Prevalence of human papillomavirus infection and associated factors among women attending cervical cancer screening in setting of Addis Ababa, Ethiopia.

Human papillomaviruses (HPVs) are circular, nonenveloped small double-stranded DNA viruses that infect stratified epithelium and can cause a number of life-threatening diseases. HPV is the central risk factor for developing cervical cancer and is estimated that approximately 98% of this disease is associated with oncogenic types of HPV. HPV infection leads to an estimated 266,000 cervical cancer deaths annually. Therefore, the objective of this study was to determine the prevalence of HPV infection and risk factors associated with cervical lesion among women attending the cervical cancer screening clinic at the Ethiopian Family Guidance Association, Addis Ababa. A cross-sectional study was conducted to determine the prevalence of HPV infection. Data were collected using a questionnaire and samples leftover from cervical screening were taken. The leftover swab was air dried and DNA was extracted and amplified by using a PCR. A total of 247 women were included in the study. The prevalence of HPV was 9.72% among the population studied. Of all participants, 27.13% were positive for cervical intraepithelial neoplasia-1 (CIN1). CIN1 positivity was found in half of HPV positive women. Among HPV positive women, half of them had started sexual intercourse at ages 12-17 years and 41.66% were women who gave birth at ages 12-17 years. The high prevalence of HPV and the CIN1 positive group were ages 36-57 and women with multiple sexual partners. The other groups with the highest CIN1 positive were 22.39% grade (9-12) and 20.9% primary (1-8) and uneducated women. Among HPV positive women, 83.33% had an abortion history and 80% miscarried in the first trimester. Among the CIN1 positives, 53.73% had more than two sexual partners. Among HPV positive women, half of them were users of contraception methods. In conclusion, the highest prevalence of HPV is among women who began sexual intercourse earlier and who gave birth at 12-17 years of age, have an abortion history, with MSP and oral contraceptive methods users. In addition to HPV, early pregnancy and sexual intercourse at 12-17 years of age, abortion, MSP, and oral hormonal contraceptives are factors in cervical cancer. Finally, most women do not have enough knowledge and awareness about cervical cancer and the risk factor.

Cumulative exposure to estrogen may increase the risk of migraine in women.

BACKGROUND: Migraine is a common disorder, particularly affecting women during their reproductive years. This female preponderance has been linked to exposure to female sex hormones. METHODS: We used self-reported data from women born in 1943-1965 enrolled in the Norwegian Women and Cancer Study to examine the differences between women with migraine and women without migraine in a prospective design with respect to both endogenous and exogenous female sex hormone exposure. RESULTS: In total, 62,959 women were included in the study, of whom 24.8% reported previous migraine (n = 15,635). Using a Cox proportional hazards model, we found that higher age at menarche reduced the risk of migraine (hazards ratio (HR) = 0.96, 95% confidence interval (CI) = 0.95-0.98) and that oral contraceptive use and parity increased the risk of migraine (HR = 1.12, 95% CI = 1.06-1.18 and HR = 1.37, 95% CI = 1.29-1.46, respectively). CONCLUSIONS: Older age at menarche appears to reduce migraine risk, whereas oral contraceptive use and having children appear to increase the risk. Further research is required to investigate the causality of these associations.

Contraceptives and Thrombosis: An Intertwined Revolutionary Road.

The development of oral contraceptives (OCs) began in 1921 and continued in the following years until the first regulatory approval from the Food and Drug Administration was granted in 1960. However, it took several years to realize that OCs presented an important but not frequent risk of venous thrombosis. Several reports ignored this dangerous effect and only in 1967 the Medical Research Council clearly stated this as an important risk. Later, research led to the formulation of second-generation OCs containing progestins, which nevertheless presented an increased thrombotic risk. In early 1980s, OCs containing third-generation progestins were introduced into the market. Only in 1995, it became clear that these new compounds induced a higher thrombotic risk than that related to the second-generation progestins. It appeared clear that the modulating action of progestins was against the procoagulant activity of estrogens. Lastly, at the end of the 2000s, OCs containing natural estrogens and a fourth-generation progestin (dienogest) became available. The prothrombotic effect of those natural products was not different from that of preparations containing second-generation progestins. Moreover, research over the years has produced much data on risk factors associated with OCs use such as age, obesity, cigarette smoking, and thrombophilia. These findings allowed us to better assess the individual thrombotic risk (both arterial and thrombotic) of each woman before offering an OC. Furthermore, research has shown that in high-risk people the use of single progestin is not dangerous as far as thrombosis is concerned. In conclusion, the OCs road has been long and difficult but has led to a great and unthinkable scientific and social enrichment since the 1960s.

Hormones and thrombosis: the dark side of the moon.

BACKGROUND: The main drawback of oral contraceptives (OC) and hormone replacement therapy (HRT) is an increased risk of venous and, to a lesser extent, arterial thrombosis. MATERIALS AND METHODS: This narrative, case-based review describes the effect of available estrogens and progestogens on the hemostatic system and their potential impact on the risk of thrombosis. Clinical cases are used to illustrate different options for prescribing OC and HRT in the real-word. The aim is to offer discussion topics that could be helpful to guide the choice of different hormonal treatments over a woman's lifetime and in the presence of risk factors. RESULTS: We describe physio-pathological changes occurring during the administration of hormonal therapies. Furthermore, we analyze the risk of venous and arterial thrombosis associated with different products, routes of administration and additional risk factors. New hormonal preparations, such as estradiol combined with dienogest, as well as non-oral hormonal therapies, are suggested to decrease thrombotic risk significantly. DISCUSSION: The availability of many products and different routes of administration allow most women to safely use contraception, as well as HRT. We encourage careful counselling instead of inflexible or fearful behavior, as expanding options and choices will allow women to make the best decisions for their health.

Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis.

Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.

Venous Thromboembolism in Exploration Class Human Spaceflight.

INTRODUCTION: A recent finding of a deep venous thrombosis during spaceflight has prompted the need to clarify mechanisms and risks of venous thromboembolism (VTE). In turn, mitigation countermeasures, diagnostic modalities, and treatment options must be explored. The objective of this review was to synthesize current evidence on VTE in spaceflight.METHODS: A literature review was performed from inception to April 2023 pertaining to VTE in the context of spaceflight or ground-based analogs with human participants. PubMed was searched for papers written in English using the terms "spaceflight" or "weightlessness" and "thrombotic" or "embolism" or "thromboembolism" in "venous" or "veins". Papers using cellular or animal models were excluded.RESULTS: There were 63 papers captured; 7 original scientific studies, 3 narrative reviews, 2 systematic reviews, and 3 commentaries discussed VTE in spaceflight. Reference lists were screened. Important themes included: altered venous hemodynamics, increased fibrinogen and coagulation markers, hypoalbuminemia, and immune dysfunction. Additional risk factors may be seen in women, such as the use of oral contraceptives.DISCUSSION: Venous stasis and decreased shear stress secondary to fluid shifts may induce inflammatory changes in the venous system, resulting in endothelial damage and upregulation of the coagulation cascade. Additionally, women in space are subject to physiological factors increasing their VTE risk, such as the use of oral contraceptives, inducing increased blood viscosity and hypoalbuminemia. Efforts should also be placed in optimizing sensitivity and specificity of imaging markers, payload, and training ability, notably the use of vector flow imaging, and improving point-of-testing biomarkers, such as albumin and p-selectin.Levasseur S, Purvis N, Trozzo S, Chung SH, Ades M, Drudi LM. Venous thromboembolism in exploration class human spaceflight. Aerosp Med Hum Perform. 2024; 95(1):45-53.

Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women.

There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis.

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Drospirenone and estetrol: evaluation of a newly approved novel oral contraceptive.

INTRODUCTION: Estetrol (E4) is a native estrogen produced only by the fetal liver during pregnancy. E4 is the first new estrogen to be used in hormonal contraception since the introduction of oral contraceptives in 1960. Ethinyl estradiol, the most commonly used estrogen in oral contraceptives today, increases the risks of thromboembolism and has other significant hepatic impacts, which induce important drug-drug interactions. On the other hand, Phase 2 E4 characterization studies demonstrated that E4 has negligible impacts on liver, breast, and vascular endothelium due to its distinct tissue selectivity. Combined with drospirenone (DRSP), E4 offers an improved safety profile for oral contraception. AREAS COVERED: This paper briefly highlights the unique pharmacokinetic and pharmacodynamic features of E4. The efficacy, safety, and tolerability results from the Phase 2 and 3 studies of the E4/DRSP pill are discussed to provide the reader with a thorough understanding of E4 and information to use when counseling potential users. EXPERT OPINION: The estetrol/drospirenone oral contraceptive is effective and well tolerated and provides good cycle control. In the future, estetrol may be the estrogen of choice if subsequent evidence verifies that it reduces the risks associated with current estrogens, such as venous thromboembolism and drug-drug interactions.

Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. RESULTS: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. CONCLUSION: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Associations of Oral Contraceptive Use With Cardiovascular Disease and All-Cause Death: Evidence From the UK Biobank Cohort Study.

Background The associations of oral contraceptive (OC) use with cardiovascular disease (CVD) and all-cause death remains unclear. We aimed to determine the associations of OC use with incident CVD and all-cause death. Methods and Results This cohort study included 161 017 women who had no CVD at baseline and reported their OC use. We divided OC use into ever use and never use. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs for cardiovascular outcomes and death. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI, 0.86-0.99) for all-cause death, 0.91 (95% CI, 0.87-0.96) for incident CVD events, 0.88 (95% CI, 0.81-0.95) for coronary heart disease, 0.87 (95% CI, 0.76-0.99) for heart failure, and 0.92 (95% CI, 0.84-0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the associations of OC use with CVD events were stronger among participants with longer durations of use (P for trend<0.001). Conclusions OC use was not associated with an increased risk of CVD events and all-cause death in women and may even produce an apparent net benefit. In addition, the beneficial effects appeared to be more apparent in participants with longer durations of use.

Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage. METHODS: This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review. RESULTS: Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2). CONCLUSION: The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.

Acquired SERPINC1/antithrombin deficiency during oral contraceptive consumption: a case report.

BACKGROUND: SERPINC1 is a glycoprotein that regulates blood coagulation. SERPINC1 congenital or acquired deficiencies represent a significant risk factor for thromboembolic disease. SERPINC1 acquired defects are observed in very few cases and can occur in many clinical conditions such as treatment with L-asparaginase or oral contraceptive (particularly estrogen derivatives), but these conditions are not routinely investigated. CASE PRESENTATION: A 50-year-old Caucasian woman who took gestodene 75 µg/ethinylestradiol 20 µg as oral contraceptive, was sent to our thrombophilia clinic because, on thrombophilia testing, a reduction of SERPINC1 (74%) and a slight increase in circulating D-dimer and homocysteine were found. We investigated triggers of such SERPINC1 reduction, and identified gestodene 75 µg/ethinylestradiol 20 µg use as the most likely candidate. Two months after the discontinuation of the oral contraceptive, SERPINC1 value returned to normal (92%) and D-dimer and homocysteine were normalized. CONCLUSION: Each patient has a different sensitivity to contraceptive use. Genetic (or epigenetic) regulation of anticoagulant proteins might account for a different rate of consumption of anticoagulant proteins as oral contraceptives and probably determine the susceptibility to thrombotic events.

Population-based cohort study of oral contraceptive use and risk of depression.

AIM: Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. METHODS: This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. RESULTS: We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. CONCLUSIONS: Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

Thromboembolism Triggered by a Combination of Electronic Cigarettes and Oral Contraceptives: A Case Report and Review of Literature.

Genetic predisposition, oral contraceptive (OCP) use, tobacco smoking, cancers, and trauma are well-known triggers for hypercoagulability and thromboembolism. Multiple reports have been published on the health risk of combining OCP and traditional cigarettes smoking in the context of thromboembolism. However, limited information is available on the health consequences of combining OCP use with electronic cigarettes. Here, we report a case of a young female patient with a past medical history of ovarian cysts and electronic cigarettes use who came into the hospital with a complaint of "recurrent seizures" and tachycardia. This patient was subsequently diagnosed with bilateral pulmonary emboli, subacute cerebrovascular accident (CVA), and possible patent foramen ovale. Therapeutic Lovenox was initiated. Reasons to educate young females on the risks of combining OCP and electronic cigarettes use were explained.

Women consuming oral contraceptives containing cyproterone acetate and ethinylestradiol show a higher risk of thyroid cancer than nonusers.

This study explored whether the risk of thyroid cancer in Asian women is associated with consumption of oral contraceptives (Diane-35). We conducted a population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database. From the database, 9865 women aged 18 to 65 years who were prescribed Diane-35 between 2000 and 2012 were included in the Diane-35 group, and 39,460 women who were not prescribed Diane-35 were included in the comparison group and were frequency-matched by age and index year. Both groups were followed until 2013 to calculate the incidence of thyroid cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard model. The median (standard deviation) follow-up duration was 7.08 (3.63) and 7.04 (3.64) years in the Diane-35 and the comparison group, respectively. The incidence of thyroid cancer was 1.80-fold higher in the Diane-35 group than in the comparison group (2.72 vs 1.51 per 10,000 person-years). The cumulative incidence of thyroid cancer was significantly higher in the Diane-35 group than in the comparison group (log-rank test, P = .03). An elevated hazard ratio of thyroid cancer was observed in the Diane-35 group than in the comparison group (HR: 1.91, 95% CI: 1.10-3.30). In subgroup analysis, patients aged 30 to 39 years showed a higher hazard ratio of developing thyroid cancer after consuming Diane-35 than those in the comparison group (HR: 5.58, 95% CI: 1.84-16.91). The study provides evidence that women aged 30 to 39 years consuming Diane-35 are at increased risk of thyroid cancer. Nevertheless, a larger population with a longer follow-up may be necessary to confirm causality.

Heart rate variability between hormone phases of the menstrual and oral contraceptive pill cycles of young women.

INTRODUCTION: The interplay between the sympathetic and parasympathetic branches of the autonomic nervous system contribute to adequate hemodynamic responses to stressors, reflected by the variation in intervals between heart beats, known as heart rate variability. The sex hormones estrogen and progesterone have been shown to affect autonomic function. The extent to which autonomic function may vary between different hormone phases of the natural menstrual cycle and how this relationship may differ in women taking oral contraceptives has yet to be fully elucidated. PURPOSE: To investigate differences in heart rate variability between the early follicular and early luteal phases of the menstrual cycle in naturally menstruating women and in oral contraceptive pill users. METHODS: Twenty-two young (22 ± 3 years), healthy women who were naturally menstruating or taking oral contraceptive pills participated in this study. Heart rate variability was measured at rest and during two sympathomimetic stressors: isometric handgrip exercise and cold pressor test. RESULTS: The proportion of successive NN intervals that differ by more than 50 ms was higher in oral contraceptive pill users during the placebo pill phase. Absolute high-frequency power was higher in the naturally menstruating women during the early luteal phase, relative to the early follicular phase. Other indices of vagal modulation were not different at rest or during sympathetic activation between hormone phases or groups. CONCLUSIONS: Vagal modulation may be increased in the early luteal menstrual cycle phase. Further,oral contraceptive use does not appear to adversely affect this modulation in young, healthy women.