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OYEYEMI Fatai Bolaji, ADEBAYO John Oluwafemi, OYEYEMI Adekunle Wahab, ADEOL AIyabo Cecilia, AYANWOLE Elizabeth Tope, JEGEDE Febisola Oluwatoyin, OGUNSAKIN Ruth Oluwakemi. Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria[J]. Biomedical and Environmental Sciences, 2018, 31(7): 539-544. doi: 10.3967/bes2018.073
Citation: OYEYEMI Fatai Bolaji, ADEBAYO John Oluwafemi, OYEYEMI Adekunle Wahab, ADEOL AIyabo Cecilia, AYANWOLE Elizabeth Tope, JEGEDE Febisola Oluwatoyin, OGUNSAKIN Ruth Oluwakemi. Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria[J]. Biomedical and Environmental Sciences, 2018, 31(7): 539-544. doi: 10.3967/bes2018.073

Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria

doi: 10.3967/bes2018.073
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  • Corresponding author: OYEYEMI Fatai Bolaji, E-mail:bolaji@icgeb.res, in or bollergene@gmail.com
  • Received Date: 2018-01-26
  • Accepted Date: 2018-06-15
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  • [1] Manning JT, Scutt D, Wilson J, et al. The ratio of 2nd to 4th digit length:a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod (Oxford, England), 1998; 13, 3000-4. doi:  10.1093/humrep/13.11.3000
    [2] Zheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios. Proc Natl Acad Sci USA, 2011; 108, 16289-94. doi:  10.1073/pnas.1108312108
    [3] Manning J, Bundred P. The ratio of second to fourth digit length and age at first myocardial infarction in men:a link with testosterone? Br J Cardiol, 2001; 8, 720-3.
    [4] Oyeyemi BF, Iyiola OA, Oyeyemi AW, et al. Sexual dimorphism in ratio of second and fourth digits and its relationship with metabolic syndrome indices and cardiovascular risk factors. J Res Med Sci, 2014; 19, 234-9. http://www.ncbi.nlm.nih.gov/pubmed/24949031
    [5] Fink B, Manning J, Neave N. The 2nd-4th digit ratio (2D:4D) and neck circumference:implications for risk factors in coronary heart disease. Int J Obes (Lond), 2006; 30, 711-4. doi:  10.1038/sj.ijo.0803154
    [6] Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome-a new worldwide definition. The Lancet, 2005; 366, 1059-62. doi:  10.1016/S0140-6736(05)67402-8
    [7] Bolat D, Kocabas GU, Kose T, et al. The relationship between the second-to-fourth digit ratios and lifelong premature ejaculation:a prospective, comparative study. Andrology, 2017; 5, 535-40. doi:  10.1111/andr.12318
    [8] Klimek M, Galbarczyk A, Nenko I, et al. Digit ratio (2D:4D) as an indicator of body size, testosterone concentration and number of children in human males. Ann Hum Biol, 2014; 41, 518-23. doi:  10.3109/03014460.2014.902993
    [9] García-Cruz E, Huguet J, Piqueras M, et al. Second to fourth digit ratio, adult testosterone level and testosterone deficiency. BJU International, 2012; 109, 266-71. doi:  10.1111/j.1464-410X.2011.10249.x
    [10] Manning JT, Wood S, Vang E, et al. Second to fourth digit ratio (2D:4D) and testosterone in men. Asian J Androl, 2004; 6, 211-5. http://kns.cnki.net/KCMS/detail/detail.aspx?filename=yznk200403004&dbname=CJFD&dbcode=CJFQ
    [11] Klimek M, Galbarczyk A, Colleran H, et al. Digit ratio (2D:4D) does not correlate with daily 17beta-estradiol and progesterone concentrations in healthy women of reproductive age. Am J Hum Biol, 2015; 27, 667-73. doi:  10.1002/ajhb.22717
    [12] Hönekopp J, Bartholdt L, Beier L, et al. Second to fourth digit length ratio (2D:4D) and adult sex hormone levels:New data and a meta-analytic review. Psychoneuroendocrinology, 2007; 32, 313-21. doi:  10.1016/j.psyneuen.2007.01.007
    [13] Faul F, Erdfelder E, Buchner A, et al. Statistical power analyses using G*Power 3.1:tests for correlation and regression analyses. Behav Res Methods, 2009; 41, 1149-60. doi:  10.3758/BRM.41.4.1149
    [14] Oyeyemi BF, Ologunde CA, Olaoye AB, et al. FTO Gene Associates and Interacts with Obesity Risk, Physical Activity, Energy Intake, and Time Spent Sitting:Pilot Study in a Nigerian Population. Journal of obesity, 2017; 2017. doi: 10.1155/2017/3245270.
    [15] Manning JT, Fink B. Digit ratio (2D:4D), dominance, reproductive success, asymmetry, and sociosexuality in the BBC Internet Study. Am J Hum Biol, 2008; 20, 451-61. doi:  10.1002/(ISSN)1520-6300
    [16] Hönekopp J, Voracek M, Manning JT. 2nd to 4th digit ratio (2D:4D) and number of sex partners:Evidence for effects of prenatal testosterone in men. Psychoneuroendocrinology, 2006; 31, 30-7. doi:  10.1016/j.psyneuen.2005.05.009
    [17] Kelly DM, Jones TH. Testosterone and obesity. Obes Rev, 2015; 16, 581-606. doi:  10.1111/obr.2015.16.issue-7
    [18] Moon H, Choi I, Kim S, et al. Cross-sectional association between testosterone, sex hormone-binding globulin and metabolic syndrome:The Healthy Twin Study. Clin Endocrinol, 2017; 87, 523-531. doi:  10.1111/cen.2017.87.issue-5
    [19] Reue K. Sex differences in obesity:X chromosome dosage as a risk factor for increased food intake, adiposity and co-morbidities. Physiol Behav, 2017; 176, 174-82. doi:  10.1016/j.physbeh.2017.02.040
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Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria

doi: 10.3967/bes2018.073
    Corresponding author: OYEYEMI Fatai Bolaji, E-mail:bolaji@icgeb.res, in or bollergene@gmail.com
OYEYEMI Fatai Bolaji, ADEBAYO John Oluwafemi, OYEYEMI Adekunle Wahab, ADEOL AIyabo Cecilia, AYANWOLE Elizabeth Tope, JEGEDE Febisola Oluwatoyin, OGUNSAKIN Ruth Oluwakemi. Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria[J]. Biomedical and Environmental Sciences, 2018, 31(7): 539-544. doi: 10.3967/bes2018.073
Citation: OYEYEMI Fatai Bolaji, ADEBAYO John Oluwafemi, OYEYEMI Adekunle Wahab, ADEOL AIyabo Cecilia, AYANWOLE Elizabeth Tope, JEGEDE Febisola Oluwatoyin, OGUNSAKIN Ruth Oluwakemi. Second to Fourth Digit Ratio (2D: 4D) as a Predictor of Adult Circulating Sex Hormones and Overweight/Obesity in Ado-Ekiti Nigeria[J]. Biomedical and Environmental Sciences, 2018, 31(7): 539-544. doi: 10.3967/bes2018.073
  • The ratio of the second-to-fourth digit length (2D:4D) has been shown to be sexually dimorphic, with males having lower mean than females[1] and the ratio relates to masculinity and femininity in adults. 2D:4D is influenced by digit growth pattern which is related to the ratio of prenatal androgen to estrogen levels in the later part of the first trimester[2]. Hormonal modulation during puberty and postnatal sex hormone exposure have minimal effect on 2D:4D because it is slightly affected by puberty and there is a little increase during childhood once it is determined prenatally. This trait is likely to be a viable biological marker of early developmental processes[1]. In particular, 2D:4D can be described as an indicator of prenatal hormonal levels in which ratio/balance of androgen (testosterone) to estrogen is inversely related to 2D:4D[2].

    From the above, it could be suggested that 2D:4D have an impact on later life phenotypes. Researchers have shown that a high 2D:4D ratio may be a pointer to early myocardia infraction (MI) in men[3], it is also a positive correlated of body mass index (BMI), neck circumference (NC), waist circumference (WC), waist to height ratio (WHtR) and waist to hip ratio (WHR)[4, 5]. Since previous studies have suggested that BMI, WHtR, WC and NC can be a simple screening tool for identifying overweight and metabolic syndrome (MetS)[5, 6], 2D:4D measure could serve as a simple tool for measuring overweight and metabolic syndrome.

    Furthermore, 2D:4D ratio have been implicated in sexual dysfunction, fertility/infertility and reproductive success[7]. Due to its relationship with fertility and reproductive success, some studies have shown that 2D:4D is related with adult sex hormone concentrations[1, 8-10], but others have reported no significant relationship[7, 11, 12]. The purpose of this study is to evaluate the association between 2D:4D, sex hormone levels, and overweight.

    This study was performed at the Federal Polytechnic Ado-Ekiti, Ekiti State, Nigeria (FPA), the protocol for the study was approved by FPA ethics committee. Written informed consent was obtained from all participants in response to a full description of the study. The study was conducted in accordance with the Declaration of Helsinki, and all the relevant legislation and ethical procedures recommended for assays for human beings. Participants with unstable hormone level and females on mensuration were excluded.

    The G* Power software version 3.1.9.2[13] was used for power analysis. A priori power analysis was based on bivariate correlation model at α = 0.05 significance level, to reveal a medium effect size (d = 0.5) with 80% power, 110 participants in each study arm (making a total of 220 participants) were recruited for this study.

    About 1 mL of venous blood was taken from all participants between 08:00 and 10:00 (approximately five to ten days after onset of menstruation in female participants because sex hormone levels remain relatively stable during this period). Serum was obtained, aliquoted, and stored at -20 ℃ before hormone assays. Serum testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured with enzyme-linked immunosorbent assay (ELISA) method using Calbiotech ELISA kits.

    The lengths of the second and fourth digits were directly obtained by measuring the shortest distance in 0.01 mm increments between the ventral proximal crease of the digit and the fingertip using a digital Vernier caliper. If there was a band of creases at the base of the digit, we measured from the most proximal of these. This measure was conducted two times at 2- or 4- days interval in 70 subjects to assess measurement repeatability.

    Body weight, height, WC, hip circumference (HC), and NC were measured with standard procedure, while overweight predictors: BMI, WHtR, and WHR were calculated as weight (kg) divided by height (m) squared, WC divided by height, and WC divided by HC, respectively. Overweight was defined as BMI ≥ 25.0 kg/m2; abdominal overweight was defined as WC > 80 cm and > 90 cm for female and male respectively; WHR > 0.85 and > 0.90 for female and male respectively, and WHtR > 0.5. A P value of < 0.05 was deemed statistical significance in this two-tailed test.

    Continuous and discrete variables were expressed as mean ± standard deviation (SD) and numbers and percentages respectively. Shapiro-Wilk (P > 0.05) was used for normality tests to evaluate the distributions of numeric variables. Parametric Student's t-test was employed to assess difference in normally distributed data, and Cohen's d was used to calculate effect sizes of group differences, while Mann-Whitney U-tests was applied to test differences in variables with a skewed distribution. Correlation coefficient was computed by Pearson's and Spearman test for normal and skewed data respectively. Partial correlation was also calculated to remove confounding effects of age. For ease of comparison with findings from other studies, parametric statistical analysis for non-normally distributed data was used. Similar statistical significance in both instances was observed.

    Reliability and reproducibility of finger length measurement was confirmed with intra-class correlation coefficients (ICC) (two-way mixed, single measures with absolute agreement). Association between 2D:4D ratio and other parameters (Normalized sex steroid levels and overweight) was computed using both normal and adjusted logistic regression. All statistical analyses were conducted using IBM SPSS (Statistical Package for Social Sciences, release 24.0) for Mac.

    This study recruited 220 participants (50% are female) age between 17 and 34 years, (mean ± standard deviation; female 23.10 ± 3.61 and male 23.62 ± 3.57). Most parameters tested (except 2D:4D, BMI, age and sex hormones) were significantly higher in male (P < 0.05) (Table 1). Sexual dimorphism was reported in both left and right-hand 2D:4D, as the ratio was significantly higher in female than in male.

    Description Female (n = 110) Male (n = 110) P
    Age (years) 23.10 ± 3.61 23.62 ± 3.57 0.286
    Height (cm) 161.03 ± 4.51 169.10 ± 5.20 < 0.01
    Body weight (kg) 64.05 ± 8.51 68.45 ± 13.66 < 0.01
    BMI (kg/m2) 24.67 ± 2.96 24.02 ± 5.10 0.25
    NC (cm) 32.69 ± 4.47 36.56 ± 4.65 < 0.01
    WC (cm) 74.56 ± 16.82 84.16 ± 10.26 < 0.01
    WHtR 0.463 ± 0.10 0.499 ± 0.07 < 0.01
    HC (cm) 89.57 ± 8.76 98.04 ± 7.12 < 0.01
    WHR 0.823 ± 0.127 0.857 ± 0.064 < 0.05
    R2D:4D 0.9904 ± 0.032 0.9565 ± 0.037 < 0.01
    L2D:4D 0.9839 ± 0.031 0.9560 ± 0.034 < 0.01
    Testosterone (ng/mL) 0.66 ± 0.29 5.42 ± 2.82 < 0.01
    FSH (mIU/mL) 13.58 ± 5.73 4.57 ± 2.38 < 0.01
    LH (mIU/mL) 13.47 ± 7.61 4.09 ± 2.52 < 0.01
    Note. BMI: Body mass index; NC: Neck circumference; WC: Waist Circumference; WHtR: Waist to height ratio; HC: Hip ratio; WHR: Waist to hip ratio; R2D:4D: right second to fourth digit ratio; L2D:4D: left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: leuteinizing hormone.

    Table 1.  Demographics, Anthropometric Parameters, and Sex Hormones Level of a Study Population in Ado-Ekiti, Nigeria

    There was a strong significant correlation between 2D:4D calculated at first and second measurement of digit lengths [ICC (95% CI; P < 0.01) 0.974 (0.958-0.984) and 0.931 (0.888-0.957) for right and left hand respectively].

    Both Pearson and Spearman's correlation showed significant (P < 0.01) positive relationship between 2D:4D and overweight measures (BMI, NC, WC, WHtR, and WHR), even after adjusting for confounding factor (age). We reported positive correlation with testosterone but negative correlation with LH and FSH in females (Table 2). This implies that 2D:4D can be used as their predictor. As shown in Table 3, regression model revealed that 2D:4D can predict overweight measures (BMI, NC, WC, WHtR, and WHR) and sex hormones (P < 0.01).

    Description Female Male
    R2D:4D L2D:4D R2D:4D L2D:4D
    Pearson's (r) SP Pearson's (r) SP Pearson's (r) SP Pearson's (r) SP
    BMI (kg/m2) 0.766** 0.650** 0.729** 0.637** 0.754** 0.822** 0.798** 0.853**
    BMI (kg/m2)CA 0.765** 0.731** 0.750** 0.795**
    NC (cm) 0.713** 0.672** 0.722** 0.676** 0.880** 0.875** 0.902** 0.913**
    NC (cm)CA 0.712** 0.722** 0.879** 0.902**
    WC (cm) 0.591** 0.541** 0.563** 0.527** 0.864** 0.823** 0.934** 0.914**
    WC (cm)CA 0.589** 0.563** 0.862** 0.934**
    WHtR 0.577** 0.549** 0.550** 0.536** 0.858** 0.821** 0.925** 0.921**
    WHtRCA 0.575** 0.550** 0.856** 0.925**
    WHR 0.453** 0.397** 0.418** 0.388** 0.636** 0.559** 0.692** 0.607**
    WHRCA 0.450** 0.417** 0.632** 0.689**
    Testosterone (ng/mL) 0.397** 0.411** 0.405** 0.429** -0.592** -0.619** -0.591** -0.589**
    Testosterone (ng/mL)CA 0.396** 0.405** -0.601** -0.598**
    FSH (mIU/mL) -0.426** -0.449** -0.425** -0.440** 0.728** 0.735** 0.771** 0.800**
    FSH (mIU/mL)CA -0.426** -0.424** 0.725** 0.768**
    LH (mIU/mL) -0.337** -0.303** -0.292** -0.246** 0.573** 0.497** 0.580** 0.532**
    LH (mIU/mL)CA -0.333** -0.293** 0.566** 0.574**
    Note. All correlations reported are two-tailed. CAControlled for age. **significant at P < 0.01. SP: Spearman's rho. BMI: Body mass index; NC: Neck circumference; WC: Waist Circumference; WHtR: Waist to height ratio; HC: Hip ratio; WHR: Waist to hip ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone.

    Table 2.  Correlations between 2D:4D with Both Overweight/Obesity and Sex Hormones in the Study Population

    Description Female, β (95% CI)* Male, β (95% CI)*
    R2D:4D L2D:4D R2D:4D L2D:4D
    BMI (kg/m2) 1.27 (1.06; 1.48) 1.23 (1.01; 1.46) 1.92 (1.59; 2.25) 2.19 (1.87; 2.52)
    BMI (kg/m2)CA 1.26 (1.05; 1.47) 1.23 (1.00; 1.46) 1.92 (1.58; 2.25) 2.19 (1.86; 2.51)
    NC (cm) 1.35 (1.08; 1.62) 1.42 (1.15; 1.69) 1.34 (1.20; 1.48) 1.47 (1.33; 1.61)
    NC (cm)CA 1.34 (1.07; 1.62) 1.41 (1.14; 1.69) 1.33 (1.19; 1.47) 1.46 (1.32; 1.59)
    WC (cm) 1.93 (1.42; 2.44) 1.88 (1.34; 2.41) 1.24 (1.11; 1.37) 1.43 (1.34; 1.53)
    WC (cm)CA 1.93 (1.41; 2.44) 1.87 (1.34; 2.41) 1.24 (1.10; 1.37) 1.43 (1.33; 1.52)
    WHtR 1.89 (1.37; 2.41) 1.84 (1.30; 2.38) 1.33 (1.18; 1.47) 1.53 (1.42; 1.64)
    WHtRCA 1.88 (1.36; 2.40) 1.84 (1.29; 2.38) 1.32 (1.17; 1.46) 1.52 (1.41; 1.63)
    WHR 0.98 (0.61; 1.34) 0.91 (0.54; 1.29) 0.56 (0.43; 0.69) 0.66 (0.53; 0.79)
    WHRCA 0.97 (0.61; 1.34) 0.91 (0.53; 1.29) 0.56 (0.43; 0.69) 0.66 (0.52; 0.79)
    Testosterone (ng/mL) 2.95 (1.65; 4.25) 3.34 (2.04; 4.63) -3.83 (-4.83; -2.83) -4.10 (-5.17; -3.03)
    Testosterone(ng/mL)CA 2.97 (1.66; 4.27) 3.34 (2.04; 4.64) -3.90 (-4.91; -2.90) -4.16 (-5.24; -3.08)
    FSH (mIU/mL) -2.18 (-3.25; -1.10) -2.20 (-3.30; -1.10) 4.99 (4.17; 5.80) 5.74 (4.97; 6.51)
    FSH (mIU/mL)CA -2.16 (-3.25; -1.08) -2.19 (-3.30; -1.09) 5.04 (4.22; 5.86) 5.79 (5.01; 6.57)
    LH (mIU/mL) -2.67 (-4.08; -1.25) -2.15 (-3.63; -0.67) 4.95 (3.72; 6.18) 5.44 (4.13; 6.74)
    LH (mIU/mL)CA -2.56 (-3.94; -1.18) -2.09 (-3.53; -0.65) 4.91 (3.67; 6.16) 5.39 (4.08; 6.71)
    Note. CAControlled for age, *regression was significant at P < 0.01. BMI: Body mass index; NC: Neck circumference; WC: Waist Circumference; WHtR: Waist to height ratio; HC: Hip ratio; WHR: Waist to hip ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone.

    Table 3.  Regression Analysis of 2D:4D as a Predictive Factor for Overweight/Obesity and Sex Hormones in an Adult Population in Ado-Ekiti Nigeria

    More so, as shown in Supplementary Table S1 (available in www.besjournal.com), overweight individuals had significantly higher 2D:4D at P < 0.01. Also, serum testosterone level was significantly higher and lower (high effect size and P < 0.01) in overweight females and males respectively, while a direct opposite was observed in both FSH and LH levels (Supplementary Tables S1-S8, available in www.besjournal.com).

    Description Female Male
    Normal (n = 55) Obesity (n = 55) Z (η2) Normal (n = 55) Obesity (n = 55) Z (η2)
    R2D:4D 0.9727
    (0.9349-1.0112)
    1.0112
    (0.9597-1.1070)
    -5.455
    (0.2730)**
    0.9312
    (0.8670-0.9736)
    0.9823
    (0.9522-1.0691)
    -8.086
    (0.5998)**
    L2D:4D 0.9719
    (0.8911-0.9997)
    1.0003
    (0.9541-1.1028)
    -5.455
    (0.2730)**
    0.9300
    (0.8707-0.9619)
    0.9822
    (0.9632-1.0380)
    -9.042
    (0.7501)**
    Testosterone
    (ng/mL)
    0.4496
    (0.1529-1.040)
    0.9129
    (0.4244-1.2525)
    -7.856
    (0.5662)**
    7.5898
    (2.5208-9.9924)
    3.0538
    (1.6429-9.7627)
    -4.621
    (0.1959)**
    FSH
    (mIU/mL)
    16.6604
    (4.4151-26.8491)
    9.1132
    (5.3396-23.6415)
    -6.035
    (0.3341)**
    2.4717
    (1.0019-4.1698)
    6.0943
    (4.3396-10.3396)
    -9.042
    (0.7501)**
    LH
    (mIU/mL)
    16.9018
    (4.2277-30.4286)
    8.732
    (4.4911-28.9553)
    -3.611
    (0.1196)**
    2.4375
    (0.7411-8.1517)
    5.0268
    (1.8125-11.9018)
    -4.420
    (0.1792)**
    Note. Data are presented as median (minimum - maximum) but Z2) column represent effect size. BMI: Body mass index; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table S1.  Relationship between Overweight/Obesity (BMI > 25.0 kg/m2), 2D:4D, and Sex Hormones

    Description Female Male
    Normal Obesity t (Cohen's d) Normal Obesity t (Cohen's d)
    R2D:4D 0.9732 ± 0.021 1.0075 ± 0.032 -6.66 (1.27)** 0.9295 ± 0.028 0.9834 ± 0.023 -11.10 (2.10)**
    L2D:4D 0.9687 ± 0.024 0.9991 ± 0.030 -5.81 (1.12)** 0.9279 ± 0.023 0.9841 ± 0.017 -14.61 (2.78)**
    Testosterone (ng/mL) 0.4403 ± 0.192 0.8823 ± 0.187 -12.25 (2.33)** 6.619 ± 2.78 4.221 ± 2.33 4.90 (0.93)**
    FSH (mIU/mL) 16.97 ± 5.82 10.19 ± 3.02 7.68 (1.46)** 2.639 ± 0.88 6.497 ± 1.75 -14.64 (2.79)**
    LH (mIU/mL) 16.59 ± 8.30 10.34 ± 5.30 4.71 (0.90)** 3.106 ± 2.20 5.076 ± 2.45 -4.44 (0.85)**
    Note. Data are presented as mean ± standard deviation. BMI: Body mass index; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 2.  Relationship between Overweight/Obesity (BMI > 25.0kg/m2), 2D:4D, and Sex Hormones

    Description Female (n = 55) Male (n = 55)
    Normal Obesity t (Cohen's d) Normal Obesity t (Cohen's d)
    R2D:4D 0.9759 ± 0.024 1.0049 ± 0.033 -5.33 (1.01)** 0.9320 ± 0.032 0.9809 ± 0.024 -9.21 (1.73)**
    L2D:4D 0.9705 ± 0.026 0.9973 ± 0.031 -4.94 (0.94)** 0.9301 ± 0.026 0.9819 ± 0.019 -11.84 (2.27)**
    Testosterone (ng/mL) 0.4813 ± 0.243 0.8413 ± 0.214 -8.23 (1.57)** 6.675 ± 2.74 4.165 ± 2.31 5.19 (0.99)**
    FSH (mIU/mL) 16.57 ± 6.16 10.59 ± 3.18 6.39 (1.22)** 2.761 ± 1.05 6.376 ± 1.91 -12.30 (2.35)**
    LH (mIU/mL) 16.28 ± 8.56 10.65 ± 5.25 4.15 (0.79)** 2.996 ± 2.02 5.186 ± 2.55 -5.04 (0.95)**
    Note. Data are presented as mean ± standard deviation. WHtR: Waist to height ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 3.  Relationship between Overweight/Obesity (WHtR > 0.50), 2D:4D, and Sex Hormones

    Description Female (n = 55) Male (n = 55)
    Normal Obesity Z2) Normal Obesity Z2)
    R2D:4D 0.9727
    (0.9349-1.0139)
    0.9994
    (0.9570-1.1070)
    -4.397
    (0.1774)**
    0.9312
    (0.8670-1.0127)
    0.9795
    (0.9518-1.0691)
    -7.096
    (0.4620)**
    L2D:4D 0.9719
    (0.8911-1.0031)
    0.9920
    (0.9541-1.1028)
    -4.397
    (0.1774)**
    0.9300
    (0.8707-0.9841)
    0.9785
    (0.9489-1.0380)
    -8.101
    (0.6021)**
    Testosterone
    (ng/mL)
    0.4522
    (0.1529-1.2525)
    0.8452
    (0.1658-1.2525)
    -6.442
    (0.3807)**
    7.5898
    (2.5208-9.9924)
    3.0381
    (1.6429-9.7627)
    -4.660
    (0.1992)**
    FSH
    (mIU/mL)
    16.6604
    (4.8302-26.8491)
    10.3585
    (4.4151-23.6415)
    -5.070
    (0.2358)**
    2.5283
    (1.0019-5.8868)
    6.0943
    (2.1698-10.3396)
    -8.439
    (0.6534)**
    LH
    (mIU/mL)
    16.9018
    (4.2277-30.4286)
    8.9107
    (4.4911-28.9554)
    -2.861
    (0.0751)**
    2.2589
    (0.7411-7.9732)
    5.0268
    (1.8125-11.9018)
    -4.906
    (0.2208)**
    Note. Data are presented as median(minimum - maximum) but Z2) column represent effect size. WHtR: Waist to height ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 4.  Relationship between Overweight/Obesity (WHtR > 0.50) and 2D:4D and Sex Hormones

    Description Female Male
    Normal (n = 56) Obesity (n = 54) t (Cohen's d) Normal (n = 80) Obesity (n = 30) t (Cohen's d)
    R2D:4D 0.9766 ± 0.024 1.0047 ± 0.033 -5.14 (0.97)** 0.9453 ± 0.034 0.9862 ± 0.028 -5.88 (1.31)**
    L2D:4D 0.9712 ± 0.026 0.9971 ± 0.031 -4.75 (0.91)** 0.9428 ± 0.029 0.9913 ± 0.020 -8.38 (1.95)**
    Testosterone (ng/mL) 0.490 ± 0.249 0.839 ± 0.216 -7.87 (1.50)** 5.832 ± 2.77 4.324 ± 2.69 2.56 (0.55)**
    FSH (mIU/mL) 16.41 ± 6.23 10.65 ± 3.18 6.07 (1.16)** 3.777 ± 2.06 6.679 ± 1.82 -678 (1.49)**
    LH (mIU/mL) 16.10 ± 8.53 10.74 ± 5.26 3.93 (0.76)** 3.598 ± 2.24 5.404 ± 2.77 -3.52 (0.72)**
    Note.Data are presented as mean ± standard deviation. WC: Waist Circumference; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 5.  Relationship between Overweight/Obesity (WC > 80 cm for Female and > 90 cm for male) and 2D:4D and Sex Hormones

    Description Female Male
    Normal (n = 56) Obesity (n = 54) Z (η2) Normal (n = 80) Obesity (n = 30) Z (η2)
    R2D:4D 0.9731
    (0.9349-1.0139)
    0.9994
    (0.9570-1.1070)
    -4.180
    (0.1603)**
    0.9498
    (0.8670-1.0127)
    0.9810
    (0.9535-1.0691)
    -5.000
    (0.2294)**
    L2D:4D 0.9720
    (0.8911-1.0074)
    0.9919
    (0.9541-1.1028)
    -4.177
    (0.1601)**
    0.9443
    (0.8707-0.9876)
    0.9873
    (0.9669-1.0380)
    -6.896
    (0.4363)**
    Testosterone
    (ng/mL)
    0.4529
    (0.1529-1.2525)
    0.8315
    (0.1658-1.2525)
    -6.264
    (0.3600)**
    6.4833
    (2.3627-9.0024)
    3.2744
    (1.6429-9.7627)
    -2.316
    (0.0492)**
    FSH
    (mIU/mL)
    16.5849
    (4.8302-26.8491)
    10.3774
    (4.4151-23.6415)
    -4.843
    (0.2152)**
    3.2642
    (1.0019-9.6604)
    6.1321
    (4.8491-10.3396)
    -5.960
    (0.3259)**
    LH
    (mIU/mL)
    16.2098
    (4.2277-30.4286)
    8.9554
    (4.4911-28.9554)
    -2.661
    (0.0650)**
    2.8170
    (0.7411-8.1518)
    4.8036
    (1.8125-11.9018)
    -2.933
    (0.0789)**
    Note.Data are presented as median (minimum - maximum) but Z (η2) column represent effect size. WC: Waist Circumference; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 6.  Relationship between Overweight/Obesity (WC > 80 cm for Female and > 90 cm for male), 2D:4D and Sex Hormones

    Description Female Male
    Normal (n = 57) Obesity (n = 53) t (Cohen's d) Normal (N = 58) Obesity (n = 52) t (Cohen's d)
    R2D:4D 0.9778 ± 0.025 1.0039 ± 0.033 -4.67 (0.89)** 0.9364 ± 0.035 0.9788 ± 0.024 -7.27 (1.41)**
    L2D:4D 0.9723 ± 0.027 0.9964 ± 0.031 -4.37 (0.83)** 0.9353 ± 0.031 0.9791 ± 0.021 -8.53 (1.65)**
    Testosterone (ng/mL) 0.502 ± 0.259 0.832 ± 0.219 -7.19 (1.38)** 6.610 ± 2.64 4.035 ± 2.35 5.48 (1.03)**
    FSH (mIU/mL) 16.28 ± 6.24 10.68 ± 3.22 5.85 (1.13)** 3.189 ± 1.46 6.107 ± 2.26 -8.12 (1.53)**
    LH (mIU/mL) 15.84 ± 8.64 10.92 ± 5.31 3.57 (0.69)** 3.354 ± 2.26 4.913 ± 2.56 -3.39 (0.65)**
    Note. Data are presented as mean ± standard deviation. WHR: Waist to hip ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **Significant at P < 0.01.

    Table Supplementary Table 7.  Relationship between Overweight/Obesity (WHR > 0.85 for Female and > 0.90 for male), 2D:4D and Sex Hormones

    Description Female Male
    Normal (n = 57) Obesity (n = 53) Z (η2) Normal (N = 58) Obesity (n = 52) Z (η2)
    R2D:4D 0.9734
    (0.9349-1.0160)
    0.9992
    (0.9570-1.1070)
    -3.694
    (0.1252)**
    0.9324
    (0.8670-1.0127)
    0.9743
    (0.9504-1.0691)
    -5.718
    (0.3000)**
    L2D:4D 0.9721
    (0.8911-1.0091)
    0.9901
    (0.9541-1.1028)
    -3.691
    (0.1252)**
    0.9308
    (0.8707-0.9932)
    0.9737
    (0.9468-1.0380)
    -6.352
    (0.3702)**
    Testosterone
    (ng/mL)
    0.4536
    (0.1529-1.2525)
    0.8027
    (0.1658-1.2525)
    -5.902
    (0.3196)**
    7.3212
    (2.4650-9.9924)
    2.9883
    (1.6429-9.7627)
    -4.903
    (0.2205)**
    FSH
    (mIU/mL)
    16.5094
    (4.8302-26.8491)
    10.3962
    (4.4151-23.6415)
    -4.705
    (0.2031)**
    3.0094
    (1.0019-7.0566)
    5.7830
    (2.1509-10.3396)
    -6.616
    (0.4016)**
    LH
    (mIU/mL)
    15.5179
    (4.2277-30.4286)
    9.0000
    (4.4911-28.9554)
    -2.351
    (0.0507)*
    2.3482
    (0.7411-7.9732)
    4.5134
    (1.8125-11.9018)
    -3.497
    (0.1122)**
    Note. Data are presented as median (minimum - maximum) but Z (η2) column represent effect size. WHR: Waist to hip ratio; R2D:4D: Right second to fourth digit ratio; L2D:4D: Left second to fourth digit ratio; FSH: Follicle stimulating hormone; LH: Leuteinizing hormone. **, * Significant at P < 0.01 and 0.05 respectively.

    Table Supplementary Table 8.  Relationship between Overweight/Obesity (WHR > 0.85 for Female and > 0.90 for male), 2D:4D and Sex Hormones

    The 2D:4D have been considered to be an indicator of prenatal steroid exposure that affects some of the later phenotypes which include psychological behavior like sex hormone, BMI, masculinity (Masc) and femininity (Fem) of an individual in adulthood[4], but its relationship with later life reproductive hormone have given several contradictory results[7, 8, 11, 12]. Relationship between 2D:4D with overweight/obesity measures and sex hormone among young adult in Ado-Ekiti Nigeria was investigated in this study. This is to provide insights that might elucidate the relationship between prenatal sex hormone and adult phenotypes (overweight/obesity and sex hormone) in a Nigeria population.

    We reported that males have lower 2D:4D (sexual dimorphism in 2D:4D) which is in line earlier studies[1, 4]. This is because balance in fetal sex steroid (FT/FE) exposure have varying influence on digit development in males and females[2], resulting in differences in the average 2D:4D values in later life.

    The current results showed that both left and right-hand 2D:4D might be used to predict overweight (BMI, WC, NC, WHtR, and WHR), this contributes to the growing evidence that prenatal steroid exposure (as measured by 2D:4D) is related with overweight/obesity[4, 5]. A recent genetic study buttresses this by reporting that occurrence an essential gene variant associated with obesity (FTO gene variant) might be predicted by 2D:4D[14].

    Both Spearman correlation and regression model significantly showed that 2D:4D can be used to predict reproductive functions described by adult sex steroids (FSH, LH and testosterone) levels.

    Data from this study are congruent with earlier reports that revealed a relationship between 2D:4D and reproductive success with evidence showing that 2D:4D might be a valuable predictor of male reproductive characteristics, number of children and infertility[8, 15]. More so, fertility markers like sperm count[1], sex drive, level of sexual excitement[15] and number of sexual partners per individual[16] were all related to 2D:4D. Pre-natal testosterone levels (reflected in 2D:4D values) have also been reported to predict adult testosterone concentration[8]. Similarly, another report, in males referred for prostate biopsy (those with high 2D:4D) had lower testosterone serum levels[9]. Lastly, adult testosterone concentration have been suggested to be a negative correlates of 2D:4D in men attending infertility clinic (compromised testicular function) but the relationship is weaker among non-overweight subjects[10]. Thus, they suggested that 2D:4D might be a weak correlate of adult concentrations of testosterone in men who are sampled without regard to fertility.

    The strong correlations between 2D:4D and sex hormones reported here is in congruent with previous observations[1, 8, 10]. This supported the claim that 2D:4D was an indicator of prenatal sex hormones[2], and therefore, it should have influence on adult sex hormone levels. On the other hand, other studies have reported that 2D:4D was not associated with some adult sex hormone levels[7, 10-12]. Finally, Bolat et al.[7] suggested that fetal testosterone regulates the ejaculatory process rather than the adult circulating testosterone because they reported no significant correlations between their level and self-estimated ejaculatory parameter.

    Both correlation and regression model data from this study provide evidence of an inverse and direct relationship between overweight (BMI, WHtR, WC, NC, and WHR) and testosterone in males and females, respectively. This is in line with report by Kelly and Jones[17] and a study among Korean men[18]. One possible explanation is the evidence that normal function of reproductive axis in term of gonadal hormonal play a substantial influence on energy balance and regulation of fat storage[19]. Hence, it may be explained that testosterone levels have different impact on fat storage depending on gender, reducing the storage rate in males and increasing it in females.

    A few limitations in this study should be taken into account. First, our results should be replicated in a study in which assessment of adult serum testosterone level would be based on a higher number of samples for each participant over time, since testosterone level can be influenced by many physiological and behavioural factors. Sampling over several periods will lead to more reliable and robust results. Since larger sample size gives better results, it will be essential to confirm this study with increased sample size. Lastly, measurement variability between assays due to methodology and antibodies employed will not make this an absolute result but rather a guide to the relationship between 2D:4D and adult testosterone level. Thus, validated and robust proof is warranted. Our study has some strengths which include the reliability and reproducibility of our 2D:4D measurement, collection of all female samples before mensuration, as well as objective measures of overweight.

    Our results suggest that 2D:4D ratio (a possible proxy for the prenatal hormonal environment) might have a life-long connection to adult phenotypes like overweight and reproductive fitness, with an impact on testosterone, FSH and LH in both genders.

    We thank all participants for their cooperation Adebayo S. Adewale (PhD) and Onile Olugbenga Samson (PhD) for their suggestions during manuscript drafting.

    Authors declare no competing interests.

    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

    Conceived and designed the experiments: OFB OAW. Performed the experiments: OFB AJO AIC AET JFO ORO. Analyzed the data: OFB OAW. Contributed reagents/materials/analysis tools: OFB AJO AIC AET JFO ORO. Wrote the manuscript: OFB OAW. Sample collection: OFB AJO AIC AET JFO ORO. All author read and approved the final manuscript.

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