During the reproductive years, females are more susceptible than males to mood disorders and outnumber males in the prevalence of mood-related disorders (Bromet et al., 2011, LeGates et al., 2019, O’Donnell et al., 2016, Sundström Poromaa et al., 2017). Thus, focusing on female-specific times of greater susceptibility for mood disorders by developing targeted preclinical models is an important step towards precision medicine for these diseases. Furthermore, there are sex-specific disorders, such as Premenstrual Dysphoric Disorder (PMDD) and perinatal depression (PND), which specifically affect females. Although males can also have mental health disorders during the perinatal period, these typically occur in the late postpartum with different timing and etiological factors (Munk-Olsen et al., 2006). Typically, PMDD is characterized by psychiatric and/or somatic symptoms that appear during the late luteal phase of the menstrual cycle and symptoms improve within the first week after menstruation (American Psychiatric Association, 2013). However, a report indicated subtypes of PMDD in terms of the timing onset of PMDD symptoms (Eisenlohr-Moul et al., 2020) which were not necessarily committed to the temporal course as suggested in the classical diagnosis. PND comprises both antenatal and postnatal depression, although the DSM-5 does not distinguish between the two, there are differences in etiology and timing onset of antenatal versus postnatal depression (Fisher et al., 2016, Qiu et al., 2020b). Thus, for both disorders, there is a heterogeneous presentation in terms of timing of symptoms. Because of the unique female experiences of menstruation and pregnancy, it is important to undercover how these different experiences may be contributing to mood disorder susceptibility as this may aid in the discovery of novel treatment strategies and interventions. In this review, we will highlight the similarities in symptoms and biomarkers that are related to these two disorders.

There are several similarities between the pathoetiology of PMDD and PND, including hormonal sensitivity, and alterations in the stress response system (Hantsoo and Epperson, 2015, Serati et al., 2016), which will be discussed. Here we will mainly focus on postpartum depression (PPD) which manifests in the postpartum and is most likely associated with de novo depression compared to antenatal depression which is associated with a history of depression (reviewed in (Qiu et al., 2020b; Yin et al., 2021). Interestingly, there is some evidence that females who suffer from PMDD are more likely to suffer from PPD (Amiel Castro et al., 2018). Both PMDD and PPD are associated with fluctuating steroid hormones, particularly a sudden drop in estrogens and progestins. Symptomatology is similar in both PMDD and PPD, with symptoms including depressed mood, anhedonia, fatigue, emotional lability, anxiety, and panic attacks (American Psychiatric Association, 2013, Wisner et al., 2013). For both PMDD and PND, there are challenges with the diagnosis and categorization by the DSM-5.

PMDD is often referred to as a severe form of Premenstrual Syndrome (PMS), and although both conditions involve physical and psychological symptoms, PMDD symptoms are more intense and disabling than in PMS, affecting daily life functioning (American Psychiatric Association, 2013, Mishra et al., 2022). Due to this, some authors claim both PMS and PMDD are menstrually-related mood disorders (MRMDs; (Bunevicius et al., 2013, Fleischman et al., 2014, Islas-Preciado et al., 2021). As symptoms across the menstrual cycle present in a cyclical manner and the severity varies over time (Yonkers and Simoni, 2018), diagnosis becomes more difficult as well as the definition of the clinical condition (Schmalenberger et al., 2021). The prevalence of MRMDs is estimated to affect about 30 % of human females of reproductive age (Dennerstein et al., 2012). Similarly, the prevalence of PND is approximately 15–30 %, depending on the criteria used for diagnosis (Gavin et al., 2005, Vesga-López et al., 2008) and the population studied (Fisher et al., 2012). PPD is distinguished from the postpartum blues. The postpartum blues is a mild and transient mood alteration that typically occurs in the first five days after delivery and can occur in up to 80 % of parturient people (Buttner et al., 2012). As noted earlier, there are several differences in symptoms, timing, and biomarkers associated with PND, depending on whether onset occurs during gestation or postpartum (for review see (Serati et al., 2016), suggesting heterogeneity in the disorder ((Kiewa et al., 2024, Qiu et al., 2020b). As the odds ratio of first-time admission to hospital is increased substantially during the first three months after giving birth (Munk-Olsen et al., 2006) this suggests that the definition needs to be broadened to beyond the 4–6 weeks postpartum as is currently defined in the DSM-5 and the ICD-11, respectively (American Psychiatric Association, 2013, International Classification of Diseases, Eleventh Revision (ICD-11), 2021). Interestingly, to our knowledge, large scale epidemiological studies on the co-prevalence of MRMD and PPD is missing in the literature. This is perhaps due to the difficulty in the proper diagnoses of MRMDs and PPD, but may also be due to symptoms of PPD and MRMDs being dismissed by health care practitioners as ‘part of being a woman' or part of cultural beliefs in some populations. However, these disorders impact quality of life and there are associated costs of these disorders on emotional and physical health, including economic costs to the individuals.

Several reports indicate that women who experience MRMDs have an increased risk for PPD (Sylvén et al., 2013). Accordingly, Buttner et al., 2013 found that severe MRMD significantly increased the risk of developing PPD by nearly twofold (O.R. = 1.97) and Lee et al., 2015 found a significant correlation and a prevalence of 34.8 % for MRMDs in PPD women. It is important to acknowledge that these studies evaluated MRMDs retrospectively and the risk for a potential recall bias should not be discarded (Sato and Kawahara, 2011). As well, Bloch et al., 2006 reported that retrospective MRMDs were significantly associated with PPD that manifests early in the postpartum period. This finding is important as it further suggests that the large fluctuation in hormones from pregnancy to early postpartum contributes to the greater risk for both disorders. Collectively, studies suggest that there is a subgroup of people who are more prone to depression given their responsiveness to hormonal fluctuations across menses cycle phase, and pregnancy to the postpartum. This information is useful in terms of etiology, prevention, and the development of new relevant therapeutic targets to target these disorders.

For both MRMDs and PPD, many consider hormonal oscillations as a core component in the etiology, but environmental factors such as stressful events also play a role (Studd and Nappi, 2012, Uchida et al., 2018). Intriguingly, changes in the hypothalamic–pituitary–adrenal (HPA) axis are also seen in MRMDs and PPD . In this review, we will highlight common changes across the menstrual cycle and pregnancy/postpartum to identify common pathways that could contribute to greater sensitivity in poeple affected by both MRMDs and PPD (Fig. 1). The present review summarizes steroid hormone sensitivity including HPA axis response, neurosteroids in GABAergic transmission, serotonin and inflammation biomarkers, and the potential role of chronic stress in the etiology of these disorders.