Hormonal contraception and cognition: Considering the influence of endogenous ovarian hormones and genes for clinical translation.

Despite the well-known influence of ovarian hormones on the brain and widespread use of hormonal contraception (HC) since the 1960s, our knowledge of HC's cognitive effects remains limited. To date, the cognitive findings have been inconsistent. In order to establish what might make HC studies more consistent, we surveyed the literature on HCs and cognition to determine whether studies considered HC formulation, phase, pharmacokinetics, duration, and gene interactions, and assessed whether oversight of these factors might contribute to variable findings. We found that synthetic HC hormones exert dose-dependent effects, the day of oral contraceptive (Pill) ingestion is critical for understanding cognitive changes, and gene-cognition relationships differ in women taking the Pill likely due to suppressed endogenous hormones. When these factors were overlooked, results were not consistent. We close with recommendations for research more likely to yield consistent findings and be therefore, translatable.

Ovulatory cycle shifts in human motivational prioritisation of sex and food.

Previous research on the endogenous effects of ovarian hormones on motivational states in women has focused on sexual motivation. The Motivational Priority Shifts Hypothesis has a broader scope. It predicts a shift from somatic to reproductive motivation when fertile. In a highly powered preregistered online diary study across 40 days, we tested whether 390 women report such an ovulatory shift in sexual and eating motivation and behaviour. We compared 209 naturally cycling women to 181 women taking hormonal contraceptives (HC) to rule out non-ovulatory changes across the cycle as confounders. We found robust ovulatory decreases in food intake and increases in general sexual desire, in-pair sexual desire and initiation of dyadic sexual behaviour. Extra-pair sexual desire increased mid-cycle, but the effect did not differ significantly in HC women, questioning an ovulatory effect. Descriptively, solitary sexual desire and behaviour, dyadic sexual behaviour, appetite, and satiety showed expected mid-cycle changes that were diminished in HC women, but these failed to reach our strict preregistered significance level. Our results provide insight into current theoretical debates about ovulatory cycle shifts while calling for future research to determine motivational mechanisms behind ovulatory changes in food intake and considering romantic partners' motivational states to explain the occurrence of dyadic sexual behaviour.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

An age-related nomogram for antral follicle count: an observational study of 3821 women.

RESEARCH QUESTION: What is the relationship between antral follicle count (AFC) and chronological age, and what are the expected values for AFC? DESIGN: This was a retrospective cohort study at a specialist gynaecological ultrasound centre in London, UK. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound (TVUS) examinations, between 1 January 2017 and 22 September 2022 were included in this study. RESULTS: In total, 8821 TVUS records from 7573 patients were analysed. The relationship between AFC and age was estimated to develop an AFC nomogram independent of the stage in the menstrual cycle. AFC corresponding to the 10th, 25th, 50th, 75th and 90th centiles for each patient and age group were calculated. Both nomogram and condition-specific populations displayed a Gaussian relationship between AFC and age. For the nomogram population (scans n = 4256, patients n = 3821), a peak median AFC of 30 was observed between 21-23 years of age. The AFC distribution of the group with previous ovarian cystectomy (scans n = 534, patients n = 443) was found to be significantly different compared with the nomogram population (P < 0.0001). However, the same did not hold true for those on hormonal contraception (scans n = 566, patients n = 534) (P = 0.43). CONCLUSIONS: An AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years was developed. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments, and can be taken any time in the menstrual cycle, including in women on hormonal contraceptives or who have undergone previous ovarian cystectomy.

Reproductive healthcare in adolescents with autism and other developmental disabilities.

BACKGROUND: Adults with developmental disabilities often have less access to reproductive health services than adults without these disabilities. However, little is known about how adolescents with developmental disabilities, including autism, access reproductive healthcare. OBJECTIVE: We aimed to characterize the use of reproductive healthcare services among adolescents with autism and those with other developmental disabilities in comparison with adolescents with typical development. STUDY DESIGN: We conducted a cohort study of a sample of adolescents who were continuously enrolled members of Kaiser Permanente Northern California, an integrated healthcare system, from ages 14 to 18 years. The final analytical sample included 700 adolescents with autism, 836 adolescents with other developmental disabilities, and 2187 typically developing adolescents who sought care between 2000 and 2017. Using the electronic health record, we obtained information on menstrual conditions, the use of obstetrical-gynecologic care, and prescriptions of hormonal contraception. We compared healthcare use between the groups using chi-square tests and covariate-adjusted risk ratios estimated using modified Poisson regression. RESULTS: Adolescents with autism and those with other developmental disabilities were significantly more likely to have diagnoses of menstrual disorders, polycystic ovary syndrome, and premenstrual syndrome than typically developing adolescents. These 2 groups also were less likely than typically developing peers to visit the obstetrician-gynecologist or to use any form of hormonal contraception, including oral contraception, hormonal implants, and intrauterine devices. Adolescents in all 3 groups accessed hormonal contraception most frequently through their primary care provider, followed by an obstetrician-gynecologist. CONCLUSION: Adolescents with autism and those with other developmental disabilities are less likely than their typically developing peers to visit the obstetrician-gynecologist and to use hormonal contraception, suggesting possible care disparities that may persist into adulthood. Efforts to improve access to reproductive healthcare in these populations should target care delivered in both the pediatric and obstetrics-gynecology settings.

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.

The association between lifestyle factors and the composition of the vaginal microbiota: a review.

PURPOSE: The vaginal microbiota offers valuable insights into women's sexual health and the risk of developing sexually transmitted infections (STIs) and bacterial vaginosis. Despite the public health implications of changes in the vaginal environment, existing data on this topic remain sparse. METHODS: Following the PRISMA statement guidelines, we consulted five bibliographic databases, focusing on five main daily habits and behaviors. We included only studies published up to October 2023, investigating the influence of personal hygiene, sexual behaviors, hormonal contraception, smoking, alcohol consumption, and psychosocial stress on the vaginal microbiota using next-generation sequencing. RESULTS: Based on our inclusion criteria, we incorporated 37 studies into this review. Hormonal contraception and personal hygiene were found to promote eubiosis of the vaginal microbiota. In contrast, sexual behaviors, smoking, alcohol consumption, and psychosocial stress were associated with an increased susceptibility to bacterial vaginosis, STIs, and severe pelvic inflammatory diseases due to a modified vaginal microbiota. Black ethnicity emerged as a confounding factor, with this population showing unstable vaginal microbiota. Oral contraception and a stable male sexual partner were found to favor Lactobacillus colonization, acting as a protective factor. Conversely, non-hormonal contraception and unprotected or non-penile/vaginal sexual activity increased the incidence of vaginal inflammation and bacterial vaginosis by disturbing the vaginal microbiota and reducing Lactobacillus abundance. CONCLUSION: Daily habits and lifestyle can influence the composition of the vaginal microbiota, thereby affecting vaginal health. Disturbances in the vaginal microbiota could be associated factors for STIs and vaginosis. Therefore, prioritizing more appropriate management of the vaginal microbiota is crucial.

Endometriosis risk and hormonal contraceptive usage: A nationwide cohort study.

OBJECTIVE: To investigate whether an early need of hormonal contraceptive (HC), or a failure to find a suitable method, are warning signs for endometriosis. DESIGN: A retrospective cohort study. SETTING: Sweden. POPULATION: The cohort consisted of 720 805 women aged 12-27 years during the period 2005-2017. All women, regardless of whether they received a diagnosis of endometriosis or not (reference group), were included. METHODS: We used data from Swedish national registers. Risks are expressed as crude and adjusted hazard ratios (HRs and aHRs, respectively) with 95% confidence intervals (95% CIs), adjusted for age, education level, civil status, parity, country of birth, and diagnoses of infertility, dysmenorrhea or depression. MAIN OUTCOME MEASURES: A diagnosis of endometriosis between 12 and 27 years of age. RESULTS: During this period, 3268 women were diagnosed with endometriosis (0.45%). Women who started HC at the ages of 12-14 years had a higher risk of receiving the diagnosis (aHR 2.53, 95% CI 2.21-2.90) than those who began at age 17 years or older. Having tried more types of HCs was associated with a twofold increased risk of endometriosis (more that three types of HC, aHR 2.31, 95% CI 1.71-3.12). Using HC for more than 1 year was associated with a decreased risk of endometriosis (>1 year, aHR 0.53, 95% CI 0.48-0.59). Women with endometriosis more commonly had dysmenorrhea, depression or infertility. CONCLUSIONS: The use of HCs at an early age and a failure to find a suitable HC were identified as warning signs of later receiving an endometriosis diagnosis. A longer duration of HC usage reduced the risk of receiving the diagnosis.

Use of systemic hormonal contraception and risk of attempted suicide: a nested case-control study.

Evidence regarding the role of hormonal contraception (HC) as a risk factor for attempted suicide is inconclusive. Thus, this study aimed to assess the associations of use of different types of systemic HC with the risk of attempted suicide in women aged 15-49 years. Data on a population-based cohort (n = 587,823) of HC users and non-users in 2017 was derived from national registers in Finland. In a nested case-control design we examined the risk of attempted suicide in relation to current HC use (past six months) via multivariable conditional logistic regression models. During the follow-up (from 2018 to 2019) there were 1.174,346 million person-years of which 818 cases of suicide attempts were observed (incidence rate: 0.70 per 1000 person-years). Use of HC, especially combined hormonal contraceptives, was not associated with a higher risk of attempted suicide compared to non-use (OR 0.68, 95% CI 0.45-1.02) after controlling for marital status, socioeconomic status, education, chronic diseases, recent delivery, recent psychiatric hospitalizations, and current use of psychotropic medications. In women without psychiatric history, current HC use (OR 0.73, 95% CI 0.58-0.91), especially ethinylestradiol-containing preparations (OR 0.54, 95% CI 0.40-0.73), was associated with a lower risk of attempted suicide. After adjusting for recent psychiatric hospitalizations and use of psychotropic medications, current use of progestin-only preparations was not associated with attempted suicide. In conclusion, current HC use was not associated with an increased risk of attempted suicide in fertile-aged women.

A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers.

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women's hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women's health.

Hormonal Contraceptive Use Is Associated With a Decreased Incidence of Hypothyroidism.

OBJECTIVE: Hypothyroidism is one of the most common endocrine disorders affecting 5 to 10 times more women than men. Given this higher incidence in women, it is possible that hormonal differences or medications more commonly used by women may play a role in the risk of developing hypothyroidism. We hypothesized that hormonal contraception affects the risk of developing hypothyroidism. METHODS: Using the TriNetX database, we developed a case-control study and identified women aged 18 to 45 years in 4 distinct groups: (1) estrogen-progestin contraceptive (EPC) use, (2) progestin-only contraceptive (POC) use, (3) progestin-containing intrauterine device (IUD) use, and (4) controls. For each group, we ascertained data including the diagnosis of hypothyroidism, alcohol use, tobacco use, and body mass index. RESULTS: We identified 18 578 patients with sufficient data: EPC use, n = 5849; POC use, n = 5052; IUD use, n = 1000; and controls, n = 6677. A total of 118 individuals (1.8%) in the control group and 165 individuals (1.4%) who received hormonal contraception developed hypothyroidism. After using a logistic model to account for cofounding variables, all forms of hormonal contraception (EPC, POC, and IUD) had a protective effect against the diagnosis of hypothyroidism. POC and IUD uses had the greatest protective effect, with odds ratios of 0.14 and 0.12, respectively. EPC had a less pronounced but still significant effect, with an odds ratio of 0.30 (P < .001). CONCLUSION: This study of >18 000 women and the risk of developing hypothyroidism demonstrates a protective effect of hormonal contraceptive use. Our data, both unadjusted and adjusted using a logistic model to account for cofounding variables, suggest that the use of hormonal contraception, in any form, decreases the risk of developing hypothyroidism.

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.

Comparison of the cytokine responses to acute strength exercise between oral contraceptive users and naturally cycling women.

PURPOSE: Cytokines are released as part of an inflammatory reaction in response to strength exercise to initiate muscle repair and morphological adaptations. Whether hormonal fluctuations induced by the menstrual cycle or oral contraceptives affect inflammatory responses to strength exercise remains unknown. Therefore, we aimed to compare the response of cytokines after acute strength exercise in naturally menstruating women and oral contraceptive users. METHODS: Naturally menstruating women (MC, n = 13, 24 ± 4 years, weekly strength training: 4.3 ± 1.7 h) and women using a monophasic combined pill (> 9 months) (OC, n = 8, 22 ± 3 years, weekly strength training: 4.5 ± 1.9 h) were recruited. A one-repetition-maximum (1RM) test and strength exercise in the squat (4 × 10 repetitions, 70%1RM) was performed in the early follicular phase or pill free interval. Concentrations of oestradiol, IL-1ß, IL-1ra, IL-6, IL-8, and IL-10 were assessed before (pre), directly after (post) and 24 h after (post24) strength exercise. RESULTS: IL-1ra increased from pre to post (+ 51.1 ± 59.4%, p = 0.189) and statistically decreased from post to post24 (- 20.5 ± 13.5%, p = 0.011) only in OC. Additionally, IL-1ß statistically decreased from post to post24 (- 39.6 ± 23.0%, p = 0.044) only in OC. There was an interaction effect for IL-1ß (p = 0.038) and concentrations were statistically decreased at post24 in OC compared to MC (p = 0.05). IL-8 increased across both groups from post to post24 (+ 66.6 ± 96.3%, p = 0.004). CONCLUSION: We showed a differential regulation of IL-1ß and IL-1ra between OC users in the pill-free interval and naturally cycling women 24 h after strength exercise, while there was no effect on other cytokines. Whether this is associated with previously shown compromised morphological adaptations remains to be investigated.

Assessing Student and Patient Perspectives on Pharmacist Prescribed Hormonal Contraceptives.

BACKGROUND: Increasing convenient, accessible, and cost effective contraceptive access is critically important. Two-thirds of US states permit pharmacists to prescribe hormonal contraceptives. Community pharmacies are ideal settings for patients to be offered contraceptive therapeutic options including hormonal contraceptives, emergency contraception (EC), and over-the-counter (OTC) oral contraception. OBJECTIVE: The objective of this study was to assess college student and community pharmacy patients' perspectives on pharmacist prescribed hormonal contraceptives, likelihood of accessing contraceptives from a pharmacist, and perspectives regarding EC and OTC oral contraception. METHODS: The researchers conducted an observational study distributed to college students and patients accessing care at community-based pharmacies from October 2022 to February 2023. The survey population included those who were 18 years or older, English speaking, and recruited both in person and online. Survey questions assessed barriers to contraception access, perspectives towards pharmacist prescribed hormonal contraception, likelihood of receiving pharmacist prescribed hormonal contraception as well as EC and OTC oral contraception at the community pharmacy. Results from the pharmacist and clinician surveys were previously published, therefore this report will focus on the student and patient data. RESULTS: Ninety-one percent of all respondents strongly agreed or agreed with pharmacist-prescribed hormonal contraception. Students and patients reported convenience, time saving, and money saving as reasons for obtaining from their pharmacist. In regard to EC, 36% reported having ever purchased from a pharmacy and 58% were extremely or somewhat likely to purchase OTC oral contraception. CONCLUSIONS: The majority of students and community pharmacy patients surveyed in Rhode Island support pharmacist prescribed hormonal contraceptives. State-level policy advancements with reimbursement for services provide pharmacists an opportunity to provide contraceptive care for all people.

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

BACKGROUND: Health 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: Differences 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.

Associations of reproductive factors and exogenous estrogens with global and domain-specific cognition in later life.

INTRODUCTION: Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain-specific cognition in later life. METHODS: We studied a population-based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing. RESULTS: The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular-related covariates did not attenuate the results. DISCUSSION: Multiple reproductive risk factors are associated with cognitive decline in later life. HIGHLIGHTS: The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain-specific z-scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.

Longitudinal associations of reproductive factors and exogeneous estrogens with neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease.

INTRODUCTION: Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies. METHODS: We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures. RESULTS: Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume. DISCUSSION: HC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies. HIGHLIGHTS: Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

Effects of Endocrine Interventions Targeting ERα or PR on Breast Cancer Risk in the General Population and Carriers of BRCA1/2 Pathogenic Variants.

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers.

A pioneer of hormonal contraception: Joseph W. Goldzieher.

On 19 July, 2024, at the age of almost 105 years, Joseph W. Goldzieher, the last survivor of the group of pioneers who created oral contraception, peacefully passed away. Here we briefly reconstruct the salient points in his long, productive life, and highlight his achievements in the development of hormonal contraception. His work is indissolubly enshrined in the complex history of hormonal contraception, from the first, fundamental observations, to the first clinical trials, both in the form of combined oestrogen-progestin oral pills and long-acting injectable contraceptives. After Pincus and his Group created an oral contraceptive containing an oestrogen and a progestin, Goldzieher was the second international scientist to conduct clinical trials of the new modality. He teamed-up with investigators in Mexico creating a fruitful, long-lasting collaboration. They produced evidence that ovulation inhibition could be achieved with all the progestins used at the time. Of importance, he was among the first to explore the possibility of using oestrogens to block ovulation, and developed the concept of sequential contraception. For all this lifetime of work, we believe he deserves to be named a 'giant in reproductive endocrinology'.