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Cited by 77Attention Deficit Hyperactivity DisorderSexual Differentiation and DisordersNeural and Behavioral Psychology Studies

Reproductive steroids and ADHD symptoms across the menstrual cycle

Open access
Roberts, Bethan, Eisenlohr-Moul, Tory, Martel, Michelle M.·2018·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2017.11.015PMC PMC5803442
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Abstract

Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance, females are significantly impaired and exhibit additional comorbid disorders during adolescence. However, no empirical work has examined the influence of cyclical fluctuating steroids on ADHD symptoms in women. The present study examined estradiol (E2), progesterone (P4), and testosterone (T) associations with ADHD symptoms across the menstrual cycle in regularly-cycling young women (N=32), examining trait impulsivity as a moderator. Women completed a baseline measure of trait impulsivity, provided saliva samples each morning, and completed an ADHD symptom checklist every evening for 35days. Results indicated decreased levels of E2 in the context of increased levels of either P4 or T was associated with higher ADHD symptoms on the following day, particularly for those with high trait impulsivity. Phase analyses suggested both an early follicular and early luteal, or post-ovulatory, increase in ADHD symptoms. Therefore, ADHD symptoms may change across the menstrual cycle in response to endogenous steroid changes.

Integrity signals

Registry

Crossref · 10.1016/j.psyneuen.2017.11.015

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 41 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Greater progesterone variance predicted lower Sensation Seeking.

    “Higher average P4 correlated with lower inattention, Positive Urgency, Sensation Seeking, and Lack of Premeditation, and greater P4 variance predicted lower Negative Urgency, Positive Urgency, Sensation Seeking, and inattention.”
    Quote in the paperSubstantial claim
  • Findingown data

    Higher average progesterone correlated with lower inattention.

    “Higher average P4 correlated with lower inattention, Positive Urgency, Sensation Seeking, and Lack of Premeditation, and greater P4 variance predicted lower Negative Urgency, Positive Urgency, Sensation Seeking, and inattention.”
    Quote in the paperSubstantial claim
  • Findingown data

    Only in women high on Sensation Seeking, Positive Urgency, and Lack of Premeditation (+1 SD), the follicular and postovulatory phases each had greater inattentive symptoms than all other phases.

    “Only in women high on Sensation Seeking, Positive Urgency, and Lack of Premeditation (+1 SD), the follicular and postovulatory phases were each characterized by greater inattentive symptoms relative to all other phases (all p’s < .05).”
    Quote in the paperSubstantial claim
  • Findingown data

    Only for women high in Positive Urgency (+1 SD), postovulatory symptoms were higher than follicular symptoms.

    “Only for women high in Positive Urgency (+1 SD), symptoms in the postovulatory phase were higher than the follicular phase (p < .05).”
    Quote in the paperSubstantial claim
  • Findingcitation

    This work replicates antagonistic effects of estradiol and progesterone in externalizing disorders.

    “Our work replicates antagonistic effects of E2 and P4 in externalizing disorders (Eisenlohr-Moul et al., 2015; Klump et al., 2008; 2013; Singh, Su, & Ng, 2013) and is the first to indicate an antagonistic relationship of E2 and T.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Eisenlohr-Moul et al., 2015 source

      Not checked in the free run.

    • cites Klump et al., 2008 source

      Not checked in the free run.

    • cites Singh, Su, & Ng, 2013 source

      Not checked in the free run.

  • Borderline: one of the tests for a substantial claim is unclear. 2
  • Not yet classified. 2
  • May combine two claims. 14
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 12

  • Borderline on S1 (asserted), S3 (load-bearing), S4 (based): unclear from the text.

    Findingnone given

    All five UPPS-P subscales moderated at least one steroid-symptom association.

    “All five UPPS-P subscales moderated at least one steroid-symptom association.”
    Quote in the paperNot a substantial claim

  • Borderline on S1 (asserted), S4 (based): unclear from the text.

    Findingnone given

    The postovulatory phase had higher inattentive symptoms than all other phases.

    “Within-person analysis revealed no significant differences between phases for hyperactivity/impulsivity, but the postovulatory phase was characterized by higher inattentive symptoms than all other phases (all p’s < .01).”
    Quote in the paperNot a substantial claim

  • Not yet classified.

    Finding

    Higher average estradiol predicted less inattention.

    “Higher average E2 predicted less inattention, and greater E2 variance was associated with lower Negative Urgency.”
    Quote in the paperNot yet classified

  • May combine two claims.

    Findingown data

    ICCs showed 15% stable between-person variance for Inattentive Symptoms and 10% for Hyperactive/Impulsive symptoms.

    “ICCs revealed that the majority of variance in symptoms was at the within-person level for Inattentive Symptoms (15% stable between-person variance; ICC = .15, NMI = .18, NMISE = .048) and Hyperactive/Impulsive symptoms (10% stable between-person variance; ICC = .10, NMI = .13, NMISE = .031).”
    Quote in the paperSubstantial claim

  • Not yet classified.

    Finding

    Random effects of estradiol, progesterone, and testosterone indicated that steroid impact varied by between-person factors.

    “However, the existence of random effects of E2, P4, and T indicated that the impact of steroids varied as a function of between-person factors.”
    Quote in the paperNot yet classified

  • The quote only partly states this claim.

    Findingown data

    When progesterone was higher than average (luteal phase), lower-than-average estradiol predicted higher symptoms.

    “These interactions took a similar form in each case: in the context of higher-than-average P4 (the luteal phase), lower-than-average E2 predicted higher symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Sensation-Seeking may be specifically associated with hyperactivity-impulsivity and with higher testosterone.

    “Sensation-Seeking (tendency to seek adventure) may be more specifically associated with hyperactivity-impulsivity (Lopez et al., 2015), as well as related to higher T (Campbell et al., 2010; Daitzman & Zuckerman, 1980; Roberti, 2004).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Lopez et al., 2015 source

      Not checked in the free run.

    • cites Campbell et al., 2010 source

      Not checked in the free run.

    • cites Daitzman & Zuckerman, 1980

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Total Hyperactive-Impulsive symptoms ranged from 0 to 9 (M = .32, SD = .66; α = .66), and total Inattentive symptoms ranged from 0 to 9 (M = .20, SD = .65; α = .72).

    “Total Hyperactive-Impulsive symptoms ranged from 0 to 9 (M = .32, SD = .66; α = .66), and total Inattentive symptoms ranged from 0 to 9 (M = .20, SD = .65; α = .72).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    ADHD is best characterized as a continuum of symptoms.

    “Symptom counts were used for analysis rather than diagnosis, as the sample was community-recruited, and ADHD appears best characterized as a continuum of symptoms (Haslam et al., 2006; Marcus & Barry, 2011).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Haslam et al., 2006 source

      Not checked in the free run.

    • cites Marcus & Barry, 2011

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study had 80% power to detect conventionally small-to-medium effects.

    “Using the Intraclass Correlations (ICCs) for each outcome and equations provided by Snijders and Bosker (1999), calculations indicated 80% power to detect conventionally small-to-medium effects (Klump et al., 2013; smallest detectible effects for cross-level interaction were f2 = .085 – .091).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Snijders and Bosker (1999)

      Not checked in the free run.

    • cites Klump et al., 2013 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Visual inspection indicated that assumptions of normality and homoscedasticity were met.

    “Visual inspection of distributions and residuals indicated that assumptions of normality and homoscedasticity were met.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Moderation analyses were repeated excluding the highest and lowest 10% of observations on the moderator to assess robustness.

    “In order to evaluate their robustness, moderation analyses were also carried out excluding the highest and lowest 10% of observations on the moderator.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Steroids showed expected menstrual-cycle trajectories: estradiol had a midcycle peak and a secondary midluteal peak, progesterone was low in the follicular phase and peaked in the luteal phase, and testosterone had a small midcycle peak.

    “Finally, steroids generally showed expected trajectories across the menstrual cycle: E2 demonstrated a midcycle peak and secondary peak during the midluteal phase, P4 was low during the follicular phase and peaked during the luteal phase, and T showed a small mid-cycle peak.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ADHD is diagnosed more often in males, but females with ADHD become notably impaired and develop comorbid disorders starting in adolescence.

    “Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance, females are significantly impaired and exhibit additional comorbid disorders during adolescence.”
    • Also stated in: § 1. Introduction · plain
      “Although ADHD is more frequently diagnosed in males, females with ADHD often become particularly impaired and exhibit comorbid disorders beginning during adolescence (Biederman et al., 1999; Hinshaw et al., 2012; Hosain, et al., 2012; Lahey et al. 1994; Quinn, 2005; Robison et al., 2008).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Biederman et al., 1999 source

      Not checked in the free run.

    • cites Hinshaw et al., 2012 source

      Not checked in the free run.

    • cites Hosain, et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because weak executive function is a correlate and possible marker of ADHD, prior work suggests that cycling reproductive steroids may play a role in daily ADHD symptom expression.

    “Given that weak EF is a prominent correlate and possible marker of ADHD, this prior work suggests a potential role for cycling reproductive steroids in daily ADHD symptom expression.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Negative Urgency may be related to fluctuations in estradiol and progesterone through its links with affect.

    “with Negative Urgency potentially related to fluctuations in E2 and P4 through its links with affect (Eisenlohr-Moul et al., 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Eisenlohr-Moul et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Estradiol effects on dopaminergic striatal circuits, by reducing dopamine receptors and increasing dopamine release, may mediate these effects, particularly in the prefrontal cortex.

    “E2 effects on dopaminergic striatal circuits by reducing dopamine receptors and increasing dopamine release may therefore mediate these effects (Archer, 1999; Gibbs, 2010), particularly in the prefrontal cortex (Berman et al., 1997).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Archer, 1999

      Not checked in the free run.

    • cites Gibbs, 2010 source

      Not checked in the free run.

    • cites Berman et al., 1997 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Trait impulsivity appears prominently associated with both adult ADHD symptoms and steroid effects.

    “Overall, trait impulsivity appears prominently associated with both adult ADHD symptoms and steroid effects.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Body mass index impacts reproductive steroids.

    “Height and weight were measured since body mass index impacts reproductive steroids (Lukanova et al., 2004; BMI Mean = 24.37, SD = 6.33).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lukanova et al., 2004 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The UPPS-P Trait Impulsivity Scale has excellent reliability and validity.

    “The scales demonstrate excellent reliability and validity (Lynam et al., 2006; Cyders et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Lynam et al., 2006

      Not checked in the free run.

    • cites Cyders et al., 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    In this sample, Lack of Perseverance had fair reliability (α = .56), while Lack of Premeditation, Negative Urgency, Positive Urgency and Sensation Seeking had good reliability (α = .82-.93).

    “In the current sample, Lack of Perseverance exhibited fair reliability (α = .56) and Lack of Premeditation, Negative Urgency, Positive Urgency and Sensation Seeking exhibited good reliability (α = .82–.93).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Log transformations produced normally distributed residuals in all analyses.

    “Log transformations were applied and resulted in normally distributed residuals in all analyses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In women, testosterone administration appears to improve verbal fluency, verbal learning and memory, while response inhibition performance decreases.

    “Further, verbal fluency, verbal learning and memory appear to improve with administration of T in women (Davison et al., 2011; Drake et al., 2000), whereas response inhibition performance decreases (Bjork et al., 2001).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Davison et al., 2011 source

      Not checked in the free run.

    • cites Drake et al., 2000 source

      Not checked in the free run.

    • cites Bjork et al., 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Prior research indicates that organizational testosterone contributes to ADHD symptoms in both sexes, especially in males.

    “Prior work suggests a role for organizational testosterone (T) in ADHD symptoms in both sexes (Wang et al., 2017), but particularly males (Martel, 2009; McFadden et al., 2005).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wang et al., 2017 source

      Not checked in the free run.

    • cites Martel, 2009 source

      Not checked in the free run.

    • cites McFadden et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These results suggest that executive function and psychostimulant response might vary across the menstrual cycle.

    “These results also suggest the possibility that EF and psychostimulant response might vary across the cycle.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The impact of hormones on ADHD symptoms occurs with a one-day lag.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Use of a nonclinical sample may limit the generalizability of these findings.

    “In addition, use of a nonclinical sample may limit generalizability of these findings, despite a consensus that ADHD is best conceptualized dimensionally (Barkley, 2006; Haslam et al., 2006; Larsson et al., 2012; Marcus & Barry, 2011).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Barkley, 2006

      Not checked in the free run.

    • cites Haslam et al., 2006 source

      Not checked in the free run.

    • cites Larsson et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Moderated cycle phase findings suggest strong postovulatory worsening of symptoms, rather than premenstrual worsening, with a secondary early follicular peak.

    “Notably, although our interactive steroid findings (high P4, low E2) might be initially seen as suggestive of a premenstrual exacerbation such as those described in case studies (Quinn, 2005), moderated cycle phase findings instead suggest strong postovulatory (rather than premenstrual) worsening of symptoms with a secondary early follicular peak.”
    Quote in the paperSubstantial claim
27 of 27

  • The authors state this as an assumption.

    The impact of hormones on ADHD symptoms occurs with a one-day lag.

    “A one-day lag was assumed for the impact of hormones on ADHD symptoms based on a study of rats (Bless et al., 1997).”

  • The paper relies on this without support.

    No prior empirical work has examined how cyclical fluctuating steroids influence ADHD symptoms in women.

    “However, no empirical work has examined the influence of cyclical fluctuating steroids on ADHD symptoms in women.”

  • The paper relies on this without support.

    Women and girls are under-studied, and activational hormonal effects remain essentially unstudied in ADHD.

    “Women and girls are under-studied and in particular, activational hormonal effects remain essentially unstudied in ADHD.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The interrelationship between fluctuating sex hormones and ADHD (symptoms) must be addressed in both pharmacological and non-pharmacological treatment for women with ADHD.

    “We agree that the interrelationship between fluctuating sex hormones and ADHD (symptoms) must be addressed in both pharmacological and non-pharmacological treatment for women with ADHD [30,62].”

    From A Female-Specific Treatment Group for ADHD—Description of the Programme and Qualitative Analysis of First Experiences (2024) · cites this paper as [30]

    The Abstract reports an association between changing reproductive steroids and ADHD symptoms in 32 regularly cycling young women. The Conclusions suggest asking about cycle phase during ADHD assessment and raise possible variation in psychostimulant response, but frame these as conditional implications and future research. They do not say that both pharmacological and non-pharmacological treatment for women with ADHD must address hormone fluctuations. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Fluctuations in ovarian hormones influence dopaminergic and noradrenergic signaling, with clinical reports describing symptom worsening during low-estrogen phases and across reproductive transitions.

    “fluctuations in ovarian hormones influence dopaminergic and noradrenergic signaling, with clinical reports describing symptom worsening during low-estrogen phases and across reproductive transitions [137,138,139,140]”

    From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [139]

    The Discussion links estradiol to dopaminergic circuits and reports increased ADHD symptoms when estradiol was low and progesterone or testosterone was high; it also mentions case reports of premenstrual worsening. It does not address noradrenergic signaling or report symptom worsening across reproductive transitions. Its Conclusions raise stage of life as a question for future assessment, not as an observed finding. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • During periods of low oestrogen, increased ADHD symptoms and decreased response to psychostimulant medication have been described.

    “Additionally, during periods of low oestrogen, increased ADHD symptoms [30,41,91,92] and decreased response to psychostimulant medication [25,42,93,94,95] have been described.”

    From A Female-Specific Treatment Group for ADHD—Description of the Programme and Qualitative Analysis of First Experiences (2024) · cites this paper as [30]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Testosterone assay sensitivity uses inconsistent units

    Major

    The text reports testosterone measured in pg/mL, but the assay sensitivity is given as 1 pg/dL. These units are not consistent with the stated analyte units and differ by a factor of 100, so the sensitivity as written is not directly comparable to the reported concentrations.

    Reported 1 · recomputed 0.01

  • Sample type changes from saliva to serum

    Minor

    The methods say participants provided saliva and that those samples were analyzed, but the assay description identifies the measured steroids as serum steroids. The text does not describe collecting serum.

2 of 2

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2 of the 75 references couldn’t be matched to a known paper.

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Related

Authors
Roberts, B., Eisenlohr-Moul, T., & Martel, M. M.
Affiliations
  • University of Kentucky (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Martel, Michelle M.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2018-02
Volume
88
Pages
105-114
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2017.11.015
PMC
PMC5803442
OpenAlex
W2769096198
Cited by
77
References
75
Citations by year
2026: 15 · 2025: 19 · 2024: 11 · 2023: 10 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 1
FWCI
2.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-nd)
  • UNC Libraries
Funders
  • National Institutes of Health (M.M., UL1R000117)
  • National Institute of Mental Health (T.E., T32MH093315, K99MH109667)
  • National Institute on Drug Abuse (M.M., DA005312, DA035150)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
ADHD symptoms, menstrual cycle, estradiol, progesterone, testosterone, reproductive steroids, trait impulsivity, women, phase analysis, follicular phase, luteal phase, endogenous sex hormones
MeSH terms
Adolescent, Attention Deficit Disorder with Hyperactivity, Estradiol, Female, Follicular Phase, Humans, Luteal Phase, Menstrual Cycle, Progesterone, Steroids, Testosterone, Young Adult

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