Current use of estrogen-containing oral contraceptives or hormone therapy and risk of COVID-19 infection and hospitalization: a population-based cohort study.

This population-based cohort study evaluated the association between current use of oral contraceptives (OC) among women under 50 years (n=306,541), and hormone therapy (HT) among women aged 50 or older (n=323,203), and COVID-19 infection and hospitalization. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified March 2020-February 2021. COVID-19 infection and hospitalization were identified through diagnosis codes and laboratory tests. Weighted generalized estimating equations models estimated multivariable-adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models evaluated OC/HT use and COVID-19 hospitalization. Over 12 months, 11,727 (3.8%) women <50 years and 8,661 (2.7%) women ≥50 years experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR=1.05; 95%CI: 0.97, 1.12). There was a modest association between HT use and infection (aOR=1.19; 95%CI: 1.03, 1.38). Women using OC had a 39% lower risk of hospitalization (aOR=0.61; 95%CI: 0.38, 1.00), but there was no association of HT use with hospitalization (aOR=0.89; 95%CI: 0.51, 1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

The role of sex hormones, oral contraceptive use, and its parameters on visuospatial abilities, verbal fluency, and verbal memory.

Sex hormones can cross the blood-brain barrier and access brain regions underlying higher-order cognition. Containing synthetic sex hormones, oral contraceptives (OC) have been found to modulate visuospatial and verbal abilities, though inconsistencies have been found in the literature. Among possible explanations, certain OC use parameters (progestin androgenicity, synthetic hormone levels, duration of use) have not received consistent consideration. Thus, the objectives were to (1) examine group differences between men, combined OC users, and naturally cycling women (NC women; not using OC) in visuospatial abilities, verbal fluency, and verbal memory and (2) investigate the contribution of endogenous and exogenous sex hormones on these effects. We also aimed to (3) identify OC use parameters relevant to cognitive outcomes. In total, 70 combined OC users, 53 early follicular (EF) women, 43 pre-ovulatory (PO) women, and 47 men underwent cognitive tests. Performance was compared based on hormonal milieus (OC, EF, PO, men) and OC users' contraceptive androgenicity (anti, low, high). Correlations between performance, hormone levels and OC use duration were also conducted. OC use dampened the sex difference that typically favors men in 3D visuospatial abilities, whereas its duration of use positively predicted verbal fluency. Androgenicity and hormone levels did not predict performance in any task. These results highlight the importance of considering OC use duration. Results also did not support a role for androgenicity in cognition. Importantly, combined OC use (including prolonged use) does not impair visuospatial, verbal, and memory functions in a healthy young sample.

Hormonal contraceptives and behavior: Updating the potent state of the nascent science.

Hundreds of millions of people worldwide use hormonal contraceptives (HCs), which have been an essential part of women's reproductive health care for decades. Throughout that time, however, research on the neural and behavioral consequences of HCs was minimal and plagued by poor methodology. HC effects - and users - were assumed to be homogenous. Fortunately, there has been a recent upswell in the number and quality of investigations, affording tentative conclusions about the roles of HCs in spatial cognition and mental health, particularly depression. Thus, this paper leverages findings from the past few years to highlight the heterogeneous aspects of use that seem to matter for behavior - ranging from variation in hormonal contraceptive formulations and routes of administration to individual differences among users linked to age and reproductive health history. This paper closes with five tips for future research that will help capture and clarify heterogeneity in potential relations between HCs and behavior, namely data collection, regional access, lifespan factors, gender, and collaboration. HCs are sociopolitically provocative and research on their potential behavioral neuroendocrine impacts is becoming increasingly popular. It is, therefore, imperative for scientists to conduct replicable and robust empirical investigations, and to communicate findings with the nuance that the heterogeneity among users and effects requires.

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.

The risk of venous thromboembolism in oral contraceptive users: the role of genetic factors-a prospective cohort study of 240,000 women in the UK Biobank.

BACKGROUND: More than 150 million women worldwide use oral contraceptives. Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V Leiden and the prothrombin, are at an increased risk for venous thromboembolism, especially when combined with oral contraceptive use. Venous thromboembolism is a complex disorder involving many genetic risk factors, and recently, polygenic risk scores have been proposed to capture a significant proportion of the genetic risk of venous thromboembolism. OBJECTIVE: The aim of this study was to estimate the risk for developing venous thromboembolism when initiating oral contraceptive use (first 2 years) and during continued use among women with a high genetic liability. STUDY DESIGN: We used a prospective study design in which 244,420 participants from the UK Biobank were followed from birth. The effect of oral contraceptive use during the first 2 years and in the remaining years of oral contraceptive use on the risk of developing venous thromboembolism was estimated using a Cox regression with a time-dependent exposure variable. Women were stratified according to their polygenic risk scores and whether they were carriers of factor V Leiden and/or prothrombin variants. RESULTS: When genetic risk was not considered, an increased risk for venous thromboembolism was observed during the first 2 years of oral contraceptive use (hazard ratio, 3.09; 95% confidence interval, 3.00-3.20) but not during continued use (hazard ratio, 0.92; 95% confidence interval, 0.80-1.05). However, when genetic risk was considered, women in the highest polygenic risk score category had a more pronounced risk of developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 6.35; 95% confidence interval, 4.98-8.09), and a high risk was also observed among factor V Leiden (hazard ratio, 5.73; 95% confidence interval, 5.31-6.17) and prothrombin variant carriers (hazard ratio, 5.23; 95% confidence interval, 4.67 - 5.87). A high polygenic risk score in combination with being a factor V Leiden and prothrombin variant carrier conferred the highest risk for developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 14.8; 95% confidence interval, 9.28-23.6). Women with a high genetic liability also had an increased risk during continued use but it was less pronounced, and the highest risk was conferred to carriers of both factor V Leiden and the prothrombin variant (hazard ratio, 4.93; 95% confidence interval, 3.16-7.7). CONCLUSION: Evaluating polygenic risk can identify additional venous thromboembolism risk that is not captured in the commonly investigated genes for inherited thrombophilia. Our results indicate that oral contraceptive use is associated with an increased risk for developing a venous thromboembolism, particularly among women with a high genetic predisposition, and that oral contraceptive use dramatically increases the risk thereof short after initiation of use, which decreases with continued use. This suggests that the polygenic risk score could be used to identify women who are at high risk for developing a venous thromboembolism and advise them on alternative methods of contraception.

Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods.

BACKGROUND: Hormonal contraceptive use has been related to adverse effects, including impacts on sexual function and sexual satisfaction, although the difference in the effects on sexual function with the use of hormonal vs nonhormonal contraceptive methods remains controversial. AIM: In this study we sought to compare the prevalence of dyspareunia, sexual function, sexual satisfaction, quality of life, anxiety, and depression between women using hormonal, nonhormonal, or no contraceptive methods and to compare these outcomes between the most frequently used contraceptive methods. METHODS: This cross-sectional study included sexually active women of reproductive age who were stratified into 3 groups: women using hormonal, nonhormonal, or no contraceptive methods. Based on the use of questionnaires administered to the study participants, we compared sexual function in the 3 groups and more specifically among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. OUTCOMES: Participants completed 4 questionnaires to assess sexual function (Female Sexual Function Index), sexual satisfaction (Sexual Quotient-Feminine Version), quality of life (12-item Medical Outcomes Short Form Health Survey), and anxiety and depression (Hospital Anxiety and Depression Scale). RESULTS: This study included 315 women classified into 3 groups on the basis of contraceptive use: 161 in the hormonal contraceptives group (median [interquartile range] age, 24 [23-28] years), 97 in the nonhormonal contraceptives group (age 26 [23-30] years), and 57 in the no contraceptive methods group (age 28 [24-35] years). Dyspareunia prevalence showed no difference between the groups. In the quality of life domain, compared with women in the nonhormonal contraceptive group, women in the hormonal contraceptive group were younger and had lower sexual function satisfaction, reduced arousal, and heightened pain (P < .05), as well as higher anxiety and depression levels (P = .03, for both), increased pain (P = .01), and poorer overall health (P = .01). No difference was found between these groups in other quality of life domains. Regarding contraceptive methods, women using copper intrauterine devices had better sexual function, including higher rates of arousal and lower anxiety, than women using oral contraceptives (P < .05). CLINICAL IMPLICATIONS: The results of this study highlight worse sexual function and sexual satisfaction and higher levels of anxiety and depression in women using hormonal contraceptive methods than in women using nonhormonal methods. STRENGTHS AND LIMITATIONS: The findings of this study strengthen the evidence of differences in sexual function between women using oral contraceptives and those using copper intrauterine devices. Sexual function was also compared among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. However, less frequently used contraceptive methods, such as hormonal injections and vaginal rings, could not be compared in this sample. CONCLUSION: Women using hormonal contraceptive methods were younger, had lower sexual function and satisfaction, and experienced higher anxiety and depression levels than women using nonhormonal contraceptive methods.

An empirical evaluation of approximate and exact regression-based causal mediation approaches for a binary outcome and a continuous or a binary mediator for case-control study designs.

BACKGROUND: In the causal mediation analysis framework, several parametric regression-based approaches have been introduced in past years for decomposing the total effect of an exposure on a binary outcome into a direct effect and an indirect effect through a target mediator. In this context, a well-known strategy involves specifying a logistic model for the outcome and invoking the rare outcome assumption (ROA) to simplify estimation. Recently, exact estimators for natural direct and indirect effects have been introduced to circumvent the challenges prompted by the ROA. As for the approximate approaches relying on the ROA, these exact approaches cannot be used as is on case-control data where the sampling mechanism depends on the outcome. METHODS: Considering a continuous or a binary mediator, we empirically compare the approximate and exact approaches using simulated data under various case-control scenarios. An illustration of these approaches on case-control data is provided, where the natural mediation effects of long-term use of oral contraceptives on ovarian cancer, with lifetime number of ovulatory cycles as the mediator, are estimated. RESULTS: In the simulations, we found few differences between the performances of the approximate and exact approaches when the outcome was rare, both marginally and conditionally on variables. However, the performance of the approximate approaches degraded as the prevalence of the outcome increased in at least one stratum of variables. Differences in behavior were also observed among the approximate approaches. In the data analysis, all studied approaches were in agreement with respect to the natural direct and indirect effects estimates. CONCLUSIONS: In the case where a violation of the ROA applies or is expected, approximate mediation approaches should be avoided or used with caution, and exact estimators favored.

Lower affective empathy in oral contraceptive users: a cross-sectional fMRI study.

Evidence accumulates that oral contraceptive (OC) use modulates various socio-affective behaviors, including empathic abilities. Endogenous and synthetic sex hormones, such as estrogens and progestogens, bind to receptor sites in brain regions (i.e. frontal, limbic, and cerebellar) involved in socio-affective processing. Therefore, the aim of this study was to investigate the role of OC use in empathy. In a cross-sectional functional magnetic resonance imaging study, women in different hormonal states, including OC use (n = 46) or being naturally cycling in the early follicular (fNC: n = 37) or peri-ovulatory phase (oNC: n = 28), performed a visual, sentence-based empathy task. Behaviorally, OC users had lower empathy ratings than oNC women. Congruently, whole-brain analysis revealed significantly larger task-related activation of several brain regions, including the left dorsomedial prefrontal gyrus (dmPFG), left precentral gyrus, and left temporoparietal junction in oNC compared to OC women. In OC users, the activity of the left dmPFG and precentral gyrus was negatively associated with behavioral and self-reported affective empathy. Furthermore, empathy-related region-of-interest analysis indicated negative associations of brain activation with synthetic hormone levels in OC women. Overall, this multimodal, cross-sectional investigation of empathy suggests a role of OC intake in especially affective empathy and highlights the importance of including synthetic hormone levels in OC-related analyses.

How have changes in accessibility and public funding influenced contraceptive use among Norwegian adolescents? A cohort study.

INTRODUCTION: The Norwegian Government introduced in 2002 a reimbursement scheme for hormonal contraceptives to adolescents at the same time as public health nurses and midwives received authorization to prescribe hormonal contraceptives. This study examines the impact of increased accessibility and public funding on hormonal contraceptive use among adolescents. MATERIAL AND METHODS: The Norwegian Prescription Database, Statistics Norway, and Norwegian Institute of Public Health served as data sources for this cohort study. The study population comprised 174 653 Norwegian women born 1989-1990, 1994-1995, and 1999-2000. We examined use of hormonal contraceptives through dispensed prescriptions from age 12 through age 19 with duration of first continuous use as primary outcome. The statistical analyses were done in SPSS using chi-squared test, survival analysis, and Joinpoint regression analysis with p-values < 0.05. RESULTS: By age 19, ~75% of the cohorts had used at least one hormonal method. The main providers of the first prescription were general practitioners and public health nurses. Starters of progestogen-only pills (POPs) have increased across the cohorts, while starters of combined oral contraceptives (COCs) have decreased. The use of long-acting reversible contraceptives (LARCs) has increased since its inclusion in the reimbursement scheme (2015). Most switchers shifted from COCs or POPs as a start method to implants after LARCs became part of the reimbursement scheme. There has been a significant increase across the cohorts in the number of women who continuously used hormonal contraceptives from start to the end of the calendar year they became 19 years with the same method and after switching methods. We could not correlate changes in decreasing trends for teenage births or induced abortions (Joinpoint analysis) to time for implementation or changes in the reimbursement of hormonal contraceptives from 2002. CONCLUSIONS: Primarily public health nurses and to a lesser extent midwives became soon after they received authorization to prescribe COCs important providers. The expansion of the reimbursement scheme to cover POPs, patches, vaginal ring, and depot medroxyprogesterone acetate in 2006 had minor impact on increasing the proportion of long-term first-time users. However, the inclusion of LARCs in 2015 significantly increased the proportion of long-term first-time hormonal contraceptive users.

Recurrent stroke in a reproductive age women with patent foramen ovale.

BACKGROUND: Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. CASE PRESENTATION: A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. CONCLUSION: This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

Precancerous lesion determinants in women attending cervical cancer screening at public health facilities in North Shoa Zone, Amhara, Ethiopia: an unmatched case-control study.

BACKGROUND: Precancerous cervical lesions develop in the transformation zone of the cervix and progress through stages known as cervical intraepithelial neoplasia (CIN) 1, 2, and 3. If untreated, CIN2 or CIN3 can lead to cervical cancer. The determinants of cervical precancerous lesions are not well documented in Ethiopia. Therefore, this study aims to find the determinants of cervical precancerous lesions among women screened for cervical cancer at public health facilities. METHODS: A study conducted from January to April 2020 involved 216 women, consisting of 54 cases (positive for VIA during cervical cancer screening) and 162 controls (negative for VIA). It focused on women aged 30 to 49 undergoing cervical cancer screening. Multivariable logistic regression analysis assessed the link between precancerous lesions and different risk factors, considering a significance level of p < 0.05. RESULTS: Women who used oral contraceptives for a duration exceeding five years showed a nearly fivefold increase in the likelihood of developing precancerous lesions (Adjusted Odds Ratio (AOR) = 4.75; 95% CI: 1.48, 15.30). Additionally, early age at first sexual intercourse (below 15 years) elevated the odds of developing precancerous lesions fourfold (AOR = 3.77; 95% CI: 1.46, 9.69). Furthermore, women with HIV seropositive results and a prior history of sexually transmitted infections (STIs) had 3.4 times (AOR = 3.45; 95% CI: 1.29, 9.25) and 2.5 times (AOR = 2.58; 95% CI: 1.10, 6.09) higher odds of developing cervical precancerous lesions compared to their counterparts. CONCLUSION: In conclusion, women who have used oral contraceptives for over five years, started sexual activity before the age of 15 and have a history of sexually transmitted infections, including HIV, are at higher risk of developing precancerous cervical lesions. Targeted intervention strategies aimed at promoting behavioural change to prevent early sexual activity and STIs are crucial for avoiding cervical precancerous lesions. It is crucial to introduce life-course principles for female adolescents early on, acknowledging the potential to prevent and control precancerous lesions at critical stages in life, from early adolescence to adulthood, encompassing all developmental phases.

Differences in anxiety, worry, and perceived stress among naturally cycling women and oral contraceptives users: a cross-sectional study investigating the role of contraceptive types.

The goal of our study was to test whether the types of OC affect the link between anxiety and its main maintenance factors: worry and perceived stress. Women are particularly at risk of being affected by excessive worrying, a core component of generalized anxiety disorder (GAD), and they are twice as likely as men to suffer from GAD. The literature suggests that gonadal hormones and types of oral contraceptives (OC) should be taken into account when exploring anxiety disorders in women, but the precise mechanism of this link remains understudied. We performed an observational cross-sectional study on a sample of 908 women, including 499 women naturally cycling (NC) and 409 taking OC (277 in the anti-androgenic group, 132 in the androgenic group). The participants filled in a battery of online questionnaires. Anxiety positively correlated with worry and perceived stress in the whole sample and in the three groups: androgenic OC, anti-androgenic OC, and NC. There was no significant difference between the groups on all the variables apart from the age of the participants. However, we found that women taking anti-androgenic OC had significantly higher levels of worry than NC women (after controlling for stress and age). The differences in OC types should be taken into account in future studies which might also lead to a better choice of OC based on women's individual needs.

A phase I/II study evaluating the pharmacokinetics, pharmacodynamics, and safety of drospirenone as an oral contraceptive in Japanese women.

AIM: Drospirenone (DRSP) is a synthetic progestogen approved as a progestin-only pill for contraception in both the United States and Europe. Herein, we conducted a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, and safety of DRSP in Japanese women. METHODS: Single and multiple doses of 4 mg of DRSP were orally administered to healthy premenopausal Japanese women. In the multiple-dose period, 4 mg of DRSP was administered once daily for 24 days. Pharmacokinetics, hormone levels, and adverse events (AEs) were investigated. RESULTS: Twelve Japanese women participated in this study. The single- and multiple-dose pharmacokinetics of DRSP was similar to that reported in previous studies in Caucasians. In the multiple-dose period, no subject displayed a progesterone level of more than 5.03 ng/mL. AEs were observed in 11 (91.7%) subjects. The most common AE was genital hemorrhage, which was observed in six (50.0%) subjects, followed by diarrhea and acne in four (33.3%) subjects each. All AEs resolved or improved at the end of the study, and complete recovery was confirmed in all subjects at follow-up. CONCLUSIONS: The pharmacokinetics of DRSP in Japanese women was similar to that of previous studies performed in Caucasian women. Repeated administration of DRSP maintained low plasma progesterone levels indicating effective inhibition of ovulation. No notable safety concerns were observed. In this phase I/II study, DRSP had no obvious pharmacokinetic, pharmacodynamic, or safety issues to consider in Japanese women.

Auditing the representation of hormonal contraceptives in studies assessing exercise performance in women.

Hormonal contraceptive (HC) users have a different ovarian hormonal profile compared to eumenorrheic women. Due to the prevalence of HC use amongst sportswomen, there has been increased research efforts to understand their impact on exercise performance. The aim was to audit this research. Studies identified were assessed for HC type, athlete calibre, performance outcome, study design, and quality of methodological control regarding ovarian hormonal profiles. Sixty-eight different HCs were reported across 61 studies. Monophasic combined oral contraceptive (OCP) pills represented 60% of HCs, followed by other pills [34%, phasic-combined, progestogen-only, and un-specified], phasic and long acting reversible contraceptives [5%, vaginal ring, patch, implant, injection, intrauterine system] and unspecified HCs (1%). Eleven percent of participants using HCs were classified as highly trained or elite/international with no participants being classed as world class. Whilst the number of studies involving HCs has increased two-fold over the past decade, the number of studies ranked as gold standard has not increased (HC; 2003-57%, 2011-55%, 2022-43%. OCP; 2003-14%, 2011-17%, 2022-12%). Future research assessing HCs and exercise performance should adopt high-quality research designs and include a broader range of HCs in highly trained to world-class populations to increase the reach and impact of research in this area.

Adult Female Acne: Managing the Hormones.

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.

A Narrative Review of the Role of Estrogen (Receptors) in Melanoma.

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor ß (ERß) instead of estrogen receptor α (ERα) in CM is notable, with ERß potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field.

Knowledge of non-contraceptive benefits of and willingness to consider taking oral contraceptive pills among a low-risk female population: a cross-sectional study.

BACKGROUND: In addition to its widely-appreciated contraceptive applications, the oral contraceptive pill (OCP) conveys both oncological and non-oncological benefits. Oncological benefits include a decreased risk of endometrial, ovarian, and colorectal cancer. Non-oncological benefits include reducing androgenic effects and alleviating menstruation-related problems. This study aimed to ascertain knowledge levels of non-contraceptive benefits and risks of OCP use among participants without contraindications to OCPs. This study also assessed factors associated with participants being more likely to consider taking OCPs. METHODS: 263 women aged 21 to 40 years old with no contraindications for OCP usage participated in this study. An anonymous questionnaire collected sociodemographic information and assessed participants' knowledge of the non-contraceptive benefits and risks associated with OCP use. Multivariate linear regression was used to assess factors associated with knowledge levels. Multivariate logistic regression was used to investigate factors associated with being more likely to consider taking OCPs among women who did not presently take them. RESULTS: Multivariate logistic regression revealed that participants who were more knowledgeable overall about the non-contraceptive benefits of OCPs were more likely to consider taking OCPs (coefficient = 0.184, p-value = 0.00). Knowledge of both oncological and non-oncological benefits of OCP use was relatively poor, especially among older women. Current OCP users were found to be more knowledgeable about their benefits. CONCLUSIONS: As women with greater knowledge of non-contraceptive benefits of OCPs are more likely to consider taking them, knowledge gaps regarding OCPs should be filled, so that more women may reap the non-contraceptive benefits of OCPs.

A sample of women with a low risk profile for oral contraceptive pills in Singapore demonstrated poor overall knowledge of their non-contraceptive benefits. Greater knowledge of the non-contraceptive benefits of oral contraceptive pills was associated with a greater willingness to consider taking oral contraceptive pills.

Contraceptive switch and abandonment among women using the pill, condoms and injectables in Brazil.

OBJECTIVE: The aim of our study was to assess the covariates of contraceptive switching and abandonment among Brazilian women stratified by oral pills, condoms and injectables. MATERIALS AND METHODS: Women attending primary health care services in three Brazilian mid- to large-sized cities were interviewed face-to-face about their contraceptive practices (n = 2,051). Data were collected using a contraceptive calendar. Analysis included estimates using Kaplan-Meier multiple-decrement life-table probabilities and discrete-time hazards modelling of switching from a method to another or to no method. RESULTS: Among 3,280 segments of contraceptive use, we observed that five-year contraceptive switching rates ranged from 34.9% among injectable users to 56.1% among pill users. Of particular concern were the high discontinuation rates of abandonment, which ranged from 50.9% among injectable users to 77.4% among pill users. Covariates of method switching and abandonment varied by type of method, but age, race/ethnicity, religion and relationship status must be highlighted as key elements of discontinuation. CONCLUSION: Contraceptive method switching and abandoning are frequent outcomes of contraceptive use. Understanding the factors that shape women's decisions to continue or discontinue the use of a contraceptive method can help tailoring comprehensive contraceptive counselling that meet their expectations and reproductive needs when starting using a method.

Contraceptive discontinuation among women in need of contraception may difficult the achievement of their fertility desires, which can lead to unintended pregnancies.

Oestrogens in oral contraception: considerations for tailoring prescription to women's needs.

BACKGROUND: The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control. PURPOSE: To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women's needs. RESULTS: All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation. CONCLUSION: Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women's needs and preferences.

For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women's needs and desires.