Gendering the Menstrual Cycle in Behavioral Neuroendocrinology.

In light of calls for translatable evidence on the role of the menstrual cycle in mental health, numerous syntheses of the literature have been conducted related to structural and functional brain dynamics (Dubol et al.  2021 ; Pletzer et al.  2025 ), psychiatric symptoms (Green and Graham  2022 ; Handy et al.  2022 ; Reilly et al.  2020 ), cerebrovascular functions (Skinner et al.  2021 ), pharmacokinetics of psychotropic medication (Gillessen et al.  2025 ), and cognitive (Jang et al.  2025 ) and affective processes (Schmalenberger et al.  2019 ). A common conclusion has been that overall effects are small, and that the strength of supporting evidence is substantially limited by methodological heterogeneity. To address this problem, numerous recommendations for investigating menstrual cycle effects have been published, collectively establishing what constitutes the current methodological gold standard to enhance the quality and generalizability of research findings (Barone and Eisenlohr‐Moul  2025 ; Gloe et al.  2023 ; Klusmann et al.  2023 ; Nagpal et al.  2025 ; Schmalenberger et al.  2021 ). In this section, we summarize key recommendations, provide an overview of research that employs them, and describe ongoing limitations identified as pressing to address in future research. A central goal of behavioral neuroendocrinology is to establish the fundamental brain and behavioral changes that accompany the regular fluctuations in ovarian hormones, and to identify what constitutes normal and healthy cycle‐related fluctuations (Pletzer et al.  2025 ). Standardizing the operationalization of what constitutes a normal menstrual cycle and how normativity should be asserted in empirical design have been identified as critical priorities for deriving normative and nonnormative cycle‐related brain and behavioral effects (Gloe et al.  2023 ; Hampson  2020 ; Schmalenberger et al.  2021 ). The menstrual cycle refers to a series of ovarian, uterine, and neuroendocrine cyclical changes preparing the body for reproduction (Hall  2019 ; Figure  1 ). The hypothalamic–pituitary–ovarian (HPO) axis plays a central role, coordinating the sequential release of ovarian hormones necessary for ovulation and pregnancy. The HPO axis is initiated by the release of gonadotropin‐releasing hormones (GnRH) from the hypothalamus, which, depending on its pulsatility, will induce the release of follicle‐stimulating hormone (FSH) or luteinizing hormone (LH) from the anterior pituitary (Hall  2019 ). FSH and LH then act on ovarian tissue to release various hormones, most prominently estradiol (E2) and progesterone (P4), which are considered the main effectors of ovarian and uterine physiological changes. Inhibin (A and B) are also cyclically released throughout the menstrual cycle providing negative feedback to FSH release (Figure  1 ). Although E2 and P4 fluctuation play a critical role in the ovarian reproductive system and are generally referred to as “sex hormones”, these hormones have pleiotropic functions in the human body, with target sites for E2 and P4 observed in most physiological systems including the nervous system (Figure  2 ; Chen et al.  2022 ; Mauvais‐Jarvis et al.  2022 ; Wendler and Wehling  2022 ). Key to the operationalization of the menstrual cycle in neuroendocrinology is the ability to characterize the role of fluctuating levels of E2 and P4 in brain structure and function (Figure  2 ). Key hormonal and physiological changes across a typical menstrual cycle. The onset of menses marks the beginning of the follicular phase (i.e., shedding of the proliferated endometrium), also known as the early follicular phase. HPO axis activity during the mid‐follicular phase is characterized by the rising of follicle‐stimulating hormone (FSH) levels, which in turn lead to the release of estradiol (E2) from ovarian granulosa cells, contributing to the maturation of a dominant follicle and stimulating endometrial production (not represented in the figure). Through a positive feedback loop system, E2 also contributes to increasing gonadotrophin‐releasing hormone (GnRH) pulsatility, leading to the rapid release of luteinizing hormone (LH) and FSH. The late follicular phase is characterized by elevated levels of E2, FSH, and LH, with LH initiating numerous ovarian events (e.g., breakdown of the follicle wall) contributing to the release of the oocyte and the termination of the follicular phase. After ovulation, the luteal phase begins with the luteinization, a process during which the remains of the dominant follicle are transformed into the corpus luteum. The luteal phase is typically characterized by a gradual increase in progesterone (P4) and E2 levels from the corpus luteum, with both hormones contributing to the thickening of the uterine lining, thereby preparing the endometrium for the potential implantation of a fertilized oocyte. The mid‐luteal phase is characterized by a peak in P4 levels and a secondary peak in E2. Increases in circulating P4 levels downregulate GnRH release, leading to decreased production of ovarian hormones. In the absence of fertilization, the corpus luteum involutes, resulting in the perimenstrual withdrawal of E2 and P4 during the late luteal phase. The withdrawal of ovarian hormones contributes to endometrial shedding and the rise in GnRH; both of these changes signify the beginning of another cycle (reviewed in Hall  2019 ). The menstrual cycle is also characterized by the cyclical variations in A and B, which inhibit FSH release. Testosterone, along with other ovarian hormones not shown in the figure (e.g., activin and anti‐Mullerian hormone) is associated with the regulation of follicle development (Kissell et al.  2014 ; Muttukrishna et al.  1996 ). This figure is adapted from “Translatable diagram of the menstrual cycle (based on several different sources)” by Isometrik, Kaldari; Begoon; Marnanel, retrieved from https://commons.wikimedia.org/wiki/Category:Menstrual_cycle#/media/File:Menstrual_cycle.svg . Used under Creative Commons Attribution‐ShareAlike 3.0 Unported ( https://creativecommons.org/licenses/by‐sa/3.0/ ). Action sites of ovarian and pituitary hormones involved in the regulation of the menstrual cycle. The expression of E2 and P4 receptors have been documented in most physiological system (Asavasupreechar et al. 2020 ; Chen et al. 2022 ). Within the nervous system, the expression of FSH, LH, E2 and P4 receptors have been documented in various cortical and subcortical brain regions reviewed in (Barth et al.  2015 ; Rehbein et al.  2021 ; Ryu et al. 2022 ; Mey et al. 2021 ). In addition, P4 can act in the absence of progesterone receptors by its neuroactive metabolite allopregnanolone (via GABAergic modulation), or bind with lower affinity to glucocorticoid receptors expressed in key prefrontal, medial temporal, and limbic brain regions (Kapur and Joshi  2021 ; Paul et al.  2020 ). Experimental manipulation of ovarian hormones in humans has also been shown to regulate the autonomic nervous system (Matthews et al.  1998 ) as well as the hypothalamic pituitary adrenal axis, both of which are key stress‐related systems (Roca et al.  2003 ). Sites of actions for inhibin have been observed within the nervous, immune and endocrine systems (Namwanje and Brown 2016 ). According to the International Federation of Gynecology and Obstetrics, a normal menstrual cycle should occur every 24–38 days, with cycle length variation not exceeding 9 days and menstrual bleeding not exceeding 8 days (Munro et al.  2018 ). Normative variation of cycle length primarily impacts the follicular phase, reviewed in (Schmalenberger et al.  2021 ). Age has been associated with variation in endocrine profiles (Ellison  1996 ) and cycle length (Lenton et al.  1984 ) with a higher proportion of normally cycling individuals observed between 20 and 25 years old. Anovulatory cycles are also a common occurrence in normally cycling individuals. For instance, in a population‐based study conducted in Norway, researchers estimated the prevalence of ovulation among over 3000 respondents aged 20–49.9 to be about 63% (Prior et al.  2015 ). Another recent study conducted among 112 regularly cycling individuals aged 20–25 years found that 10% of menstrual cycles were anovulatory (Gloe et al.  2023 ). Despite anovulatory cycles being a relatively common occurrence, most operationalizations of a normal cycle in behavioral neuroendocrinology are restricted to ovulatory cycles. The menstrual cycle is conceptualized as a cyclical neurohormonal phenomenon with significant intra‐ and interindividual variability. Consequently, current gold standard research designs and methods prioritize the ability to control or account for expected cycle variability to facilitate measurement and analysis of normative cyclical changes in E2, P4, brain, and behaviors with high temporal resolution (Gloe et al.  2023 ; Hampson  2020 ; Pletzer et al.  2025 ; Schmalenberger et al.  2021 ). Numerous factors have been associated with whether menstrual cycle fluctuations fall within a normative range. Gynecological conditions (e.g., polycystic ovary syndrome, endometriosis), age (under 25 and over 35), body mass index (under 18 and over 30), stress exposure, diet, smoking and levels of exercise have all been associated with variation in the amplitudes of hormonal changes and with greater likelihood of cycle irregularities (Hampson  2020 ; Vollmar et al.  2025 ). Although menstrual‐cycle related conditions such as Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) (APA  2013 ) are not systematically associated with cycle irregularities, growing evidence suggests that people with PMS/PMDD may be differentially sensitive to ovarian hormone changes, particularly towards the late luteal phase (reviewed in Schmalenberger et al.  2021 ). Then, in order to characterize normative cycle‐changes, participants presenting these demographic characteristics, experiences, conditions or habits are generally excluded from research samples. In addition, because cycle irregularities can happen in otherwise regularly cycling individuals, tracking of cycle lengths and ovulation before and during testing is also recommended to exclude data from any anovulatory or irregular cycles (Hampson  2020 ; Schmalenberger et al.  2021 ). Considering that the rise in progesterone during the luteal phase is contingent on the presence of the corpus luteum, it has also been recommended that ovulation should be confirmed in any research that relies on identifying normative cycle‐related changes (either directly with ovarian ultrasound or indirectly with LH surge or vaginal temperature) (Hampson  2020 ; Schmalenberger et al.  2021 ). All these documented sources of cycle ‘irregularity’ are intended to ensure that menstrual cycle effects are characterized in a healthy population. However, this amounts to a problem for conducting generalizable research, as only a minority of otherwise healthy menstruating people meet the screening criteria currently denoting the ‘normally cycling’ population. Person‐centred dense sampling designs are now considered the gold standard for capturing both intra‐and inter‐individual variations in E2 and P4 across the menstrual cycle (Gloe et al.  2023 ; Pritschet et al.  2021 ; Schmalenberger et al.  2021 ). This approach typically involves collecting daily measures across one or more complete menstrual cycles, capturing variation at high temporal resolution to identify cycle‐related changes in brain and behavior. Recent work adopting this design suggests cyclical neural plasticity in subregions of the hippocampus covarying with E2 levels, moderated by P4 (Zsido et al.  2023 ). This finding echoes similar findings in rodents that suggests a possible fundamental role of ovarian hormones in cyclical hippocampal plasticity (Woolley and McEwen  1992 ). Research examining self‐reported psychiatric symptoms in relation to normal ovulatory cycling (ovulation confirmed via LH measurement) also suggests cycle‐related fluctuation in suicidal symptoms, peaking in the perimenstrual phase (Ross et al.  2024 ), identifying a potentially optimal interval for therapeutic interventions. Person‐centred dense sampling also facilitates the exploration of varied temporal dynamics, including current and time‐lagged effects across the menstrual cycle under different hormonal conditions (e.g., normally cycling vs. hormonal contraceptive administration) within a single person (Pritschet et al.  2020 ). Although current gold‐standard practices undoubtedly help standardize the measurement of the menstrual cycle, improve temporal resolution and reduce methodological heterogeneity, several persistent limitations have been identified, orienting future directions. At a conceptual level, most characterizations of the menstrual cycle focus exclusively on E2 and P4, overlooking other critical processes which covary with their fluctuation (Figure 1; Rizor et al.  2024 ). For instance, inhibins have effects on the body outside of the HPO axis (Figure  2 ) (Namwanje and Brown  2016 ) that are important to understand when considering neuroendocrine processes associated with the menstrual cycle (Link et al.  2016 ). Methodologically, current recommendations for operationalizing what constitutes a normal menstrual cycle generate significant exclusion biases in research samples, sometimes excluding upwards of 50% of participants, for example, Zsido et al. ( 2023 ). Person‐centred dense sampling designs, in addition to being resource‐intensive, are also difficult to generalize due to sample‐related biases arising from the risk of participant attrition or reliance on single‐subject data. Lastly, menstrual cycle research is inherently nonexperimental, rendering causal inferences about the influence of hormones on the brain and behavior speculative. To overcome these limitations, larger and more diverse person‐centred dense sampling studies, which include a wider range of biomarkers, combined with experimental research (crossover, randomized, and double‐blind design) manipulating ovarian hormone fluctuations, have been identified as future priorities for continuing to build high‐quality and generalizable evidence of healthy cycle‐related changes (Schmalenberger et al.  2021 ; Zsido et al.  2023 ). Despite calls to increase the diversity of participant samples, the current gold standard and proposed future directions continue to rely on a stringent definition of the “normal” menstrual cycle that controls for as much variability as possible. This approach will continue to produce a skewed characterization of basic cycle‐related effects from which the mapping of “abnormal changes” will be derived, resulting in a significant risk of pathologizing normative variation in the menstrual cycle. A second lingering problem with this operationalization is that it assumes that cycle‐related changes are caused by core sex‐related components of the menstrual cycle, which can be identified a contextually. More diverse research designs require contending with the phenomenological complexity of the menstrual cycle. Developing a context‐contingent operationalization of the menstrual cycle can broaden neuroendocrinological inquiry to address limitations to generalizable evidence faced by the field through integrating menstrual variability as an adaptive feature.

This work was supported by Micheal Smith Health Research BC SHC‐2023‐3199.

Operationalizing the menstrual cycle as a stress‐contingent, sex/gender‐entangled phenomenon changes how research questions are formulated, informs which variables should be measured, and constrains the interpretation and reach of inferences and assumptions about study outcomes. By considering adaptiveness as a normative aspect of the menstrual cycle, the language used to describe parameters of menstrual cycle research must become more specific and constrained, as observed cycle‐related brain changes are situated within population‐ and context‐specific features, thereby avoiding normative language and broad descriptors. Placing context, and in particular, stress at the forefront of the operationalization, research will lead to greater consideration of the impact that various aspects of the research design may have on cycle‐related effects. Such an approach can significantly change how findings are interpreted, shifting our focus from characterizing fundamental cycle‐related brain and behavioral changes to characterizing types of configurations under specific contextual constraints, and situating outcomes within a broader understanding of the menstrual cycle as tied to local ecologies. Finally, translational research can also be advanced by providing more nuance for identifying meaningful translational findings and clarifying what “fundamental” means as we continue to pursue characterization of fundamental mechanisms. By situating hormone‐related findings within an integrated body of knowledge, the proposed operationalization will minimize pathologizing and essentialist interpretations and translations of research findings. Currently, the notion that only regular ovulatory menstrual cycles should serve as the model of a healthy cycle renders irregular and/or anovulatory cycles as unhealthy and abnormal by default. Although it is undeniably useful to have a clinical definition of normative functioning that supports high‐quality reproductive healthcare, there is a growing tendency in behavioral neuroendocrinology and clinical recommendations to categorize variation in the menstrual cycle as unhealthy (Heller et al.  2025 ; Vollmar et al.  2025 ). This has the consequence of potentially pathologizing processes that may constitute normative, adaptive changes to environmental stressors. By overlooking the possibility that variation in menstrual cycle regularity and/or ovulation according to context is itself normative, this operationalization of the menstrual cycle risks overlooking important avenues for advancing more representative research as well as overlooking potential socio‐structural targets for intervention to support the health and wellbeing of menstruating people. The proposed operationalization is grounded in an assumption that menstrual cycle variability is an adaptive, continuous (rather than categorical) and environmentally situated phenomenon. This approach can resist pathologization of the menstrual cycle while also directly contributing to a better understanding of adaptive and maladaptive cycle‐related changes. Relatedly, conceptualizing the relationship between hormones, brain, and behavior as bidirectional will advance investigation of the interplay between the individual and their environment. Behavior plays an integral role in shaping the environment, which, in turn, impacts the body. Within such a framework, characterizing and assessing a diversity of stressful experiences will become a central domain of investigation. Investigating how gendered experiences may change parameters of the menstrual cycle and its impact on brain and behavior will advance an understanding of sex‐related aspects of the menstrual cycle as entangled with gender, leading to possible re‐interpretation of previously observed effects and the development of new questions. For instance, cyclical effects may arise from the menstrual cycle itself and/or alongside cyclical changes in the environments of menstruating people. Novel questions emerge regarding the degree of adaptability or change of the cycle. Do associations between ovarian hormones, brain, and behavior within a person vary according to different types or levels of stress experienced? To what degree are menstrual restrictions, beliefs, and attitudes associated with hormone‐brain covariation? Combined with current gold‐standard recommendations for measurement (e.g., tracking cyclicality, confirming ovulation), this framework invites a richer exploration of the menstrual cycle while continuing to develop biologically plausible models. Measures of constructs such as menstrual stigma, menstrual restriction and body dissatisfaction can be integrated into a gendered account of varied axes of oppression and privilege a person might be experiencing. Re‐operationalizing the menstrual cycle in this manner is not without challenges for behavioral neuroendocrinology. That said, researchers can engage with this framework at multiple levels, the most widely accessible of which is to reinterpret existing research and new findings through a context‐contingent lens. We do not advocate abandoning the currently proposed methodological recommendations or the general idea of studying a phenomenon “in isolation,” as these approaches remain necessary for producing mechanistic insights. However, we urge researchers to situate their research findings within a context‐contingent framework, transparently address limitations to generalizability, and consider environment‐ and gender‐oriented research projects as an equally important research priority, so that there can be complementarity between knowledge produced from constrained, controlled designs and diversity‐oriented research.

Menstrual physiology encompasses a complex set of processes that unfold within cultural systems that construct meaning and value around them. We have argued that current gold standard recommendations to operationalize the menstrual cycle and standardize its measurement will be significantly advanced by adopting a context‐contingent view of the menstrual cycle as a sex/gender‐entangled, adaptive phenomenon. Specifically, a context‐contingent operationalization of the menstrual cycle in neuroendocrinology enables both more general and nuanced articulations of the diversity of experiences among people who menstruate, while avoiding the biological essentialism and sexism characteristic of early research on the menstrual cycle. Cultural meaning and environmental conditions are not only integral to lived experiences and internalized beliefs related to the menstrual cycle, but also to neuroendocrine function.

Prior to the advent of effective contraception and stable nutritional intake, the menstrual cycle was a relatively rare physiological occurrence. Today, in contrast, menstruating people in industrialized nations will experience, on average, over 400 cycles in their lifetime (Jasienska et al.  2017 ; Strassmann  1997 ). Correspondingly, research on the menstrual cycle is expanding across all domains of human biology, with literature in neuroendocrinology suggesting the existence of fundamental, cyclical brain and behavioral changes (Barth et al.  2015 ; Beltz and Moser 2020 ; Pletzer et al.  2025 ). The menstrual cycle is increasingly described as an all‐encompassing health indicator, a “vital sign of the female body,” and a prime site of intervention for the advancement of personalized medicine (Vollmar et al.  2025 ). Despite inconsistencies in the empirical literature (Dubol et al.  2021 ; Pletzer et al.  2025 ), the notion of cycle‐dependent brain changes has entered public discourse (Chrisler and Gorman  2019 ), sometimes framed positively (e.g., Gorvett  2018 ), but often as an added vulnerability (e.g., Gross  2025 ). Menstruating people increasingly refer to practices such as cycle syncing to modulating their habits and activities according to anticipated cycle‐related behavioral benefits (Pfender et al.  2025 ). Given how quickly scientific knowledge about sex/gender differences travels into the public sphere, particularly from research in neuroscience (Bennett and McLaughlin  2024 ; Maney  2016 ; Rippon et al.  2021 ), a critical examination of how the menstrual cycle is currently operationalized in behavioral neuroendocrinology is timely. The menstrual cycle, or estrous cycle in most nonhuman mammals, is characterized by cyclical variation in ovarian hormones and is generally considered a sex‐related hormonal phenomenon. In behavioral neuroendocrinology, fundamental hormonal effects tend to be derived through the isolation and experimental manipulation of ovarian hormone fluctuations (Dalla et al.  2024 ; Eliot et al.  2023 ). Rather than isolating sex‐related endocrine components for empirical study, approaches such as human reproductive ecology (HRE) consider variability and environmental adaptivity as key aspects of the menstrual cycle's biology (Clancy  2023 ; Ellison et al.  1993 ; Vitzthum  2009 ). Therefore, within this framework, fundamental hormonal effects are best understood as context‐contingent. Extensive research comparing aspects of the menstrual cycle across populations (e.g., industrialized vs. traditional) and environmental stressors underscores the importance of characterizing the sociocultural contexts in which menstruators live to understand the relation between ovarian hormone fluctuations, health and well‐being. Feminist/queer scholars have also offered critiques of the acontextual operationalization of sex‐related phenomena, including the menstrual cycle (e.g., Cosgrove and Riddle  2003 ; Fausto‐Sterling  2008 ; Fine  2013 ). This work demonstrates the risks of reinforcing essentialist and deterministic biases regarding the influence of hormones on brain and behavior that are associated with overlooking the gendered realities under which sex‐related components develop and function. One approach to addressing these limitations is to adopt a framework of sex/gender entanglement, which assumes a dynamic interplay between sexed bodies and gendered environments (Fausto‐Sterling  2000 ; Springer et al.  2012 ). This framework shifts perspectives away from a binary, predetermined, and culture‐free understanding of sex to a more diverse, iterative, and culturally informed view (Ritz et al.  2025 ; DuBois and Shattuck‐Heidorn 2021 ). To date, this broad framework has been employed in social neuroendocrinology (Van Anders  2013 ), but remains underexplored in neuroendocrinological research on the menstrual cycle (Poitras et al.  2024 ; Duchesne  2025 ). Decades of stress research supports the value of adopting a context‐contingent, sex/gender‐entangled operationalization of the menstrual cycle. Stressful social and environmental conditions have been found to impact various neuroendocrinological aspects of the menstrual cycle, including cycle‐related variation in brain and behavior (Andersen et al.  2024 ; Hokenson et al.  2021 ; Prior  2019 ). Further, numerous distal and proximal gendered sources of stress shape the experiences of menstruating people, and therefore comprise a relevant, yet overlooked, source of context to consider when interrogating cycle‐related brain and behavioral correlates (Johnston‐Robledo and Chrisler  2020 ). By overlooking variability and stress‐contingency as normative aspects of the menstrual cycle, the current neuroendocrinological operationalization contributes to research on the “normative” menstrual cycle that reflects a specific context and a minority of menstruating people. This renders findings difficult to generalize across contexts and to the broader population, and risks inadvertently pathologizing a large proportion of menstruating people whose cycles do not meet these criteria. In this narrative review, we provide a critical reflection on the current operationalization and methodological gold standard for investigating the menstrual cycle in behavioral neuroendocrinology, and propose an alternative operationalization that considers context, in particular, gendered sources of stress. We argue that such a context‐contingent operationalization has significant potential for advancing generalizable neuroendocrinological understanding of the menstrual cycle that resists essentialist/biologically deterministic discourse.

The authors declare no conflicts of interest.