TABLE 2

Methodological considerations in studying the role of ovarian hormones in drug craving and relapse in humans and animal models

Method UsedLimitationsReferences
Clinical studies
Identification of the phases based on self-report of menses onset combined with radioimmunoassay from estradiol and progesterone plasma concentrations1. Assumption of similar cycle length between women.
2. Does not take in consideration the variation of hormones concentration within each phase.
3. Cycle can be disrupted by drug intake.
4. Only one or two blood samples per participant, which is restricted to a specific time point and does not fully represent estradiol and progesterone concentrations across the full cycle.
(Collins et al., 2007; Evans et al., 2002; Lukas et al., 1996; Sofuoglu et al., 1999)
Saliva sample of estradiol and progesteroneOnly one or two blood samples per participant, which is restricted to a specific time point and does not fully represent estradiol and progesterone concentrations across the full cycle.(Fox et al., 2008)
Preclinical studies
Vaginal swab1. Based on the proportion of leukocytes, cornified and nucleated cells in the vaginal sample, which can be subjective.
2. Some studies pool different phases together based on similar behavior responses, which excludes the role of hormones variations between the different phases.
3. Does not take in consideration the variation of hormone concentration within each phase.
(Bechard et al., 2018; Cox et al., 2013; Feltenstein et al., 2009; Feltenstein and See, 2007; Fuchs et al., 2005; Kerstetter et al., 2008; Kippin et al., 2005; Nicolas et al., 2019)
Radioimmunoassay for plasma levels of estradiol and progesteroneOnly one or two blood samples per animal, which is restricted to a specific time-point and does not fully represent estradiol and progesterone concentrations across the full cycle.(Feltenstein et al., 2009; Feltenstein and See, 2007)