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Contraception Dec 2022To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.
OBJECTIVE
To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.
STUDY DESIGN
We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors.
RESULTS
Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m, 25 to 29.9 kg/m, and ≥30 kg/m of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception.
CONCLUSION
E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable.
IMPLICATIONS STATEMENT
Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.
Topics: Humans; Pregnancy; Female; United States; Adolescent; Young Adult; Adult; Estetrol; Androstenes; Contraceptives, Oral, Combined; Contraception; Estrogens
PubMed: 35921870
DOI: 10.1016/j.contraception.2022.07.009 -
Acta Obstetricia Et Gynecologica... Oct 2022Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin.
MATERIAL AND METHODS
We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover).
CLINICAL TRIAL REGISTRATION
NCT02352090.
RESULTS
Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers.
CONCLUSIONS
Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.
Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Estradiol; Estrogens; Ethinyl Estradiol; Female; Fibrin; Humans; Levonorgestrel; Nandrolone; Progestins; Thrombin; Thromboplastin; Young Adult
PubMed: 35909329
DOI: 10.1111/aogs.14428 -
Journal of the National Cancer Institute May 2023The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors...
BACKGROUND
The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.
METHODS
LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source.
RESULTS
LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes.
CONCLUSIONS
LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
Topics: Pregnancy; Humans; Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Risk Factors; Parity; Contraceptives, Oral; Case-Control Studies
PubMed: 36688720
DOI: 10.1093/jnci/djad011 -
Danish Medical Journal May 2021Hormonal contraception (HC) celebrates its 60th anniversary this year. Thanks to thousands of scientific studies on these products, we now have solid knowledge about the...
INTRODUCTION
Hormonal contraception (HC) celebrates its 60th anniversary this year. Thanks to thousands of scientific studies on these products, we now have solid knowledge about the short- and long-term effects and also the adverse effects of different contraceptive types. The aim of this study was to analyse trends in the use of different types of HC through the latest decade in different age groups of Danish women and to study reasons for any changes.
METHODS
Individual-level HC sale statistics were provided from the National Registry of Medicinal Products. All statistics were stated as defined daily doses per 1,000 women per day. Absolute numbers and distributions among users were calculated.
RESULTS
The overall use of HC was stable in women from 15 to 25 years, decreased among women aged 25-34 years and increased among women aged 35 years or more. On average, an increase from 35% to 39% was recorded. Across all age groups, the use of second-generation combined oral contraceptives (COC) has almost completely replaced the use of third- and fourth-generation pills, and from the age of 20 years of age, the use of COC has decreased contrasting a steep increase in use of the hormone-intrauterine device (IUD). The magnitude of this shift increased with increasing age.
CONCLUSIONS
Whereas the overall use of hormonal contraception has increased over the latest decade from 35% to 39% among all women aged 15-49 years, hormone-IUDs have increasingly replaced COCs so that they are now dominating among women aged 30 years or more. These changes are expected to have decreased venous thrombosis and menorrhagic complaints in young women substantially.
FUNDING
Expenses were covered by Department of Gynaecology, Rigshospitalet.
TRIAL REGISTRATION
The Danish Data Protection Agency (R. no. 2015-41-4481).
Topics: Adult; Contraceptives, Oral, Combined; Denmark; Female; Humans; Venous Thrombosis; Young Adult
PubMed: 34060463
DOI: No ID Found -
Clinical Oral Investigations Mar 2024To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods. (Review)
Review
OBJECTIVES
To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods.
MATERIALS AND METHODS
This review is based on the PRISMA statement. A literature search incorporated observational studies from the last 21 years. An investigative question was formulated using the PICO model, studies were selected, and a quality analysis was performed using the modified STROBE guidelines. A bibliometric analysis was performed, and the data were examined.
RESULTS
Thirteen articles were included, with the majority evaluating periodontal status. Others analyzed factors such as the presence of alveolar osteitis, oral candidiasis, and salivary microbiome dysbiosis. Ten articles were deemed to have a low risk of bias.
CONCLUSIONS
Hormonal contraceptives may increase the risk of alveolar osteitis following tooth extraction and increase the presence of the Candida species in the oral cavity. They also affect the periodontium, such as the frequent development of gingivitis, but do not lead to changes in the salivary microbiome.
CLINICAL RELEVANCE
The increasing number of women using hormonal contraceptives and the knowledge that these contraceptives can produce oral cavity alterations underscore the need to evaluate the oral manifestations found in these women.
Topics: Female; Humans; Dry Socket; Contraceptives, Oral, Hormonal; Periodontium; Gingivitis; Contraception
PubMed: 38427087
DOI: 10.1007/s00784-024-05573-x -
Contraception Apr 2023To examine challenges accessing contraception in the past year and their association with interest in using an over the counter (OTC) oral contraceptive pill (OCP) among...
Challenges accessing contraceptive care and interest in over-the-counter oral contraceptive pill use among Black, Indigenous, and people of color: An online cross-sectional survey.
OBJECTIVE
To examine challenges accessing contraception in the past year and their association with interest in using an over the counter (OTC) oral contraceptive pill (OCP) among Black, Indigenous, and people of color (BIPOC) in the United States.
STUDY DESIGN
From May 2021 to March 2022, a collaborative research team conducted a cross-sectional online survey using convenience sampling to recruit people who identify as Asian American, Native Hawaiian, or Pacific Islander, Black or African American, Indigenous, or Latina/Latinx and used or wanted to use a contraceptive method in the past year. Respondents were recruited through reproductive justice and community-based organizations.
RESULTS
Among 727 respondents, 45% reported experiencing at least one challenge accessing contraception in the past year of which 37% reported a logistical challenge, and 20% reported an interpersonal challenge. Sixty-seven percent of respondents said they were likely to use an OTC OCP. Respondents who reported experiencing at least one challenge accessing contraception in the past year were more likely to say they would use an OTC OCP. Fifty-seven percent of respondents who were not using a contraceptive method in the past year reported they were likely to use an OTC OCP.
CONCLUSION
Among people in this study, interest in an OTC OCP is high, particularly among those who have faced challenges accessing contraception, and among those who are not currently using a contraceptive method.
IMPLICATIONS
Availability of an OCP OTC has the potential to address challenges accessing contraceptive care among BIPOC in the United States, who are often impacted by structural inequities and racism. Findings from this study can inform future OTC implementation strategies to ensure OTC access addresses logistical and interpersonal challenges.
Topics: Female; Humans; Contraception; Contraceptive Devices; Contraceptives, Oral; Cross-Sectional Studies; United States; Black or African American; Indigenous Peoples; Racial Groups; Health Services Accessibility
PubMed: 36641098
DOI: 10.1016/j.contraception.2023.109950 -
European Journal of Sport Science May 2022The aim of this review is to discuss sexual dimorphism of energy metabolism, and to describe the impact of women's hormonal status on substrate oxidation during... (Review)
Review
The aim of this review is to discuss sexual dimorphism of energy metabolism, and to describe the impact of women's hormonal status on substrate oxidation during exercise. Many evidences indicate that sex steroids play a pivotal role in the sex-related differences of body composition and energy substrate storage. Compared with men, women rely more on fat and less on carbohydrates at the same relative exercise intensity. Scientific data suggest that 17-β oestradiol is a key hormone for the regulation of body composition and substrate metabolism. However, in women, measurements with stable isotopic tracers did not highlight any difference in whole-body substrate oxidation rates between the follicular and luteal phases of the menstrual cycle during endurance exercise. The remaining discrepancies about the effect of menstrual cycle-related hormone fluctuations on substrate oxidation could be partly explained by the exercise intensity, which is an important regulator of substrate oxidation. Due to their specific nature and concentration, the synthetic ovarian hormones contained in oral contraceptives also influence substrate metabolism during endurance exercise. However, more studies are needed to confirm that oral contraceptives increase lipolytic activity during endurance exercise without any substantial (or detectable) effect on substrate utilization. Pregnancy and menopause also modify body composition and substrate utilization during exercise through specific hormonal fluctuations. This review highlights that the hormonal status is likely to affect substrate oxidation during exercise in women emphasizing the need to take it into consideration to optimize their health and performance.
Topics: Contraceptives, Oral; Energy Metabolism; Exercise; Female; Humans; Male; Menstrual Cycle; Progesterone; Sex Characteristics
PubMed: 34134602
DOI: 10.1080/17461391.2021.1943713 -
Journal of Assisted Reproduction and... May 2023
Topics: Humans; Female; Progestins; Reproductive Health; Contraceptives, Oral, Hormonal
PubMed: 37256529
DOI: 10.1007/s10815-023-02840-w -
Frontiers in Neuroendocrinology Jan 2024Worldwide, 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adult; Adolescent; Humans; Female; Contraceptives, Oral; Mental Disorders; Contraception
PubMed: 37967755
DOI: 10.1016/j.yfrne.2023.101111 -
Experimental Physiology Apr 2022What is the central question of this study? Are there differences in blood pressure, arterial stiffness and indices of pressure waveforms between young oral...
NEW FINDINGS
What is the central question of this study? Are there differences in blood pressure, arterial stiffness and indices of pressure waveforms between young oral contraceptive pill-using and naturally menstruating women during lower and higher hormone phases of their cycles? What is the main finding and its importance? Blood pressure, arterial stiffness and indices of pressure waveforms are influenced similarly by exogenous and endogenous hormones. However, lower levels of exogenous hormones moderately increase blood pressure among oral contraceptive pill-using women.
ABSTRACT
Elevations in blood pressure (BP) are understood as having a bidirectional relationship with stiffening of central and peripheral arteries. Arterial stiffness is mitigated by oestrogen, which aides in arterial vasorelaxation. To evaluate whether BP, stiffness, and pressure waveforms were different between young healthy naturally menstruating (non-OCP) and oral contraceptive pill (OCP)-using women, we measured brachial and aortic BPs, carotid-to-femoral pulse wave velocity, carotid β-stiffness, elastic modulus, central augmentation index and augmentation index normalized to a heart rate of 75 bpm, and forward and backward pressure waveforms in 22 women (22 (1) years, OCP: n = 12). To assess phasic differences, women were studied during the early follicular (≤5 days of menstruation onset) and early luteal (4 (2) days post-ovulation) phases of non-OCP and compared to the placebo pill (≤5 days of onset) and active pill (≤5 days of highest-dose active pill) phases of OCP. During the lower hormone phases, OCP users had significantly higher brachial systolic blood pressure (SBP) (119.3 (8.3) vs. 110.2 (8.3) mmHg, P = 0.02) and aortic SBP (104.10 (7.44) vs. 96.80 (6.39) mmHg, P = 0.03) as compared to non-OCP users; however, during the higher hormone phases, there were no differences in measures of brachial or aortic BP, arterial stiffness, or indices of BP waveforms between OCP and non-OCP users (P ≥ 0.05). In conclusion, exogenous and endogenous hormones have similar influences on BP and arterial stiffness; however, lower levels of exogenous hormones augment both central and peripheral BPs.
Topics: Blood Pressure; Brachial Artery; Contraceptives, Oral; Estrogens; Female; Humans; Menstrual Cycle; Menstruation; Pulse Wave Analysis; Vascular Stiffness
PubMed: 35199392
DOI: 10.1113/EP090151