Digit ratio (2D:4D) and month of birth: A link to the solstitial-melatonin-testosterone effect

Szwed, Anita; Kosińska, Magdalena; Manning, John T.

doi:10.1016/j.earlhumdev.2016.11.005

Cited by 21 publications

(30 citation statements)

References 15 publications

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“…It might therefore be surprising if 2D:4D were a predictor of sexually dimorphic phenotypic outcomes but was only a weak correlate of testosterone in amniotic fluid. However, this could be consistent with the suggestion that the 'critical period' for development of 2D:4D exists within a larger time-window of neuromuscular and cerebral sexual differentiation [15].…”

Section: Although Van Desupporting

confidence: 89%

Digit ratio (2D:4D) and prenatal/perinatal sex hormones: A response to Manning and Fink (2017)

Richards

2017

Early Human Development

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I published a Letter to the Editor of Early Human Development [1] to provide an overview and discussion of the literature examining digit ratio (2D:4D) in relation to sex hormone concentrations measured from amniotic fluid and umbilical cord blood in humans. My reason was that there exist a vast number of papers reporting on 2D:4D as a proxy for prenatal sex hormone exposure, yet relatively few that have established associations with hormones assayed during the prenatal/perinatal periods of development. My conclusion was that although the literature points towards a negative correlation between 2D:4D and prenatal/perinatal androgen exposure, the link remains tenuous, with most reported effects not being statistically significant. Manning and Fink [2] responded to this Letter with three main points: (1) that there are currently six (rather than four) papers relating to 2D:4D and sex hormones measured from umbilical cord blood, (2) that statistically significant correlations between 2D:4D and perinatal androgen levels in males have been reported, and (3) that examination of maternal circulating sex hormones during the first trimester may present an opportunity to better understand how early exposure to sex hormones relates to 2D:4D in humans. I would like to take the opportunity to extend my thanks to Manning and Fink for raising these important points, and to Early Human Development for inviting me to write this response.

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Section: Although Van Desupporting

confidence: 89%

Digit ratio (2D:4D) and prenatal/perinatal sex hormones: A response to Manning and Fink (2017)

Richards

2017

Early Human Development

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“…(2) The 2D:4D appears to be lower in people born in late autumn, possibly because of the effects of melatonin on fetal testosterone. 40 This time of season overlaps with the same period (late summer to early winter) in which ALS birth rates have been reported to be increased. 41 A future study on season/ALS/2D:4D interactions will be possible once sufficient data on these variables are collected.…”

Section: Discussionmentioning

confidence: 74%

Does the index-to-ring finger length ratio (2D:4D) differ in amyotrophic lateral sclerosis (ALS)? Results from an international online case–control study

Kullmann

Pamphlett

2017

BMJ Open

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ObjectivesThe ratio of the length of the index finger (2D) to the ring finger (4D) (2D:4D) has been reported to be lower (ie, 2D<4D) in people with amyotrophic lateral sclerosis (ALS) than non-ALS controls. This has led to suggestions that exposure to increased prenatal testosterone, which also lowers this ratio, could be a risk factor for ALS. In an attempt to test this hypothesis, we examined 2D:4Ds from large numbers of patients with ALS and controls.SettingAn online multilingual questionnaire enabling respondents to measure their own index and ring finger lengths.ParticipantsOf the initial 949 respondents, 572 remained for analysis after elimination for inability to straighten fingers, not answering the question, statistical outliers and aged <40 years. Respondents remaining for analysis were 202 patients with ALS (125 males, 77 females) and 370 non-ALS controls (112 males, 258 females).ResultsUnpaired t-tests with 95% CIs were used to assess differences in mean 2D:4Ds. Males had significantly lower mean 2D:4Ds than females, in both ALS and control groups, for both left and right hands. No significant differences were found in 2D:4Ds between ALS and control groups, in either males or females, for either left or right hands. Receiver operating characteristic curves showed no power for 2D:4Ds to predict ALS status in either males or females.Conclusions2D:4Ds did not differ between patients with ALS and controls in this study. This was despite the dataset being large enough to confirm the established finding of lower 2D:4Ds in males compared with females. These findings do not support the hypothesis that exposure to increased prenatal testosterone is a risk factor for ALS. A putative lower 2D:4D has been proposed to explain the link between ALS and exercise, but our results indicate that other exercise-related factors are more likely to explain this association.

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“…[21][22][23] Finally, metacarpophalangeal growth, as measured by the 2nd-to-4th digit ratio (2D:4D), is another process that has been shown to be quite sensitive to intra-uterine sex steroid exposure. [24][25][26][27][28][29][30] For all of the aforementioned parameters, a rise in sex steroid levels is expected to lead to a similar, incremental, linear change in the hormonal markereither as an increase or a decrease in that specific parameter, 31,32 based on both molecular and clinical studies of animal and human samples. [9][10][11][12][13][14][15][16][17][18][19][20][21] One marker may be positively correlated with androgen exposure and negatively correlated with estrogen exposure (e.g., AGD 11,12 ), and another positively correlated with estrogen exposure and negatively correlated with androgen exposure (e.g., 2D:4D 12,25,27,30 ).…”

Section: Introductionmentioning

confidence: 99%

“…For example, penile length/width and AGD are androgenic markers that show significant development during the first [8-14 gestational weeks (gw) 12,33 ] or second trimester (12-20 gw 12 ), respectively. Significant alterations in 2D:4D ratio and VMI may be first detectable at the end of the first (12-14 gw 12,25,27,30 ) or second trimester (24 gw onward 34 ), respectively. Finally, vulvar/scrotal pigmentation and areolar pigmentation may be most responsive to sex steroid levels throughout the first (8-14 gw 35 ) or second trimester (20 gw onward 36 ), respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Some hormonal markers, which have been better studied than others, were shown to be sexually dimorphic traits (AGD: males > > females -Cohen's d~1.00; 2D:4D: male < females -Cohen's d~0.4-0.6), with the important distinction that the sex difference in AGD can be altered by additional sex steroid exposures at any point during an individual's lifetime, 11,13,40 while the sex difference in 2D:4D ratio is largely determined in utero in a narrow time window at the end of the first trimester, with little further variation until adulthood. [24][25][26][27]30,41 In contrast to the data available for AGD and 2D:4D ratio, there are little or no newborn/infant data on other putative androgenic or estrogenic indices such as VMI or vulvar/scrotal/areolar pigmentation. Even for those hormonal markers that have been better studied (e.g., AGD), the most reliable and accurate method of measurement is still unclear (i.e., in boys, whether AGD should be measured from the anus to the base of the penis -AGD-penisor from the anus to the scrotum -AGD-scrotum-; in girls, whether it should be measured from the anus to the clitoris -AGDclitoris-or from the anus to the rear rim of the vulva -AGDfourchette- 9,10,42,43 ).…”

Section: Introductionmentioning

confidence: 99%

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Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study

Nguyen

Monnier

Muckle

et al. 2019

J Dev Orig Health Dis

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Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) – the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (β=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: β=0.338, P=0.031; 2D:4D – right: β=−0.207, P=0.040; left: β=−0.276, P=0.006; AGD-fourchette − β=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (β=0.290, P=0.048), as well as right arm circumference (β=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.

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Digit ratio (2D:4D) and month of birth: A link to the solstitial-melatonin-testosterone effect

Cited by 21 publications

References 15 publications

Digit ratio (2D:4D) and prenatal/perinatal sex hormones: A response to Manning and Fink (2017)

Digit ratio (2D:4D) and prenatal/perinatal sex hormones: A response to Manning and Fink (2017)

Does the index-to-ring finger length ratio (2D:4D) differ in amyotrophic lateral sclerosis (ALS)? Results from an international online case–control study

Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study

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