Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, physical activity, stress, and smoking). Some of the epidemiological data were conflicting; consequently, further studies are needed to better understand the factors that influence fibroid prevalence. There is little known about fibroids prevalence in Uganda and therefore, the aim of this study is to assess the prevalence of fibroids in our population of women aged 25 to 56 and to discover possible risk factors for the occurrence of this common gynecological pathology so as to decrease the prevalent cases of infertility and maternal mortality due to uterine fibroids in Uganda.

Uterine fibroids are the most common pelvic tumors in women, occurring globally with a prevalence of 21.4%. Uterine leiomyomata, also referred to as fibroids, are benign growths arising from myometrial smooth muscle cells. As the most common pelvic tumor in women, prevalence of fibroids ranges from 20 to 77%, and accounts for $9.4-$34 billion dollars annually in healthcare costs. As the leading indication for hysterectomy (33%) in US women of reproductive age, it represents a significant source of burden for women and the healthcare system.

There are large disparities in fibroid risk across racial and ethnic populations. Compared with European American (EA) women, African American (AA) women are two to three times more likely to be diagnosed with fibroids, which are also larger in size and greater in number. AAs also have an approximately 10 year earlier onset of fibroids, are more likely to have hysterectomy and seven-fold more likely to have myomectomies for the treatment of fibroids. The role of genetic predisposition in this disparity is supported by two admixture mapping studies of AAs which demonstrated that greater proportion of European ancestry was inversely associated with fibroids in AA women.

Uterine benign tumors of the uterus, are the most common pelvic tumors in women. According to Italian Seveso Women’s Health Study (SWHS), 21.4% of women aged 30 to 60 years were diagnosed with fibroids, which provide one of the best prevalence estimated for fibroids in a European population. Because of their frequency, fibroids represent an important pathology, hence can be the cause of abnormal uterine bleeding, pelvic pain/pressure and may have reproductive effects on infertility and adverse pregnancy outcomes. The etiology of uterine fibroids is poorly understood. Previous studies suggest multiple risk factors for developing fibroids, such as: age, African ethnicity, early age at menarche, reduced fertility, frequent alcohol and caffeine consumption, obesity, consumption of red meat, hypertension, diabetes mellitus, previous pelvic inflammatory disease and genetics. Protective factors are prolonged menstrual cycles, (multi)parity, prolonged use of oral contraceptives, late age at first birth, breast feeding, post menopause, smoking and vegetarian food.

Obesity is associated with higher fibroid risk with most studies reporting a positive but non-linear relationship with categories of body mass index (BMI), an association that may be mediated by elevated bio available estrogen and/or testosterone associated with obesity. The role of endogenous sex hormones in the etiology of fibroids is widely accepted, with factors related to higher cumulative exposure showing increased risk, such as greater age at menopause, after which fibroid risk decreases, and earlier age at menarche.
Interestingly, the Uterine Fibroid Study (UFS) showed positive associations between categories of BMI and fibroids, irrespective of fibroid number or size in black women, but not in white women.
Non-modifiable factors such as race/ethnicity and genetics, and modifiable risk factors such as obesity likely interact together to provide the right conditions for fibroid growth. However, most existing studies relating to fibroids have largely focused on these factors individually rather than their interaction. Recognizing this crucial gap in the literature, the primary goal of this study is to evaluate interactions between local genetic ancestry across the genome and BMI in relation to fibroid presence in Africa-Ugandan women.

Characteristics of fibroid cases and controls in the Vanderbilt University Synthetic Derivative (SD) and CARDIA. Showed that, Nine hundred and twenty-one of the 2,000 women (46.1%) responded to their invitation and uterine fibroids were identified in 21.1% of them. The prevalence of fibroids was statistically significantly lower (6.7%) in the younger group (25-35 years) than in the group aged 36-45 years (prevalence of 33.3%, ?2=34.4, p=0.0001) and that of 46-56 years (prevalence of 60%, ?2=53.7, p=0.0001). The prevalence of fibroids was higher in women who had never used oral contraceptives when compared to those who had (27.0% vs. 19.7%; ?2=4.8, p=0.028). Women with fibroids had a 1.2 kg/m2 (95% CI: 0.4-1.9) higher BMI (t=-3.0, p=0.003).

Comparing women with data available on fibroid status and genotype information in BioVU and CARDIA, cases were more likely to be obese (59.2% and 58.7% in BioVU and CARDIA, respectively) than controls (50.7% and 47.3% in BioVU and CARDIA, respectively). Average age at fibroid diagnosis was 40.6 in the BioVU and 40.0 in the CARDIA; age distribution of controls was similar to those of cases. On average, cases had lower proportion of average European ancestry across the genome than controls. Similar trends of lower European ancestry in cases versus controls were observed when median European ancestry was visualized by strata of BMI category. Distribution of characteristics of cases and controls in the larger SD and CARDIA datasets (including women with and without genotype data) were similar to those described above. AA race was positively associated with fibroids in both the SD and CARDIA, as expected. AA women in BioVU with genetic data available were comparable to AA women in the larger SD, with the exception of age, where average age was more balanced across cases and controls in BioVU than in the larger SD.
Fibroid incidence showed statistically significant correlation with age.
In the age group of 25-35 years, the incidence of fibroids was significantly lower (6.7%), than in the latter two groups: 33,3% in the 36-45 years of age (?2=34.4, p=0.0001) and 60% in the 46-56 years of age group (?2=53.7, p=0.0001). 732 women (79.5%) were using hormonal contraception pills this contraception at some point of their life. In women who have never used these pills, the prevalence of fibroids was higher (27.0%), than in women who have used hormonal contraception pills (19.7%) (?2=4.8, p=0.028). In women who have used combined oral contraceptives a lower prevalence of fibroids was observed (13.3%) as compared to those who have used only gestagens (33.3%) (?2=4.3, p=0.038). According to Association between BMI and fibroid presence by race/ethnicity status in the Vanderbilt University Synthetic Derivative. https://doi.org/1
In reference to Fibroids; Prevalence; Risk factors; Age; Contraceptive pills; Body mass index; Smoking https://doi.org/10.1371/journal.pgen.1006871.t001, Average body mass index (BMI) of women with fibroids detected in our study was 25.8 kg/m2, while BMI of women without fibroids was 24.7 kg/m2. Women with fibroids had a 1.2 kg/m2 (95% CI: 0.4- 1.9) higher BMI than women without fibroids (t (919) = -3.0, p=0.003). Women were divided into four categories based on their BMI score; comparison of individual categories of BMI showed that women with a BMI of 25 kg/m2 to 29.9 kg/m2 had a higher prevalence of fibroids (27.4%), than women with a BMI of 18.5 kg/m2 to 24.9 kg/m2 (17.6%) (?2=9.6, p=0.002).

The sturdy Comparison of key characteristics for African American women in the SD and BioVU. Conducted by https://doi.org/10.1371/journal.pgen.1006871.s001 indicates that, Age of the patients was significantly associated with the prevalence of fibroids. The prevalence of fibroids was lower in women who were younger than 35 years. The prevalence of fibroids increased from 6.7% in patient from the young group (<35 years) to 33.3% in women between 36-45 years of age and to 60% in the age group of 46-56 years. We were also able to confirm that the prevalence of fibroids decreased significantly after age of 50. In their sample the peak of detected fibroids was at the age of 49, after which the prevalence of fibroids was decreasing until the age of 56 where they did not find any fibroid. The most likely explanation is that growth of fibroid is hormone-dependent; therefore, the prevalence is different among age groups. Furthermore, women in menopause are exposed to lower levels of female sex hormones; accordingly, fibroids may significantly reduce their size during this period.

Oral contraceptives may affect the development and growth of fibroids with the time-dependent fashion. Beneficial effect is attributed to the progesterone components of a combined oral contraceptive. It was found that the higher the dose of progesterone norethisterone acetate at the same amount of ethinylestradiol, the lower the incidence of fibroids.

In contrast, all the prescriptions containing gestagen ethynodioldiacetate irrespective of the quantity and type of estrogen, increased the incidence of fibroids. The results showed a protective role of contraceptives on the prevalence of fibroids. The prevalence of fibroid was higher in women who have never used contraceptives (27.0%), than in women who have used contraceptive pills at some point of their live (19.7%), from which we could conclude that taking birth control pills might have a protective role in the occurrence of fibroids. Additionally, the results showed that the occurrence of fibroids is dependent of the type of contraceptives. In women who used combined oral contraceptives fibroids occurred less often (13.3%) than in women who used gestagen tablets (33.3%). In contrast to some reports in the literature the duration of the oral contraceptive pills was not found to be statistically important for the occurrence of fibroids in our patients.

It was observed that fibroids are more frequent in obese women (body mass index – BMI > 30 kg/m2). Body weight of 70 kg or more represents a nearly three-fold increased risk of incidence of fibroids compared with a body weight of 50 kg. Similar results were obtained by monitoring the BMI. In a case–control study from Thailand, a 6% increase in risk was observed for each unit increase in BMI. The results showed that BMI in women with fibroids was in average 1.2 kg/m2 higher compared to women without fibroids. Elevated BMI has a greater impact on the risk of the incidence of fibroids after the age of 18, if it is higher than 20 kg/m2. Its greatest impact has been seen between 27.5 kg/m2 and 29.9 kg/m2. The results showed that the prevalence of fibroids was higher (27.4%) in women with BMI between 25 and 29.9 kg/m2 than in women with a BMI between 18.5 to 24.9 kg/m2 (17.6%). These results are consistent with reports in the literature.

In their study they also assessed the importance of the other risk factors which might have a possible role in the occurrence of fibroids. Three major groups of risk factors were analyzed: gynecological history, lifestyle and medical history. Although early age at menarche showed to be important in association with fibroids development, they did not find any significance. Moreover, they did not find any significant correlation between some of the lifestyle habits, like cigarette smoking, consumption of alcohol, consumption of red meat, vegetarian diet, and occurrence of fibroids, even though some authors describe these features as significant. Some reports in the literature showed fibroids to be more frequent in women who experience arterial hypertension and diabetes; however their results do not support this association.

There are some studies that show connection between different types of fibroids and reproductive outcomes. Results from this study showed that intramural fibroids are associated with greater risk for spontaneous abortion. This may be important for those fertile women who are trying to get pregnant and experience asymptomatic intramural fibroids. This study was limited to Caucasian women, since in Slovenia there is mostly Caucasian race present in the population. Thus, this result could be generalized to the Slovenian population; other countries with diverse races could have other results of similar studies.

Methodology

The study is based on a random sample of 200 women within the age group of 25 to 56 years. Living in the four districts of Central Region of Uganda and the data will be processed with the statistical program PASW 18, and p values < 0.05 will be taken to statistically significant differences. Participation will be completely voluntary. Eligible participants will sign an Informed Consent Form, fill out a questionnaire and will undergo a trans-vaginal ultrasound and hormonal analysis, the results are recorded. In addition to basic information regarding the age, height, weight, and education, the questionnaire will also ask about smoking, alcohol and caffeine consumption, nutrition, sexual and reproductive life, participant’s health status (hypertension, diabetes mellitus) and about the family history of the disease (fibroids), history of abortion or miscarriage, UTIs/STIs.

After completing the questionnaire, the participants will be invited to an ultrasonography office where the screening for uterine fibroids will be performed by certified gynecologists trained in transvaginal ultrasonography. For this purpose, the Medison Accuvix XQ ultrasound machine with the EC4-9IS endovaginal probe will be used. During an ultrasound examination, uterine dimensions and structure will be assessed and the number, location and size of largest fibroid defined.

Data management

The data will be analyzed with the statistical program PASW 18 (SPSS Inc., Chicago, Illinois, USA). Numeric variables will be represented by the arithmetic mean and standard deviation and descriptive variables will be presented with frequencies. The relationship between descriptive hormonevariables will be analyzed with the »Pearson chi-square test« or »Fisher's exact test of independence« by testing equality between the observed and expected frequencies. The differences in the average value of the numeric variables will be assessed using t-test for independent samples or one-way analysis of variance (ANOVA). The multiple comparisons as "a post hoc" analysis will be performed using Bonferroni error correction of the first type. The limit of statistical significance will be at p <0.05.

Project Beneficiaries

The need for this project was identified during the field visits and local community meetings as marginalized women groups of reproductive age expressed concerns over risk factors and prevalence of fibroids among women in Uganda.

The direct beneficiaries of the project are the entire population of marginalized women groups of reproductive age of 25 to 56 years. Facing risk factors and prevalence of fibroids in the local communities living in the four districts of Central Region of Uganda such as Wakiso, Kampala, Mukono and Mpigi District. These districts have been selected on the basis of having the highest number of population in Uganda as per the National Housing and Population Census (UBOS Report 2014).

Project Activities

i) Project Initiation,
ii) Recruitment of staff,
iii) Procurement of Resources & Equipment,
iv) Data collection
v) Ultrasonographic diagnosis
vi) Hormonal analysis
vii) Monitoring and Evaluation,
viii) Reporting & Documentation.

Main objective

To provide a research data-base on fibroids risk and prevalence in Uganda

Specific objectives

i) Evaluate the relations between fibroids and infertility.
ii) Assess the prevalence of fibroids in a patient population.
iii) Assess the relationship between body mass index and the fibroids growth.
iv) Reveal the risk factors for uterine fibroids in our population.
v) Evaluate interactions between local genetic ancestry across the genome and BMI in relation to fibroid presence in Ugandan women.

Expected Results

i) Project Initiated,
ii) Staff recruitment conducted,
iii) Resources & equipment procured,
iv) Carried out Data collected on fibroids,
v) Conducted Ultrasonographic diagnosis,
vi) Hormonal analysis conducted,
vii) Monitoring & Evaluation,
viii) Project Reporting.

Sustainability

The sustainability for the project is crucial and to ensure the long-term success of the project sustainability, there are methods that have been identified as below:

• Mainstreaming with Government

The target of the project is to build replicable model of support and access to quality healthcare without compromising that can be adopted by the Government. This will ensure the overall long-term sustainability of the project. Significant effort will be placed on liaising with the Government and promoting this successful model of healthcare for people with HIV/AIDS in the communities.

Monitoring and Evaluation Plan

Basically, the monitoring and evaluation system will be inbuilt where diversions will be identified as soon as they occur. Monitoring tools such as reporting, monthly meetings, project visits and advisory meetings will be held regularly and information will be channelized to review the progress of the project with all stakeholders including the primary beneficiaries and the donors. Further, a deliberate effort will be made to make reports quarterly about the progress of the project, and these will be shared among project donors, stakeholders especially the donors and other supporters.