, culturally sensitive and more non-invasive treatment options and establishing support groups in the community to increase public awareness and education in African countries regarding the nature and symptoms of uterine fibroids.
Introduction
Uterine fibroids (UFs), also termed leiomyomas or myomas, are the most common benign gynecologic tumors in women. Evidence from ultrasound shows that more than 80% of African American women and approximately 70% of Caucasian American women develop uterine fibroid by the age 50. Most fibroids are asymptomatic and only 20% to 50% of women with fibroids experience associated symptoms (1). In African regions, fibroids are a significant health issue for women and their families. It leads to severe anemia, pain, and bleeding in women of reproductive age significantly interfering with women’s ability to work, their employment prospects and their overall quality of life while receiving no proper attention in the region.
UFs are an endemic health issue in the African regions (2). However, it is hard to ascertain true prevalence in an environment where data collection and management are poor and research opportunities are woefully inadequate and underfunded (3). UFs result in greater morbidity and high rates of mortality due to delayed presentation, existing myths, misconceptions, and unjust cultural norms. In villages, women are ostracized, many unable to marry, and many have died from the consequences of UFs. This is an overlooked, understudied, underreported, and underfunded chronic condition that should be listed as a reproductive health priority in these endemic regions. Large tumors are seen in young women between the ages of 22 to 24 and the fear of surgery and scorn from family members cause patients to suffer in silence and turn to unapproved phytotherapy and spiritual practices that only lead to the worsening of their condition. Lack of information and education, unavailable data, and inaccessible and unaffordable treatment options brought the clinician, researchers and policymakers together for this first-ever meeting “the Premier African Conference” to look at the scourge of this health issue plaguing African families.
Prevalence and data collection
Adequate data on the prevalence of UFs is paramount for treatment and management. The cause of UFs is largely unknown but the racial disparity and some of the risk factors associated with UFs are well documented (4).
Nearly all the presenters expressed their concerns that the UFs in African regions are widely underreported and understudied. Only a few studies have some information on the prevalence of UFs in African countries, and those studies used different populations, sample sizes, and different study designs (5). No population-based study with adequate statistical power and sampling strategy has been published which can generate generalizable information on the incidence, prevalence, and risk factors of UFs among indigenous black African women (5).
Some women with fibroids remain asymptomatic throughout their life, and some with fibroids can have successful full-term pregnancies without any complications. For others, however, living with UFs can have a largely negative impact on their quality of life. The African data solely captures women reporting symptoms of UFs at established health facilities. Patients who cannot afford or do not have access to these facilities or experience no symptoms or less severe symptoms are not included in these data. Some cannot get pregnant and are therefore labeled as infertile in their community. This existing stigma prevents many women from seeking medical attention to hide their disease. These cultural practices or beliefs deterring women from seeking help also result in under-presenting women with UFs in national data. The experts and clinicians called for national programs in the African countries to establish greater access to facilities and basic diagnostic procedures for early detection of UFs. Better funding of well-designed and adequately powered studies is also required to improve data collection and our understanding of the prevalence of UFs in Africa.
Research
Critical areas suggested for research include but are not limited to 1. Investigating the pathogenesis of the disease. 2. Conducting clinical trials in African countries to collect data on the efficacy of newly FDA-approved medications among the African population, (6). 3. Approving and conducting clinical trials in African regions to study the impact of natural treatments such as Vit D, EGCG, (7) indigenous herbal remedies in alleviating UFs and associated symptoms for approved usage. 4. Exploring the possibility of studying emerging and novel treatments such as Collagenase injection (8) for approval of usage among African women. 5. Translating the standard quality-of-life (QoL) questionnaires into various languages to make available and facilitate better data collection from the African population.
Research studies identifying some of the genetic drivers in uterine leiomyomas were discussed during the meeting. These genetic drivers include high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen type IV, alpha 5 and collage, type IV, alpha 6 (COL4A5- COL4A6) deletion. (9) HMGA2 and MED12 contribute to 80-90% of all leiomyomas. Further investigation is needed to determine whether these are biomarkers can be used to diagnose and manage UFs.
One of the speakers, Dr. Leppert, explored the novel management of symptomatic UFs using the FDA-approved bacterial collagenase as a possible treatment for UF (8). This collagenase-digested types I and III collagen fibers in fibroid tissues (10,11). UFs are composed of extracellular matrix (ECM) consisting mainly of disorganized and highly cross-linked collagen fibers. Bacterial collagenase digests type I and type III collagens that are abundant in fibroids subsequently debulking the fibroid tumor and through the mechanism of mechanotransduction could prevent regrowth. Evidence from minimally invasive procedures suggests that a reduction in UFs contributes to a reduction in fibroid-related symptoms. Phase 1 clinical trial of this injectable collagenase in the United States proved to be safe and well tolerated when injected directly into the center of a uterine leiomyoma and resulted in a reduction in fibroid size and a notable reduction in fibroid-related pain reported by the patients (8). It was further suggested that this less invasive option can be funded and implemented to improve the QoL among African women living with UFs. Dr. Leppert also stated that UF are very heterogenous as all fibroids are dissimilar which makes treatment difficult (12).
Dr. Othman, one of the speakers, also touched on research studies in understanding the basic science and cellular origin of UF including assessing Bisphenol A concentration (13), the role of telocytes (13) and lower levels of Vitamin D in human uterine leiomyomas (14). ABottom of Form Top of Formsignificantly higher concentration of Bisphenol A (BPA) has been documented in UFs compared to leiomyoma-free uterine tissue. BPA is involved in a cellular signaling cascade that induces myometrial cell proliferation leading to development of leiomyomas. The molecular mechanism of BPA on human uterine leiomyoma via transmembrane estrogen receptor has been further explored (15). Higher numbers and activity of telocytes in leiomyoma tissues also suggest their role as hormonal sensors for UFs stem cell growth and organization. Significantly lower levels of 1, 25 dihydroxyvitamin D3 in uterine leiomyomas tissues has also been reported to contribute to the tumor development. These findings alongside other research studies on the molecular mechanism and pathogenesis of uterine leiomyomas facilitate developing targeted treatments and potentially preventive interventions.
Prevention, Diagnosis and Management
Africa is a continent with a population of 1.4 billion. Women constitute nearly half of that population with an estimated 80% risk to develop UFs in their lifetime. Therefore, early diagnosis and treatment of UFs should be one of the public health priorities. UFs presentation, diagnosis and management depends on the patient’s state of health, knowledge of the condition, economic resources, marital status, and available health services within her community. Presenters and participants strongly advocated for early screening for the management of UFs. Many young patients are not detected during the symptomatic stages of the tumor. In some situations where some symptoms manifest, patients are not given the required attention.
A clinical diagnosis is relatively easy to make for a well-trained physician from a simple physical and/or abdominal/pelvic ultrasound (16). It was suggested that portable ultrasound equipment that can be managed by community health workers must be deployed in low-resourced communities for screening, early detection, and prompt management. Management of this condition can be complex. Less invasive management includes medical intervention to alleviate symptoms such as excessive bleeding, anemia, and pelvic pain. Other medical interventions include hormonal treatments to shrink the size of UFs or slow down their growth. However, cessation of these medical interventions often leads to disease recurrence and patients are left to seek more invasive interventions.
Minimally invasive surgical options include laparoscopic surgery, uterine artery embolization (UAE), magnetic resonance image-guided focused ultrasound (MRgFUS), and robotic-assisted hysterectomy and myomectomy and interventional therapies. These are novel treatments, (17) technologies, and tools for UFs currently not available to African women. Minimally invasive procedures are either unavailable or unaffordable in the region. Thus, clinicians see hysterectomy and myomectomy (in that order) as the easiest and most readily available treatment options. However, these invasive treatment options hinder treatment-seeking behavior in patients due to cultural norms and beliefs. For instance, myomectomy is largely believed to hinder fertility in communities. In Senegal women prefer not to undergo myomectomy even if it is the only available treatment option. These invasive procedures are also often done under subpar conditions leading to intra-operative or post-operative complications compromising patient safety and their reproductive health. For these reasons and more, women prefer less invasive options.
Presenters recommended preventive and management alternatives to surgery that will help to significantly reduce the burden of fibroids in pre-symptomatic, early, or late disease stages. It has been documented that appropriate doses of vitamin D can slow the growth of existing fibroids and reduce the formation of new fibroids (18). A daily oral dose of Vit D supplementation from the age of 18 to 30 has been documented as a highly beneficial, inexpensive, readily available treatment for UFs (18) There were little or no side effects and reduced the burden of UFs if supplemented early and for a minimum of 8 weeks at dosage of 50K IU/day followed by a maintaince dose of 2k IU daily (18). Previous studies in a xenograft model demonstrating the effect of Vitamin D on uterine fibroids provided the impetus for this clinical trial (19). Recently, studies have demonstrated that this treatment was effective independent of MED12 mutation (20). Another non-invasive intervention mentioned during the meeting was EGCG (epigallocatechin gallate) for the treatment of UFs in Africa. EGCG has been shown to exhibit anti-inflammatory, antiproliferative, and antioxidant effects and also inhibits key pathways for tumor growth. In a smaller randomized pilot study, daily 800mg of oral EGCG administered for four months decreased total uterine fibroid volume in patients and improved menstrual bleeding patterns among women with symptomatic UFs (21). No adverse effects of any kind have been documented and it is currently being used in one multi-site US-based clinical trial involving unexplained infertility and UFs (FRIEND study).
Existing Policy and Policy Change
Presenters and participants advocated for national strategies to revise reproductive health policies and guidelines to provide a robust policy on UFs as a public health concern (22) in all African countries given the magnitude of the situation. National reproductive health policies must be more comprehensive for the treatment of UFs especially under the National Health Insurance Schemes (NHIS) to meet the vision of Universal Health Coverage (UHC). More attention needs to be paid to women’s health care services at the primary level to provide care for women with fibroids. Policies should cover the annual screening of women in their preconception ages for early detection, management and treatment. Reproductive health educational programs to factor in UFs awareness campaigns are necessary. Monitoring and evaluation policies and frameworks must provide guidelines for capturing data on UFs services in health facilities.
Public education, advocacy, and communication
Conference presenters and participants agree that an effective communication strategy is essential to successfully managing and treating UFs in Africa. The myths and misconceptions are many and widespread, and a deliberate attempt should be made to debunk them. Accurate information, awareness, and deepened knowledge about UFs can empower women to recognize early warning signs, overcome their fear of surgery and the misconceptions they harbor, and promptly seek medical care (23).
The meeting attendees called for the establishment of strategic health education and advocacy programs provided to meet the needs of the population. Civil society groups and school health clubs as collaborators in public health education campaigns was recommended. Strong media engagement is encouraged to help to alert the public about UFs as well as a means to fight misconceptions and myths on UFs.
A CALL FOR ACTION: International collaboration and partnership
The conference recognized that intercontinental and inter-country collaboration, coordination, and global connectivity are needed to drive UFs interventions in Africa. A multistakeholder global TASK FORCE with academia, the private and public sectors, and individuals is key to generating knowledge to inspire action on the African continent and must be established. This partnership will also serve as a learning platform to provide a timely opportunity to share best practices, innovations, and experiences and leverage novel trends in the care and treatment of UFs in Africa.
References
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List of Presenters
1. Triphonie Nkurunziza, Obstetrician-Gynecologist. Team Lead for the Reproductive, Maternal health and Aging in the Universal Health Coverage and Life Course cluster, WHO Regional Office for Africa, Brazzaville, Congo.
2. Chris Opoku Fofie, Consultant Obstetrician-Gynaecologist and Head of Safe Motherhood Programme, Ghana Health Service.
3. Prosper Igboeli, Obstetrician-Gynecologist, with 45 years of experience in the medical field managing women’s health in Nigeria and the US. Founder and Director of M&M Hospital in Abuja and Aba, Nigeria.
4. Essam Othman, Obstetrics and Gynecology Department, University of Assiut, Egypt, Amsterdam UMC, Vrije, Universiteit Amsterdam, Netherlands, Member of FIGO Menstrual Disorders Committee
5. George Bryn Makoni, Medical Practitioner at Hwange Medical Centre, Zimbabwe, with a special interest in Mother and Child Health, Industrial Health, anesthesia and pain management, Mental Health, training and development, and Business management.
6. Mama Sy, Head of the Department of Histology, Embryology, and Human Cytogenetics, Faculty of Medicine, The University of Cheikh Anta Diop de Dakar in Senegal.
7. Awa Bineta, Genomic Specialist, Senegal Gates Project at Cheikh Anta Diop University.
8. Phyllis Leppert, Professor Emerita of Obstetrics and Gynecology, Duke University School of Medicine, Durham NC, USA.
9. Tanja Hohenester, professionally trained micronutrient coach and nutritionist who is passionate about alternative medicine for UF treatment. Founder of Tigovit, Germany
10. Ayman Al-Hendy, Professor and Vice-Chair for Research, Department of Obstetrics and Gynecology, Advisor to the Dean of Medicine, Pritzker School of Medicine, University of Chicago. Dr. Al-Hendy is a Gynecologist and Endoscopic Surgeon at UC Medical Center, Chicago, Illinois.
11. Charlotte Tchente Nguefack, Chief of the Obstetrics and Gynecology Department of the Douala General Hospital (DGH) and member of the medical department responsible for the mother-child sector at DGH. She is a member of 6 societies of Obstetrics and Gynaecology: SOGOC, CFS, SAGO, GIERAF, CNGOF, and FIGO.
12. Muyingo Mark Tamusang, Managing Director and Fertility Specialist at Neogenesis Fertility Centre in Uganda. He is also a Laparoscopic Gynecological Surgeon at Mulago Women’s Specialized Hospital and at the Doctors Hospital, Seguku, Uganda.
13. Godfrey Jacob Chale, Obstetrician/ Gynaecologist in Dar es Salaam, Tanzania, with interest in gynecologic oncology clients for possible laparoscopic inventions. He has several publications in gynecologic oncology to his credit.
14. Daniel Kofi Yeboah, General Practitioner at Hawa Saviour Memorial Hospital in Ghana, with a surgical inclination in Obstetrics & Gynaecology including pediatric surgery.
15. Olutosin A. Awolude, Department of Obstetrics and Gynaecology, College of Medicine, University of Ibadan, Nigeria and an honorary Consultant Obstetrician & Gynaecologist to University College Hospital, Ibadan, Nigeria. 16. John Jude Kweku Annan, Department of Obstetrics and Gynaecology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Honorary Consultant in Reproductive Endocrinology and Infertility (REI), Directorate of Obstetrics and Gynaecology, Komfo Anokye Teaching Hospital, Kumasi.