-
Frontiers in Neuroendocrinology Oct 2022Incidents of strokes are increased in young women relative to young men, suggesting that oral contraceptive (OC) use is one of the causes of stroke among young women.... (Review)
Review
Incidents of strokes are increased in young women relative to young men, suggesting that oral contraceptive (OC) use is one of the causes of stroke among young women. Long-term exposures to the varying combinations of estrogen and progestogen found in OCs affect blood clotting, lipid and lipoprotein metabolism, endothelial function, and de novo synthesis of neurosteroids, especially brain-derived 17β-estradiol. The latter is essential for neuroprotection, memory, sexual differentiation, synaptic transmission, and behavior. Deleterious effects of OCs may be exacerbated due to comorbidities like polycystic ovary syndrome, sickle cell anemia, COVID-19, exposures to endocrine disrupting chemicals, and conventional or electronic cigarette smoking. The goal of the current review is to revisit the available literature regarding the impact of OC use on stroke, to explain possible underlying mechanisms, and to identify gaps in our understanding to promote future research to reduce and cure stroke in OC users.
Topics: Male; Female; Humans; Contraceptives, Oral; Friends; Electronic Nicotine Delivery Systems; COVID-19; Stroke
PubMed: 35870646
DOI: 10.1016/j.yfrne.2022.101016 -
Revista Brasileira de Ginecologia E... Apr 2022
Topics: Contraceptives, Oral; Female; Humans; Progestins
PubMed: 35623623
DOI: 10.1055/s-0042-1748754 -
Obstetrics and Gynecology May 2023To assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive.
OBJECTIVE
To assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive.
METHODS
We performed a secondary analysis for which we pooled data from two parallel, multicenter, phase 3 trials (United States and Canada, Europe and Russia) that enrolled participants 16-50 years of age to receive estetrol 15 mg and drospirenone 3 mg in a 24 hormone and four placebo pills regimen for up to 13 cycles. Participants reported pill intake, sexual intercourse, and other contraceptive use on paper diaries. We limited this efficacy analysis to at-risk cycles (one or more reported acts of intercourse and no other contraceptive use) in participants 16-35 years of age at screening. We excluded cycles with other contraceptive use unless pregnancy occurred in that cycle. We assessed primarily the relationship between number of pills not taken per cycle and pregnancies and, secondarily, when pregnancies occurred during product use with a test for trend and χ 2 analyses as appropriate.
RESULTS
Among 2,837 participants in this analysis, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles. Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants reported they took all hormone pills (n=25,613 cycles) or did not take one (n=405 cycles), two (n=121 cycles), and more than two (n=314 cycles) hormone-containing pills, respectively ( P <.001). No pregnancies occurred in 2,216 cycles when one or more pills were missed and missed-pill instructions were followed. All pregnancies related to not taking pills occurred in the first three cycles. Pregnancy rates ranged from 0% to 0.21% per cycle with no significant trend by cycle ( P =.45).
CONCLUSION
Pregnancy occurs more frequently when combined oral contraceptive users report not taking all hormone-containing pills per 28-day cycle and exceeds 1% only when more than two pills are not taken. Pregnancies in participants who reported missed pills occurred only when missed-pill instructions were not followed. A 0.09% pregnancy risk per cycle among users of a 24 hormone and four placebo pills formulation who report taking all pills likely approximates a true method-failure rate.
FUNDING SOURCE
Estetra SRL, an affiliate company of Mithra Pharmaceuticals.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov , NCT02817828 and NCT02817841.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Pregnancy Rate; Estetrol; Europe; Canada
PubMed: 37023457
DOI: 10.1097/AOG.0000000000005155 -
Menopause (New York, N.Y.) Nov 2020
Topics: Contraceptives, Oral, Combined; Female; Hormones; Humans; Menopause, Premature; Primary Ovarian Insufficiency
PubMed: 33201028
DOI: 10.1097/GME.0000000000001689 -
JAMA Network Open Sep 2023Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of...
IMPORTANCE
Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation.
OBJECTIVE
To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs.
DESIGN, SETTING, AND PARTICIPANTS
This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria.
EXPOSURE
COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses.
MAIN OUTCOMES AND MEASURES
Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed.
RESULTS
A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause.
CONCLUSIONS AND RELEVANCE
In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.
Topics: Infant, Newborn; Female; Humans; Young Adult; Adult; Mental Health; Case-Control Studies; Contraceptives, Oral, Combined; Contraception; Hormones
PubMed: 37755829
DOI: 10.1001/jamanetworkopen.2023.35957 -
Expert Opinion on Drug Metabolism &... Dec 2023Drospirenone/estetrol (DRSP/E4) is a combined oral contraceptive (COC) recently approved in several countries. It is composed of 15 mg of E4, a natural estrogen... (Review)
Review
INTRODUCTION
Drospirenone/estetrol (DRSP/E4) is a combined oral contraceptive (COC) recently approved in several countries. It is composed of 15 mg of E4, a natural estrogen produced by human fetal liver throughout pregnancy, and 3 mg of DRSP, the first synthetic progestin used in oral contraception derived from 17-α-spirolactone. E4 and DRSP synergistically prevent pregnancy by inhibiting ovulation. E4 differs from 17-β-estradiol or ethinylestradiol because it represents a native estrogen with selective action in tissues (NEST), therefore it displays both agonist and antagonist estrogenic effects in different tissues.
AREAS COVERED
In this paper, we reviewed the scientific literature published in English prior to April 2023 and gathered information on the pharmacodynamics and pharmacokinetics of DRSP, E4 and their combination for contraception. We also proposed possible clinical applications based on the characteristics of the components of this COC.
EXPERT OPINION
E4/DRSP-based COC has shown high tolerability, safety and satisfaction and may represent a viable choice in young girls in need of oral contraception and pill users who suffer from high cholesterol, breast tenderness or water retention. Moreover, this new COC shows higher scheduled bleeding rate compared to other pills containing natural estrogens. All the data are reassuring, permitting long-term use.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Estetrol; Ethinyl Estradiol; Estrogens; Androstenes
PubMed: 37942662
DOI: 10.1080/17425255.2023.2279752 -
Menopause (New York, N.Y.) Nov 2020
Topics: Contraceptives, Oral, Combined; Female; Hormones; Humans; Menopause, Premature; Primary Ovarian Insufficiency
PubMed: 33201027
DOI: 10.1097/GME.0000000000001690 -
Expert Opinion on Pharmacotherapy 2023Estetrol (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... (Review)
Review
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.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral; Estetrol; Estrogens; Contraception; Contraceptives, Oral, Combined
PubMed: 37691580
DOI: 10.1080/14656566.2023.2247979 -
Best Practice & Research. Clinical... Oct 2019Autoimmune diseases (AIDs) affect women and men with a 2:1 ratio, which suggests that hormonal contraceptives play a role in their clinical course. Combined oral... (Review)
Review
Autoimmune diseases (AIDs) affect women and men with a 2:1 ratio, which suggests that hormonal contraceptives play a role in their clinical course. Combined oral contraceptives have complex, sometimes contradictory, effects on AIDs; they can worsen the situation in women with systemic lupus erythematosus and with anti-phospholipid syndrome, conditions in which they are contraindicated. Early studies indicated a positive effect on rheumatoid arthritis (RA), whereas more recent trials failed to do so, possibly because of the lowering of oestrogen content. Evidence of effects on multiple sclerosis (MS) is conflicting: risk may vary depending on the progestin used. Minor adverse effects may exist on inflammatory bowel diseases, and no significant effect was found on autoimmune thyroid diseases. Women can become sensitised to sex hormones. Progestin-only contraceptives may be used, although copper-releasing intra-uterine devices represent the best option. Finally, several organisations have issued guidelines for contraceptive use in women with AIDs.
Topics: Autoimmune Diseases; Contraception; Contraceptive Devices; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans
PubMed: 31160225
DOI: 10.1016/j.bpobgyn.2019.05.003 -
Contraception Mar 2023To synthesize published literature on POP effectiveness and efficacy. (Review)
Review
OBJECTIVES
To synthesize published literature on POP effectiveness and efficacy.
STUDY DESIGN
We searched PubMed Central, PubMed, and the Cochrane library through March 07, 2022. We included articles written in English reporting a Pearl Index or life table rate for pregnancy. We excluded articles only assessing formulations that: were never marketed globally, are only sold in combination with estrogen, are currently sold only for noncontraceptive purposes, or were not given to participants continuously. Four researchers independently extracted data and two analyzed data using Excel and R.
RESULTS
We included 54 studies. Among studies at low or moderate risk of bias, the median Pearl Index rate (the failure rate during typical use) was 1.63 (range 0.00-14.20, IQR 4.03) and the median method failure Pearl Index rate (the failure rate during perfect use) was 0.97 (range 0.40-6.50, IQR 0.68). Excluding the newer formulations, Desogestrel and Drospirenone, which are closer to combined oral contraceptives in that they prevent pregnancy by inhibiting ovulation, the median Pearl Index rate is 2.00 (range 0.00-14.12, IQR 2.5) and the median method failure Pearl Index rate is 1.05 (range 0.00-10.90, IQR 1.38).
CONCLUSIONS
Among studies at low or moderate risk of bias, the median Pearl Index rate during typical POP use was much lower than currently estimated (7.00), while the median perfect use rate was similar to current estimates.
IMPLICATIONS
Future research should investigate the possibility that POPs may be much more effective during typical use than currently believed.
Topics: Pregnancy; Female; Humans; Desogestrel; Progestins; Contraceptives, Oral, Combined; Estrogens; Ovulation
PubMed: 36535414
DOI: 10.1016/j.contraception.2022.109925