Awareness about venous thromboembolism among saudi females who use oral contraceptive pills: a descriptive cross-sectional study

Background: Oral contraceptive pills (OCPs) are a widely used method of contraception, and use of OCPs is a well-known risk factor for venous thromboembolism (VTE). This study aimed to assess the level of awareness of the association between OCP use and the risk of VTE and the level of knowledge of symptoms and signs of VTE among Saudi females who are users of OCPs. Methods: This cross-sectional study was conducted among the Saudi female population between October and November 2020. Knowledge about VTE risk with the use of OCPs and awareness of VTE symptoms and signs among Saudi females were assessed using a structured online questionnaire distributed through social media platforms. Results: Of 1173 participants, 726 used or had been using OCPs. Only 329 (45%) and 303 (41%) were aware of deep vein thrombosis (DVT) and pulmonary embolism (PE), respectively, as a medical condition, while 312 (43%) were aware of the association of OCPs use with DVT risk. Leg swelling was the most commonly identified symptom of DVT in 297 patients (40%), while shortness of breath was the most common symptom of PE in 331 patients (46%). Conclusion: This study showed that the Saudi female population had a low level of knowledge and awareness of DVT and PE in OCP users. Efforts are needed to increase awareness of these preventable diseases in the Saudi female population.


Introduction:
Venous thromboembolism (VTE), includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common disease that leads to substantial morbidity, mortality, and healthcare costs (1). The worldwide incidence of VTE is 1 per 1000 individuals annually (2). Surgery, hospital admission, immobility, pregnancy, and oral contraceptive pills (OCPs) are independent risk factors for VTE (3). An association between OCP use and increased risk of VTE was observed in the first reported case in 1961 after contraception use gained approval in 1960 (4). This association was later confirmed in many studies (3,5,6). Since then, estrogen doses have been reduced to less than 35 µg in most cases of OCP. Studies also showed a direct correlation between estrogen dose and VTE risk (7). OCPs are the most commonly used method of contraception, with more than 100 million users worldwide (4). A variety of OCPs with different estrogen doses and progestin types are available. The mechanism of estrogen-induced thrombosis is currently unclear; however, increased levels of von Willebrand factor; factors II, VII, VIII, X; and fibrinogen and decreased levels of protein S were observed in users of OCP containing estrogen (6). Moreover, recent studies have shown an increased risk of VTE among third and fourth generations of progesterone with similar estrogen doses. The frequency of OCP use among Saudi females ranges from 27% to 74.9% (8,9). Globally, public awareness of VTE has been limited (10)(11)(12). This study therefore aimed to evaluate the level of awareness of the association between OCP use and VTE risk and the level of knowledge about VTE symptoms and signs among Saudi females who are users of OCPs.

Methodology:
A descriptive cross-sectional study was conducted to evaluate the level of knowledge about the risk of VTE with the use of OCPs and the level of awareness of VTE symptoms and signs among the Saudi female population. For this purpose, we used a structured online questionnaire that was distributed through social media platforms and WhatsApp groups to female populations with diverse education levels, socioeconomic status, and background characteristics. All Saudi women aged 14-65 years were included. Ethical approval was granted by the ethical committee of the College of Medicine, Imam Mohammad Ibn Saud Islamic University. Data were collected for one month, from October 7, 2020, to November 7,2020, and a sample size of 1300 individuals was achieved. One hundred twenty-seven individuals were excluded because they were non-Saudi responders; the final sample was therefore 1173. Data of demographic characteristics, age, education level, occupation, use of OCPs, type and indication of OCPs, and symptoms and signs of PE and DVT were collected. The questionnaire was revised by a thrombosis specialist and gynecologist to increase the reliability and validity of the results. The questionnaire was developed in English and then translated to Arabic; the translated version was reviewed by a specialist in gynecology and thrombosis, and tested on a sample of 46 participants. Before starting the survey, a message stating that answering questions is considered a consent to use the results for medical research. Additionally, a completion message was showed at the end of the survey.
Data analysis was performed using the Statistical Package for the Social Sciences, SPSS 23rd version. Categorical variables were expressed as frequency and percentages. Bivariate and multivariate logistic regressions were also performed to determine factors predicting DVT as a possible complication of using OCPs. P values less than 0.05 were considered statistically significant.

Results:
A total of 1173 women participated in this study. Almost all the participants were living in Saudi Arabia. The majority of them were living in four major cities (Riyadh, Makkah, Jeddah, and Dammam), and more than half were living in Riyadh. Sixty percent of the participants were aged 18-39 years, followed by 40-60 years (30%). Two-thirds of the participants were married; details of socio-demographic data are shown in Table 1. Hypothyroidism, dyslipidemia, and diabetes, which accounted for 82 (7%), 81 (6.9%), and 60 (5.1%), were the most common chronic diseases in participants; however, 78% had no chronic diseases ( Figure  1).   (Table 3).
Among OCP users, the most commonly recognized symptoms or signs of DVT were leg swelling (41%), followed by leg pain and leg discoloration (32%), while those of PE were shortness of breath (45%), chest pain (34%), and palpitation (18%). Incorrect symptoms or signs were included to validate the measures of awareness. Paralysis of the leg (13%) in DVT and arm pain (12%) in PE were believed to be related symptoms or signs (Table 4).  In multivariate logistic regression analysis, higher education, residence in major cities, and use of OCPs were associated with high awareness of DVT as a risk factor related to the use of OCPs (Table 5).

Discussion:
OCPs are a widely used method of contraception. In the present study, the frequency of OCP use was 62% among Saudi females. Saudi females were found to have a low level of awareness of DVT and PE as a risk factor related to OCP use. DVT was a known risk factor for OCP use in 34% of all participants and 312 (43%) of participants who used OCP, while PE was not a known risk factor in all participants. However, 40% participants had awareness of DVT and PE as a medical condition. Similar to our result, a global public awareness study reported a low level of awareness of VTE in the general population (44% for DVT and 54% for PE) (10). In a recent cross-sectional study conducted in Riyadh City, Saudi Arabia, evaluated the level of awareness and knowledge of signs and symptoms of VTE and reported relative lack of awareness (38% for PE and 19% for DVT) [11]. In 340 Saudi pregnant women, the level of knowledge of DVT and PE was determined in 26% and 13% of participants, respectively (12). Lack of awareness was also consistent with the finding of a previous study conducted in Al-Qassim, Saudi Arabia, among women who have attended primary health care centers. That study showed that 50% of participants had a low level of knowledge regarding OCP use (13).
One important factor for evaluating OCP is the current usage or history of usage of OCPs. Our study showed that, among 62% of participants using or have used OCPs in the past, similar to a study conducted in the Riyadh region, 57% used OCP during their lifetime (14). Other studies showed similar numbers, between 40% and 70% (13,15,16). In this study, 20% of the participants were using OCP at the time of the survey, compared to a study that showed 34% of their respondents were using OCPs (17). Our study showed that the majority of participants who used OCPs had used them for more than 18 months (47%), while 15.1% used them for less than three months. A study conducted in Jeddah reported that in those who used OCP, there was a variation in the duration of use, with 22% having used OCPs for less than a year, 32.7% having used between two and five years, and only 13.1% having used for >5 years (18).
In the present study, the first use of OCPs was prescribed by physicians in the majority of participants (80%), while 88 (12.3%) participants bought the medications without a prescription; for 6% and 1.9% of participants, OCPs were recommended by a non-health care provider and by a pharmacist, respectively. Similarly, another study conducted in Riyadh showed that 15% of the participants used OCPs without medical prescriptions (14).
Estrogen and progestin or progestin-only OCPs are the main types of OCPs prescribed. Of those who used OCPs, 34.2% believed that their medication contained estrogen and progestin and 5.6% thought it contained only progestin, while the majority were unaware of the type of OCPs. The most common indication for OCPs in this study was contraception (86%). Two studies from Saudi Arabia showed the same indications in 70% and 62% of participants (14,18).
Similar to non-OCP users, almost half of OCP users were unaware of any symptoms or signs of DVT or PE. The most commonly identified symptoms of DVT were leg swelling, followed by pain and discoloration. Similar to our results, two studies from Saudi Arabia showed that the most identified symptoms of DVT were leg swelling, followed by pain. Similarly, the most common identified symptoms of PE were shortness of breath, followed by chest pain, in both studies (11,12). The least identified incorrect symptoms of DVT were leg paralysis and leg itching, in 15% and 4%, respectively, while in a global public study, leg paralysis and itching were identified in 35% and 22% of participants, respectively (10).
The limitations of this study include the use of closed-ended questions and survey distribution through social media platforms and WhatsApp groups. However, the sample size of this study was large (n=1173) and included participants from multiple cities in Saudi Arabia, while similar studies were conducted in one city. This study assessed the level of knowledge of VTE risk among OCP users, which has not been assessed previously in Saudi Arabia.
In conclusion, this study showed that Saudi females have a low level of awareness and knowledge about the association between VTE and use of OCPs; moreover, they had a low level of awareness about VTE as a medical condition in addition to knowledge on the symptoms and signs. It is important to encourage physicians/pharmacists to educate patients about the risk of VTE with use of OCPs and increase awareness about the symptoms and signs of VTE through public campaigns and social media.