Nonhormonal Male Contraceptive Development-Strategies for Progress.

Despite the widely demonstrated public health benefits of contraception, limited contraceptive options are available for men, placing both the contraceptive burden and opportunity solely on women. This review outlines the need for an increased focus on male contraceptive development and highlights several related topics, including the perspectives of women and men on male contraceptives, historical challenges, and reasons behind the persistent delays in male contraceptive development. It also discusses the importance of serendipitous observations in drug discovery and the limitations of depleting sperm or spermatogenic cells as a contraceptive approach. It further provides an overview of ongoing research and development on novel methods, with a goal to offer insights into the multifaceted aspects of nonhormonal male contraceptive development, addressing its implications for the health of men and women. SIGNIFICANCE STATEMENT: Despite well over half a century of effort in developing male contraceptives, there are no approved male contraceptive drugs on the market. This review aims to present strategies for progress in nonhormonal male contraception based on lessons learned from history, with the hope of expediting development and bringing a male contraceptive drug closer to reality.

U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.

The 2024 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by persons who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. MEC (CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR 2016:65[No. RR-3]:1-103). Notable updates include 1) the addition of recommendations for persons with chronic kidney disease; 2) revisions to the recommendations for persons with certain characteristics or medical conditions (i.e., breastfeeding, postpartum, postabortion, obesity, surgery, deep venous thrombosis or pulmonary embolism with or without anticoagulant therapy, thrombophilia, superficial venous thrombosis, valvular heart disease, peripartum cardiomyopathy, systemic lupus erythematosus, high risk for HIV infection, cirrhosis, liver tumor, sickle cell disease, solid organ transplantation, and drug interactions with antiretrovirals used for prevention or treatment of HIV infection); and 3) inclusion of new contraceptive methods, including new doses or formulations of combined oral contraceptives, contraceptive patches, vaginal rings, progestin-only pills, levonorgestrel intrauterine devices, and vaginal pH modulator. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.

U.S. Selected Practice Recommendations for Contraceptive Use, 2024.

The 2024 U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR) addresses a selected group of common, yet sometimes complex, issues regarding initiation and use of specific contraceptive methods. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. SPR (CDC. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR 2016;65[No. RR-4]:1-66). Notable updates include 1) updated recommendations for provision of medications for intrauterine device placement, 2) updated recommendations for bleeding irregularities during implant use, 3) new recommendations for testosterone use and risk for pregnancy, and 4) new recommendations for self-administration of injectable contraception. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.

The causal effect of a family planning intervention on women's contraceptive use and birth spacing.

Studies have suggested that improving access to family planning (FP) may improve contraceptive use and reduce fertility. However, high-quality evidence, particularly from randomized implementation trials, of the effect of FP programs and interventions on longer-term fertility and birth spacing is lacking. We conduct a nonblinded, randomized, controlled trial to assess the causal impact of improved access to FP on contraceptive use and pregnancy spacing in Lilongwe, Malawi. A total of 2,143 married women aged 18 to 35 who were either pregnant or had recently given birth were recruited through home visits between September 2016 and January 2017 and were randomly assigned to an intervention arm or a control arm. The intervention arm received four services over a 2-y period: 1) up to six FP counseling sessions; 2) free transportation to an FP clinic; 3) free FP services at the clinic or financial reimbursement for FP services obtained elsewhere; and 4) treatment for contraceptive-related side effects. Contraceptive use after 2 y of intervention exposure increased by 5.9 percentage points, mainly through an increased use of contraceptive implants. The intervention group's hazard of pregnancy was 43.5% lower 24 mo after the index birth. Our results highlight the positive impact of increased access to FP on a woman's contraceptive use. In addition, we show that exposure to the FP intervention led to a prolongation of birth intervals among intervention women relative to control women and increased her control over birth spacing and postpartum fertility, which, in turn, may contribute to her longer-term health and well-being.

A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives.

We identified the anti-Mullerian hormone (also known as Müllerian inhibiting substance or MIS) as an inhibitory hormone that induces long-term contraception in mammals. The type II receptor to this hormone, AMHR2 (also known as MISR2), represents a promising druggable target for the modulation of female reproduction with a mechanism of action distinct from steroidal contraceptives. We designed an in vitro platform to screen and validate small molecules that can activate MISR2 signaling and suppress ovarian folliculogenesis. Using a bone morphogenesis protein (BMP)­response element luciferase reporter cell­based assay, we screened 5,440 compounds from a repurposed drug library. Positive hits in this screen were tested for specificity and potency in luciferase dose­response assays, and biological activity was tested in ex vivo Mullerian duct regression bioassays. Selected candidates were further evaluated in ex vivo follicle/ovary culture assays and in vivo in mice and rats. Here, we report that SP600125, CYC-116, gandotinib, and ruxolitinib can specifically inhibit primordial follicle activation and repress folliculogenesis by stimulating the MISR2 pathway.

Hormonal contraceptives and the brain: A systematic review on 60 years of neuroimaging, EEG, and biochemical studies in humans and animals.

Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.

Progesterone and contraceptive progestin actions on the brain: A systematic review of animal studies and comparison to human neuroimaging studies.

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.

Use of Model-Informed Drug Development to Streamline Development of Long-Acting Products: Can These Successes Be Translated to Long-Acting Hormonal Contraceptives?

Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challenging. This review provides (a) an overview of representative development programs for long-acting antipsychotics as cases for conceptual translation to long-acting contraceptives, (b) several case examples on how modeling and simulation have been used to streamline the development of long-acting products, and (c) examples of challenges andopportunities in developing long-acting contraceptives and information on how exposure-response relationships of commonly used progestins may enable regulators and developers to rely on prior findings of effectiveness and safety from an approved contraceptive to streamline the development of long-acting contraceptives. The US Food and Drug Administration is seeking assistance from stakeholders to provide data from studies in which pharmacokinetic and pharmacodynamic or clinical outcomes of hormonal contraceptives were evaluated and not previously submitted.

Mapping heterogeneity in family planning indicators in Burkina Faso, Kenya, and Nigeria, 2000-2020.

BACKGROUND: Family planning is fundamental to women's reproductive health and is a basic human right. Global targets such as Sustainable Development Goal 3 (specifically, Target 3.7) have been established to promote universal access to sexual and reproductive healthcare services. Country-level estimates of contraceptive use and other family planning indicators are already available and are used for tracking progress towards these goals. However, there is likely heterogeneity in these indicators within countries, and more local estimates can provide crucial additional information about progress towards these goals in specific populations. In this analysis, we develop estimates of six family indicators at a local scale, and use these estimates to describe heterogeneity and spatial-temporal patterns in these indicators in Burkina Faso, Kenya, and Nigeria. METHODS: We used a Bayesian geostatistical modelling framework to analyse geo-located data on contraceptive use and family planning from 61 household surveys in Burkina Faso, Kenya, and Nigeria in order to generate subnational estimates of prevalence and associated uncertainty for six indicators from 2000 to 2020: contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), traditional contraceptive prevalence rate (tCPR), unmet need for modern methods of contraception, met need for family planning with modern methods, and intention to use contraception. For each country and indicator, we generated estimates at an approximately 5 × 5-km resolution and at the first and second administrative levels (regions and provinces in Burkina Faso; counties and sub-counties in Kenya; and states and local government areas in Nigeria). RESULTS: We found substantial variation among locations in Burkina Faso, Kenya, and Nigeria for each of the family planning indicators estimated. For example, estimated CPR in 2020 ranged from 13.2% (95% Uncertainty Interval, 8.0-20.0%) in Oudalan to 38.9% (30.1-48.6%) in Kadiogo among provinces in Burkina Faso; from 0.4% (0.0-1.9%) in Banissa to 76.3% (58.1-89.6%) in Makueni among sub-counties in Kenya; and from 0.9% (0.3-2.0%) in Yunusari to 31.8% (19.9-46.9%) in Somolu among local government areas in Nigeria. There were also considerable differences among locations in each country in the magnitude of change over time for any given indicator; however, in most cases, there was more consistency in the direction of that change: for example, CPR, mCPR, and met need for family planning with modern methods increased nationally in all three countries between 2000 and 2020, and similarly increased in all provinces of Burkina Faso, and in large majorities of sub-counties in Kenya and local government areas in Nigeria. CONCLUSIONS: Despite substantial increases in contraceptive use, too many women still have an unmet need for modern methods of contraception. Moreover, country-level estimates of family planning indicators obscure important differences among locations within the same country. The modelling approach described here enables estimating family planning indicators at a subnational level and could be readily adapted to estimate subnational trends in family planning indicators in other countries. These estimates provide a tool for better understanding local needs and informing continued efforts to ensure universal access to sexual and reproductive healthcare services.

Usual Source of Care and Contraceptive Use.

BACKGROUND: A high proportion of people in the United States at risk of unintended pregnancy also have limited primary care access. STUDY DESIGN: We pooled data for analyses from separate 2015-2017 and 2017-2019 waves of the National Survey of Family Growth. Multivariable logistic regression was used to estimate associations between the usual source of health care and self-reported use of a comprehensive range of contraceptive options, as well as alignment between patient preference and the current method. RESULTS: Compared with having a private doctor or Health Maintenance Organization, not having a usual source of care was associated with lower odds of using short-term hormonal methods (OR=0.54, 95% CI: 0.40-0.73, for an 11 percentage point lower rate); higher odds of using time-based methods (OR=1.47, 95% CI: 1.10-1.97, for a 6 percentage point higher rate); and higher odds of preferring a contraceptive method other than the one most recently used (OR=1.39, 95% CI: 1.01-1.90, for a 6 percentage point higher probability). Reliance on an emergency department as a usual source of care was not associated with contraceptive use or satisfaction with the method used. Reliance on urgent care was associated only with higher odds of using time-based methods (OR=1.60, 95% CI: 1.03-2.50, for a 7 percentage point higher rate). Clinic-based usual care was not associated with any differences in contraceptive use but was associated with preferring a contraceptive method other than the one most recently used (OR=1.65, 95% CI: 1.21-2.25, for an 8 percentage point higher probability). CONCLUSIONS: All sources of usual care can improve contraceptive access.

ABCC4 is a PGE2 efflux transporter in the ovarian follicle: A mediator of ovulation and a potential non-hormonal contraceptive target.

The role of prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is significantly upregulated in preovulatory human granulosa cells (GCs). We found that PGE2 efflux in cultured human GCs is mediated by ABCC4 thus regulating its extracellular concentration. The ABCC4 inhibitor probenecid demonstrated effective blocking of ovulation and affects key ovulatory genes in female mice in vivo. We postulate that the reduction in PGE2 efflux caused by the inhibition of ABCC4 activity in GCs decreases the extracellular concentration of PGE2 and its ovulatory effect. Treatment of female mice with low dose of probenecid as well as with the PTGS inhibitor indomethacin or Meloxicam synergistically blocks ovulation. These results support the hypothesis that ABCC4 has an important role in ovulation and might be a potential target for non-hormonal contraception, especially in combination with PGE2 synthesis inhibitors. These findings may fill the gap in understanding the role of ABCC4 in PGE2 signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment and control of fertility.

Hormonal contraceptive use is associated with differences in women's inflammatory and psychological reactivity to an acute social stressor.

Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.

Levonorgestrel maintains goal-directed behavior in habit-trained intact female rats.

Hormonal contraceptives are utilized by millions of women worldwide. However, it remains unclear if these powerful endocrine modulators may alter cognitive function. Habit formation involves the progression of instrumental learning as it goes from being a conscious goal-directed process to a cue-driven automatic habitual motor response. Dysregulated goal and/or habit is implicated in numerous psychopathologies, underscoring the relevance of examining the effect of hormonal contraceptives on goal-directed and habitual behavior. This study examined the effect of levonorgestrel (LNG), a widely used progestin-type contraceptive, on the development of habit in intact female rats. Rats were implanted with subcutaneous capsules that slowly released LNG over the course of the experiment or cholesterol-filled capsules. All female rats underwent operant training followed by reward devaluation to test for habit. One group of females was trained at a level that is sub-threshold to habit, while another group of females was trained to a level well over the habit threshold observed in intact females. The results reveal that all sub-threshold trained rats remained goal-directed irrespective of LGN treatment, suggesting LNG is not advancing habit formation in female rats at this level of reinforcement. However, in rats that were overtrained well above the threshold, cholesterol females showed habitual behavior, thus replicating a portion of our original studies. In contrast, LNG-treated habit-trained rats remained goal-directed, indicating that LNG impedes the development and/or expression of habit following this level of supra-threshold to habit training. Thus, LNG may offset habit formation by sustaining attentional or motivational processes during learning in intact female rats. These results may be clinically relevant to women using this type of hormonal contraceptive as well as in other progestin-based hormone therapies.

Shortcomings and disparities in contraception counseling and use by hypertensive individuals at risk for unintended pregnancy: a comparative analysis of the National Survey of Family Growth.

BACKGROUND: Hypertension is a leading cause of adverse pregnancy outcomes. These outcomes disproportionately affect Black individuals. Reproductive life planning that includes patient-centered contraception counseling could mitigate the impact of unintended pregnancy. OBJECTIVE: The primary objective of the study is to compare contraception counseling and use between hypertensive and nonhypertensive individuals at risk for unintended pregnancy. Our secondary objectives are the following: (1) to evaluate the effect of race on the probability of counseling and the use of contraception, and (2) to evaluate the methods used by individuals with hypertension. METHODS: Data from the 2015-2017 and 2017-2019 National Survey of Family Growth Female Respondent Files were used to analyze whether individuals who reported being informed of having high blood pressure within the previous 12 months received counseling about contraception or received a contraceptive method. Covariates considered in the analysis included age, race, parity, educational attainment, body mass index, smoking, diabetes, and experience with social determinants of health. The social determinants of health covariate was based on reported experiences within 5 social determinants of health domains: food security, housing stability, financial security, transportation access, and childcare needs. Linear probability models were used to estimate the adjusted probability of receiving counseling and the use of a contraceptive. Using difference-in-difference analyses, we compared the change in counseling and use between hypertensive and nonhypertensive respondents by race, relative to White respondents. RESULTS: Of the 8625 participants analyzed, 771 (9%) were hypertensive. Contraception counseling was received by 26.2% (95% confidence interval, 20.4-31.9) of hypertensive individuals and 20.7% (95% confidence interval, 19.3-22.2) of nonhypertensive individuals. Contraception use was reported by 39.8% (95% confidence interval, 33.2-46.5) of hypertensive and 35.3% (95% confidence interval, 33.3-37.2) of nonhypertensive individuals. The linear probability model adjusting for age, parity, education attainment, body mass index, smoking, diabetes, and social determinants of health indicated that hypertensive individuals were 8 percentage points (95% confidence interval, 3-18 percentage points) more likely to receive counseling and 9 percentage points (95% confidence interval, 3-16 percentage points) more likely to use contraception. Hypertensive Black individuals did not receive more counseling or use more contraceptives compared with nonhypertensive Black individuals. The difference in counseling when hypertension was present was 13 percentage points lower than the difference observed for White respondents when hypertension was present (P=.01). The most frequently used contraceptive method among hypertensive individuals was combined oral contraceptive pills (54.0%; 95% confidence interval, 44.3%-63.5%). CONCLUSION: Despite the higher likelihood of receiving contraception counseling and using contraception among hypertensive individuals at risk for unintended pregnancy, two-thirds of this population did not receive contraception counseling, and <40% used any contraceptive method. Furthermore, unlike White individuals, Black individuals with hypertension did not receive more contraception care than nonhypertensive Black individuals. Of all those who used contraception, half relied on a method classified as Centers for Disease Control and Prevention Medical Eligibility Criteria Category 3. These findings highlight a substantial unmet need for safe and accessible contraception options for hypertensive individuals at risk for unintended pregnancy, emphasizing the importance of targeted interventions to improve contraceptive care and counseling in this population.

Impact of Estrogen and Progesterone on Immune Cells and Host-Pathogen Interactions in the Lower Female Reproductive Tract.

Microbial infections are a threat to women's reproductive health. Although reproductive cycles and pregnancy are controlled by sex hormones, the impact of hormones on host-pathogen interactions and immune function in the female reproductive tract are understudied. Furthermore, the changing endocrine environment throughout pregnancy may influence how and when women are susceptible to ascending infection. Because most intrauterine microbial infections originate in the lower reproductive tract, it is vital that future studies determine how different hormonal conditions influence the lower reproductive tract's susceptibility to infection to understand temporal components of infection susceptibilities across pregnancy. These studies should also extend to nonpregnant women, as it is critical to establish how hormonal fluctuations across the menstrual cycle and hormonal contraceptives may influence disease susceptibility. This review summarizes current knowledge of how estrogen and progesterone impact vaginal and cervical mucosal immunity, barrier function, and interactions with microbial communities.

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.

The Relationships between Drought Exposure, Fertility Preferences, and Contraceptive Behaviors: A Multicountry Study.

The interplay between population dynamics and the environment has long interested demographers. Although studies have explored how climate patterns affect macrolevel population processes, such as mortality and migration, little is known about their impact on individual-level demographic behaviors. This study fills this research gap by examining the linkages between exposure to drought and women's fertility preferences and contraceptive behaviors in sub-Saharan Africa. We analyze data from the Demographic and Health Surveys Program, focusing on 17 countries in East, Southern, and West Africa. We investigate whether women's recent exposure to drought episodes in their community affects their fertility preferences and modern contraceptive use. Generally, the findings show that drought is relevant to understanding women's fertility preferences and behaviors in the vast majority of countries; however, drought exposure has variable impacts. Moreover, whereas in some countries, drought exposure encourages contraceptive behaviors that align with women's preferences, in select countries it is associated with behavior that is misaligned with women's stated preferences. Overall, the study emphasizes the importance of examining climate events as complex forces that have localized meanings for demographic outcomes.

Evaluation of Emergency Contraceptive Pill Use with Health Management Information Systems Data in Pakistan.

According to the WHO, all clients should have access to a range of contraceptive methods, including at least one short-term, one long-term, one permanent, and one emergency method of contraception. While there are data on the contraceptive method mix available for many low- and middle-income countries, there are limited data on emergency contraception (EC). This is likely due to some surveys not routinely collecting this information, how survey questions are asked, dual method use, and/or low levels of reported use of EC pill (ECP). Even with low reported use in surveys, contraceptive social marketing statistics from DKT International. show a trend in recent years of increasing product sales of ECPs. To understand a more complete scope of ECP use, we use Pakistan as a case study and analyze Pakistan's Demographic Health Survey (DHS) surveys and Pakistan's Contraceptives Logistics Management Systems. Based on commodities dispensed data for ECPs in 2021, about 0.4 percent of all married women in Pakistan use ECPs. While there is currently a small proportion of women, it is growing and the use of ECPs is not zero as indicated by the DHS. Therefore, where available, countries should review their health management information systems data alongside survey data for ECP use.

Adaptive Calibration of Dyadic Sexual Desire Is Sex Differentiated and Disrupted by Hormonal Contraceptives.

Adaptive calibration models suggest that features of people's childhood ecologies can shape their reproductive outcomes in adulthood. Given the importance of dyadic sexual desire (i.e., desire for sex with a partner) for relationships and reproduction, we examined the extent to which people's childhood ecologies-especially the unpredictability of those ecologies-adaptively calibrate such desire. Nevertheless, because female (versus male) sexual desire is presumed to be more sensitive to situational factors, and because hormonal contraceptives alter myriad aspects of female physiology that influence female sexual desire, we predicted that adaptive calibration of dyadic sexual desire would emerge more strongly for naturally cycling females (versus females who use hormonal contraceptives and versus males). In Study 1, a total of 630 participants (159 males, 203 naturally cycling females, and 268 females using hormonal contraceptives) completed questionnaires assessing the harshness and unpredictability of their childhood ecologies as well as their sexual desire. Consistent with predictions, childhood unpredictability (but not harshness) was positively associated with dyadic (but not solitary) sexual desire among naturally cycling females (but not among females using hormonal contraceptives nor among males). Study 2, which consisted of 736 females (307 naturally cycling females, 429 females using hormonal contraceptives), replicated this pattern of results for females. These findings add to a growing literature suggesting that the instability of people's early childhood ecologies can adaptively calibrate their adult reproductive motivations and behaviors, including their dyadic sexual desire. Not only is the current finding among the first to show that some adaptive calibration processes may be sex differentiated, it further highlights that hormonal contraceptives, which alter the evolved reproductive physiology of females, may disrupt adaptive calibration processes (though such disruption may not be inherently negative).

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.