Oral Hormonal Contraceptives Research Articles

Effect of glucagon-like peptide 1 receptor agonists on oral hormonal contraception (literature review)

Background. Glucagon-like peptide 1 (GLP-1) is an incretin hormone whose mechanism of action also includes a slight delay in gastric emptying (GE). Due to the prevalence of type 2 diabetes mellitus and obesity, GLP-1drugs are prescribed to many patients, including women of reproductive age who are also taking COCs. For oral contraceptives, malabsorption may result in ineffective pregnancy prevention.The purpose of this literature review was to review data from studies on the effect of GLP-1 agonists on oral hormonal contraceptives (COCs) and to analyze data on the safety of concomitant use of COCs and GLP-1 agonists.Methods. PubMed and ClinicalTrials.gov were searched for publications using keywords. A total of 3 clinical studies were selected for inclusion in the literature review.Results. Studies involving GLP-1 have not revealed a statistically or clinically significant difference in drug-drug interactions with COC drugs.Conclusion. This review compared the effects of currently available GLP-1 on COCs in three clinical studies. Due to the prevalence of type 2 diabetes and obesity, GLP-1 is likely to be prescribed to many patients, including women of reproductive age who are also taking COCs. These drugs may affect the pharmacokinetics of COCs. Changes in the area under the curve, maximum concentration, and time to maximum plasma concentration of oral drugs can be avoided by taking these drugs 1 hour after GLP-1.

WITHDRAWN: Comparing English- and Spanish-Reading Patients’ Comprehension of the Drug Facts Label for a New Over-The-Counter Oral Contraceptive

BackgroundHealth literacy is known to impact health outcomes in a multitude of ways and is impacted by language barriers. Lower health literacy is also associated with higher rates of unintended pregnancies. A progestin-only oral hormonal contraception product, norgestrel (Opill-Perrigo), was approved for over-the-counter (OTC) use in the United States in July 2023. Objective(s): The objective was to utilize a knowledge assessment survey to determine participants’ comprehension of norgestrel from its drug facts label and compare the comprehension between primarily English- and Spanish-reading participants. MethodsA 7-item knowledge assessment was developed and distributed to English and Spanish readers at one site within a network of federally qualified health centers. English-reading participants completed the English survey alongside use of an English copy of norgestrel’s drug facts label. Spanish-reading participants completed the Spanish survey and were randomized in a 1:1 fashion to either receive an English or Spanish copy of norgestrel’s drug facts label. ResultsThe English-reading/English label (E/E) group had a higher level of comprehension of norgestrel’s drug facts label compared to the Spanish-reading/English label (S/E) or Spanish-reading/Spanish label (S/S) groups. ConclusionDifferences exist in OTC label comprehension for norgestrel based on primary language able to be read. Advocacy for OTC labels to be readily available in languages other than English is imperative to mitigate unintended pregnancies associated with lower levels of health literacy.

Comparison of dienogest or combinations with ethinylestradiol/estradiol valerate on the pain score of women with endometriosis: A prospective cohort study.

Endometriosis is one of the most frequent gynecologic disorders. The pathognomonic symptom of endometriosis is pelvic pain. The recommended pain medications are oral hormonal contraceptives, progestin therapy, danazol, gonadotropin-releasing hormone analogs, nonsteroidal anti-inflammatory drugs, and aromatase inhibitors. In this study, we aimed to compare the efficiency of costing dienogest (DNG) and low-cost oral contraceptives regarding visual analog scores (VAS) score of pelvic pain and also cancer antigen-125 (CA-125), anti-Mullerian hormone (AMH) levels, and size of endometrioma in the patients with endometriosis which is a chronic disease that requires a lifelong management plan. In our study, 18 to 45-year-old patients presented to our institution's gynecology and obstetrician department for various complaints over 2 years, and endometriosis diagnoses were included. Patients were divided into 3 groups (20 patients in each medication group) according to the given medication: cyclic DNG (Visanne) or 0.03 mg ethinylestradiol combined with 2 mg DNG (Dienille) or estradiol valerate combined with 2 mg DNG (Qlarista). We recorded all patients' CA-125/AMH values and VAS scores of pelvic pain. All patients gave informed consent. There was no statistically significant difference between pre-medication and post-medication levels of CA-125, AMH, VAS score, and cyst size in all groups. However, statistically, significant decreases were seen in the cyst size and VAS score, indicating response to therapy in all groups. In conclusion, we think it is more reasonable to use cost-effective oral contraceptive medications, which also cause common side effects, instead of costing DNG since all drugs have the same efficiency and success.

Oral hormonal contraceptives and cardiovascular risks in females.

Oral hormonal contraception (OHC) is a widely employed method in females for the prevention of unintended pregnancies, as well as for the treatment of menstrual disorders, endometriosis, and polycystic ovarian syndrome. However, it is believed that with OHCs use, some females may have higher risk of cardiovascular diseases, such as hypertension, diabetes, myocardial infarction, thrombosis, and heart failure. Although such risks are infrequently detected in healthy young females with the use of oral contraceptives, slightly elevated risks of cardiovascular diseases have been observed among reproductive-aged healthy females. However, prolonged use of OHC has also been claimed to have protective cardiac effects and may contribute to reduced risk of cardiovascular disease. In fact, the debate on whether OHC administration increases the risk of cardiovascular diseases has been ongoing with inconsistent and controversial viewpoints. Nevertheless, a great deal of work has been carried out to understand the relationship between OHC use and the occurrence of cardiovascular risk in females who use OHC for preventing the unwanted pregnancy or treatment of other disorders. Therefore, in this review we summarize the most recent available evidence regarding the association between the use of oral hormonal contraceptives and the risk for cardiovascular disease in females who are using OHC to prevent unintended pregnancy.

College student perceptions of pharmacist-provided hormonal contraception

BackgroundNorth Carolina immunizing pharmacists are authorized to provide oral and transdermal hormonal contraception to eligible patients. In March 2022, implementation of this enhanced patient care service began statewide, after approval of standing orders and published training from the North Carolina Association of Pharmacists. Two pharmacy locations on a college campus began offering pharmacist-provided hormonal contraception shortly after approval. ObjectiveThe objective of this study was to assess the willingness of students to seek pharmacist-provided hormonal contraception and the willingness of students to pay for this service. MethodsThis cross-sectional study was conducted on the campus of a public, research-intensive university. To be included, individuals must have been 18 years of age or older, enrolled as a student or postdoc at the university, and must have used prescribed hormonal oral contraception within the last year. Individuals who declined consent or surveys that were not at least 90% complete were excluded. The survey was administered via Qualtrics and distributed via e-mail and printed flyers with a QR code. The survey opened February 10, 2023, and closed April 24, 2023. ResultsIn total, 170 survey responses were analyzed. Almost three-fourths of participants (72.9%) were not aware that pharmacists could provide hormonal contraception in North Carolina. All participants identified at least one benefit to pharmacist-provided contraception, with the most common responses being “I believe it would save time” (85.3%) and “appointment not needed” (89.4%). Almost two-thirds of participants (65.3%) identified at least one barrier that would prevent them from seeking pharmacist-provided contraception. The most common barrier identified was privacy at the pharmacy (20.0%). Most participants (81.8%) reported that they are willing to pay for this service, with the majority willing to pay up to $29. ConclusionStudents on this campus seem to have a receptive attitude toward pharmacist-provided hormonal contraception and are willing to pay for a consultation.

CONTRACEPTION IN WOMEN WITH CARDIOVASCULAR RISK; UNIVERSITY HOSPITAL CENTER OF TLEMCEN, ALGERIA

Objective: Study the vascular risk in women using oral hormonal contraception. Design and method: Descriptive study, interested in studying the blood pressures of women using contraception compared to women not using it. The data were entered and analyzed by Epi-info 6 software. Results: In total, 122 women were included in our study, 36 of whom were aged between 21 and 55 years, or 29.5% of cases. Women aged over 60 represented 73.7% of cases; 54.1% were married. There were 98 women users of oral contraception (OC), all ages combined, or 80.3%, compared to 25 women who did not use OC, or 20.5%. The prevalence of hypertension was 74.2% among female OC users; and 68% among women who do not use CO. Epidemiological profile and associated risk factors of hypertensive women using oral contraception: In number of 72. Women aged under 50 represented 23.6% and those aged over 60: 76.4%. A low socioeconomic level was noted for 72.2% and medium for 23.6%. Low educational level: 45.8%, Women who did not have a profession represented 70%. Married women represented 60% of cases and widows 38.9% with an average number of children of five. The average duration of hypertension was 12.15 ± 7.75 years, with a length of service ranging from one year to 40 years. The average duration of contraception was 24 ±7.6 years. Associated risk factors: diabetes 44.4%, hypercholesterolemia: 18.1%, migraine 14%, obesity: 12.5% and tobacco 4.2%. Conclusions: Many epidemiological data has investigated the link between oral contraceptive use and elevated blood pressure. In our study, hypertensive women who used oral contraception had significant risk factors; long-standing high blood pressure with an average of more than ten years and taking oral contraception for a long time with an average of more than twenty years. A woman with high blood pressure will be more limited than other women in her choice of contraceptive method.

Considerations for Contraception Following Spinal Cord Injury: A Systematic Review.

Counseling and education on women's health, specifically contraception, following spinal cord injury (SCI) is an important component of care for women with SCI. While a plethora of available contraceptive options exists, research in this area is scarce. This systematic review assesses the quality and quantity of research on contraception for individuals with SCI. Literature searches of three medical databases were performed to identify articles that addressed contraception and family planning for women with SCI. Articles were then screened in a two-stage selection process and evaluated for content. Of 165 articles, 21 were identified that fit the inclusion criteria. The majority (66%) of articles were literature reviews or professional practice guidelines. Fourteen (66%) included information on short-acting hormonal oral contraception, 11 (52%) included information on long-acting reversible contraception, 15 (71%) included information on barrier methods, 6 (29%) included information on fertility awareness, 9 (43%) included information on permanent contraception, and one (5%) included information on emergency contraception. This systematic review demonstrates a paucity of evidence-based information on contraception tailored to women with SCI. It highlights a need for research and comprehensive guidelines on primary and emergency contraception in this population.

Menstrual cycle phases and dosage of synthetic hormonal contraceptives influence diurnal rhythm characteristics of distal skin temperature

ABSTRACT This study aimed to explore how natural menstrual cycle phases and dosage of oral hormonal contraceptives (OC) influence the diurnal rhythm of distal skin temperature (DST) under real-life conditions. Participants were 41 healthy females (23.9 ± 2.48 y), comprising 27 females taking monophasic hormonal oral contraceptives (OC users) and 14 females with menstrual cycles (non-OC users). Wrist DST was continuously recorded and averaged over two consecutive 24-hour days during (pseudo)follicular and (pseudo)luteal menstrual phases. Diurnal rhythm characteristics, i.e. acrophase and amplitude, describing timing and strength of the DST rhythm, respectively, were calculated using cosinor analysis. Results show that non-OC users experienced earlier diurnal DST maximum (acrophase, p = 0.019) and larger amplitude (p = 0.016) during the luteal phase than during the follicular phase. This was observed in most (71.4%) but not all individuals. The OC users showed no differences in acrophase or amplitude between pseudoluteal and pseudofollicular phases. OC users taking a higher dosage of progestin displayed a larger amplitude for DST rhythm during the pseudoluteal phase (p = 0.009), while estrogen dosage had no effect. In conclusion, monophasic OC cause changes in diurnal DST rhythm, similar to those observed in the luteal phase of females with menstrual cycles, suggesting that synthetic progestins act in a similar manner on skin thermoregulation as progesterone does.

Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals.

Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that abrocitinib is a weak time-dependent inhibitor of cytochrome P450 (CYP)2C19/3A and a weak inducer of CYP1A2/2B6/2C19/3A. To assess the potential effect of abrocitinib on concomitant medications, drug-drug interaction (DDI) studies were conducted for abrocitinib with sensitive probe substrates of these CYP enzymes. The impact of abrocitinib on hormonal oral contraceptives (ethinyl estradiol and levonorgestrel), as substrates of CYP3A and important concomitant medications for female patients, was also evaluated. Three Phase 1 DDI studies were performed to assess the impact of abrocitinib 200 mg once daily (QD) on the probe substrates of: (1) 1A2 (caffeine), 2B6 (efavirenz) and 2C19 (omeprazole) in a cocktail study; (2) 3A (midazolam); and (3) 3A (oral contraceptives). After multiple doses of abrocitinib 200 mg QD, there is a lack of effect on the pharmacokinetics of midazolam, efavirenz and contraceptives. Abrocitinib increased the area under the concentration time curve from 0 to infinity (AUCinf) and the maximum concentration (Cmax) of omeprazole by approximately 189 and 134%, respectively. Abrocitinib increased the AUCinf of caffeine by 40% with lack of effect on Cmax. Based on the study results, abrocitinib is a moderate inhibitor of CYP2C19. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolized by CYP2C19 enzyme. Abrocitinib is a mild inhibitor of CYP1A2; however, the impact is not clinically relevant, and no general dose adjustment is recommended for CYP1A2 substrates. Abrocitinib does not inhibit CYP3A or induce CYP1A2/2B6/2C19/3A and does not affect the pharmacokinetics of contraceptives. ClinicalTrials.gov registration IDs: NCT03647670, NCT05067439, NCT03662516.

Hormonal Contraception and Risk of Cardiometabolic Disease in Women with HIV.

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

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.

Frequency of same-day contraceptive initiation, recent unprotected intercourse, and pregnancy risk: a prospective cohort study of multiple contraceptive methods

BackgroundSame-day start removes barriers to contraceptive initiation and may reduce the risk of unintended pregnancy. Same-day start may be appropriate for all contraceptive methods, but we lack data comparing methods. ObjectivesTo assess the frequency of same-day initiation among six contraceptive methods selected for “same-day start” among new contraceptive users and describe the efficacy of same-day start first cycle pregnancy risk by all contraceptive methods and by each method. Study DesignUsing prospective data from the HER Salt Lake Contraceptive Initiative, we identified and assessed outcomes for participants initiating a new method of contraception beyond the first seven days of their menstrual cycle (same-day start). Enrolled participants at four family planning clinics in Salt Lake County, Utah between September 2015-March 2017 received their method of choice regardless of their cycle day or recent unprotected intercourse. All participants self-reported last menstrual period data and unprotected intercourse events in the previous 2 weeks. We excluded participants that received care immediately after or within two weeks of abortion care. Clinical electronic health records provided information on contraceptive method initiation and use of oral emergency contraception. Participants reported pregnancy outcomes in 1-, 3-, and 6-month follow-up surveys with clinic verification to identify any pregnancy resulting from same-day initiation. The primary outcomes report the frequency of same-day start use and first cycle pregnancy risk among same-day start users of all contraceptive methods. The secondary outcomes include frequency of and pregnancy risk in the first cycle of use among same-day start contraception users by method. We also report frequency of unprotected intercourse within 5 days and 6-14 days of contraception initiation, frequency of concomitant receipt of oral emergency contraception with initiation of ongoing contraception, and pregnancy risk with these exposures. We analyzed pregnancy risk by contraceptive method initiated same-day and assessed for simultaneous use of oral emergency contraception. ResultsOf the 3,568 individuals enrolled, we identified the majority as same-day start users (n=2,575/3,568, 72.2%), with one in eight of those reporting unprotected intercourse in the previous 5 days (n=322/2,575, 12.5%) and one in ten reporting unprotected intercourse 6-14 days prior to contraceptive method initiation (n=254/2,575, 9.9%). We identified 11 pregnancies among same-day start users (0.4%, 95% CI 0.2%-0.7%) compared to 1 (0.1%. 95% CI 0.002%-0.6%) among those who initiated contraception within seven days from the last menstral period. Users of oral hormonal contraception and vaginal hormonal methods reported the highest 1st cycle pregnancy rates (1.0 – 1.2%). Among same-day start users, 174 (6.8%) received oral emergency contraception at enrollment in conjunction with another method. Of the same-day user who received emergency contraception at initiation, 4 (2.3%) pregnancies were reported. Conclusion(s)Same-day start is common and associated with a low pregnancy risk. Using the “any method, any-time” approach better meets contraceptive clients’ needs and maintains a low risk of pregnancy.

Comparison of Combined Parenteral and Oral Hormonal Contraceptives: A Systematic Review and Meta-Analysis of Randomized Trials.

Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Influence of oral hormonal contraception on the concentration of anti-Müllerian and reproductive hormones in patients with polycystic ovary syndrome

Aim: To investigate the effects of three-month use of oral hormonal contraception (OHC) on hormonal status and ovarian reserve indicator (anti-Müllerian hormone, AMH) in patients with polycystic ovary syndrome (PCOS).Methods: 19 patients with diagnosed PCOS and clinical and laboratory signs of hyperandrogenism without additional comorbidities and co-medication were included in the study. All participants received therapy with the same oral hormonal contraceptive (fixed combination of 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate). The main outcomes were the concentrations of reproductive hormones measured before starting therapy and in the first cycle following therapy. Hormone concentrations were analysed using the immunochemical electrochemiluminescence (ECLIA) method.Results: Initial concentrations of total and free testosterone and AMH were elevated, while initial concentrations of other reproductive hormones were within reference values. By applying the therapy, the concentrations of AMH, luteinizing hormone (LH) and estradiol decreased by more than 20% and those of free testosterone by 85%. The concentration of sex hormone binding globulin (SHBG) increased by 44%.Conclusions: Three months of oral hormonal contraception with 35 μg ethinyl estradiol and 2 mg cyproterone acetate reduced elevated concentrations of AMH and free testosterone in PCOS patients. The decrease in serum AMH concentration indicates a temporary interruption of folliculogenesis as well as the selection of follicles from preantral to antral, and the decrease in androgens has a positive effect on the clinical condition and symptoms of patients with PCOS.

Abstract B125: Reproductive factors and thyroid cancer risk: The multiethnic cohort study

Abstract Background : Thyroid cancer is the most common endocrine cancer worldwide, with the incidence in women being three times that of men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and hormone replacement therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods : A prospective cohort study of women of diverse racial and ethnic groups in the Multiethnic Cohort Study (n=118,344) was used. Included were 373 papillary thyroid cancer cases, linked to SEER cancer incidence and statewide death certificate files in Hawaii and California. Exposures investigated include age at menarche, parity, menopausal status and type, birth control use, and outcomes of first pregnancy. Cox proportional hazards models of papillary thyroid cancer were used to obtain relative risk (RR) and 95% confidence intervals (CI) to examine the associations with reproductive/hormonal factors. Results : We observed a statistically significant increased risk of papillary thyroid cancer for hysterectomy, oophorectomy, surgical menopause, and not having a child by age 20. The adjusted estimates for oophorectomy RR 1.66 (95% CI: 1.31, 2.11) and hysterectomy RR 1.82 (95% CI: 1.42, 2.34). Menopause due to surgery was associated with a 55% increase in risk (RR 1.55, 95% CI: 1.22, 1.97) and nulliparity vs ≤ 20 years of age at first livebirth was related to a 51% increased risk (adjusted RR 1.51, 95% CI: 1.07, 2.15). Adjustment factors included age and race/ethnicity and menopausal status, menopausal type, and oral contraception where appropriate. Former use of estrogen menopausal hormone therapy was associated with a 35% increased risk (adjusted RR: 1.35, 95% CI: 1.02, 1.79). No significant heterogeneity was seen in these associations by race/ethnicity (p het >0.48). Conclusion : The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in our multiethnic population. Our analysis finds having a hysterectomy or oophorectomy and the use of MHT are associated with an increased risk of papillary thyroid cancer, and having a child at a younger age is associated with a reduction in thyroid cancer risk. Citation Format: Janine V. Abe, Song-Yi Park, Christopher A. Haiman, Loïc Le Marchand, Brenda Y. Hernandez, Lynne R. Wilkens. Reproductive factors and thyroid cancer risk: The multiethnic cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B125.

Abstract 071: Oral Contraceptive Use and Development of Acute Ischemic Stroke: A Population‐Based Retrospective Cohort Study

Introduction Existing evidence remains conflicting regarding the association between oral hormonal contraceptive (OCP) use and the risk of acute ischemic stroke (AIS). Large‐scale analyses and observational data evaluating this clinical question in recent years are scarce, despite widespread use of hormonal contraception in adult females of child‐bearing age. Modern OCP formulations contain lower doses of estrogen, the putative causative agent for AIS in this population, and underscores the need to re‐evaluate the risk initially demonstrated in older formulations containing higher levels of estrogen. Methods Hospitalizations for female patients aged 15‐50 were identified in the National Inpatient Sample (NIS) registry from 2015‐2020, excluding admissions associated with pregnancy or the postpartum period. The study exposure was use of OCPs and the primary endpoint was AIS, identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) coding. Propensity score (PS) adjustment by inverse probability weighting (IPW) was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between OCP and non‐OCP users to reduce measured confounding. In addition to age and race/ethnicity, a battery of more than forty confounding covariates representing established risk factors for AIS in the general and young population were identified (cardiovascular disease, lifestyle risk factors, congenital abnormalities, vasculopathies, hypercoagulable states, migraine with aura, among others) and balanced between OCP and non‐OCP users. Sensitivity testing was performed by evaluating stroke incidence in a sub‐group of patients without any risk factors present and by assessing a negative control (head trauma), with which an association of OCP use would not be expected. The effect size of the association between OCPs and AIS was presented as an adjusted odds ratio (aOR) with 95% confidence interval (CI), with statistical significance evaluated at p < 0.001. Results PS adjustment by IPW to balance all available AIS risk factors between OCP users and non‐users yielded 23,253,209 hospitalizations, 11,654,398 (50.1%) of which were associated with OCP use. The incidence of AIS was significantly greater in OCP users compared to non‐OCP users (2.8% vs. 0.4%; aOR 7.50, 95% CI 7.43 to 7.58; p < 0.001). Sub‐group analysis of hospitalizations without any stroke risk factors also demonstrated a significant association of OCP use with the development of AIS (1.3% vs. 0.1%; aOR 14.84, 95% CI 13.16 to 16.72; p < 0.001) following adjustment for age and race/ethnicity. In negative control analysis, OCP use was not associated with admissions associated with head trauma (1.4% vs. 1.4%; OR 1.03, 95% CI 0.95 to 1.10; p = 0.485). Conclusion Retrospective observational data from the United States in recent years suggests an association between OCP use and AIS, independent of well‐established risk factors for stroke and despite widespread adoption of lower estrogen formulations.

Naturally menstruating women exhibit lower cardiovagal baroreflex sensitivity than oral contraceptive users during the lower hormone phase.

The present study evaluated cardiovagal baroreflex sensitivity (BRS) across the menstrual/pill cycle in naturally menstruating women (NAT women) and women using oral hormonal contraceptives (OCP women). In 21 NAT women (23±4 years old) and 22 OCP women (23±3 years old), cardiovagal BRS and circulating concentrations of estradiol and progesterone were evaluated during the lower hormone (early follicular/placebo pill) and higher hormone (late follicular to early luteal/active pill) phases. During the lower hormone phase, cardiovagal BRS up, down and mean gain were lower in NAT women (15.6±8.3, 15.2±6.1 and 15.1±7.1ms/mmHg) compared with OCP women (24.7±9.4, 22.9±8.0 and 23.0±8.0ms/mmHg) (P=0.003, P=0.002 and P=0.003, respectively), and higher oestrogen (R2 =0.15, P=0.024), but not progesterone (R2 =0.06, P=0.18), concentrations were predictive of lower BRS mean gain. During the higher hormone phase, higher progesterone concentrations were predictive of lower BRS mean gain (R2 =0.12, P=0.024). A multivariate regression model revealed group (NAT or OCP) to be a significant predictor of cardiovagal BRS mean gain in the lower hormone phase when hormone concentrations were adjusted for (R2 =0.36, P=0.0044). The multivariate regression model was not significant during the higher hormone phase (P>0.05). In summary, cardiovagal BRS is lower in NAT compared with OCP women during the lower hormone phase of the menstrual/pill cycle and might be associated with higher oestrogen concentrations. In contrast, during the higher hormone phase of the menstrual/OCP cycle, higher progesterone concentrations were predictive of lower cardiovagal BRS. NEW FINDINGS: What is the central question of this study? Does cardiovagal baroreflex sensitivity (BRS) differ between naturally menstruating women (NAT women) and women using oral contraceptives (OCP women)? What is the main finding and its importance? The main findings are as follows: (1) NAT women exhibit lower cardiovagal BRS than OCP women during the lower hormone phase of the menstrual or pill cycle; and (2) circulating oestrogen concentrations are significant predictors of cardiovagal BRS during the lower hormone phase, with higher oestrogen concentrations predicting lower BRS. The present data advance our understanding of the effect of endogenous ovarian hormones and OCP use on cardiovascular control mechanisms.

High-amplitude network co-fluctuations linked to variation in hormone concentrations over the menstrual cycle.

Many studies have shown that the human endocrine system modulates brain function, reporting associations between fluctuations in hormone concentrations and brain connectivity. However, how hormonal fluctuations impact fast changes in brain network organization over short timescales remains unknown. Here, we leverage a recently proposed framework for modeling co-fluctuations between the activity of pairs of brain regions at a framewise timescale. In previous studies we showed that time points corresponding to high-amplitude co-fluctuations disproportionately contributed to the time-averaged functional connectivity pattern and that these co-fluctuation patterns could be clustered into a low-dimensional set of recurring "states." Here, we assessed the relationship between these network states and quotidian variation in hormone concentrations. Specifically, we were interested in whether the frequency with which network states occurred was related to hormone concentration. We addressed this question using a dense-sampling dataset (N = 1 brain). In this dataset, a single individual was sampled over the course of two endocrine states: a natural menstrual cycle and while the subject underwent selective progesterone suppression via oral hormonal contraceptives. During each cycle, the subject underwent 30 daily resting-state fMRI scans and blood draws. Our analysis of the imaging data revealed two repeating network states. We found that the frequency with which state 1 occurred in scan sessions was significantly correlated with follicle-stimulating and luteinizing hormone concentrations. We also constructed representative networks for each scan session using only "event frames"-those time points when an event was determined to have occurred. We found that the weights of specific subsets of functional connections were robustly correlated with fluctuations in the concentration of not only luteinizing and follicle-stimulating hormones, but also progesterone and estradiol.

A life-threatening benign vascular lesion of the uterus, cavernous hemangioma: A case report

The objective of this clinical report is to present the first local case of rare cavernous uterine hemangioma. This is a case of a 28-year-old G2P1 (1001) during her first trimester of pregnancy who was admitted to our institution for the second time due to profuse vaginal bleeding and severe anemia. The transvaginal scan revealed an embryonic demise of 8 weeks age of gestation noted at the endocervical canal. There is a posterofundal heterogeneous mass measuring 6.3 cm × 5.7 cm × 5.0 cm (volume: 94.2 ml) with multiple cystic spaces, which on Doppler studies showed abundant vascularity suggestive of uterine hemangioma. Antifibrinolytics were administered. The patient underwent emergency hysterectomy with bilateral salpingectomy due to profuse vaginal bleeding with histopathology result of cavernous hemangioma of the uterus. Cavernous uterine hemangioma is a rare vascular lesion that poses a great challenge in the diagnosis and management. There were limited published articles regarding cavernous hemangioma of the uterus. There were conservative treatment options such as uterine artery embolization, the use of hormonal oral contraception, intralesional glucocorticoid therapy, the use of interferon-α, laser therapy, and surgical excision. Hysterectomy is the definitive treatment for intractable bleeding. It is recommended to establish an international registry for this rare case. The experts in different specialties such as obstetrician-gynecologists, interventional radiologists, and vascular surgeons, can also formulate an algorithm for its diagnosis and treatment.